ORCID Profile
0000-0002-4705-452X
Current Organisations
Clinical Neuropsychologist
,
Monash University
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Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1016/J.BIOPSYCH.2015.12.002
Abstract: Cannabis use has been associated with impaired cognition during acute intoxication as well as in the unintoxicated state in long-term users. However, the evidence has been mixed and contested, and no systematic reviews of the literature on neuropsychological task-based measures of cognition have been conducted in an attempt to synthesize the findings. We systematically review the empirical research published in the past decade (from January 2004 to February 2015) on acute and chronic effects of cannabis and cannabinoids and on persistence or recovery after abstinence. We summarize the findings into the major categories of the cognitive domains investigated, considering s le characteristics and associations with various cannabis use parameters. Verbal learning and memory and attention are most consistently impaired by acute and chronic exposure to cannabis. Psychomotor function is most affected during acute intoxication, with some evidence for persistence in chronic users and after cessation of use. Impaired verbal memory, attention, and some executive functions may persist after prolonged abstinence, but persistence or recovery across all cognitive domains remains underresearched. Associations between poorer performance and a range of cannabis use parameters, including a younger age of onset, are frequently reported. Little further evidence has emerged for the development of tolerance to the acutely impairing effects of cannabis. Evidence for potential protection from harmful effects by cannabidiol continues to increase but is not definitive. In light of increasing trends toward legalization of cannabis, the knowledge gained from this body of research needs to be incorporated into strategies to minimize harm.
Publisher: Springer Science and Business Media LLC
Date: 14-08-2023
DOI: 10.1038/S41593-023-01404-6
Abstract: The substantial in idual heterogeneity that characterizes people with mental illness is often ignored by classical case–control research, which relies on group mean comparisons. Here we present a comprehensive, multiscale characterization of the heterogeneity of gray matter volume (GMV) differences in 1,294 cases diagnosed with one of six conditions (attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, depression, obsessive–compulsive disorder and schizophrenia) and 1,465 matched controls. Normative models indicated that person-specific deviations from population expectations for regional GMV were highly heterogeneous, affecting the same area in % of people with the same diagnosis. However, these deviations were embedded within common functional circuits and networks in up to 56% of cases. The salience–ventral attention system was implicated transdiagnostically, with other systems selectively involved in depression, bipolar disorder, schizophrenia and attention-deficit/hyperactivity disorder. Phenotypic differences between cases assigned the same diagnosis may thus arise from the heterogeneous localization of specific regional deviations, whereas phenotypic similarities may be attributable to the dysfunction of common functional circuits and networks.
Publisher: American Psychological Association (APA)
Date: 05-2012
DOI: 10.1037/A0027693
Abstract: Inhibitory control is associated with temperament and intelligence, which together form an essential component of the ability to adaptively regulate behavior. Impairments in inhibitory control have been linked with a host of common and debilitating conditions, often in a sex-dependent manner. However, sex differences in inhibitory control are often not expressed experimentally during task performance. Here, we sought to examine how sex, temperament, and intelligence are related to different aspects of inhibitory control. We recruited a large s le of early adolescents (n = 153 mean age 12.6 years) to comprehensively investigate the relationship between sex, self-reported and parent-reported temperamental effortful control, and intelligence with different aspects of inhibitory control--namely, strategic (or proactive) control and evaluative (or reactive) control, assessed using a modified Stroop task. Compared with males, females were more efficient in their use of strategic control to reduce the magnitude of response conflict. There was no sex difference in evaluative control. Further, whereas high intelligence was associated with fewer errors for both males and females, effortful control was associated with performance accuracy only in females. These findings highlight sex differences in the relationship of inhibitory control to in idual differences in temperamental effortful control in early adolescents and reinforce the generalized positive effects of intelligence.
Publisher: Elsevier BV
Date: 12-2010
DOI: 10.1016/J.JAD.2010.02.117
Abstract: It has been suggested that patients with psychotic bipolar disorder (BDP+) might have more severe cognitive deficits than non-psychotic bipolar disorder patients (BDP-). However, only a handful of studies have compared cognition between BDP+ and BDP-. Our aim was to examine cognitive deficits associated with psychosis in BD using meta-analytic methods. After a systematic literature review, we conducted a meta-analysis on studies that compared cognition in bipolar disorder (BD) patients with and without a history of psychosis. In addition the effects of clinical and demographic confounder factors were examined with meta-regression analyses. There were no significant differences for gender and duration of illness between groups. Compared with BDP-, BDP+ patients had more inpatient admissions, a younger onset of illness and used antipsychotics more commonly. BDP+ patients also performed significantly worse in 4 of 6 cognitive domains (planning and reasoning, working memory, verbal memory and processing speed). There were also differences for some in idual tasks (List Learning, Delayed Recall, Trail Making B, Wisconsin Card Sorting Test, Digits Backwards, Stroop Interference, Semantic Fluency) with BDP+ patients showing moderately greater impairment on these tasks (d=0.30-0.55). A history of psychosis is associated with greater severity of cognitive deficits in BD. However, this effect is modest, and these findings do not suggest a complete categorical distinction between BDP+ and BDP-. Psychosis in BD might reflect partly distinct neurobiological processes.
Publisher: Frontiers Media SA
Date: 2014
Publisher: Elsevier BV
Date: 12-2022
Publisher: Oxford University Press (OUP)
Date: 25-07-2010
Publisher: Elsevier BV
Date: 07-2010
DOI: 10.1016/J.DRUGALCDEP.2010.02.012
Abstract: While long-term heroin addiction is associated with hypothalamus-pituitary-adrenal (HPA) axis dysregulation, few studies have used in vivo brain imaging to examine the impact on pituitary gland volume (PGV) or its relationship with substitution pharmacotherapy. We examined 28 heroin users stable on methadone or buprenorphine and 28 healthy controls. Heroin users exhibited larger PGVs than healthy controls, and this was particularly evident among the buprenorphine-treated group. These findings indicate that substitution pharmacotherapy may have differential effects on normalising HPA axis activity.
Publisher: Elsevier BV
Date: 05-2010
DOI: 10.1016/J.PSCYCHRESNS.2010.01.006
Abstract: This structural magnetic resonance imaging study investigated insular cortex volume in 26 patients with bipolar I disorder and 24 matched controls. While insular volume did not differ between these groups, exploratory analyses demonstrated that the number of depressive episodes correlated negatively with the anterior insular volume in the patients, suggesting it may have a role in the pathophysiology of bipolar disorder.
Publisher: Cambridge University Press
Date: 10-2009
Publisher: Elsevier BV
Date: 03-2009
DOI: 10.1016/J.SCHRES.2008.12.011
Abstract: Voxel-based morphometry (VBM) is a popular tool for mapping neuroanatomical changes in schizophrenia patients. Several recent meta-analyses have identified the brain regions in which patients most consistently show grey matter reductions, although they have not examined whether such changes reflect differences in grey matter concentration (GMC) or grey matter volume (GMV). These measures assess different aspects of grey matter integrity, and may therefore reflect different pathological processes. In this study, we used the Anatomical Likelihood Estimation procedure to analyse significant differences reported in 37 VBM studies of schizophrenia patients, incorporating data from 1646 patients and 1690 controls, and compared the findings of studies using either GMC or GMV to index grey matter differences. Analysis of all studies combined indicated that grey matter reductions in a network of frontal, temporal, thalamic and striatal regions are among the most frequently reported in literature. GMC reductions were generally larger and more consistent than GMV reductions, and were more frequent in the insula, medial prefrontal, medial temporal and striatal regions. GMV reductions were more frequent in dorso-medial frontal cortex, and lateral and orbital frontal areas. These findings support the primacy of frontal, limbic, and subcortical dysfunction in the pathophysiology of schizophrenia, and suggest that the grey matter changes observed with MRI may not necessarily result from a unitary pathological process.
Publisher: Springer Science and Business Media LLC
Date: 16-07-2013
DOI: 10.1038/TP.2013.41
Publisher: Wiley
Date: 02-2021
DOI: 10.1111/ADD.15411
Abstract: Following the recognition of ‘internet gaming disorder’ (IGD) as a condition requiring further study by the DSM‐5, ‘gaming disorder’ (GD) was officially included as a diagnostic entity by the World Health Organization (WHO) in the 11th revision of the International Classification of Diseases (ICD‐11). However, the proposed diagnostic criteria for gaming disorder remain the subject of debate, and there has been no systematic attempt to integrate the views of different groups of experts. To achieve a more systematic agreement on this new disorder, this study employed the Delphi expert consensus method to obtain expert agreement on the diagnostic validity, clinical utility and prognostic value of the DSM‐5 criteria and ICD‐11 clinical guidelines for GD. A total of 29 international experts with clinical and/or research experience in GD completed three iterative rounds of a Delphi survey. Experts rated proposed criteria in progressive rounds until a pre‐determined level of agreement was achieved. For DSM‐5 IGD criteria, there was an agreement both that a subset had high diagnostic validity, clinical utility and prognostic value and that some (e.g. tolerance, deception) had low diagnostic validity, clinical utility and prognostic value. Crucially, some DSM‐5 criteria (e.g. escapism/mood regulation, tolerance) were regarded as incapable of distinguishing between problematic and non‐problematic gaming. In contrast, ICD‐11 diagnostic guidelines for GD (except for the criterion relating to diminished non‐gaming interests) were judged as presenting high diagnostic validity, clinical utility and prognostic value. This Delphi survey provides a foundation for identifying the most diagnostically valid and clinically useful criteria for GD. There was expert agreement that some DSM‐5 criteria were not clinically relevant and may pathologize non‐problematic patterns of gaming, whereas ICD‐11 diagnostic guidelines are likely to diagnose GD adequately and avoid pathologizing.
Publisher: Frontiers Media SA
Date: 14-06-2016
Publisher: Wiley
Date: 24-05-2008
DOI: 10.1002/HBM.20412
Publisher: JMIR Publications Inc.
Date: 25-08-2023
DOI: 10.2196/44414
Abstract: Many people with harmful addictive behaviors may not meet formal diagnostic thresholds for a disorder. A dimensional approach, by contrast, including clinical and community s les, is potentially key to early detection, prevention, and intervention. Importantly, while neurocognitive dysfunction underpins addictive behaviors, established assessment tools for neurocognitive assessment are lengthy and unengaging, difficult to administer at scale, and not suited to clinical or community needs. The BrainPark Assessment of Cognition (BrainPAC) Project sought to develop and validate an engaging and user-friendly digital assessment tool purpose-built to comprehensively assess the main consensus-driven constructs underpinning addictive behaviors. The purpose of this study was to psychometrically validate a gamified battery of consensus-based neurocognitive tasks against standard laboratory paradigms, ascertain test-retest reliability, and determine their sensitivity to addictive behaviors (eg, alcohol use) and other risk factors (eg, trait impulsivity). Gold standard laboratory paradigms were selected to measure key neurocognitive constructs (Balloon Analogue Risk Task [BART], Stop Signal Task [SST], Delay Discounting Task [DDT], Value-Modulated Attentional Capture [VMAC] Task, and Sequential Decision-Making Task [SDT]), as endorsed by an international panel of addiction experts namely, response selection and inhibition, reward valuation, action selection, reward learning, expectancy and reward prediction error, habit, and compulsivity. Working with game developers, BrainPAC tasks were developed and validated in 3 successive cohorts (total N=600) and a separate test-retest cohort (N=50) via Mechanical Turk using a cross-sectional design. BrainPAC tasks were significantly correlated with the original laboratory paradigms on most metrics (r=0.18-0.63, P .05). With the exception of the DDT k function and VMAC total points, all other task metrics across the 5 tasks did not differ between the gamified and nongamified versions (P .05). Out of 5 tasks, 4 demonstrated adequate to excellent test-retest reliability (intraclass correlation coefficient 0.72-0.91, P .001 except SDT). Gamified metrics were significantly associated with addictive behaviors on behavioral inventories, though largely independent of trait-based scales known to predict addiction risk. A purpose-built battery of digitally gamified tasks is sufficiently valid for the scalable assessment of key neurocognitive processes underpinning addictive behaviors. This validation provides evidence that a novel approach, purported to enhance task engagement, in the assessment of addiction-related neurocognition is feasible and empirically defensible. These findings have significant implications for risk detection and the successful deployment of next-generation assessment tools for substance use or misuse and other mental disorders characterized by neurocognitive anomalies related to motivation and self-regulation. Future development and validation of the BrainPAC tool should consider further enhancing convergence with established measures as well as collecting population-representative data to use clinically as normative comparisons.
Publisher: Elsevier BV
Date: 11-2008
DOI: 10.1016/J.BIOPSYCH.2008.05.032
Abstract: Abnormalities of the anterior cingulate cortex (ACC) are frequently implicated in the pathophysiology of psychotic disorders, but whether such changes are apparent before psychosis onset remains unclear. In this study, we characterized prepsychotic ACC abnormalities in a s le of in iduals at ultra-high-risk (UHR) for psychosis. Participants underwent baseline magnetic resonance imaging and were followed-up over 12-24 months to ascertain diagnostic outcomes. Baseline ACC morphometry was then compared between UHR in iduals who developed psychosis (UHR-P n = 35), those who did not (UHR-NP n = 35), and healthy control subjects (n = 33). Relative to control subjects, UHR-P in iduals displayed bilateral thinning of a rostral paralimbic ACC region that was negatively correlated with negative symptoms, whereas UHR-NP in iduals displayed a relative thickening of dorsal and rostral limbic areas that was correlated with anxiety ratings. Baseline ACC differences between the two UHR groups predicted time to psychosis onset, independently of symptomatology. Subdiagnostic comparisons revealed that changes in the UHR-P group were driven by in iduals subsequently diagnosed with a schizophrenia spectrum psychosis. These findings indicate that anatomic abnormalities of the ACC precede psychosis onset and that baseline ACC differences distinguish between UHR in iduals who do and do not subsequently develop frank psychosis. They also indicate that prepsychotic changes are relatively specific to in iduals who develop a schizophrenia spectrum disorder, suggesting they may represent a diagnostically specific risk marker.
Publisher: Wiley
Date: 10-03-2010
DOI: 10.1002/HBM.20895
Publisher: Elsevier BV
Date: 06-1999
DOI: 10.1016/S0028-3932(98)00067-0
Abstract: On the covert orienting of visual attention task (COVAT), responses to targets appearing at the location indicated by a non-predictive spatial cue are faster than responses to targets appearing at uncued locations when stimulus onset asynchrony (SOA) is less than approximately 200 ms. For longer SOAs, this pattern reverses and RTs to targets appearing at uncued locations become faster than RTs to targets appearing at the cued location. This facilitation followed by inhibition has been termed the biphasic effect of non-predictive peripheral spatial cues. Currently, there is debate about whether these two processes are independent. This issue was addressed in a series of experiments where the temporal overlap between the peripheral cue and target was manipulated at both short and long SOAs. Results showed that facilitation was present only when the SOA was short and there was temporal overlap between cue and target. Conversely, inhibition occurred only when the SOA was long and there was no temporal overlap between cue and target. The biphasic effect, with an early facilitation followed by a later inhibition, occurred only when the cue duration was fixed such that there was temporal overlap between the cue and target at short but not long SOAs. In a final experiment, the duration of targets the temporal overlap between cue and target and the SOA were manipulated factorially. The results showed that facilitation occurred only when the SOA was short, there was temporal overlap between cue and target and the target remained visible until the subject responded. These results suggest that the facilitation and inhibition found on COVATs which use non-informative peripheral cues are independent processes and their presence and magnitude is related to the temporal properties of cues and targets.
Publisher: Cold Spring Harbor Laboratory
Date: 09-09-2020
DOI: 10.1101/2020.09.09.288910
Abstract: Working memory (WM) refers to the capacity to temporarily retain and manipulate finite amounts of information a critical process in complex behaviours such as reasoning, comprehension, and learning. This cognitive function is supported by a parietal-prefrontal network and linked to the activity of key neurotransmitters, such as gamma-aminobutyric acid (GABA). Impairments in WM are seen in a range of psychiatric and neurological disorders, and there are currently no effective treatments. In this study, we analysed secondary outcome measures from a trial investigating the effects of multi-day rTMS on cognition. Participants received four days of 20 Hz rTMS to an in idualised region of left parietal cortex in one week, and an in idualised region of pre-supplementary motor area (pre-SMA) in a separate week. We assessed changes to WM function before and after each week of stimulation (N = 39), and changes to GABA concentration before and after stimulation in week one using MR spectroscopy (N = 18 per stimulation condition). We hypothesised that parietal rTMS would enhance WM and alter GABA concentration at the site of stimulation, but this was not observed. Instead, we report some evidence of improved WM function following the first week of pre-SMA rTMS stimulation, and a generalised increase in GABA concentration across both parietal and pre-SMA voxels following pre-SMA rTMS. Additionally, we found that higher cardiorespiratory fitness was associated with greater WM improvement following pre-SMA stimulation. This study does not support the use of parietal multi-day rTMS for the enhancement of working memory. In contrast, the results suggest that increasing cardiorespiratory fitness may provide a novel approach to enhance the effects of pre-SMA rTMS on cognition.
Publisher: Elsevier BV
Date: 03-2007
DOI: 10.1016/J.SCHRES.2006.12.027
Abstract: Task-induced deactivations (TIDs) of midline cortical regions are readily observed in fMRI studies and may reflect elements of a 'default-mode' of brain function associated with self-directed mental processes at rest. In this study, we examined this TID phenomenon in schizophrenia and its relevance to patients' symptoms, task performance and level of emotional awareness. Relative to control subjects, patients showed significantly greater TID of the rostral anterior cingulate (rAC)/medial prefrontal cortex (mPFC) and precuneus (PrC) osterior cingulate cortex (PC). The magnitude of prefrontal TIDs was associated with patients' task performance and emotional awareness for others. The nature of these associations suggests a complex interchange between cognitive and emotional influences on the resting-state activity of these prefrontal 'default mode' regions in schizophrenia.
Publisher: SAGE Publications
Date: 02-2007
DOI: 10.1080/10398560601083191
Abstract: Objective: We sought to identify neurobiological correlates of Melbourne–Sydney rivalry through neuroimaging measures of a key brain region involved in cognitive and emotional regulation. Method: Twenty subjects from each city were recruited from two large neuroimaging databases, and were scanned on a GE Signa 1.5T magnetic resonance imaging scanner. Cortical thickness of the anterior cingulate cortex (ACC) was measured using a tessellated mesh method, after image segmentation. These measures were compared with key sporting, financial and academic variables. Results: Residents of Melbourne had a significantly thicker ACC (p 0.0001) than Sydney residents, and this difference remained significant when age and intracranial volume were controlled for (p = 0.001). This difference mirrored that in variables measuring wealth, sporting and academic success. Conclusions: The thinner ACC seen in Sydney-siders may reflect the effects of increased stress due to elevated property prices, relative lack of sporting success and other variables. An alternative explanation is that a thinner ACC is the result of increasing cortical refinement and efficiency, and a marker of a more mature city. However, if these findings are a result of latitudinal effects, this may have significant implications for residents of more northern regions of the Australian continent.
Publisher: Wiley
Date: 20-02-2007
DOI: 10.1111/J.1600-0447.2007.01002.X
Abstract: Functional abnormalities of the dorsal anterior cingulate (dAC) region have been emphasized in schizophrenia, particularly in relation to cognitive deficits. In this study, we sought to further evaluate the notion of dAC hypofunction in chronic schizophrenia patients using a cognitive task specifically designed to activate this region, enabling both group and single-subject level analyses. Twelve male schizophrenia patients and 14 male healthy subjects were studied with functional magnetic resonance imaging (fMRI) and the multi-source interference task (MSIT). Patients and healthy subjects were matched for age, gender, education, task performance and gross surface morphology of the AC region. fMRI analyses were conducted at the group and single-subject levels using stringent whole-brain activation thresholds. Multi-source interference task performance was associated with large and significant activation of the dAC and supplementary motor area (SMA) in patients and healthy subjects. Standard comparison of the two groups indicated that the patients were comparable with healthy subjects in their dAC activation, but had a small cluster of greater SMA activation, while single-subject analyses identified minimal differences in the magnitude or spatial dispersion of dAC activation between the groups. These findings challenge existing notions of impaired dAC activation in chronic schizophrenia and suggest that the functional pathophysiology of this medial-wall region should be considered beyond straightforward models of hypoactivation.
Publisher: Wiley
Date: 24-11-2010
DOI: 10.1111/J.1600-0447.2010.01638.X
Abstract: The clinical distinction between bipolar II disorder (BD II) and bipolar I disorder (BD I) is not clear-cut. Cognitive functioning offers the potential to explore objective markers to help delineate this boundary. To examine this issue, we conducted a quantitative review of the cognitive profile of clinically stable patients with BD II in comparison with both patients with BD I and healthy controls. Meta-analytical methods were used to compare cognitive functioning of BD II disorder with both BD I disorder and healthy controls. In iduals with BD II were less impaired than those with BD I on verbal memory. There were also small but significant difference in visual memory and semantic fluency. There were no significant differences in global cognition or in other cognitive domains. Patients with BD II performed poorer than controls in all cognitive domains. Our findings suggest that with the exception of memory and semantic fluency, cognitive impairment in BD II is as severe as in BD I. Further studies are needed to investigate whether more severe deficits in BD I are related to neurotoxic effects of severe manic episodes on medial temporal structures or neurobiological differences from the onset of the illness.
Publisher: Elsevier BV
Date: 10-2006
DOI: 10.1016/J.PSCYCHRESNS.2006.03.002
Abstract: Obsessive-compulsive disorder (OCD) has been linked to a dysfunction of brain corticostriatal networks, although functional imaging studies of OCD rarely apply network-sensitive analysis methods. In this study, we compared a univariate and a multivariate analysis of PET data in OCD patients and healthy subjects the latter approach was considered more suitable for characterizing functional networks of brain activity. Although both methods suggested there was abnormal corticostriatal activity in OCD patients, the nature, extent and magnitude of this activity was clearly enhanced by the multivariate approach. Implications for the analysis of such studies are discussed.
Publisher: CMA Joule Inc.
Date: 07-2012
DOI: 10.1503/JPN.110074
Publisher: Elsevier BV
Date: 04-2010
DOI: 10.1016/J.PSCYCHRESNS.2009.10.014
Abstract: This magnetic resonance imaging study investigated the superior temporal gyrus (STG) subregion volumes in 20 teenagers with first-presentation borderline personality disorder (BPD) and 20 healthy controls. While the STG volume early in the course of BPD did not differ from that of healthy controls, the BPD participants with violent episodes had a smaller left caudal STG volume compared with those without such episodes during the previous 6 months. Our preliminary findings might reflect the neurobiological heterogeneity of the disorder.
Publisher: Elsevier BV
Date: 08-2009
DOI: 10.1016/J.PNPBP.2009.03.035
Abstract: Brain morphologic changes have been reported in borderline personality disorder (BPD), but it remains largely unknown whether BPD is associated with midline brain abnormalities. We used magnetic resonance imaging to investigate the length of the adhesio interthalamica (AI) and cavum septum pellucidum (CSP) as well as third ventricular volume in 20 teenagers with first-presentation BPD and 20 healthy controls. While the CSP length did not differ between the groups, the AI was significantly shorter in BPD patients than in controls. Furthermore, the BPD patients had a significantly larger third ventricle than controls. These preliminary findings suggest that ongoing neuroimaging studies should further evaluate a potential involvement of midline brain structures in the pathogenesis of BPD.
Publisher: American Medical Association (AMA)
Date: 09-2016
Publisher: Springer Netherlands
Date: 29-09-2015
Publisher: Elsevier BV
Date: 04-2009
DOI: 10.1016/J.SCHRES.2008.12.020
Abstract: There is now substantial evidence for Theory of mind (ToM) impairment in schizophrenia. Despite this, we know little about how dynamic (state) variables and broad clinical, cognitive and medication characteristics moderate the precise magnitude of the observed ToM deficit during task performance. Meta-analyses were conducted using 36 studies that reported continuous data regarding ToM performances of schizophrenia patients and healthy control subjects. These 36 studies included 1,181 (67% male) patients with schizophrenia and 936 (58.3% male) healthy control subjects. In idual analyses were also conducted for the Hinting and the Eyes tasks. The effects of moderator variables were studied by both subgroup and meta-regression analyses. The effect sizes (Cohen's d) for overall ToM performance and the in idual tasks were large (d=0.90-1.08). In "remitted" patients, the degree of ToM impairment was less pronounced than non-remitted patients (d=1.21) but it was still significant (d=0.80). Moreover, the distribution of effect sizes was more homogeneous for the in idual tasks, especially in "remitted" patients. General intellectual deficits observed in schizophrenia patients contributed to their ToM impairment only in the remission phase of the illness. While state variables and task specific differences explain a large degree of the heterogeneity of the ToM findings observed in previous studies, the persistence of ToM deficits in "remitted" patients suggests there are trait related mentalising impairments in schizophrenia. Our review also suggests that future research should consider the potential moderating influence of IQ deficits on ToM performance in "remitted" patients, as well as the potential effects of residual symptoms.
Publisher: Cambridge University Press (CUP)
Date: 05-04-2011
DOI: 10.1017/S003329171100050X
Abstract: The cerebellum is rich in cannabinoid receptors and implicated in the neuropathology of schizophrenia. Long-term cannabis use is associated with functional and structural brain changes similar to those evident in schizophrenia, yet its impact on cerebellar structure has not been determined. We examined cerebellar grey and white matter in cannabis users with and without schizophrenia. Seventeen patients with schizophrenia and 31 healthy controls were recruited 48% of the healthy group and 47% of the patients were long-term heavy cannabis users (mean 19.7 and 17.9 years near daily use respectively). Cerebellar measures were extracted from structural 3-T magnetic resonance imaging (MRI) scans using semi-automated methods, and examined using analysis of covariance (ANCOVA) and correlational analyses. Cerebellar white-matter volume was reduced in cannabis users with and without schizophrenia compared to healthy non-users, by 29.7% and 23.9% respectively, and by 17.7% in patients without cannabis use. Healthy cannabis users did not differ in white-matter volume from either of the schizophrenia groups. There were no group differences in cerebellar grey matter or total volumes. Total cerebellar volume decreased as a function of duration of cannabis use in the healthy users. Psychotic symptoms and illness duration correlated with cerebellar measures differentially between patients with and without cannabis use. Long-term heavy cannabis use in healthy in iduals is associated with smaller cerebellar white-matter volume similar to that observed in schizophrenia. Reduced volumes were even more pronounced in patients with schizophrenia who use cannabis. Cannabis use may alter the course of brain maturational processes associated with schizophrenia.
Publisher: Oxford University Press (OUP)
Date: 18-09-2009
Publisher: Oxford University Press (OUP)
Date: 23-09-2009
Publisher: Oxford University Press (OUP)
Date: 09-04-2008
Publisher: Elsevier BV
Date: 07-2008
DOI: 10.1016/J.NEUBIOREV.2008.01.006
Abstract: Organic solvent abuse is associated with increased risk for serious medical, neurological, and neuropsychological impairments. While animal research suggests that exposure to organic solvents (especially toluene) may be neurotoxic, much less is known about the consequences of long-term exposure in humans. We reviewed neuroimaging and neuropsychological studies examining chronic toluene misuse in humans. Thirty empirical studies fulfilled the inclusion and exclusion criteria, including case studies (n=9) as well as group studies with (n=11) and without a control group (n=10). Our review indicates that toluene preferentially affects white matter (relative to gray matter) structures and periventricular/subcortical (relative to cortical) regions. The lipid-dependent distribution and pharmacokinetic properties of toluene appears to explain the pattern of MRI abnormalities, as well as the common symptoms and signs of toluene encephalopathy. The commonly observed neuropsychological deficits such as impairments in processing speed, sustained attention, memory retrieval, executive function and language, are also consistent with white matter pathology. We discuss the implications of these findings in the context of a neurodevelopmental framework, as well as the neuropathology and pathophysiology of toluene abuse. We also propose a set of recommendations to guide future research in this area.
Publisher: Elsevier BV
Date: 2011
DOI: 10.1016/J.NEUBIOREV.2010.10.001
Abstract: There is now strong evidence of progressive neuropathological processes in bipolar disorder (BD). On this basis, the current understanding of the neurobiology of BD has shifted from an initial focus on monoamines, subsequently including evidence of changes in intracellular second messenger systems and more recently to, incorporating changes in inflammatory cytokines, corticosteroids, neurotrophins, mitochondrial energy generation, oxidative stress and neurogenesis into a more comprehensive model capable of explaining some of the clinical features of BD. These features include progressive shortening of the inter-episode interval with each recurrence, occurring in consort with reduced probability of treatment response as the illness progresses. To this end, emerging data shows that these biomarkers may differ between early and late stages of BD in parallel with stage-related structural and neurocognitive alterations. This understanding facilitates identification of rational therapeutic targets, and the development of novel treatment classes. Additionally, these pathways provide a cogent explanation for the efficacy of seemingly erse therapies used in BD, that appear to share common effects on oxidative, inflammatory and neurotrophic pathways.
Publisher: Springer Science and Business Media LLC
Date: 12-03-2013
DOI: 10.1038/MP.2013.26
Publisher: Elsevier BV
Date: 09-2012
DOI: 10.1016/J.NEUROIMAGE.2012.05.040
Abstract: We examined the neural basis of the capacity to resist an immediately rewarding stimulus in order to obtain a larger delayed reward. This was investigated with a Go/No-go task employing No-go targets that provided two types of reward outcomes. These were contingent on inhibitory control performance: failure to inhibit Reward No-go targets provided a small monetary reward with immediate feedback while successful inhibitory control resulted in larger rewards with delayed feedback based on the highest number of consecutive inhibitions. We observed faster Go trial responses with maintained levels of inhibition accuracy during the Reward No-go condition compared to a neutral No-go condition. Comparisons between conditions of BOLD activity showed successful inhibitory control over rewarding No-Go targets was associated with hypoactivity in regions previously associated with regulating emotion and inhibitory control, including insula and right inferior frontal gyrus. In addition, regions previously associated with visual processing centers that are modulated as a function of visual attention, namely the left fusiform and right superior temporal gyri, were hypoactive. These findings suggest a role for attentional disengagement as an aid to withholding response over a rewarding stimulus and are consistent with the notion that gratification can be delayed by directing attention away from immediate rewards.
Publisher: Springer Science and Business Media LLC
Date: 06-05-2021
DOI: 10.1038/S41398-021-01382-Y
Abstract: Males and females show different patterns of cannabis use and related psychosocial outcomes. However, the neuroanatomical substrates underlying such differences are poorly understood. The aim of this study was to map sex differences in the neurobiology (as indexed by brain volumes) of dependent and recreational cannabis use. We compared the volume of a priori regions of interest (i.e., amygdala, hippoc us, nucleus accumbens, insula, orbitofrontal cortex (OFC), anterior cingulate cortex and cerebellum) between 129 regular cannabis users (of whom 70 were recreational users and 59 cannabis dependent) and 114 controls recruited from the ENIGMA Addiction Working Group, accounting for intracranial volume, age, IQ, and alcohol and tobacco use. Dependent cannabis users, particularly females, had (marginally significant) smaller volumes of the lateral OFC and cerebellar white matter than recreational users and controls. In dependent (but not recreational) cannabis users, there was a significant association between female sex and smaller volumes of the cerebellar white matter and OFC. Volume of the OFC was also predicted by monthly standard drinks. No significant effects emerged the other brain regions of interest. Our findings warrant future multimodal studies that examine if sex and cannabis dependence are specific key drivers of neurobiological alterations in cannabis users. This, in turn, could help to identify neural pathways specifically involved in vulnerable cannabis users (e.g., females with cannabis dependence) and inform in idually tailored neurobiological targets for treatment.
Publisher: Wiley
Date: 29-09-2013
DOI: 10.1111/J.1369-1600.2011.00364.X
Abstract: Inhalants, frequently abused during adolescence, are neurotoxic to white matter. We investigated the impact of inhalant misuse on the morphology of the corpus callosum (CC), the largest white matter bundle in the brain, in an adolescent s le of inhalant users [n = 14 mean age = 17.3 standard deviation (SD) = 1.7], cannabis users (n = 11 mean age = 19.7 SD = 1.7) and community controls (n = 9 mean age = 19.5 SD = 2.6). We identified significant morphological differences in the CC among inhalant users compared with community controls. There were no morphological differences between inhalant and cannabis users. Our findings may represent the early stages of neurobiological damage associated with chronic inhalant misuse.
Publisher: Elsevier BV
Date: 08-2010
DOI: 10.1016/J.NEUROIMAGE.2010.04.012
Abstract: Although the hippoc us is a key brain region in the pathophysiology of schizophrenia, it is unclear whether structural or biochemical abnormalities predate illness onset. In this study, we used magnetic resonance imaging and spectroscopy data acquired prior to both the onset of psychosis and treatment with antipsychotics to determine this. Sixty-six young people clinically at ultra high-risk of development of psychosis were recruited, 59 of whom did not later develop a psychotic disorder and 7 who had done so after at least 24 months follow-up. These participants were compared with 29 healthy comparison subjects on multiple independent magnetic resonance measures: hippoc al volume, hippoc al T2 relaxation time, and medial temporal lobe metabolite concentrations (including N-acetylaspartate). We found similar reductions in left hippoc al volume in the at-risk group compared to comparison subjects regardless of later transition status on the right this only reached significance for the at-risk group who did not transition to psychosis. T2 relaxation time in the left hippoc al head was significantly elevated in the later-psychotic group, and this elevation positively correlated with total positive symptoms in the UHR group as a whole. Medial temporal lobe metabolite concentrations did not differ. These findings suggest that there are subtle pathological changes in the hippoc us prior to the development of psychosis, but that they are limited to the left hippoc al head. However, standard measures of neuroanatomical disturbance do not appear to be predictive of later transition, and instead are likely to be non-specific and common in cases that later develop a non-psychotic disorder.
Publisher: Cambridge University Press (CUP)
Date: 09-01-2017
DOI: 10.1017/S1092852916000535
Abstract: To determine the rates and associated illness characteristics of obsessive-compulsive disorder (OCD) patients who describe their symptoms as either rewarding or habitual. Seventy-three treatment-seeking OCD patients had their dominant compulsive behavior assessed with a structured interview (the Temporal Impulsive-Compulsive Scale–Revised) to track the progression of rewarding (ie, gain in positive affect), aversive (ie, decrease in negative affect), and neutral (or non-affective) states and a self-report scale (the Self-Report Habit Index) to evaluate their habitual features. Additional measures included structured diagnostic interviews for axis I and II disorders, measures of OCD symptoms severity, and a battery of instruments to comprehensively assess relevant aspects of sensitivity to reward and fear. Almost half (49%) of our OCD patients (particularly washers) endorsed that they anticipated obtaining a reward (ie, positive affect) from the enactment of their dominant compulsive behavior. Washers stood out in that their positive affects during and after compulsive behaviors were highly (and positively) correlated with duration of illness. In contrast, habit strength did not differ between washers, checkers, and arrangers, although it also correlated with duration of illness among checkers. Furthermore, the severity of OCD and comorbidity with impulse control disorders predicted up to 35% of the variance in the habit strength of OCD behaviors. Compulsive washing may be more clearly characterized by problems in reward processing. In contrast, duration of checking, severity of OCD, and comorbidity with impulse control disorders shape compulsive behaviors by imparting them with habitual tendencies.
Publisher: Cambridge University Press
Date: 27-10-2011
Publisher: Oxford University Press (OUP)
Date: 23-09-2016
Abstract: Cognitive control (CC) and working memory (WM) are concurrently necessary for adaptive human behavior. These processes are thought to rely on similar neural mechanisms, yet little is known of the potential competitive or cooperative brain dynamics that support their concurrent engagement during complex behavioral tasks. Here, statistical interactions (synergy/competition) and dependencies (correlations) in brain function related to CC and WM were measured using functional magnetic resonance imaging. Twenty-five healthy adults performed a novel factorial cognitive paradigm, in which a 2-back verbal WM task was combined with the multisource interference task. Overlapping main effects in neural activation were evident in all regions of the "cognitive control network," together with robust behavioral main effects. However, no significant behavioral or cortical interaction effects were apparent. Conversely, robust positive correlations between the 2 main effects were evident within many components of the network. The results offer robust evidence that the neural representations of WM and CC are statistically dependent, but do not compete. These findings support the notion that CC and WM demands may be dynamically and flexibly encoded within a common brain network to support the efficient production of adaptive behavior across erse task contexts.
Publisher: Cambridge University Press
Date: 10-2009
Publisher: Springer Science and Business Media LLC
Date: 28-09-2012
DOI: 10.1007/S00213-011-2512-0
Abstract: Current neurobiological models of addiction posit that drug seeking is much more likely to occur during emotionally charged states (such as craving), as deficits in inhibitory control become more pronounced during heightened motivational states. The purpose of this study was to examine the effect of cue-induced craving states on attention and inhibitory control within addicted in iduals. We tested the performance of 39 opiate-dependent in iduals on cognitive measures of attention (Digit Span, Digit Symbol, and Telephone Search) and inhibitory control (Counting Stroop and Go-No-Go) both before and after exposure to an autobiographical craving script. A non-drug using healthy control group (n = 19) performed the same tasks before and after listening to a relaxation tape. Following craving induction, opiate-dependent in iduals demonstrated improved performance on tests of processing speed and attentional span (consistent with the practice effect observed in controls) and increased their response errors on the Stroop task (in contrast to controls), while selective attention was unaffected. In idual differences in compulsivity mediated the association between craving and Stroop performance, such that low-compulsive (but not high-compulsive) in iduals committed more response errors after craving induction. These findings challenge the notion of cue-induced craving as a primary trigger of disrupted cognition and drug-seeking behavior in addicted in iduals, and raise the need to explore in idual differences in compulsivity when addressing the links between craving and loss of control within research and clinical settings.
Publisher: Physicians Postgraduate Press, Inc
Date: 03-03-2015
DOI: 10.4088/JCP.14R09129
Publisher: Proceedings of the National Academy of Sciences
Date: 04-03-2008
Abstract: Adolescence is a key period for the development of brain circuits underlying affective and behavioral regulation. It remains unclear, however, whether and how adolescent brain structure influences day-to-day affective behavior. Because of significant changes in the nature of family relations that also typically occur during adolescence, parent–child interactions provide a meaningful context where affective behavior and its regulation may be assessed. In a s le of 137 early adolescents, we investigated the relationship between aspects of the adolescents' brain structure and their affective behavior as assessed during observation of parent–child interactions. We found a significant positive association between volume of the amygdala and the duration of adolescent aggressive behavior during these interactions. We also found male-specific associations between the volume of prefrontal structures and affective behavior, with decreased leftward anterior paralimbic cortex volume asymmetry associated with increased duration of aggressive behavior, and decreased leftward orbitofrontal cortex volume asymmetry associated with increased reciprocity of dysphoric behavior. These findings suggest that adolescent brain structure is associated with affective behavior and its regulation in the context of family interactions, and that there may be gender differences in the neural mechanisms underlying affective and behavioral regulation during early adolescence. Particularly as adolescence marks a period of rapid brain maturation, our findings have implications for mental health outcomes that may be revealed later along the developmental trajectory.
Publisher: Elsevier BV
Date: 07-2014
DOI: 10.1016/J.COMPPSYCH.2014.03.023
Abstract: There are no reported cases of factitious or simulated obsessive-compulsive disorder (OCD). However, over the last years, our clinic has come across a number of in iduals that seem to exaggerate, mislabel or even intentionally "produce" obsessive and/or compulsive symptoms in order to be diagnosed with OCD. In this study, experienced clinicians working on a university-based OCD clinic were requested to provide clinical vignettes of patients who, despite having a formal diagnosis of OCD, were felt to display non-genuine forms of this condition. Ten non-consecutive patients with a self-proclaimed diagnosis of OCD were identified and described. Although patients were diagnosed with OCD according to various structured interviews, they exhibited erse combinations of the following features: (i) overly technical and/or doctrinaire description of their symptoms, (ii) mounting irritability, as the interviewer attempts to unveil the underlying nature of these descriptions (iii) marked shifts in symptom patterns and disease course (iv) an affirmative "yes" pattern of response to interview questions (v) multiple Axis I psychiatric disorders (vi) cluster B features (vii) an erratic pattern of treatment response and (viii) excessive or contradictory drug-related side effects. In sum, reliance on overly structured assessments conducted by insufficiently trained or naïve personnel may result in invalid OCD diagnoses, particularly those that leave no room for clinical judgment.
Publisher: Springer Science and Business Media LLC
Date: 30-08-2009
DOI: 10.1007/S11065-009-9114-1
Abstract: In this review, we describe neuropsychological and brain imaging findings in the early stages of psychosis and schizophrenia. We focus on recent clinical high-risk studies and consider whether the evidence supports these as 'endophenotypes' of a vulnerability to the illness or as 'biomarkers' of illness onset and transition. The findings suggest that there are a number of processes at psychosis onset that may represent biomarkers of incipient illness. These neurobiological indices particularly implicate the integrity of frontal and temporal cortices, which may or may not be related to the genetics of psychosis (i.e. potential 'endophenotypes'). However, these brain regions are dynamically changing during normal maturation, meaning that any putative neurobiological markers identified at the earliest stages of illness may be relatively unstable.We suggest that, while such measures maybe readily identified as potential neurobiological markers of established illness, they are inconsistent at (or around) the time of illness onset when assessed cross-sectionally. Instead,identification of more valid risk markers may require longitudinal assessment to ascertain normal or abnormal trajectories of neurodevelopment. Accordingly, we assert that the current conceptualisations of potential biomarkers and/or 'endophenotypes' for schizophrenia may need to be reconsidered in the context of normal and abnormal brain maturational processes at the time of onset of psychotic disorders.
Publisher: Elsevier BV
Date: 05-2009
DOI: 10.1016/J.PSCYCHRESNS.2008.12.004
Abstract: Reports of volumetric abnormalities in the anterior cingulate cortex (ACC) in adults with established borderline personality disorder (BPD) are inconsistent, and it is not known whether such abnormalities are present early in the disorder. We aimed to investigate ACC volume in a first-presentation teenage BPD s le with minimal exposure to treatment. Fifteen female BPD patients and 15 healthy female control participants underwent magnetic resonance imaging (MRI) scanning. ACC volumes were estimated using a reliable method that accounts for inter-in idual variation in sulcal morphology, and measurements were compared between the two groups. Analysis of variance revealed a decrease in volume of the left ACC in BPD patients compared with control participants. This volumetric change was correlated with parasuicidal behavior and impulsivity. A measure of ACC volume asymmetry was also correlated with fear of abandonment symptoms. Our results suggest that ACC volumetric abnormalities early in the course of BPD might be related to clinical correlates of the disorder. Longitudinal studies are needed to examine the nature of this abnormality over the course of the disorder.
Publisher: MIT Press - Journals
Date: 05-2014
DOI: 10.1162/JOCN_A_00549
Abstract: Maturation of cognitive control abilities has been attributed to the protracted structural maturation of underlying neural correlates during adolescence. This study examined the relationship between development of two forms of cognitive control (proactive and reactive control) and structural maturation of the ACC, dorsolateral pFC, and ventrolateral pFC (vlPFC) between early and mid adolescence using a longitudinal design. Adolescents (n = 92) underwent baseline assessments when they were 12 years old and follow-up assessments approximately 4 years later. At each assessment, structural MRI scans were acquired, and a modified Stroop task was performed. Results showed longitudinal improvements in reactive control between early and mid adolescence. Furthermore, magnitude of the improvement in proactive control was associated with reduced thinning of the right vlPFC across the s le, whereas the magnitude of the improvements in reactive control was associated with reduced thinning of the left ACC in men alone. These findings suggest that in idual differences in the maturation of ACC and vlPFC underlie the development of two distinct forms of cognitive control between early and mid adolescence as well as highlight sex differences in this relationship.
Publisher: Oxford University Press (OUP)
Date: 27-04-2009
DOI: 10.1093/SCAN/NSP012
Publisher: Springer Science and Business Media LLC
Date: 21-09-2012
DOI: 10.1007/S00213-011-2486-Y
Abstract: Reflection impulsivity-a failure to gather and evaluate information before making a decision-is a critical component of risk-taking and substance use behaviours, which are highly prevalent during adolescence. The Information S ling Test was used to assess reflection impulsivity in 175 adolescents (mean age 18.3, range 16.5-20 55% female)-48 cannabis users (2.3 years use, 10.8 days/month), 65 alcohol users, and 62 non-substance-using controls-recruited from a longitudinal cohort and from the general community and matched for education and IQ. Cannabis and alcohol users were matched on levels of alcohol consumption. Cannabis users s led to the lowest degree of certainty before making a decision on the task. Group differences remained significant after controlling for relevant substance use and clinical confounds (e.g., anxiety, depressive symptoms, alcohol, and ecstasy use). Poor performance on multiple IST indices was associated with an earlier age of onset of regular cannabis use and greater duration of exposure to cannabis, after controlling for recent use. Alcohol users did not differ from controls on any IST measure. Exposure to cannabis during adolescence is associated with increased risky and impulsive decision making, with users adopting strategies with higher levels of uncertainty and inefficient utilisation of information. The young cannabis users did show sensitivity to losses, suggesting that greater impulsivity early in their drug using career is more evident when there is a lack of negative consequences. This provides a window of opportunity for intervention before the onset of cannabis dependence.
Publisher: Royal College of Psychiatrists
Date: 06-2003
Abstract: The anterior cingulate cortex (ACC) is consistently implicated in the pathophysiology of schizophrenia, and our own work has identified morphological anomalies in the ACC of people with this disorder. To examine whether ACC morphological anomalies are present in a group at ultra-high risk of psychosis and whether such anomalies can be used to predict the subsequent development of a psychotic illness. Magnetic resonance imaging of 75 healthy volunteers and 63 people at ultra-high risk of developing a psychotic disorder (all right-handed males) was used to examine ACC sulcal and gyral features. Compared with the controls, significantly fewer people in the ultra-high risk group had a well-developed left paracingulate sulcus and significantly more had an interrupted left cingulate sulcus. There was no difference between those who did ( n =21) and did not ( n =42) subsequently develop a psychotic illness. Although ACC anomalies are present in young people considered to be at ultra-high risk of psychosis, they do not identify in iduals who subsequently make the transition to psychosis.
Publisher: No publisher found
Date: 2000
Publisher: Elsevier BV
Date: 2012
DOI: 10.1016/J.PSCYCHRESNS.2011.06.010
Abstract: There are now numerous reports of neuroanatomical abnormalities in people with bipolar disorder. However, it remains unclear whether those abnormalities predate the onset of the illness. In this cross-sectional magnetic resonance imaging study, we assessed 11 young people clinically at ultra-high risk of development of psychosis (UHR), who all developed bipolar I or II disorder by follow-up (median time to onset 328 days - UHR-BP), 11 matched UHR participants, who had no psychiatric diagnosis after at least 12 months of follow-up (UHR-Well) and 11 matched healthy controls (HC). Our main outcome measures were amygdala, hippoc us, insula, lateral ventricular and whole brain volumes. Amygdala and insula volume reductions were more pronounced in the UHR-BP than in the UHR-Well and HC group. Lateral ventricle, whole-brain and hippoc al volumes did not differ between groups. If these findings are confirmed, they suggest that imaging investigations could help to distinguish people who will subsequently develop bipolar disorder from those who will not, at least in symptomatically enriched s les.
Publisher: Informa UK Limited
Date: 24-05-2011
DOI: 10.3109/10826084.2011.580216
Abstract: Volatile substance misuse is common during early adolescence however, limited work has been conducted investigating the neurobiological effects of such use on the developing brain. While both animal and human studies report cognitive and neurobiological harm associated with volatile substance misuse during adolescence (particularly involving white matter structures), the complex psychosocial characteristics of volatile substance misusers confound the specificity of reported volatile substance-related pathology in human subjects. In addition, few studies have examined whether cognitive and neurobiological recovery occurs with abstinence, although there is some literature indicating that neurological and cognitive improvement is possible, but relates to the frequency and duration of previous use. Longitudinal studies utilizing well-matched control s les are required to fully delineate the short- and long-term impact of volatile substance misuse on adolescent brain development.
Publisher: American Medical Association (AMA)
Date: 11-2009
DOI: 10.1001/ARCHGENPSYCHIATRY.2009.152
Abstract: Neurobiological models of obsessive-compulsive disorder (OCD) emphasize disturbances in the function and connectivity of brain corticostriatal networks, or "loops." Although neuroimaging studies of patients have supported this network model of OCD, very few have applied measurements that are sensitive to brain connectivity features. Using resting-state functional magnetic resonance imaging, we tested the hypothesis that OCD is associated with disturbances in the functional connectivity of primarily ventral corticostriatal regions, measured from coherent spontaneous fluctuations in the blood oxygenation level-dependent (BOLD) signal. Case-control cross-sectional study. Hospital referral OCD unit and magnetic resonance imaging facility. A total of 21 patients with OCD (10 men, 11 women) and 21 healthy control subjects matched for age, sex, and estimated intelligence. Voxelwise statistical parametric maps testing the strength of functional connectivity of 4 striatal seed regions of interest (dorsal caudate nucleus, ventral caudate/nucleus accumbens, dorsal putamen, and ventral putamen) with remaining brain areas. For both groups, there was a clear distinction in the pattern of cortical connectivity of dorsal and ventral striatal regions, consistent with the notion of segregated motor, associative, and limbic corticostriatal networks. Between groups, patients with OCD had significantly increased functional connectivity along a ventral corticostriatal axis, implicating the orbitofrontal cortex and surrounding areas. The specific strength of connectivity between the ventral caudate/nucleus accumbens and the anterior orbitofrontal cortex predicted patients' overall symptom severity (r(2) = 0.57 P < .001). Additionally, patients with OCD showed evidence of reduced functional connectivity of the dorsal striatum and lateral prefrontal cortex, and of the ventral striatum with the region of the midbrain ventral tegmental area. This study directly supports the hypothesis that OCD is associated with functional alterations of brain corticostriatal networks. Specifically, our findings emphasize abnormal and heightened functional connectivity of ventrolimbic corticostriatal regions in patients with OCD.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2009
Publisher: Cambridge University Press (CUP)
Date: 31-10-2014
DOI: 10.1017/NEU.2014.29
Abstract: Although severe hoarding symptoms have been considered rare among obsessive-compulsive disorder (OCD) s les, the prevalence of animal hoarding in OCD is unknown. To help clarifying this issue, we searched for cases of animal hoarding among patients attending a university OCD clinic ( n =420). Chart review. Only two patients from our s le exhibited animal hoarding ( .5%) and only one of them presented additional obsessive-compulsive symptoms. Both cases also collected inanimate objects, presented low insight, exhibited poor response to serotonin reuptake inhibitors and did not adhere to therapy. There seems to be a lack of relationship between animal hoarding and OCD. However, further studies with larger numbers of patients are needed to better define their psychopathological profile and more appropriate nosological insertion.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2009
Publisher: Public Library of Science (PLoS)
Date: 22-03-2016
Publisher: American Psychological Association (APA)
Date: 11-2015
DOI: 10.1037/ABN0000101
Abstract: A single imaging gene-environment (IGxE) framework that is able to simultaneously model genetic, neurobiological, and environmental influences on psychopathology outcomes is needed to improve understanding of how complex interrelationships between allelic variation, differences in neuroanatomy or neuroactivity, and environmental experience affect risk for psychiatric disorder. In a longitudinal study of adolescent development we demonstrate the utility of such an IGxE framework by testing whether variation in parental behavior at age 12 altered the strength of an imaging genetics pathway, involving an indirect association between allelic variation in the serotonin transporter gene to variation in hippoc al volume and consequent onset of major depressive disorder by age 18. Results were consistent with the presence of an indirect effect of the serotonin transporter S-allele on depression onset via smaller left and right hippoc al volumes that was significant only in family environments involving either higher levels of parental aggression or lower levels of positive parenting. The previously reported finding of S-allele carriers' increased risk of depression in adverse environments may, therefore, be partly because of the effects of these environments on a neurobiological pathway from the serotonin transporter gene to depression onset that proceeds through variation in hippoc al volume.
Publisher: SAGE Publications
Date: 10-2013
DOI: 10.2190/PM.46.3.F
Abstract: Hoarding is defined as the excessive collection and failure to discard possessions of apparently little value, leading to clutter, distress, and disability. Although patients with hoarding typically may feel ludicrous for not discarding useless, and sometimes bizarre, possessions, we are not aware of any previous description of patients displaying hoarding as a result of social anxiety. Single case report. In this article, we describe a patient with severe social anxiety disorder who displayed hoarding as a direct consequence of social anxiety-related beliefs and atypical safety behaviors. This case is of particular interest to current debates concerning the status of hoarding in new versions of classificatory systems. It also indicates that social anxiety disorder should be included in the list of conditions that needs to be excluded in order to diagnose “primary” hoarding disorder.
Publisher: Oxford University Press (OUP)
Date: 04-2004
Abstract: The neuropsychological correlates of inter-in idual variations in cortical folding are poorly understood. Anterior cingulate (AC) cortex is one region characterized by considerable variability, particularly with respect to the paracingulate sulcus (PCS), which is present in only 30-60% of in iduals and more commonly found in the left cerebral hemisphere. To investigate whether inter-in idual differences in this PCS asymmetry are related to cognitive performance, we classified 30 healthy right-handed males as displaying either a leftward, rightward or symmetric pattern of folding based on the incidence and extent of the PCS in each hemisphere, and compared their performance on tasks engaging executive cognitive processes associated with frontal lobe function. We found that the more common leftward PCS asymmetry was associated with better performance across verbal and non-verbal executive tasks, but that PCS variability had no effect on tasks less dependent on executive functions. These results suggest that the leftward pattern of folding is associated with a non-specific performance advantage on cognitively demanding executive function tasks, possibly due to differences in functional interactions between AC aracingulate cortex and connected frontal regions. It therefore appears that normal variations in brain morphology are associated with in idual differences in cognitive abilities.
Publisher: Elsevier BV
Date: 2005
DOI: 10.1016/J.NEUROIMAGE.2004.08.033
Abstract: Using covariance-based multivariate analysis, we examined patterns of functional connectivity in rCBF on a practice-extended version of the Stroop color-word paradigm. Color-word congruent and incongruent conditions were presented in six AB trials to healthy subjects during 12 H2(15)O PET scans. Analyses identified two reproducible canonical eigenimages (CE) from the PET data, which were converted to a standard Z score scale after cross-validation res ling and correction for random subject effects. The first CE corresponded to practice-dependent changes in covarying rCBF that occurred over early task repetitions and correlated with improved behavioral performance. This included many regions previously implicated by PET and fMRI studies of this task, which we suggest may represent two "parallel" networks: (i) a cingulo-frontal system that was initially engaged in selecting and mapping a task-relevant response (color naming) when the attentional demands of the task were greatest and (ii) a ventral visual processing stream whose concurrent decrease in activity represented the task-irrelevant inhibition of word reading. The second CE corresponded to a consistent paradigmatic effect of Stroop interference on covarying rCBF. Coactivations were located in dorsal and ventral prefrontal regions as well as frontopolar cortex. This pattern supports existing evidence that prefrontal regions are involved in maintaining attentional control over conflicting response systems. Taken together, these findings may be more in line with theoretical models that emphasize a role for practice in the emergence of Stroop phenomena. These findings may also provide some additional insight into the nature of anterior cingulate- and prefrontal cortical contributions to implementing cognitive control in the brain.
Publisher: Elsevier BV
Date: 08-2010
DOI: 10.1016/J.CPR.2010.04.005
Abstract: Although affective and substance use disorders frequently co-occur, the role of affective dysregulation in addiction is often overlooked. This paper reviews the role of affective dysregulation in the initiation and maintenance of substance use disorders (SUDs), presenting evidence for a relationship between SUD and three biologically-based dimensions of affective temperament and behaviour: negative affect (NA), positive affect (PA), and effortful control (EC). High NA, low EC, and both high and low PA were each found to play a role in conferring risk and maintaining substance use behaviours, although the strength of their influence differed depending on stage of illness (i.e., early onset use through to addiction). Given these findings, we argue that future research should explicitly consider how changes within affective systems may underlie the development of SUDs. A better understanding of the role of affective dysregulation in addiction will aid in clarifying how risk is conferred, as well as how addictive behaviours are maintained, thereby informing the development of preventative strategies and novel treatments. Future studies should continue to examine the role of high NA in SUDs, and further examine the respective roles of high PA, low PA, and low EC, as well as identifying the affective characteristics that predispose high-risk in iduals to later substance use problems.
Publisher: Wiley
Date: 24-11-2016
DOI: 10.1002/HBM.22905
Publisher: SAGE Publications
Date: 12-2007
DOI: 10.1080/00048670701689444
Abstract: The purpose of the present review is to describe the neuropsychological correlates of long-term substance abuse and to discuss the findings within the context of premorbid vulnerabilities, comorbidity and adolescent neurodevelopment. The authors critically review key findings from the neuropsychological literature related to the long-term sequelae of alcohol, cannabis, inhalant, opiates, psychostimulants and ecstasy use. Leading electronic databases such as PubMed were searched to identify relevant studies published in the past 20 years. References identified from bibliographies of pertinent articles and books in the field were also collected and selectively reviewed. Across substances, in iduals with long-term abuse consistently demonstrate neuropsychological impairments of executive (inhibitory) control, working memory and decision making, together with neurobiological abnormalities involving frontotemporal and basal ganglia circuits. In some instances these deficits are dose dependent, implying that they are a direct consequence of prolonged drug exposure. However, comorbid behavioural, personality and mental health problems are common among drug-using populations and are associated with similar neuropsychological deficits. Presented herein is a neuropsychological model of addictive behaviour that highlights the complex interplay between cognition, brain maturation, psychopathology and drug exposure.
Publisher: Elsevier
Date: 2013
Publisher: Informa UK Limited
Date: 04-2010
DOI: 10.3109/09638230903469111
Abstract: To review the evidence that supports early intervention in the treatment of bipolar disorder. Bipolar disorder is a pleomorphic condition, with varying manifestations that are determined by a number of complex factors including the "stage" of illness. It is consequently a notoriously difficult illness to diagnose and as a corollary is associated with lengthy delays in recognition and the initiation of suitable treatment. A literature search was conducted using MEDLINE augmented by a manual search. Emerging neuroimaging data suggests that, in contrast to schizophrenia, where at the time of a first-episode of illness there is already discernible volume loss, in bipolar disorder, gross brain structure is relatively preserved, and it is only with recurrences that there is a sequential, but marked loss of brain volume. Recent evidence suggests that both pharmacotherapy and psychotherapy are more effective if instituted early in the course of bipolar disorder, and that with multiple episodes and disease progression there is a noticeable decline in treatment response. Such data supports the notion of clinical staging, and the tailored implementation of treatments according to the stage of illness. The progressive nature of bipolar disorder further supports the concept that the first episode is a period that requires energetic broad-based treatment, with the hope that this could alter the temporal trajectory of the illness. It also raises hope that prompt treatment may be neuroprotective and that this perhaps attenuates or even prevents the neurostructural and neurocognitive changes seen to emerge with chronicity. This highlights the need for early identification at a population level and the necessity of implementing treatments and services at a stage of the illness where prognosis is optimal.
Publisher: S. Karger AG
Date: 14-12-2016
DOI: 10.1159/000452159
Abstract: b i Background: /i /b Orbitofrontal cortex (OFC) dysfunction has been proposed to increase the risk for developing a substance use disorder (SUD) during adolescence. In this study, we suggest that a reduction in OFC volumes might underlie temperament-based risk factors for SUD, and examined whether smaller OFC volumes during early adolescence could predict later development of SUD. b i Methods and Materials: /i /b Adolescents (n = 107 58 male, 49 female) underwent structural MRI and completed a self-report measure of temperamental effortful control at age 12. At 3 subsequent assessments (aged 15, 16, and 18) SUD was assessed via a semi-structured clinical interview. By the third assessment, 24 participants (22.4%) had received a lifetime diagnosis of SUD. b i Results: /i /b Smaller volumes of the left OFC, right OFC, and left medial subregions predicted lifetime history of SUD by age 18. Volumes of the left OFC and left lateral subregions were positively correlated with effortful control, and left OFC volumes mediated the relationship between effortful control and SUD. b i Conclusions: /i /b Smaller volumes of the OFC and low effortful control during adolescence appear to be associated phenotypes that increase the risk of subsequent SUD. Further studies examining the temporal sequence of these risk factors are needed to fully understand this relationship.
Publisher: Elsevier BV
Date: 05-2010
DOI: 10.1016/J.JAD.2009.09.003
Abstract: Morphologic changes of cortico-limbic regions have been reported in bipolar disorder, but it remains unclear whether midline brain abnormalities relevant to cortico-limbic connectivity are also present. We used magnetic resonance imaging to investigate the size of the adhesio interthalamica (AI) and cavum septi pellucidi (CSP), as well as third ventricular volume, in 26 patients with bipolar I disorder and 24 matched controls. CSP length and prevalence of a large CSP did not differ between the groups, but bipolar patients had significantly shorter AI and larger third ventricles compared to controls. A comprehensive investigation of medication effects was not possible due to incomplete medication data. These findings implicate a role for the AI and connected brain regions in the neurobiology of bipolar disorder.
Publisher: Royal College of Psychiatrists
Date: 2016
DOI: 10.1192/BJP.BP.114.156281
Abstract: The aetiological boundary between obsessive–compulsive related disorders (OCRDs) including obsessive–compulsive disorder (OCD) and anxiety disorders is unclear and continues to generate debate. To determine the genetic overlap and the pattern of causal relationships among OCRDs and anxiety disorders. Multivariate twin modelling methods and a new regression analysis to infer causation were used, involving 2495 male and female twins. The amount of common genetic liability observed for OCD symptoms was higher when considering anxiety disorders and OCRDs in the model v. modelling OCRD symptoms alone. OCD symptoms emerged as risk factors for the presence of generalised anxiety, panic and hoarding symptoms, whereas social phobia appeared as a risk factor for OCD symptoms. OCD represents a complex phenotype that includes important shared features with anxiety disorders and OCRDs. The novel patterns of risk identified between OCD and anxiety disorder may help to explain their frequent co-occurrence.
Publisher: Elsevier BV
Date: 07-2002
DOI: 10.1016/S0006-3223(02)01312-4
Abstract: Our previous work on sulcal-gyral brain morphology in healthy volunteers revealed that males were characterized by greater cortical folding in the left versus right anterior cingulate cortex. Given the evidence showing an absence or reversal of normal anatomical asymmetries in patients with schizophrenia, the current study examined the anterior cingulate cortex sulcal-gyral patterns in patients with schizophrenia. Using high-resolution magnetic resonance imaging, we examined anterior cingulate cortex surface morphology in a group of 55 patients with established schizophrenia and 75 healthy controls. All subjects were male and right-handed. Depending on the presence of a paracingulate sulcus and its antero-posterior extent, three types of anterior cingulate cortex sulcal patterns were identified: "prominent," "present," and "absent." Measures of overall cerebral hemispheric folding were used as independent variables and as covariates to ascertain the specificity of the findings to the anterior cingulate cortex. Examination of anterior cingulate cortex morphology showed that, compared with controls, patients with schizophrenia lacked the leftward anterior cingulate cortex sulcal asymmetry, which was explained by reduced folding in the left anterior cingulate cortex. These differences were over and above differences in cortical folding across the entire left hemisphere. These findings suggest that, in male patients with schizophrenia, there is a disturbance in the neurodevelopment of the left anterior cingulate cortex, as well as a more general aberration of left hemisphere development.
Publisher: Bentham Science Publishers Ltd.
Date: 2016
Publisher: Cambridge University Press
Date: 19-02-2009
Publisher: JMIR Publications Inc.
Date: 18-11-2022
Abstract: any people with harmful addictive behaviors may not meet formal diagnostic thresholds for a disorder. A dimensional approach, by contrast, including clinical and community s les, is potentially key to early detection, prevention, and intervention. Importantly, while neurocognitive dysfunction underpins addictive behaviors, established assessment tools for neurocognitive assessment are lengthy and unengaging, difficult to administer at scale, and not suited to clinical or community needs. The BrainPark Assessment of Cognition (BrainPAC) Project sought to develop and validate an engaging and user-friendly digital assessment tool purpose-built to comprehensively assess the main consensus-driven constructs underpinning addictive behaviors. he purpose of this study was to psychometrically validate a gamified battery of consensus-based neurocognitive tasks against standard laboratory paradigms, ascertain test-retest reliability, and determine their sensitivity to addictive behaviors (eg, alcohol use) and other risk factors (eg, trait impulsivity). old standard laboratory paradigms were selected to measure key neurocognitive constructs (Balloon Analogue Risk Task [BART], Stop Signal Task [SST], Delay Discounting Task [DDT], Value-Modulated Attentional Capture [VMAC] Task, and Sequential Decision-Making Task [SDT]), as endorsed by an international panel of addiction experts namely, response selection and inhibition, reward valuation, action selection, reward learning, expectancy and reward prediction error, habit, and compulsivity. Working with game developers, BrainPAC tasks were developed and validated in 3 successive cohorts (total N=600) and a separate test-retest cohort (N=50) via Mechanical Turk using a cross-sectional design. rainPAC tasks were significantly correlated with the original laboratory paradigms on most metrics ( i r /i =0.18-0.63, i P /i & .05). With the exception of the DDT k function and VMAC total points, all other task metrics across the 5 tasks did not differ between the gamified and nongamified versions ( i P /i & .05). Out of 5 tasks, 4 demonstrated adequate to excellent test-retest reliability (intraclass correlation coefficient 0.72-0.91, i P /i & .001 except SDT). Gamified metrics were significantly associated with addictive behaviors on behavioral inventories, though largely independent of trait-based scales known to predict addiction risk. purpose-built battery of digitally gamified tasks is sufficiently valid for the scalable assessment of key neurocognitive processes underpinning addictive behaviors. This validation provides evidence that a novel approach, purported to enhance task engagement, in the assessment of addiction-related neurocognition is feasible and empirically defensible. These findings have significant implications for risk detection and the successful deployment of next-generation assessment tools for substance use or misuse and other mental disorders characterized by neurocognitive anomalies related to motivation and self-regulation. Future development and validation of the BrainPAC tool should consider further enhancing convergence with established measures as well as collecting population-representative data to use clinically as normative comparisons.
Publisher: Oxford University Press (OUP)
Date: 27-07-2005
Abstract: The underlying neurobiology of emerging psychotic disorders is not well understood. While there is evidence from structural imaging and other studies supporting the popular notion that schizophrenia arises as a consequence of an "early neurodevelopmental" lesion, more recent findings challenge this notion. Evidence, including our own data, suggests that dynamic brain changes occur during the earliest stages of a psychotic illness, including around the time of transition to illness. In this article we review the available longitudinal and relevant cross-sectional structural neuroimaging studies focusing on both the very early neurodevelopmental markers (pre- or perinatal origin) and the later markers (late neurodevelopmental) around the period of transition to illness. Based on our review of recent findings, we suggest that the onset of psychosis is a time of active brain changes, wherein, for a proportion of in iduals, (i) an early (pre- and perinatal) neurodevelopmental lesion renders the brain vulnerable to anomalous late (particularly postpubertal) neurodevelopmental processes, as indicated by evidence for accelerated loss of gray matter and aberrant connectivity particularly in prefrontal regions and (ii) these anomalous neurodevelopmental processes interact with other causative factors associated with the onset of psychosis (e.g., substance use, stress, and dysregulation of the hypothalamic-pituitary-adrenal axis function), which together have neuroprogressive sequelae involving medial temporal and orbital prefrontal regions, as suggested by imaging studies around transition to active illness. However, the pathological processes underlying such progressive changes during "late neurodevelopment" remain unclear but may reflect anomalies of synaptic plasticity, abnormal brain maturation, the adverse effects of stress, or other environmental factors. In this context, the features of schizophrenia, including the neuropsychological deficits and behavioral manifestations, can be understood as direct effects of these multiple pathological processes at various neurodevelopmental stages, including genetic and nongenetic etiological factors.
Publisher: Informa UK Limited
Date: 06-08-2014
DOI: 10.3109/10826084.2014.935793
Abstract: Inhalant users have multiple comorbid issues (e.g., polydrug use) that complicate identifying inhalant-specific cognitive deficits. The aim of the present study was to use signal detection theory to identify inhalant-specific differences in executive control. We examined three well-matched groups: 19 inhalant users, 19 cannabis users, and 19 controls using Stroop and Go/No-Go tasks. Inhalant users demonstrated significantly lower d-prime scores relative to controls, but not cannabis users, on both tasks, suggesting possible executive deficits relative to controls. CONCLUSIONS/IMPORTANCE: The results of this study raise questions regarding inhalant toxicity and the vulnerability of the adolescent brain to drugs of abuse.
Publisher: Elsevier BV
Date: 05-2016
DOI: 10.1016/J.PSYCHRES.2016.03.020
Abstract: In iduals with obsessive-compulsive disorder (OCD) who sought treatment in seven different specialized centers (n=1001) were evaluated with a structured assessment battery. Thirteen OCD patients (1.3% of the s le) reported having been treated with electroconvulsive therapy (ECT) in the past. They were older and exhibited higher global severity of OCD symptoms, but were less likely to display symmetry/ordering and contamination/washing symptoms. They also had greater suicidality and increased rates of psychosis. Finally, OCD patients exposed to ECT were more frequently treated with antipsychotics, although they did not differ in terms of responses to adequate trials with serotonin reuptake inhibitors.
Publisher: Oxford University Press (OUP)
Date: 03-03-2014
DOI: 10.1093/SCAN/NST183
Publisher: Annual Reviews
Date: 17-07-2016
DOI: 10.1146/ANNUREV-NUTR-071715-050909
Abstract: There is a growing view that certain foods, particularly those high in refined sugars and fats, are addictive and that some forms of obesity can usefully be treated as a food addiction. This perspective is supported by a growing body of neuroscience research demonstrating that the chronic consumption of energy-dense foods causes changes in the brain's reward pathway that are central to the development and maintenance of drug addiction. Obese and overweight in iduals also display patterns of eating behavior that resemble the ways in which addicted in iduals consume drugs. We critically review the evidence that some forms of obesity or overeating could be considered a food addiction and argue that the use of food addiction as a diagnostic category is premature. We also examine some of the potential positive and negative clinical, social, and public policy implications of describing obesity as a food addiction that require further investigation.
Publisher: Elsevier BV
Date: 2010
DOI: 10.1016/J.JAD.2009.04.021
Abstract: Major Depressive Disorder is associated with amygdala volumetric alterations. To date, it is still unclear (I) whether amygdala volumetric alterations constitute a state or a trait marker of MDD (II) what influences the direction of amygdala morphometric changes (i.e., enlargement versus shrinkage) and (III) what the role of laterality is in amygdala volumetric alterations in MDD. We investigated amygdala volume in a s le of 31 currently depressed patients (cMDD), 31 healthy subjects with a previous diagnosis of MDD (rMDD) and 31 healthy controls, using images obtained from a 1.5 Tesla MRI scanner. The groups were matched for age and gender. We found that left amygdala volumes of rMDD subjects were significantly larger as compared to healthy controls, and tended to be larger when compared to cMDD subjects. There was no difference in left amygdala volumes between cMDD patients and healthy controls. Right amygdala volumes did not differ between groups. Given that amygdala alterations were present only in remitted patients, we suggest that such alterations appear to be a state marker of MDD. Further, we found evidence of a lateralization effect, with changes in the left hemisphere only. Left amygdala enlargement in the rMDD group may represent a neurobiological marker of vulnerability to relapse, or may reflect recovery from MDD, whereby volumetric changes have resulted from stress associated with the last depressive episode.
Publisher: Wiley
Date: 2007
DOI: 10.1080/09595230601036978
Abstract: Neuropsychological and neuroimaging studies have generated a wealth of data demonstrating structural and functional brain changes, as well as cognitive deficits in drug addicted populations. Despite this, it is often difficult to make generalisations or conclusive statements about the neuropsychological and neurobiological correlates of chronic drug use given variations in the nature or extent of deficits observed within or across different classes of drugs. In this review, we focus specifically on the evidence for impairments in prefrontally-mediated cognitive functions that underlie behavioural regulation, namely decision making and inhibitory control. We argue that impairments in these specific domains, which are often compounded by an earlier initiation of drug use, polydrug abuse, comorbid psychiatric conditions, previous head injury, and acute withdrawal effects can serve to increase the risk for making decisions that are impulsive, focussed on short-terms gains and lack inhibitory control. We further argue that these impairments of prefrontal functioning may underpin the compulsive and 'loss-of-control' pattern of drug-seeking and drug-taking that is characteristic of drug addiction. Finally, we consider the implications of these findings for diagnosis, treatment and prevention, suggesting that a comprehensive understanding of the nature and extent of these cognitive deficits should form a core part of the conceptualization and focus of effective treatment.
Publisher: Informa UK Limited
Date: 16-07-2020
Publisher: Springer Science and Business Media LLC
Date: 12-09-2020
DOI: 10.1038/S41386-020-00848-9
Abstract: Impulsive and compulsive symptoms are common, tend to co-occur, and collectively account for a substantive global disease burden. Latent phenotyping offers a promising approach to elucidate common neural mechanisms conferring vulnerability to such symptoms in the general population. We utilised the Neuroscience in Psychiatry Network (NSPN), a cohort of young people (aged 18–29 years) in the United Kingdom, who provided questionnaire data and Magnetic Resonance Imaging scans. Partial Least Squares was used to identify brain regions in which intra-cortical myelination (measured using Magnetisation Transfer, MT) was significantly associated with a disinhibition phenotype, derived from bi-factor modelling of 33 impulsive and compulsive problem behaviours. The neuroimaging s le comprised 126 participants, mean 22.8 (2.7 SD) years old, being 61.1% female. Disinhibition scores were significantly and positively associated with higher MT in the bilateral frontal and parietal lobes. 1279 genes associated with disinhibition-related brain regions were identified, which were significantly enriched for functional biological interactions reflecting receptor signalling pathways. This study indicates common microstructural brain abnormalities contributing to a multitude of related, prevalent, problem behaviours characterised by disinhibition. Such a latent phenotyping approach provides insights into common neurobiological pathways, which may help to improve disease models and treatment approaches. Now that this latent phenotyping model has been validated in a general population s le, it can be extended into patient settings.
Publisher: Springer Science and Business Media LLC
Date: 20-02-2014
DOI: 10.1007/S00213-014-3483-8
Abstract: In idual differences in brain structure and function are suggested to exist prior to the onset of alcohol abuse. Cross-sectional studies have demonstrated abnormalities in brain regions underlying affective processes that may form a pathway to the emergence of later alcohol abuse and dependence in vulnerable in iduals. However, no prospective studies have examined whether these abnormalities predict later problems with alcohol. This study aims to examine whether in idual differences in affect and brain volume prospectively predict alcohol-related problems in adolescence. Adolescent drinkers (n = 98) were recruited from an ongoing prospective, longitudinal study examining adolescent emotional development. At age 12, participants underwent structural magnetic resonance imaging to obtain volumetric data on the amygdala, hippoc us, orbitofrontal cortex, and anterior cingulate cortex (ACC), and completed a self-report measure of affective temperament. At age 16, participants completed a questionnaire measuring alcohol use, with 39 % reporting alcohol-related problems in the past year. Pre-existing differences in the left ACC predicted problem drinking. Alcohol-related problems were associated with higher levels of temperamental negative affectivity however, these were not correlated with anterior cingulate volumes. These findings indicate that in idual differences in the structural morphology of the anterior cingulate, a region implicated in affective processes, self-control, and drug addiction, predict later alcohol-related problems. Although this finding remained significant after controlling for other substance use and psychopathology, future research is required to test its specificity for alcohol use disorders.
Publisher: Frontiers Media SA
Date: 20-05-2014
Publisher: Public Library of Science (PLoS)
Date: 04-02-2013
Publisher: Elsevier BV
Date: 10-2009
DOI: 10.1016/J.PNPBP.2009.07.012
Abstract: Hypothalamic-pituitary-adrenal (HPA) axis dysfunction has been demonstrated in bipolar disorder (BD), but previous magnetic resonance imaging (MRI) studies of pituitary gland volume in BD have reported variable findings. In this MRI study we investigated pituitary volume in 26 patients with established bipolar I disorder (8 males and 18 females, mean age=38.4 years) and 24 matched controls (7 males and 17 females, mean age=38.7 years). The BD patients had a significantly larger pituitary volume as compared with controls, but there was no association between pituitary volume and illness duration, number of manic/depressive episodes, daily medication dosage, family history, or clinical subtype (i.e., psychotic and nonpsychotic). Pituitary volume was larger in females than in males for both groups. These results support previous neuroendocrine findings that implicate HPA axis dysfunction in the core pathophysiological process of BD.
Publisher: Elsevier BV
Date: 04-2010
DOI: 10.1016/J.NEUROIMAGE.2009.12.027
Abstract: Whole-brain anatomical connectivity in living humans can be modeled as a network with diffusion-MRI and tractography. Network nodes are associated with distinct grey-matter regions, while white-matter fiber bundles serve as interconnecting network links. However, the lack of a gold standard for regional parcellation in brain MRI makes the definition of nodes arbitrary, meaning that network nodes are defined using templates employing either random or anatomical parcellation criteria. Consequently, the number of nodes included in networks studied by different authors has varied considerably, from less than 100 up to more than 10(4). Here, we systematically and quantitatively assess the behavior, structure and topological attributes of whole-brain anatomical networks over a wide range of nodal scales, a variety of grey-matter parcellations as well as different diffusion-MRI acquisition protocols. We show that simple binary decisions about network organization, such as whether small-worldness or scale-freeness is evident, are unaffected by spatial scale, and that the estimates of various organizational parameters (e.g. small-worldness, clustering, path length, and efficiency) are consistent across different parcellation scales at the same resolution (i.e. the same number of nodes). However, these parameters vary considerably as a function of spatial scale for ex le small-worldness exhibited a difference of 95% between the widely-used automated anatomical labeling (AAL) template (approximately 100 nodes) and a 4000-node random parcellation (sigma(AAL)=1.9 vs. sigma(4000)=53.6+/-2.2). These findings indicate that any comparison of network parameters across studies must be made with reference to the spatial scale of the nodal parcellation.
Publisher: Wiley
Date: 04-08-2008
DOI: 10.1111/J.1600-0447.2008.01230.X
Abstract: Evidence related to overlapping clinical and genetic risk factors in schizophrenia and bipolar disorder (BD) have raised concerns about the validity of 'Kraepelinian dichotomy'. As controversies mainly arise in mixed psychoses that occupy the intermediate zone between schizophrenia and BD, investigating neurobiological markers of mixed psychoses may be relevant to understanding the nature of psychotic disorders. In this article, we review studies comparing magnetic resonance imaging, neuropsychological and electrophysiological findings in mixed psychoses with each other, as well as with more prototypical cases of schizophrenia and BD. The evidence reviewed suggests that mixed psychoses may be associated with different genetic and neurobiological markers compared with prototypical forms of schizophrenia and BD. These findings may be compatible with more sophisticated versions of dimensional and continuum models or, alternatively, they may suggest that there is an intermediate third category between prototypical schizophrenia and BD.
Publisher: Elsevier BV
Date: 11-2009
DOI: 10.1016/J.PNPBP.2009.07.017
Abstract: Fronto-limbic neural dysfunction has been implicated in the emotional dysregulation and impulsivity seen in borderline personality disorder (BPD). However, it remains unclear whether affected in iduals exhibit morphologic changes of the insular cortex, a fronto-limbic integration cortex engaged in emotional regulation and impulse control. This magnetic resonance imaging study examined the insular cortex volume and its relationship to clinical characteristics in a first-presentation teenage BPD s le. No significant difference was found in the insular volume between 20 BPD participants (5 males) and 20 healthy control participants (5 males). There was no association between the insular volume and parasuicidal episodes, trauma exposure, or comorbid Axis I disorders, but the BPD participants with violent episodes during the previous 6 months had a smaller insular volume bilaterally compared with those without such episodes. Furthermore, right anterior insular volume in the BPD participants was negatively correlated with impulsivity score. These preliminary findings suggest that insular cortex volume does not significantly differ in early BPD, but that there might be a relationship with violent and impulsive behavior that is often seen in the disorder. Further studies are needed to clarify whether the potential relationship between the insular cortex volume and impulsivity is specific to BPD.
Publisher: Elsevier BV
Date: 04-2021
Publisher: Elsevier BV
Date: 2008
DOI: 10.1016/J.NEUBIOREV.2007.04.016
Abstract: Adolescent development is accompanied by the emergence of a population-wide increase in vulnerability to depression that is maintained through adulthood. We provide a model for understanding how this vulnerability to depression arises, and why depression is so often precipitated by social rejection or loss of status during this phase. There is substantial remodeling and maturation of the dopaminergic reward system and the prefrontal cortex during adolescence, that coincides with the adolescent entering the complex world of adult peer and romantic relationships, where the rewards that can be obtained (feelings such as belonging, romantic love, status and agency) are abstract and temporally distant from the proximal context. Development of the prefrontal cortex makes it possible to pursue such complex and distal rewards, which are, however, tenuous and more readily frustrated than more immediate rewards. We hypothesize that when these distant rewards are frustrated they suppress the reward system, and that when such suppression is extensive and occurs for long enough, the clinical picture that results is one of depression.
Publisher: American Psychological Association (APA)
Date: 07-2021
DOI: 10.1037/PAS0000870
Publisher: Elsevier BV
Date: 07-2008
DOI: 10.1016/J.PSCYCHRESNS.2007.08.007
Abstract: It is not known whether the fronto-limbic volume reductions found in adults with established borderline personality disorder (BPD) are present early in the disorder. The aim of the study was to investigate orbitofrontal cortex (OFC), hippoc al and amygdala volumes in a first-presentation teenage BPD s le with minimal exposure to treatment. Groups of 20 BPD patients and 20 healthy control participants underwent magnetic resonance imaging. Hippoc al, amygdala, OFC and whole brain volumes were estimated and compared between the two groups. Analysis of variance revealed reversal of the normal (right>left) asymmetry of OFC grey matter volume in the BPD group, reflecting right-sided OFC grey matter loss in the BPD group compared with control participants. No significant differences were found for amygdala or hippoc al volumes comparing BPD with control participants. We identified OFC but not hippoc al or amygdala volumetric differences early in the course of BPD. Hippoc al and amygdala volume reductions observed in adult BPD s les might develop during the course of the disorder, although longitudinal studies are needed to examine this.
Publisher: Springer Science and Business Media LLC
Date: 25-01-2019
DOI: 10.1007/S10899-018-09822-Z
Abstract: During slot machine gambling, near-miss outcomes occur when the final winning icon lands one position off the pay-line. To understand how near-misses promote gambling behaviour in healthy populations, autonomic arousal is often used to index outcome response valence. Findings remain equivocal, possibly owing to the limited ecological validity of computer simulations. Relevant psychological traits, such as impulsivity, which increase the risk of problem gambling, are often not examined. Here, we used immersive virtual reality (VR) to investigate near-miss-induced changes in physiological arousal and VR gambling behaviour. Sixty adult participants with no history of problem gambling were immersed in a VR casino-bar where they engaged with a self-selected slot machine. Real-time heart rate (HR) data were acquired during immersion. Within-subjects analyses were conducted on HR and post-reinforcement pauses (PRPs i.e., time taken to initiate next-spin) across wins, losses and near-misses. Significant HR acceleration occurred for both near-misses and losses compared to wins, indexing an initial orientation response. Both types of losses were associated with faster next-spin responses. Near-misses did not apparently have unique HR or PRP profiles from losses, although this may reflect our loss control condition, which in itself may have been a subtler near-miss outcome. Impulsivity measured by the SUPPS-P was not associated with near-miss responses. Losses may encourage gambling as participants experience more immediate HR acceleration (indexing arousal unique to losing) and initiate faster responses. Future studies should clarify this effect by investigating problem gambling cohorts and develop VR paradigms taking into consideration the current findings and limitations.
Publisher: Society for Neuroscience
Date: 17-06-2015
Publisher: Cambridge University Press (CUP)
Date: 10-2006
DOI: 10.1111/J.1601-5215.2006.00154.X
Abstract: Previous studies on substance-dependent populations have shown that age of first use and duration of use are associated with alterations in regional brain volumes. However, it is not clear whether such alterations are factors that predispose young people to use, and so are also present in recreational users, or are a consequence of chronic exposure to substances and/or comorbid psychopathology. To investigate relationships between key brain structures and parameters of alcohol and cannabis use, in otherwise healthy male recreational users. High-resolution magnetic resonance imaging was used to measure hippoc al, amygdala, whole-brain and intracranial cavity (ICC) volumes in 22 young men with a history of both alcohol and cannabis use. Linear regression analyses with hippoc al, amygdala and whole-brain volumes as the dependent variables and age and ICC as covariates were performed. Findings showed that use of cannabis and alcohol at an earlier age were independently predictive of larger amygdala volumes, whereas longer duration of cannabis use was predictive of smaller hippoc al volumes. Our findings offer preliminary support for a relationship between patterns of substance use and regional brain volumes in recreational users. It is speculative, but possible that this relationship is an evidence of a neurobiological vulnerability to drug-taking behaviour.
Publisher: JMIR Publications Inc.
Date: 27-07-2020
DOI: 10.2196/18349
Abstract: High rates of cannabis and illicit drug use are experienced by young people during the final stages of neurodevelopment (aged 15-24 years), a period characterized by high neuroplasticity. Frequent drug use during this time may interfere with neurophysiological and neuropsychological development pathways, potentially leading to ongoing unfavorable neuroadaptations. The dose-response relationship between illicit drug use, exposure, and in idual neurodevelopmental variation is unknown but salient with global shifts in the legal landscape and increasingly liberal attitudes and perceptions of the harm caused by cannabis and illicit drugs. This systematic review aims to synthesize longitudinal studies that investigate the effects of illicit drug use on structural, functional, and cognitive brain domains in in iduals under the neural age of adulthood (25 years). This protocol outlines prospective methods that will facilitate an exhaustive review of the literature exploring pre- and post-drug use brain abnormalities arising during neurodevelopment. Five electronic databases (Medline, Embase, PsycINFO, ProQuest Central, and Web of Science) will be systematically searched between 1990 and 2019. The search terms will be a combination of MeSH (Medical Subject Headings), with keywords adapted to each database. Study reporting will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and if relevant, study quality will be assessed using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. Eligible studies are those that s led youth exposed to cannabis or illicit drugs and employed neurophysiological or neuropsychological assessment techniques. Studies will be excluded if participants had been clinically diagnosed with any psychiatric, neurological, or pharmacological condition. This is an ongoing review. As of February 2020, papers are in full-text screening, with results predicted to be complete by July 2020. Integrating data collected on the three brain domains will enable an assessment of the links between structural, functional, and cognitive brain health across in iduals and may support the early detection and prevention of neurodevelopmental harm. PROSPERO CRD42020151442 www.crd.york.ac.uk rospero/display_record.php?RecordID=151442 PRR1-10.2196/18349
Publisher: SAGE Publications
Date: 02-2007
DOI: 10.1080/00048670601109899
Abstract: Objective: Cognitive deficits, particularly those related to executive function and behavioural control, are a core feature of patients with schizophrenia and implicate disturbances of the prefrontal cortex (PFC). Consistent with this, functional imaging studies have identified abnormalities of PFC activity in chronically affected patients. The objective of the current study was to investigate executive-control related neural activity from first onset of the illness through to symptom stabilization. Method: The authors examined eight neuroleptic-naïve first-episode psychosis (FEP) patients within 3 days of first presentation and eight healthy agepremorbid-IQ, and gender-matched controls (CTL). All FEP patients were later confirmed with a diagnosis of schizophrenia. Subjects underwent H2-15O positron emission tomography (PET) while performing the Stroop interference task that has previously been shown to engage the PFC in healthy s les. In a double-blind paradigm, FEP patients were randomly treated with either haloperidol or risperidone for 8 weeks, after which CTLs and all but one of the FEP patients were re-scanned. Results: Behaviorally, there was no change in task performance from baseline to follow up for either the FEPs or CTLs. However, there were significant changes in functional activation in both groups across the same period. For CTLs, task-performance was associated with greater recruitment of posterior brain regions at follow up compared to baseline, while for FEP this involved greater recruitment frontal regions. Concurrently, FEP also showed significant improvement in positive symptomatology. Conclusions: These findings suggest that disturbances of the PFC often seen in FEP may be, at least partially, associated with acute symptom expression. However, it is still unclear whether this increase in frontal activity is due to symptom stabilization per se, the effects of medication, a lack of neurophysiological ‘learning’ with experience ractice, or a combination of these factors. In the context of the CTLs performance, we interpret the patient findings as reflective of greater neurophysiological effort required for task accomplishment relative to the learned, more automated, processing apparent in the CTLs.
Publisher: Cambridge University Press (CUP)
Date: 02-2008
DOI: 10.1111/J.1601-5215.2007.00236.X
Abstract: To illustrate the need to carefully consider mental health, psychosocial and motivational factors when investigating cognitive and intellectual impairment among chronic inhalant users. Two adolescent chronic inhalant users with similar psychosocial disadvantages (eg unstable and dysfunctional families, state-based care, school absenteeism and forensic issues) and histories of comorbid drug use and mental health problems were assessed using a battery of paper and pencil and computerised neuropsychological tests. Contrary to the expectations of her case manager, one participant performed within the normal range for her age in all domains of intellectual ability, while the other participant, in line with the expectations of her case manger, showed marked cognitive deficits and intellectual disability. The typically complex presentation of chronic inhalant users (ie disadvantaged psychosocial backgrounds, comorbid psychopathology and poor motivation/engagement) is rarely considered when investigating associated cognitive and intellectual functioning. Future research should more carefully consider the role of such factors, given the evidence suggesting that they can considerably alter (accentuate or diminish) the association between inhalant abuse and neuropsychological impairment.
Publisher: Wiley
Date: 05-10-2018
DOI: 10.1111/ADD.14424
Publisher: Wiley
Date: 12-2004
Publisher: Wiley
Date: 22-08-2017
DOI: 10.1002/HBM.23347
Publisher: Wiley
Date: 11-06-2013
DOI: 10.1111/DESC.12057
Abstract: Early to mid-adolescence is an important developmental period for subcortical brain maturation, but longitudinal studies of these neurodevelopmental changes are lacking. The present study acquired repeated magnetic resonance images from 60 adolescent subjects (28 female) at ages 12.5 and 16.5 years to map changes in subcortical structure volumes. Automated segmentation techniques optimized for longitudinal measurement were used to delineate volumes of the caudate, putamen, nucleus accumbens, pallidum, hippoc us, thalamus and the whole brain. Amygdala volumes were described using manual tracing methods. The results revealed heterogeneous maturation across the regions of interest (ROIs), and change was differentially moderated by sex and hemisphere. The caudate, thalamus and putamen declined in volume, more for females relative to males, and decreases in the putamen and thalamus were greater in the left hemisphere. The pallidum increased in size, but more so in the left hemisphere. While the left nucleus accumbens increased in size, the right accumbens decreased in size over the follow-up period. Increases in hippoc al volume were greater in the right hemisphere. While amygdala volume did not change over time, the left hemisphere was consistently larger than the right. These results suggest that subcortical brain development from early to middle adolescence is characterized by striking hemispheric specialization and sexual dimorphisms, and provide a framework for interpreting normal and abnormal changes in cognition, affect and behavior. Moreover, the differences in findings compared to previous cross-sectional research emphasize the importance of within-subject assessment of brain development during adolescence.
Publisher: Elsevier BV
Date: 2013
DOI: 10.1016/J.SCHRES.2012.10.040
Abstract: Abnormalities in hippoc al morphology are characteristic of schizophrenia and have also been reported in chronic cannabis users. There is a paucity of research investigating potential additive effects of cannabis use on brain pathology associated with schizophrenia. In this study, we performed hippoc al shape analysis in cannabis-using and non-using patients with schizophrenia, healthy cannabis users and healthy non-using controls. Hippoc al shape changes were observed in each group relative to controls, with the greatest degree of alterations (i.e., deflations across the hippoc us, and with an anterior predisposition), in cannabis-using schizophrenia patients. These alterations were associated with cannabis use patterns and psychotic symptoms.
Publisher: Elsevier BV
Date: 11-2010
DOI: 10.1016/J.NEUBIOREV.2010.03.001
Abstract: A principal feature of drug addiction is a reduced ability to regulate control over the desire to procure drugs regardless of the risks involved. Traditional models implicated the neural 'reward' system in providing a neurobiological model of addiction. Newer models however, have expanded on this circuitry to include two separate, but interconnecting systems, the limbic system in the incentive sensitization of drugs, and the prefrontal cortex (PFC) in regulating inhibitory control over drug use. Until the recent developments in neuroimaging and brain stimulation techniques, it has been extremely difficult to assess the involvement of the PFC in addiction. In the current review, we explore the involvement of the frontostriatal circuitry in regulating inhibitory control, and suggest how dysregulation of these circuits could be involved in an increased difficulty in ceasing drug use. Following this, we investigate the recent neuropsychological, neuroimaging and brain stimulation studies that explore the presence of these inhibitory deficits, and frontostriatal dysfunctions, across various different substance groups. Further insight into these deficits could contribute to the development of treatment strategies which target these cognitive impairments, and frontostriatal dysfunction, in reducing drug-seeking behaviors.
Publisher: Oxford University Press (OUP)
Date: 23-04-2009
Publisher: Cambridge University Press (CUP)
Date: 10-2002
DOI: 10.1017/S0033291702006128
Abstract: Background. It has been argued recently that the attentional dysfunction in schizophrenia occurs as a result of an inability to inhibit automatic attentional shifts to compelling external stimuli. However, this hypothesis is based on performance on paradigms that require overt or covert shifts of spatial attention. Method. We investigated responses to foveally presented stimuli in patients with schizophrenia and healthy controls as they performed unidimensional and bidimensional versions of the flanker task. In both tasks, centrally presented target stimuli were flanked by peripheral stimuli that were either congruent or incongruent with the behavioural goal of the subject. In the bidimensional task, the flanking stimuli could be congruent and incongruent on multiple stimulus characteristics. Results. On the unidimensional flanker task, the behavioural goal modulated the responses of the schizophrenia group such that response times (RTs) to target stimuli that were flanked by congruent stimuli were faster than RTs to target stimuli flanked by incongruent stimuli. However, on the bidimensional flanker task, the responses of schizophrenia patients were no longer constrained by the behavioural goal and RTs to both congruent and incongruent stimuli were equivalent. Conclusions. It appears that the attentional dysfunction in schizophrenia may reflect difficulty in resolving multiple and simultaneous response conflicts. These findings suggest a possible role for the anterior cingulate cortex in the attentional impairments associated with schizophrenia.
Publisher: Akademiai Kiado Zrt.
Date: 30-03-2023
Abstract: Existing research has demonstrated that problematic smartphone use (PSU) may reflect a composition of heterogeneous symptoms, with in idual PSU symptoms uniquely related to predisposing variables. The Big Five personality traits represent one of the most frequently examined predisposing variables in relation to PSU. However, no studies to date have examined the trait-to-symptom association between the Big Five personality traits and PSU. Using a network analysis approach, we aimed to understand: 1) specific pathways linking each of the Big Five personality traits to PSU symptoms and 2) the bridging effects of each Big Five personality trait on the PSU symptom cluster. A regularised graphical Gaussian model was estimated among 1,849 Chinese university students. PSU symptoms were assessed with items from the Problematic Smartphone Use Scale. Facets of the Big Five personality traits were assessed with the subscales of the Chinese Big Five Personality Inventory-15. An empirical index (i.e., bridge expected influence) was used to quantify bridge nodes. Results revealed specific and distinct pathways between the Big Five personality traits and PSU symptoms (e.g., Neuroticism-Escapism/Avoidance, Conscientiousness-Preoccupation and Extraversion-Escapism/Avoidance). Further, Neuroticism showed the highest positive bridge centrality among the Big Five personality traits, while Conscientiousness had the highest negative bridge centrality. The current study provided direct empirical evidence concerning specific pathways between the Big Five personality traits and PSU symptoms and highlighted the influential role of Neuroticism and Conscientiousness as potential targets for early detection and treatment of PSU.
Publisher: Elsevier BV
Date: 07-2012
DOI: 10.1016/J.PSYNEUEN.2011.10.004
Abstract: Early timing of puberty (i.e., advanced pubertal maturation relative to peers) has been linked to the onset of depressive symptoms during the early adolescent phase. However, the precise neurobiological mechanisms linking early pubertal timing to adolescent depressive symptoms are not clear. We investigated whether the volume of the pituitary gland, a key component of the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) axes, mediated the relationship between pubertal timing and depressive symptoms in 155 adolescents (72 females) both cross-sectionally and longitudinally. At baseline (M age 12.7, SD 0.5 years), early pubertal timing predicted larger pituitary gland volume and higher depressive symptoms (especially for girls), but there was no mediation effect. Longitudinally, however, larger pituitary gland volume at baseline was found to mediate the relationship between early pubertal timing and increased depressive symptoms over time (M follow-up period=2.57 years, SD=0.26) for both boys and girls. Our findings suggest that neurobiological mechanisms are partly responsible for the link between early pubertal timing and depressive symptoms in adolescents. We speculate that an enlarged pituitary gland in adolescents with early pubertal timing might be associated with hyperactivation of the hormonal stress response, leading to increased susceptibility to environmental stressors, and subsequent development of depressive symptoms. Given the well-established relationship between increasing depressive symptoms in adolescence and later disorder, these findings have implications for targeted prevention and early intervention strategies for depressive disorders in adolescence.
Publisher: Public Library of Science (PLoS)
Date: 21-04-2009
Publisher: Elsevier BV
Date: 04-2015
DOI: 10.1016/J.PHARMTHERA.2014.11.009
Abstract: Heavy cannabis use has been frequently associated with increased rates of mental illness and cognitive impairment, particularly amongst adolescent users. However, the neurobiological processes that underlie these associations are still not well understood. In this review, we discuss the findings of studies examining the acute and chronic effects of cannabis use on the brain, with a particular focus on the impact of commencing use during adolescence. Accumulating evidence from both animal and human studies suggests that regular heavy use during this period is associated with more severe and persistent negative outcomes than use during adulthood, suggesting that the adolescent brain may be particularly vulnerable to the effects of cannabis exposure. As the endocannabinoid system plays an important role in brain development, it is plausible that prolonged use during adolescence results in a disruption in the normative neuromaturational processes that occur during this period. We identify synaptic pruning and white matter development as two processes that may be adversely impacted by cannabis exposure during adolescence. Potentially, alterations in these processes may underlie the cognitive and emotional deficits that have been associated with regular use commencing during adolescence.
Publisher: Informa UK Limited
Date: 06-2010
DOI: 10.3109/10826084.2010.482443
Abstract: In animal studies, tetrahydrocannabinol (THC) has been found to affect brain morphology, particularly within areas rich in cannabinoid receptors (e.g., hippoc us, cerebral cortex). While cannabis remains the most widely used illicit drug worldwide, there has been limited work investigating its effects on human brain tissue. In this paper, we conducted a systematic review of existing structural magnetic resonance imaging studies to examine whether cannabis use is associated with significant changes in brain anatomy. We identified only 13 structural neuroimaging studies, which were erse in terms of s le characteristics (e.g., age of participants, duration and frequency of use) and methodology (e.g., image analysis). No study found global structural changes in cannabis users, although six studies reported regional alterations. While changes in the hippoc us and parahippoc us were frequently identified, the findings were inconsistent across studies. The available literature also provides some evidence that regional structural changes are associated with cannabis use patterns (particularly cumulative dosage and frequency of use), as well as measures of psychopathology (e.g., measures of depressive and psychotic symptoms). Together, these structural imaging findings suggest that THC exposure does affect brain morphology, especially in medial-temporal regions. Given the small literature available and the limitations of studies to date, further research is clearly required, particularly given the prevalence of cannabis use worldwide.
Publisher: Cambridge University Press (CUP)
Date: 25-11-2014
DOI: 10.1017/S0954579413000886
Abstract: Investigating etiological processes early in the life span represents an important step toward a better understanding of the development of personality pathology. The current study evaluated the interaction between an in idual difference risk factor (i.e., temperament) and a biological risk factor for aggressive behavior (i.e., atypical [larger] rightward hippoc al asymmetry) in predicting the emergence of borderline personality disorder (BPD) and antisocial personality disorder symptoms during early adolescence. The s le consisted of 153 healthy adolescents ( M = 12.6 years, SD = 0.4, range = 11.4–13.7) who were selected from a larger s le to maximize variation in temperament. Interactions between four temperament factors (effortful control, negative affectivity, surgency, and affiliativeness), based on the Early Adolescent Temperament Questionnaire—Revised, and volumetric measures of hippoc al asymmetry were examined as cross-sectional predictors of BPD and antisocial personality disorder symptoms. Boys were more likely to have elevated BPD symptoms if they were high on affiliation and had larger rightward hippoc al asymmetry. In boys, low affiliation was a significant predictor of BPD symptoms in the presence of low rightward hippoc al asymmetry. For girls, low effortful control was associated with elevated BPD symptoms in the presence of atypical rightward hippoc al asymmetry. This study builds on previous work reporting significant associations between atypical hippoc al asymmetry and poor behavioral regulation.
Publisher: Elsevier BV
Date: 2006
DOI: 10.1016/J.NEUBIOREV.2005.09.003
Abstract: The ability to characterise psychopathologies on the basis of their underlying neurobiology is critical in improving our understanding of disorder etiology and making more effective diagnostic and treatment decisions. Given the well-documented relationship between temperament (i.e. core personality traits) and psychopathology, research investigating the neurobiological substrates that underlie temperament is potentially key to our understanding of the biological basis of mental disorder. We present evidence that specific areas of the prefrontal cortex (including the dorsolateral prefrontal, anterior cingulate, and orbitofrontal cortices) and limbic structures (including the amygdala, hippoc us and nucleus accumbens) are key regions associated with three fundamental dimensions of temperament: Negative Affect, Positive Affect, and Constraint. Proposed relationships are based on two types of research: (a) research into the neurobiological correlates of affective and cognitive processes underlying these dimensions and (b) research into the neurobiology of various psychopathologies, which have been correlated with these dimensions. A model is proposed detailing how these structures might comprise neural networks whose functioning underlies the three temperaments. Recommendations are made for future research into the neurobiology of temperament, including the need to focus on neural networks rather than in idual structures, and the importance of prospective, longitudinal, multi-modal imaging studies in at-risk youth.
Publisher: Cambridge University Press (CUP)
Date: 13-09-2011
DOI: 10.1017/S0033291711001668
Abstract: Abnormalities in cortico-striatal-pallidal-thalamic (CSPT) circuits have been implicated in major depressive disorder (MDD). However, the robustness of these findings across studies is unclear, as is the extent to which they are influenced by demographic, clinical and pharmacological factors. With the aim of clarifying these questions, we conducted a meta-analysis to map the volumetric abnormalities that were most robustly identified in CSPT circuits of in iduals with MDD. A systematic search identified 41 studies meeting our inclusion criteria. There were significant volume reductions in prefrontal (especially orbitofrontal) and anterior cingulate cortices, and also in subcortical structures such as the caudate nucleus and putamen, with effect sizes ranging from small to moderate. The subgenual anterior cingulate and orbitofrontal cortices were significantly smaller in antidepressant-free s les compared to medicated patients. Late-life depression (LLD) tended to be associated with smaller volumes in circumscribed frontal and subcortical structures, with the most robust differences being found in thalamic volume. In iduals with major depression demonstrate volumetric abnormalities of CSPT circuits. However, these observations may be restricted to certain subgroups, highlighting the clinical heterogeneity of the disorder. On the basis of this meta-analysis, CSPT abnormalities were more prominent in those with LLD whereas antidepressant use seemed to normalize certain cortical volumetric abnormalities.
Publisher: Elsevier BV
Date: 04-2017
DOI: 10.1016/J.ADDBEH.2016.11.021
Abstract: The occurrence of repetitive behaviours that are often harmful has been attributed to traits traditionally described as "impulsive" or "compulsive" e.g. substance dependence, excessive gambling, and hoarding. These behaviours are common and often co-occur in both the general population and psychiatric populations. The lack of measures to concurrently index a range of such behaviours led to the development of the Impulsive-Compulsive Behaviours (ICB) Checklist. This study aims to validate the ICB Checklist in a general community s le. Factor analyses revealed a two-factor structure, demonstrating good model fit in two independent s les. These were labelled Impulsive-Compulsions and Compulsive-Impulsions, comprising of classically compulsive and impulsive behaviours respectively. Reliability and construct validity were further confirmed using correlations with existing measures of impulsivity and compulsivity. Results suggest that the ICB Checklist is a valid and practical assessment that can be used to monitor behavioural clusters characterised by deficits in inhibition.
Publisher: Cambridge University Press (CUP)
Date: 09-03-2012
DOI: 10.1017/S0033291712000323
Abstract: Depression has been associated with functional alterations in several areas of the cingulate cortex. In this study we have taken a systematic approach to examining how alterations in functional connectivity vary across the functionally erse subregions of the rostral cingulate cortex. Eighteen patients with major depressive disorder, aged 15 to 24 years, were matched with 20 healthy control participants. Using resting-state functional connectivity magnetic resonance imaging (fcMRI), we systematically investigated the functional connectivity of four subregions of the rostral cingulate cortex. Voxelwise statistical maps of each subregion's connectivity with other brain areas were compared between the patient and control groups. The depressed participants showed altered patterns of connectivity with ventral cingulate subregions. They showed increased connectivity between subgenual anterior cingulate cortex (ACC) and dorsomedial frontal cortex, with connectivity strength showing positive correlation with illness severity. Depressed participants also showed increased connectivity between pregenual ACC and left dorsolateral frontal cortex, and decreased connectivity between pregenual ACC and the caudate nucleus bilaterally. The results reinforce the importance of subgenual ACC for depression, and show a close link between brain regions that support self-related processes and affective visceromotor function. The pregenual ACC also has an important role, with its increased connectivity with dorsolateral frontal cortex suggesting heightened cognitive regulation of affect and reduced connectivity with the caudate nucleus potentially underlying symptoms such as anhedonia, reduced motivation and psychomotor dysfunction.
Publisher: Elsevier BV
Date: 04-2012
DOI: 10.1016/J.BIOPSYCH.2011.10.029
Abstract: There is growing evidence that long-term, heavy cannabis use is associated with alterations in regional brain volumes. Although these changes are frequently attributed to the neurotoxic effects of cannabis, it is possible that some abnormalities might predate use and represent markers of vulnerability. To date, no studies have examined whether structural brain abnormalities are present before the onset of cannabis use. This study aims to determine whether adolescents who have initiated cannabis use early (i.e., before age 17 years) show premorbid structural abnormalities in the amygdala, hippoc us, orbitofrontal cortex, and anterior cingulate cortex. Participants (n = 121) were recruited from primary schools in Melbourne, Australia, as part of a larger study examining adolescent emotional development. Participants underwent structural magnetic resonance imaging at age 12 years and were assessed for cannabis use 4 years later, at age 16 years. At the follow-up assessment, 28 participants had commenced using cannabis (16 female subjects [57%]), and 93 had not (43 female subjects [46%]). Smaller orbitofrontal cortex volumes at age 12 years predicted initiation of cannabis use by age 16 years. The volumes of other regions (amygdala, hippoc us, and anterior cingulate cortex) did not predict later cannabis use. These findings suggest that structural abnormalities in the orbitofrontal cortex might contribute to risk for cannabis exposure. Although the results have important implications for understanding neurobiological predictors of cannabis use, further research is needed to understand their relationship with heavier patterns of use in adulthood as well as later abuse of other substances.
Publisher: Elsevier BV
Date: 2021
Publisher: Wiley
Date: 11-11-2010
DOI: 10.1111/J.1369-1600.2010.00266.X
Abstract: Heroin addiction has been associated with impaired neuronal connectivity and cognitive deficits. One mechanism that potentially explains these findings is alterations in white matter connectivity secondary to chronic opiate use. However, few studies have quantitavely examined white matter deficits in opiate addiction (OA). Here, we investigated white matter microstructure in OA using diffusion tensor imaging (DTI). We performed voxel-wise analysis of fractional anisotropy (FA) in 24 participants with OA and 29 healthy controls. The OA group showed reduced FA in multiple pathways including the corpus callosum, thalamic radiation and inferior longitudinal fasciculus. This FA reduction was mainly the result of increased radial diffusivity (λ(⊥)), indicative of myelin pathology. Longer duration of OA was also associated with axonal diffusivity (λ(1)), most robustly in superior longitudinal fasciculi and right frontal white matter suggesting axonal injury in long-term users. Together, the findings indicate that chronic OA use has widespread and erse effects on neuronal connectivity and function.
Publisher: Cambridge University Press
Date: 19-10-2006
Publisher: Wiley
Date: 24-05-2012
DOI: 10.1002/HBM.21270
Publisher: Wiley
Date: 21-04-2008
Publisher: Informa UK Limited
Date: 31-05-2016
DOI: 10.1080/09297049.2016.1186159
Abstract: Maltreatment of children is a chronic community problem that increases the risk of future aggression. Despite several decades of research highlighting this relationship, few studies have explored the potential neuropsychological deficits that are likely to mediate it. This exploratory study aimed to examine how child maltreatment may be associated with aggression via impairment in the developing prefrontal-limbic-autonomic pathways that are implicated in neuropsychological models of aggression. Furthermore, it aimed to investigate the relationship between child maltreatment and both reactive and proactive aggression subtypes. To investigate this non-invasively in an at-risk population, children with a documented protective care history (n = 20) and a community control group (n = 30), aged between 6 and 12 years, were compared on measures of cardiovascular functioning, affect regulation and cognitive functioning aligned with this neuropsychological model. Whilst no group differences were found on cardiovascular functioning (i.e., resting heart rate, heart rate reactivity, heart rate variability), the protective care group performed significantly worse on measures of affect regulation and cognitive functioning (i.e., global intelligence, executive functioning, smell identification and social cognition). The relationship between child maltreatment and aggression was mediated by executive dysfunction and affect dysregulation but not global IQ, social cognition or olfactory identification. The results suggest that interventions targeting aggression in maltreated children will benefit from clinical assessment and psychological strategies that address the executive dysfunction and affect dysregulation that has been associated with this clinical outcome.
Publisher: Elsevier BV
Date: 03-2015
DOI: 10.1016/J.JAD.2014.10.041
Abstract: Brain abnormalities in fronto-temporal structures have been implicated in major depressive disorder (MDD). This study aims to identify their anatomical distribution and their relation to the time course of the disease. A whole-brain voxel based morphometry analysis was conducted to assess gray and white matter alterations in 56 participants with a lifetime history of MDD, including currently depressed (cMDD) and remitted patients (rMDD), and 33 matched healthy controls (HC). Compared to HC, MDD participants showed increased white matter volume (WMV) in the uncinate fasciculus (UF) and decreased gray matter density (GMD) on the ventromedial prefrontal cortex (vmPFC). The increased WMV in UF was driven by both cMDD and rMDD groups and positively correlated with depression scores. The GMD decrease in the vmPFC resulted mainly from abnormalities in rMDD and was not correlated with depression scores. Finally, temporal UF and vmPFC white matter showed strong structural covariance suggesting functional interactions between these two brain regions. The retrospective and cross-sectional design of the study limits the generalizability of the results. Information concerning ongoing treatment did not allow the exploration of interactions between medication and observed abnormalities. The duration of the remission period could have influenced abnormalities in the subgroup of remitted patients. Fronto-temporal alterations in MDD consist of alterations in a cortico-limbic network involving the ventromedial prefrontal cortex and temporal white matter tracts. State-like abnormalities in the UF survive remission and persist as trait-like abnormalities together with alteration in the vmPFC.
Publisher: Informa UK Limited
Date: 02-2013
DOI: 10.1080/87565641.2012.745547
Abstract: Inhalant misuse among adolescents is poorly understood from a neuropsychological perspective. This study aimed to identify attentional deficits related to inhalant misuse measured with the Attention Network Test (ANT). We examined three groups: 19 inhalant users, 19 cannabis users, and 18 community controls. There were no group differences on the ANT measures of orienting, alerting, and executive control. However, compared to the cannabis and control groups, inhalant users demonstrated an increased rate of response errors in the absence of any reaction time differences. These differences may reflect a selective deficit in sustained attention or greater impulsivity in the inhalant group.
Publisher: Elsevier BV
Date: 2014
Publisher: Springer Science and Business Media LLC
Date: 25-04-2012
DOI: 10.1038/NPP.2012.39
Publisher: Public Library of Science (PLoS)
Date: 19-03-2008
Publisher: Springer Science and Business Media LLC
Date: 17-02-2011
DOI: 10.1007/S00213-011-2203-X
Abstract: Long-term heavy cannabis use can result in memory impairment. Adolescent users may be especially vulnerable to the adverse neurocognitive effects of cannabis. In a cross-sectional and prospective neuropsychological study of 181 adolescents aged 16-20 (mean 18.3 years), we compared performance indices from one of the most widely used measures of learning and memory--the Rey Auditory Verbal Learning Test--between cannabis users (n=52 mean 2.4 years of use, 14 days/month, median abstinence 20.3 h), alcohol users (n=67) and non-user controls (n=62) matched for age, education and premorbid intellectual ability (assessed prospectively), and alcohol consumption for cannabis and alcohol users. Cannabis users performed significantly worse than alcohol users and non-users on all performance indices. They recalled significantly fewer words overall (p<0.001), demonstrating impaired learning (p<0.001), retention (p<0.001) and retrieval (p<0.05) (Cohen's d 0.43-0.84). The degree of impairment was associated with the duration, quantity, frequency and age of onset of cannabis use, but was unrelated to alcohol exposure or other drug use. No gender effects were detected and the findings remained after controlling for premorbid intellectual ability. An earlier age of onset of regular cannabis use was associated with worse memory performance after controlling for extent of exposure to cannabis. Despite relatively brief exposure, adolescent cannabis users relative to their age-matched counterparts demonstrated similar memory deficits to those reported in adult long-term heavy users. The results indicate that cannabis adversely affects the developing brain and reinforce concerns regarding the impact of early exposure.
Publisher: Cambridge University Press (CUP)
Date: 11-08-2011
DOI: 10.1017/S0033291711001450
Abstract: Recent evidence from genetic and familial studies revitalized the debate concerning the validity of the distinction between schizophrenia and bipolar disorder. Comparing brain imaging findings is an important avenue to examine similarities and differences and, therefore, the validity of the distinction between these conditions. However, in contrast to bipolar disorder, most patient s les in studies of schizophrenia are predominantly male. This a limiting factor for comparing schizophrenia and bipolar disorder since male gender is associated with more severe neurodevelopmental abnormalities, negative symptoms and cognitive deficits in schizophrenia. We used a coordinate-based meta-analysis technique to compare grey matter (GM) abnormalities in male-dominated schizophrenia, gender-balanced schizophrenia and bipolar disorder s les based on published voxel-based morphometry (VBM) studies. In total, 72 English-language, peer reviewed articles published prior to January 2011 were included. All reports used VBM for comparing schizophrenia or bipolar disorder with controls and reported whole-brain analyses in standard stereotactic space. GM reductions were more extensive in male-dominated schizophrenia compared to gender-balanced bipolar disorder and schizophrenia. In gender-balanced s les, GM reductions were less severe. Compared to controls, GM reductions were restricted to dorsal anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex in schizophrenia and ACC and bilateral fronto-insular cortex in bipolar disorder. When gender is controlled, GM abnormalities in bipolar disorder and schizophrenia are mostly restricted to regions that have a role in emotional and cognitive aspects of salience respectively. Dorsomedial and dorsolateral prefrontal cortex were the only regions that showed greater GM reductions in schizophrenia compared to bipolar disorder.
Publisher: Proceedings of the National Academy of Sciences
Date: 15-07-2008
Abstract: The notion of a “default mode of brain function” has taken on certain relevance in human neuroimaging studies and in relation to a network of lateral parietal and midline cortical regions that show prominent activity fluctuations during passive imaging states, such as rest. In this study, we perform three fMRI experiments that demonstrate consistency and specialization in the default mode network. Correlated activity fluctuations of default mode network regions are identified during ( i ) eyes-closed spontaneous rest, ( ii ) activation by moral dilemma, and ( iii ) deactivation by Stroop task performance. Across these imaging states, striking uniformity is shown in the basic anatomy of the default mode network, but with both tasks clearly and differentially modulating this activity compared with spontaneous fluctuations of the network at rest. Against rest, moral dilemma is further shown to evoke regionally specific activity increases of hypothesized functional relevance. Mapping spontaneous and task-related brain activity will help to constrain the meaning of the default mode network. These findings are discussed in relation to recent debate on the topic of default modes of brain function.
Publisher: Informa UK Limited
Date: 02-01-2015
Publisher: Cambridge University Press (CUP)
Date: 24-01-2011
DOI: 10.1017/S0954579410000684
Abstract: It has been suggested that biological factors confer increased sensitivity to environmental influences on depressive symptoms during adolescence, a crucial time for the onset of depressive disorders. Given the critical role of the hippoc us in sensitivity to stress and processing of contextual aspects of the environment, investigation of its role in determining sensitivity to environmental context seems warranted. This study prospectively examined hippoc al volume as a measure of sensitivity to the influence of aggressive maternal behavior on change in depressive symptoms from early to midadolescence. The interaction between aggressive maternal behavior and hippoc al volume was found to predict change in depressive symptoms. Significant sex differences also emerged, whereby only for girls were larger bilateral hippoc al volumes more sensitive to the effects of maternal aggressive behavior, particularly with respect to experiencing the protective effects of low levels of maternal aggressiveness. These findings help elucidate the complex relationships between brain structure, environmental factors such as maternal parenting style, and sensitivity to (i.e., risk for, and protection from) the emergence of depression during this life stage. Given that family context risk factors are modifiable, our findings suggest the potential utility of targeted parenting interventions for the prevention and treatment of adolescent depressive disorder.
Publisher: Research Square Platform LLC
Date: 10-03-2022
DOI: 10.21203/RS.3.RS-1071626/V1
Abstract: The ability to perform optimally under pressure is critical across many occupations, including the military, first responders, and competitive sport, and depends on a range of cognitive factors. How common these key performance factors are across application domains remains unclear. The current study sought to integrate existing knowledge in the performance field in the form of a transdisciplinary expert consensus on the cognitive mechanisms that underlie performance under pressure. International experts were recruited from four performance domains (i. Defence ii. Competitive Sport iii. Civilian High-stakes and iv. Performance Neuroscience). Experts rated constructs from the Research Domain Criteria (RDoC) framework (in addition to several expert-suggested constructs) across successive rounds, until all constructs reached consensus for inclusion or were eliminated. Finally, included constructs were ranked for their relative importance. Sixty-eight experts completed the first Delphi round, with 94% of experts retained by the end of the Delphi process. Seven of the ten constructs that reached transdisciplinary consensus came from the Cognitive Systems domain including: 1) Attention 2) Cognitive Control—Goal Selection, Updating, Representation & Maintenance 3) Cognitive Control—Performance Monitoring 4) Cognitive Control—Response Selection & Inhibition/Suppression 5) Working memory—Flexible Updating 6) Working memory—Active Maintenance and 7) Working memory—Interference Control. Other constructs that reached transdisciplinary consensus were Self-knowledge, Arousal, and Shifting (an expert-suggested construct). Our results identify a set of transdisciplinary neuroscience-informed constructs, validated through Delphi consensus. This expert consensus is critical to standardising cognitive assessment and informing mechanism-targeted interventions in the broader field of human performance optimisation.
Publisher: Informa UK Limited
Date: 09-05-2014
DOI: 10.3109/15622975.2014.902540
Abstract: Research investigating the impact of inhalant misuse on brain structure suggests abnormalities in subcortical regions. We investigated the association between inhalant misuse and subcortical brain volumes in adolescents. Based on a collaborative dataset from South Korea (inhalant users: N = 15, mean age = 16.7, SD = 1.1 controls: N = 15, mean age = 15.4, SD = 1.2) and Australia (inhalant users: N = 7, mean age = 18.2, SD = 1.4 controls: N = 7, mean age = 18.9, SD = 2.6), the volumes of caudate nucleus, putamen, pallidum, amygdala, hippoc us, and thalamus were estimated in adolescent inhalant users and healthy adolescents using FreeSurfer. The results revealed a significantly decreased right thalamic volume in adolescent inhalant users (P = 0.042), along with a trend-level decrease in left thalamic volume (P = 0.061). A negative correlation (r = -0.544 P = 0.036) between thalamic volume and severity of inhalant use (i.e., reduced volumes associated with greater use) was identified among Korean participants. These findings suggest that compared with other subcortical structures, the thalamus is particularly sensitive to damage following chronic inhalant exposure during adolescence.
Publisher: Elsevier BV
Date: 09-2012
DOI: 10.1016/J.JPSYCHIRES.2012.04.022
Abstract: Although traditionally obsessive-compulsive disorder (OCD) and impulse control disorders (ICD) have represented opposing ends of a continuum, recent research has demonstrated a frequent co-occurrence of impulsive and compulsive behaviours, which may contribute to a worse clinical picture of some psychiatric disorders. We hypothesize that in iduals with 'impulsive' OCD as characterized by poor insight, low resistance, and reduced control towards their compulsions will have a deteriorative course, greater severity of hoarding and/or symmetry/ordering symptoms, and comorbid ICD and/or substance use disorders (SUD). The s le consisted of 869 in iduals with a minimum score of 16 on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Of these, 65 had poor insight, low resistance, and reduced control towards compulsions ('poor IRC') and 444 had preserved insight, greater resistance and better control over compulsions ('good IRC'). These two groups were compared on a number of clinical and demographic variables. In iduals with poor IRC were significantly more likely to have a deteriorative course (p < 0.001), longer duration of obsessions (p = 0.017), greater severity of symmetry/ordering (p < 0.001), contamination/cleaning (p < 0.001) and hoarding (p = 0.002) symptoms, and comorbid intermittent explosive disorder (p = 0.026), trichotillomania (p = 0.014) and compulsive buying (p = 0.040). Regression analysis revealed that duration of obsessions (p = 0.037) and hoarding severity (p = 0.005) were significant predictors of poor IRC. In the absence of specific measures for impulsivity in OCD, the study highlights the utility of simple measures such as insight, resistance and control over compulsions as a phenotypic marker of a subgroup of OCD with impulsive features demonstrating poor clinical outcome.
Publisher: Elsevier
Date: 2016
Publisher: Springer Science and Business Media LLC
Date: 18-09-2014
DOI: 10.3758/S13415-014-0319-2
Abstract: Trait positive affect (PA) in childhood confers both risk and resilience to psychological and behavioral difficulties in adolescence, although explanations for this association are lacking. Neurodevelopment in key areas associated with positive affect is ongoing throughout adolescence, and is likely to be related to the increased incidence of disorders of positive affect during this period of development. The aim of this study was to prospectively explore the relationship between trait indices of PA and brain development in subcortical reward regions during early to mid-adolescence in a community s le of adolescents. A total of 89 (46 male, 43 female) adolescents participated in magnetic resonance imaging assessments during both early and mid-adolescence (mean age at baseline = 12.6 years, SD = 0.45 mean follow-up period = 3.78 years, SD = 0.21) and also completed self-report measures of trait positive and negative affect (at baseline). To examine the specificity of these effects, the relation between negative affect and brain development was also examined. The degree of volume reduction in the right caudate over time was predicted by PA. Independent of time, larger hippoc al volumes were associated with higher PA, and negative affect was associated with smaller left amygdala volume. The moderating effect of negative affect on the development of the left caudate varied as a function of lifetime psychiatric history. These findings suggest that early to mid-adolescence is an important period whereby neurodevelopmental processes may underlie key phenotypes conferring both risk and resilience for emotional and behavioral difficulties later in life.
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.JAAC.2013.06.007
Abstract: The hippoc us and amygdala have received much attention with regard to the deleterious effects of childhood maltreatment. However, it is not known if and when these effects emerge during adolescence and whether comorbid psychopathology is more likely to explain these effects. This study investigated whether childhood maltreatment was associated with hippoc al and amygdala development from early to midadolescence and whether the experience of psychopathology during this period mediated the relation. One hundred seventeen (60 male) adolescents, recruited as part of a broader adolescent development study, participated in magnetic resonance imaging assessments during early and midadolescence (mean age at baseline 12.62 years, SD 0.44 years mean follow-up period 3.78 years, SD 0.20 years), and completed self-report measurements of childhood maltreatment and diagnostic interviews assessing DSM-IV mental disorders. Childhood maltreatment was associated with larger baseline left hippoc al volumes and retarded growth of the left amygdala over time and was indirectly associated, through the experience of psychopathology, with retarded growth of the left hippoc us and accelerated growth of the left amygdala over time. Exploratory cortical analysis showed that maltreatment influenced thickening of the superior parietal region through the experience of psychopathology. Childhood maltreatment was associated with altered brain development during adolescence. The experience of Axis I psychopathology during adolescence may be one mechanism by which childhood maltreatment has continuing effects on brain development during the adolescent years. These findings highlight the importance of early intervention for in iduals who have experienced childhood maltreatment.
Publisher: Frontiers Media SA
Date: 10-05-2016
Publisher: Elsevier BV
Date: 07-2014
Publisher: Elsevier BV
Date: 04-2012
DOI: 10.1016/J.JAD.2011.03.049
Abstract: Voxel-based morphometry (VBM) has been widely used to quantify structural brain changes associated with Major Depressive Disorder (MDD). While some consistent findings have been reported, in idual studies have also varied with respect to the key brain regions affected by the illness, and how these abnormalities are related to patients' clinical characteristics. Here, we aimed to identify those brain regions that most consistently showed gray matter anomalies in MDD, and their clinical correlates, using meta-analytic techniques. A systematic search of VBM studies was applied in MDD. Signed differential mapping, a new coordinate based neuroimaging meta-analysis technique, was applied to data collated from a total of 23 studies comparing regional gray matter volumes of 986 MDD patients and 937 healthy controls. Gray matter was significantly reduced in a confined cluster located in the rostral anterior cingulate cortex (ACC). There were also gray matter reductions in dorsolateral and dorsomedial prefrontal cortex and decrease in the latter region was evident in patients with multiple-episodes. Amygdala and parahippoc al gray matter volumes were significantly reduced in studies including patients with comorbid anxiety disorders, as well as in first-episode/drug free s les. Gray matter reduction in rostral ACC was the most consistent finding in VBM studies of MDD. The evidence for reductions in other regions within fronto-subcortical and limbic regions was less consistent. The associations between these gray matter anomalies and clinical characteristics, particularly measures relating to illness duration, suggest that chronic MDD has a robust and deleterious, albeit spatially focal, effect on brain structure.
Publisher: Wiley
Date: 23-04-2014
DOI: 10.1002/AJMG.B.32233
Abstract: While past twin studies indicate moderate levels of heritability of "obsessive-compulsive related" and anxiety disorder symptoms, no single study has reported such estimates in the same twin population nor examined potential genetic sex differences. We assessed symptoms of obsessive-compulsive disorder, body dysmorphic disorder, hoarding disorder, hypochondriasis, panic disorder, social phobia and generalized anxiety disorder in 2,495 adult twins (1,468 female). Prevalence estimates for the corresponding symptom measures were determined using empirically derived cut-off scores. Twin resemblance was assessed by Pearson correlations and biometrical model-fitting analyses, incorporating sex-specific effects, using OpenMx. Prevalence estimates ranged from 1.6% in the symptoms of generalized anxiety to 16.9% for social phobia. Female twins demonstrated significantly higher prevalence rates across all domains with the exception of obsessive-compulsive symptoms. Additive genetic factors accounted for a moderate proportion of the total liability to each symptom domain. Evidence suggesting qualitative genetic sex differences (i.e., distinct genetic influences between genders) was observed for body dysmorphic concern and panic symptoms, while quantitative differences were observed for hoarding and social phobia symptoms, indicating stronger heritability in females. Novel findings in this study include the observation of probable genetic sex differences in liability towards hoarding symptoms and dysmorphic concern, as well as the lack of such differences in hypochondriasis. The trend towards qualitative sex differences in panic symptoms has some intuitive appeal with regard to biological-experimental models of panic.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2009
Publisher: Elsevier BV
Date: 10-2008
DOI: 10.1016/J.SCHRES.2008.06.021
Abstract: An increased prevalence of large cavum septum pellucidum (CSP), a marker of midline neurodevelopmental abnormality, has been reported in schizophrenia. However, not all studies have been able to replicate this finding and very few studies have been conducted in large s les. In the current study, magnetic resonance imaging was used to assess the presence of an abnormal CSP in 162 patients with first-episode psychosis (FEP), 89 patients with chronic schizophrenia, 135 ultra high-risk (UHR) in iduals, and 87 controls. The prevalence of a large CSP (>5.6 mm) did not differ between the groups (9.3% of the FEP patients, 11.2% of the chronic schizophrenia patients, 11.1% of the UHR in iduals, and 11.5% of the controls). The length of the CSP was not associated with sulcal morphology of the anterior cingulate cortex (ACC), suggesting different biological processes responsible for the CSP enlargement versus ACC folding. These findings suggest that the CSP is not a neurodevelopmental marker of psychosis and cast doubt over the notion that it plays a major role in the neurobiology of psychosis.
Publisher: Elsevier BV
Date: 06-2005
DOI: 10.1016/J.SCHRES.2004.10.008
Abstract: While structural brain imaging abnormalities have been identified in schizophrenia and related disorders, it is unclear when they arise. Some appear to predate the illness and may be genetic in origin, while others are associated with the onset of the disorder. We examined the hippoc al volumes and anterior cingulate morphology from the MRI scans of 79 male subjects at ultra-high-risk (UHR) for developing psychosis, 35 of whom had a family history of schizophrenia, and compared them with 49 healthy male volunteers. Analysis of covariance demonstrated that left hippoc al volumes were significantly smaller in the UHR group without a family history of schizophrenia, when compared to the UHR group with such history. A similar pattern was found for the left anterior cingulate region, both in terms of reduced paracingulate folding and cingulate sulcus interruptions, although this did not reach significance. We found that a family history of schizophrenia was not associated with a greater degree of structural brain abnormalities in an ultra-high-risk group, and in fact it was those UHR patients without such history who displayed greater abnormalities, although this only reached significance for the left hippoc us. Thus, it appears that the mechanisms that result in gross morphological anomalies in the hippoc us and anterior cingulate in psychosis are driven more by environmental than genetic factors.
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.NEUBIOREV.2013.06.015
Abstract: Recent studies using diffusion weighted magnetic resonance imaging (DW-MRI) have provided evidence of abnormal white matter microstructure in adults with substance use disorders (SUDs). While there is a growing body of research using DW-MRI to examine the impact of heavy substance use during adolescence, this literature has not been systematically reviewed. Online databases were searched for DW-MRI studies of adolescent substance users, and 10 studies fulfilled the inclusion and exclusion criteria. We identified consistent evidence for abnormal white matter microstructure in neocortical association pathways as well as in projection and thalamic pathways. Dose-dependent relationships between DW-MRI measures and patterns of substance use were also observed. The consistency of these findings with DW-MRI research in adults suggests that white matter microstructure is impacted in the early stages of heavy substance use. However, given the largely cross-sectional nature of the available data, important questions remain regarding the extent to which white matter abnormalities are a consequence of adolescent exposure to alcohol and other drugs of abuse or reflect pre-existing differences that increase risk for SUDs.
Publisher: American Psychiatric Association Publishing
Date: 05-2014
DOI: 10.1176/APPI.AJP.2013.13070920
Abstract: The authors sought to investigate whether the structural development of limbic, striatal, and prefrontal regions that are critically implicated in the pathophysiology of depression is associated with adolescent-onset depression. In a longitudinal design, a risk enriched community s le of 86 adolescents (41 of them female) who had no history of depressive disorders participated in neuroimaging assessments conducted during early (age 12) and midadolescence (age 16). Onset of depressive disorders was assessed for the period spanning early to late adolescence (ages 12 to 18). Thirty participants experienced a first episode of a depressive disorder during the follow-up period. The authors assessed whether onset of depressive disorder was associated with structural change in limbic, striatal, and prefrontal cortical regions from early to mid-adolescence. Volumetric change in the hippoc us, amygdala, and putamen from early to mid-adolescence was associated with the onset of depression during adolescence. Attenuated growth of the hippoc us and attenuated reduction in putamen volume over time were associated with the onset of depression. Sex moderated the association between amygdala growth and depression such that exaggerated growth and attenuated growth of the amygdala were associated with depression in females and males, respectively. Across time, smaller nucleus accumbens volume was associated with depression in females only. These findings suggest that alterations in the developmental trajectories of limbic and striatal regions during adolescence may represent a neurobiological manifestation of a risk factor for the development of depression during this critical period and thus may provide clues as to etiological mechanisms of this disorder.
Publisher: Elsevier BV
Date: 11-2013
DOI: 10.1016/J.PSYNEUEN.2013.06.028
Abstract: To investigate the longitudinal relationship between pituitary gland volume (PGV) and parameters of hypothalamic-pituitary-adrenal axis (HPAA) functioning during adolescence. Participants were 49 adolescents (19 girls and 30 boys) selected from a larger longitudinal, population-based study of adolescent development. Assessments were conducted at three time points (S1, S2 and S3). MRI sessions were at S1 (age: M=12.62, SD=0.45 years) and S3 (M=16.48, SD=0.53 years) and multiple assessments of salivary cortisol were undertaken at S2 (M=15.51, SD=0.35 years). PGV was measured via previously validated manual tracing methods, and the cortisol awakening response (CAR) and diurnal slope (DSL) were used as indices of HPAA functioning. A significant sex-linked interaction was found for PGV at S1 predicting both CAR (p=0.025) and DSL (p=0.009) at S2. Specifically, PGV at S1 significantly predicted CAR (p=0.033) and DSL (p=0.010) in boys only, with no significant results found for girls. Neither CAR nor DSL at S2 predicted growth of PGV from S1 to S3. PGV in early adolescence predicted HPAA functioning in mid-adolescent boys but not in girls. The results suggest a significant influence of sex-specific development on the relationship between PGV and HPAA activity and reactivity. The findings have potential implications for understanding and interpreting sex-linked and stress related clinical disorders that emerge during mid-to-late adolescence.
Publisher: Springer Science and Business Media LLC
Date: 10-01-2022
DOI: 10.1038/S41398-021-01773-1
Abstract: Compulsivity is a poorly understood transdiagnostic construct thought to underlie multiple disorders, including obsessive-compulsive disorder, addictions, and binge eating. Our current understanding of the causes of compulsive behavior remains primarily based on investigations into specific diagnostic categories or findings relying on one or two laboratory measures to explain complex phenotypic variance. This proof-of-concept study drew on a heterogeneous s le of community-based in iduals ( N = 45 18–45 years 25 female) exhibiting compulsive behavioral patterns in alcohol use, eating, cleaning, checking, or symmetry. Data-driven statistical modeling of multidimensional markers was utilized to identify homogeneous subtypes that were independent of traditional clinical phenomenology. Markers were based on well-defined measures of affective processing and included psychological assessment of compulsivity, behavioral avoidance, and stress, neurocognitive assessment of reward vs. punishment learning, and biological assessment of the cortisol awakening response. The neurobiological validity of the subtypes was assessed using functional magnetic resonance imaging. Statistical modeling identified three stable, distinct subtypes of compulsivity and affective processing, which we labeled “Compulsive Non-Avoidant”, “Compulsive Reactive” and “Compulsive Stressed”. They differed meaningfully on validation measures of mood, intolerance of uncertainty, and urgency. Most importantly, subtypes captured neurobiological variance on amygdala-based resting-state functional connectivity, suggesting they were valid representations of underlying neurobiology and highlighting the relevance of emotion-related brain networks in compulsive behavior. Although independent larger s les are needed to confirm the stability of subtypes, these data offer an integrated understanding of how different systems may interact in compulsive behavior and provide new considerations for guiding tailored intervention decisions.
Publisher: Bentham Science Publishers Ltd.
Date: 31-05-2014
DOI: 10.2174/13816128113199990435
Abstract: Cannabis is the most widely used illicit drug worldwide, though it is unclear whether its regular use is associated with persistent alterations in brain morphology. This review examines evidence from human structural neuroimaging investigations of regular cannabis users and focuses on achieving three main objectives. These include examining whether the literature to date provides evidence that alteration of brain morphology in regular cannabis users: i) is apparent, compared to non-cannabis using controls ii) is associated with patterns of cannabis use and with iii) measures of psychopathology and neurocognitive performance. The published findings indicate that regular cannabis use is associated with alterations in medial temporal, frontal and cerebellar brain regions. Greater brain morphological alterations were evident among s les that used at higher doses for longer periods. However, the evidence for an association between brain morphology and cannabis use parameters was mixed. Further, there is poor evidence for an association between measures of brain morphology and of psychopathology symptoms/neurocognitive performance. Overall, numerous methodological issues characterize the literature to date. These include investigation of small s le sizes, heterogeneity across studies in s le characteristics (e.g., sex, comorbidity) and in employed imaging techniques, as well as the examination of only a limited number of brain regions. These factors make it difficult to draw firm conclusions from the existing findings. Nevertheless, this review supports the notion that regular cannabis use is associated with alterations of brain morphology, and highlights the need to consider particular methodological issues when planning future cannabis research.
Publisher: Cambridge University Press (CUP)
Date: 26-10-2012
DOI: 10.1017/S0033291712002085
Abstract: There is evidence to suggest that cognitive deficits might persist beyond the acute stages of illness in major depressive disorder (MDD). However, the findings are somewhat inconsistent across the in idual studies conducted to date. Our aim was to conduct a systematic review and meta-analysis of existing studies that have examined cognition in euthymic MDD patients. Following a systematic search across several publication databases, meta-analyses were conducted for 27 empirical studies that compared euthymic adult MDD patients (895 participants) and healthy controls (997 participants) across a range of cognitive domains. The influence of demographic variables and confounding factors, including age of onset and recurrent episodes, was examined. Compared with healthy controls, euthymic MDD patients were characterized by significantly poorer cognitive functions. However, the magnitude of observed deficits, with the exception of inhibitory control, were generally modest when late-onset cases were excuded. Late-onset cases demonstrated significantly more pronounced deficits in verbal memory, speed of information processing and some executive functions. Cognitive deficits, especially poor response inhibition, are likely to be persistent features, at least of some forms, of adult-onset MDD. More studies are necessary to examine cognitive dysfunction in remitted psychotic, melancholic and bipolar spectrum MDD. Cognitive deficits overall appear to be more common among patients with late-onset depression, supporting the theories suggesting that possible vascular and neurodegenerative factors play a role in a substantial number of these patients.
Publisher: Royal College of Psychiatrists
Date: 2015
DOI: 10.1192/BJP.BP.114.151407
Abstract: We investigated the morphology of multiple brain regions in a rare s le of 15 very heavy cannabis users with minimal psychiatric comorbidity or significant exposure to other substances (compared with 15 age- and IQ-matched non-cannabis-using controls) using manual techniques. Heavy cannabis users demonstrated smaller hippoc us and amygdala volumes, but no alterations of the orbitofrontal and anterior- and paracingulate cortices, or the pituitary gland. These findings indicate that chronic cannabis use has a selective and detrimental impact on the morphology of the mediotemporal lobe.
Publisher: Society for Neuroscience
Date: 15-10-2014
DOI: 10.1523/JNEUROSCI.1634-14.2014
Abstract: Adolescence is a time when the ability to engage cognitive control is linked to crucial life outcomes. Despite a historical focus on prefrontal cortex functioning, recent evidence suggests that differences between in iduals may relate to interactions between distributed brain regions that collectively form a cognitive control network (CCN). Other research points to a spatially distinct and functionally antagonistic system—the default-mode network (DMN)—which typically deactivates during performance of control tasks. This literature implies that in idual differences in cognitive control are determined either by activation or functional connectivity of CCN regions, deactivation or functional connectivity of DMN regions, or some combination of both. We tested between these possibilities using a multilevel fMRI characterization of CCN and DMN dynamics, measured during performance of a cognitive control task and during a task-free resting state, in 73 human adolescents. Better cognitive control performance was associated with (1) reduced activation of CCN regions, but not deactivation of the DMN (2) variations in task-related, but not resting-state, functional connectivity within a distributed network involving both the CCN and DMN (3) functional segregation of core elements of these two systems and (4) task-dependent functional integration of a set of peripheral nodes into either one network or the other in response to prevailing stimulus conditions. These results indicate that in idual differences in adolescent cognitive control are not solely attributable to the functioning of any single region or network, but are instead dependent on a dynamic and context-dependent interplay between the CCN and DMN.
Publisher: Springer Science and Business Media LLC
Date: 16-09-2014
DOI: 10.1038/TP.2014.85
Publisher: Elsevier BV
Date: 11-2006
DOI: 10.1016/J.NEUROIMAGE.2006.06.061
Abstract: Human anterior cingulate (ACC) and paracingulate (PaC) cortices play an important role in cognitive and affective regulation and have been implicated in numerous psychiatric and neurological conditions. The region they comprise displays marked inter-in idual variability in sulcal and gyral architecture, and although recent evidence suggests that this variability has functional significance, it is often ignored in automated and region-of-interest (ROI) morphometric investigations. This has lead to confounded interpretation of results and inconsistent findings across a number of studies and in a variety of clinical populations. In this paper, we present a reliable method for parcellating the dorsal, ventral, and subcallosal ACC and PaC that accounts for in idual variation in the local cortical folding pattern. We also investigated the effect of one well characterized morphological variation, the incidence of the paracingulate sulcus (PCS), on regional volumes in 24 (12 male, 12 female) healthy participants. The presence of a PCS was shown to affect both ACC and PaC volumes, such that it was associated with an 88% increase in paracingulate cortex and a concomitant 39% decrease in cingulate cortex. These findings illustrate the potential confounds inherent in morphometric approaches that ignore or attempt to minimize inter-in idual variations in sulcal and gyral anatomy and underscore the need to consider this variability when attempting to understand disease processes or characterize brain structure-function relationships.
Publisher: Elsevier BV
Date: 02-2009
DOI: 10.1016/J.JAD.2008.06.009
Abstract: Our aim was to delineate neuropsychological deficits related to genetic susceptibility, illness process and iatrogenic factors in bipolar disorder (BD). Following an extensive publication search on several databases, meta-analyses were conducted for 18 cognitive variables in studies that compared performances of euthymic BD patients (45 studies 1423 subjects) or first-degree relatives of BD patients (17 studies 443 subjects) with healthy controls. The effect of demographic variables and confounding factors like age of onset, duration of illness and medication status were analysed using the method of meta-regression. While response inhibition, set shifting, executive function, verbal memory and sustained attention deficits were common features for both patient (medium to large effect sizes) and relative groups (small to medium effect sizes), processing speed, visual memory and verbal fluency deficits were only observed in patients. Medication effects contributed to psychomotor slowing in BD patients. Earlier age of onset was associated with verbal memory impairment and psychomotor slowing. Data related to some confounding variables was not reported in a substantial number of extracted studies. Response inhibition deficit, a potential marker of ventral prefrontal dysfunction, seems to be the most prominent endophenotype of BD. The cognitive endophenotype of BD also appears to involve fronto-temporal and fronto-limbic related cognitive impairments. Processing speed impairment is related, at least partly, to medication effects indicating the influence of confounding factors rather than genetic susceptibility. Patterns of sustained attention and processing speed impairments differ from schizophrenia. Future work in this area should differentiate cognitive deficits associated with disease genotype from impairments related to other confounding factors.
Publisher: American Medical Association (AMA)
Date: 12-2008
DOI: 10.1001/ARCHPSYC.65.12.1377
Abstract: Although some evidence suggests that neuroanatomic abnormalities may confer risk for major depressive disorder, findings are inconsistent. One potential explanation for this is the moderating role of environmental context, with in iduals differing in their biological sensitivity to context. To examine the influence of adverse parenting as an environmental moderator of the association between brain structure and depressive symptoms. Cross-sectional measurement of brain structure, adverse parenting, and depressive symptoms in early adolescents. General community. A total of 106 students aged 11 to 13 years (55 males [51%]), recruited from primary schools in Melbourne, Australia, and their mothers. Selection was based on affective temperament, aimed at producing a s le representing a broad range of risk for major depressive disorder. No participant evidenced current or past case-level depressive, substance use, or eating disorder. (1) Volumetric measures of adolescents' amygdala, hippoc us, and anterior cingulate cortex (ACC) (2) frequency of observed maternal aggressive behavior during a mother-adolescent conflict-resolution interaction and (3) adolescent depressive symptoms. Boys with smaller right amygdalas reported more depressive symptoms. However, neither hippoc al volume nor asymmetry measures of limbic or paralimbic ACC were directly related to level of depressive symptoms. Importantly, frequency of maternal aggressive behaviors moderated the associations between both the amygdala and ACC, and adolescent symptoms. Particularly, in conditions of low levels of maternal aggressiveness, boys with larger right amygdalas, girls with smaller bilateral amygdalas, and both boys and girls with smaller left paralimbic ACC reported fewer symptoms. These findings help elucidate the complex relationships between brain structure, environmental factors, and depressive symptoms. Further longitudinal research is required to examine how these factors contribute to the onset of case-level disorder, but given that family context risk factors are modifiable, our findings do suggest the potential utility of targeted early parenting interventions.
Publisher: Elsevier BV
Date: 04-2008
DOI: 10.1016/J.SCHRES.2007.12.489
Abstract: Diffusion Tensor Imaging (DTI) investigations in schizophrenia have provided evidence of impairment in white matter as indicated by reduced fractional anisotropy (FA). However, the neuropathological implications of these findings remain unclear. In the current study, we conducted a voxelwise analysis of the constituent parameters of FA, Axial (lambda(||)) and Radial Diffusivity (lambda( upper left and right quadrants)), in 14 male participants with schizophrenia and 14 age, gender, education, and premorbid intelligence matched healthy controls. Significantly reduced FA and higher Radial Diffusivity were concurrently observed in several major white matter tracts in the schizophrenia group. This finding suggests that the loss of white matter integrity in schizophrenia is the result of demyelination and/or changes to the axonal cytoskeleton rather than gross axonal damage.
Publisher: Elsevier BV
Date: 12-2006
DOI: 10.1016/J.SCHRES.2006.06.034
Abstract: Previous studies have shown that schizophrenia patients display a left-lateralized reduction in cortical folding of the paracingulate cortex, although the functional significance of this anomaly is unclear. We examined the influence of paracingulate sulcus (PCS) asymmetries on cognitive performance in 37 male schizophrenia patients and 43 male controls. Across both groups, a leftward PCS asymmetry was associated with better spatial working memory performance than either a rightward asymmetric or symmetric folding pattern. This suggests that prior reports of impaired performance on such tasks in schizophrenia may be partly explained by the reduced frequency of a leftward PCS asymmetry in this population.
Publisher: Elsevier BV
Date: 02-2015
DOI: 10.1016/J.NEUROIMAGE.2014.11.039
Abstract: Cognitive control and working memory rely upon a common fronto-parietal network that includes the inferior frontal junction (IFJ), dorsolateral prefrontal cortex (dlPFC), pre-supplementary motor area/dorsal anterior cingulate cortex (pSMA/dACC), and intraparietal sulcus (IPS). This network is able to flexibly adapt its function in response to changing behavioral goals, mediating a wide range of cognitive demands. Here we apply dynamic causal modeling to functional magnetic resonance imaging data to characterize task-related alterations in the strength of network interactions across distinct cognitive processes. Evidence in favor of task-related connectivity dynamics was accrued across a very large space of possible network structures. Cognitive control and working memory demands were manipulated using a factorial combination of the multi-source interference task and a verbal 2-back working memory task, respectively. Both were found to alter the sensitivity of the IFJ to perceptual information, and to increase IFJ-to-pSMA/dACC connectivity. In contrast, increased connectivity from the pSMA/dACC to the IPS, as well as from the dlPFC to the IFJ, was uniquely driven by cognitive control demands a task-induced negative influence of the dlPFC on the pSMA/dACC was specific to working memory demands. These results reflect a system of both shared and unique context-dependent dynamics within the fronto-parietal network. Mechanisms supporting cognitive engagement, response selection, and action evaluation may be shared across cognitive domains, while dynamic updating of task and context representations within this network are potentially specific to changing demands on cognitive control.
Publisher: JMIR Publications Inc.
Date: 20-02-2020
Abstract: igh rates of cannabis and illicit drug use are experienced by young people during the final stages of neurodevelopment (aged 15-24 years), a period characterized by high neuroplasticity. Frequent drug use during this time may interfere with neurophysiological and neuropsychological development pathways, potentially leading to ongoing unfavorable neuroadaptations. The dose-response relationship between illicit drug use, exposure, and in idual neurodevelopmental variation is unknown but salient with global shifts in the legal landscape and increasingly liberal attitudes and perceptions of the harm caused by cannabis and illicit drugs. his systematic review aims to synthesize longitudinal studies that investigate the effects of illicit drug use on structural, functional, and cognitive brain domains in in iduals under the neural age of adulthood (25 years). This protocol outlines prospective methods that will facilitate an exhaustive review of the literature exploring pre- and post-drug use brain abnormalities arising during neurodevelopment. ive electronic databases (Medline, Embase, PsycINFO, ProQuest Central, and Web of Science) will be systematically searched between 1990 and 2019. The search terms will be a combination of MeSH (Medical Subject Headings), with keywords adapted to each database. Study reporting will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and if relevant, study quality will be assessed using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. Eligible studies are those that s led youth exposed to cannabis or illicit drugs and employed neurophysiological or neuropsychological assessment techniques. Studies will be excluded if participants had been clinically diagnosed with any psychiatric, neurological, or pharmacological condition. his is an ongoing review. As of February 2020, papers are in full-text screening, with results predicted to be complete by July 2020. ntegrating data collected on the three brain domains will enable an assessment of the links between structural, functional, and cognitive brain health across in iduals and may support the early detection and prevention of neurodevelopmental harm. ROSPERO CRD42020151442 www.crd.york.ac.uk rospero/display_record.php?RecordID=151442 RR1-10.2196/18349
Publisher: Springer Science and Business Media LLC
Date: 12-03-2013
Abstract: The orbitofrontal cortex (OFC) has consistently been implicated in the pathology of both drug and behavioral addictions. However, no study to date has examined OFC thickness in internet addiction. In the current study, we investigated the existence of differences in cortical thickness of the OFC in adolescents with internet addiction. On the basis of recently proposed theoretical models of addiction, we predicted a reduction of thickness in the OFC of internet addicted in iduals. Participants were 15 male adolescents diagnosed as having internet addiction and 15 male healthy comparison subjects. Brain magnetic resonance images were acquired on a 3T MRI and group differences in cortical thickness were analyzed using FreeSurfer. Our results confirmed that male adolescents with internet addiction have significantly decreased cortical thickness in the right lateral OFC ( p .05). This finding supports the view that the OFC alterations in adolescents with internet addiction reflect a shared neurobiological marker of addiction-related disorders in general.
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1016/J.PSCYCHRESNS.2016.07.008
Abstract: Olfactory deficits have been reported in major depressive disorder (MDD). However, it remains largely unknown whether MDD is associated with abnormalities in olfactory sulcus morphology, a potential marker of olfactory system development. This magnetic resonance imaging study investigated the length and depth of the olfactory sulcus in 29 currently depressed patients, 27 remitted depressed patients, and 33 age- and gender-matched healthy control subjects. Both current and remitted MDD patients had significantly shallower olfactory sulci bilaterally as compared with controls. Only for male subjects, the right olfactory sulcus was significantly shorter in remitted MDD patients than in controls. The right sulcus depth was negatively correlated with number of depressive episodes in the entire MDD group and with residual depressive symptoms in the remitted MDD group. Medication status, presence of melancholia, and comorbidity with anxiety disorders did not affect the sulcus morphology. These findings suggest that abnormality of the olfactory sulcus morphology, especially its depth, may be a trait-related marker of vulnerability to major depression.
Publisher: Springer Science and Business Media LLC
Date: 04-03-2021
DOI: 10.1038/S41398-021-01204-1
Abstract: Males and females with alcohol dependence have distinct mental health and cognitive problems. Animal models of addiction postulate that the underlying neurobiological mechanisms are partially distinct, but there is little evidence of sex differences in humans with alcohol dependence as most neuroimaging studies have been conducted in males. We examined hippoc al and amygdala subregions in a large s le of 966 people from the ENIGMA Addiction Working Group. This comprised 643 people with alcohol dependence (225 females), and a comparison group of 323 people without alcohol dependence (98 females). Males with alcohol dependence had smaller volumes of the total amygdala and its basolateral nucleus than male controls, that exacerbated with alcohol dose. Alcohol dependence was also associated with smaller volumes of the hippoc us and its CA1 and subiculum subfield volumes in both males and females. In summary, hippoc al and amygdalar subregions may be sensitive to both shared and distinct mechanisms in alcohol-dependent males and females.
Publisher: American Psychiatric Association Publishing
Date: 02-2002
DOI: 10.1176/APPI.AJP.159.2.251
Abstract: The authors used single-subject functional imaging analyses to 1) corroborate the findings of anterior cingulate hypoperfusion during an attentional task in schizophrenia and 2) examine whether anterior cingulate activation is associated with underlying morphology. Five healthy subjects and six patients with schizophrenia underwent positron emission tomography scanning while they performed the Stroop task. The medial-frontal lobes were masked out for analysis, and activation peaks were in idually coregistered to each subject's magnetic resonance imaging scan. Healthy subjects showed activations in both limbic and paralimbic anterior cingulate regions. Patients with schizophrenia showed only paralimbic activations, and these were apparent only in patients having a paracingulate sulcus. These findings suggest that 1) patients with schizophrenia have limbic-anterior cingulate hypoperfusion during attentional tasks and 2) paralimbic activation is associated with underlying morphology.
Publisher: JMIR Publications Inc.
Date: 03-07-2023
Abstract: europsychological assessments have traditionally focused on executive functioning (EF) due to the significant role it plays in everyday life and its association with a variety of mental disorders. Although traditional assessment methods of EF are well established, they lack ecological validity and are limited to evaluating a single cognitive process. While these traditional EF assessment tools may be appropriate for clinical populations, they provide less information about EF in healthy in iduals. Recognizing these limitations, there has been a growing interest in Virtual Reality (VR)-based assessments of EF due to their potential to increase test sensitivity, ecological validity, and accessibility to neuropsychological assessment. his systematic review aims to explore the literature on VR assessments of EF. Specifically, we intended to identify: (1) the EF components being assessed, (2) how these assessments are validated, and (3) the monitoring strategies for potential adverse (cybersickness) and beneficial (immersion) effects. BSCOHost, Scopus, and Web of Science (WoS) were searched using keywords that reflected the main themes of Virtual Reality, Neuropsychological Tests and Executive Function. The search retrieved 555 unique articles, of which 19 met the inclusion criteria. Articles had to be an English written peer-reviewed manuscript published after 2013 that detailed an empirical, clinical or proof of concept study where a virtual environment using a head-mounted display was employed to assess EF in an adult population. he reviewed articles comprised a range of EF constructs, including inhibitory control, cognitive flexibility, working memory, planning, and attention. Although VR paradigms were typically validated against gold-standard traditional tasks, some studies did not report a-priori planned correlations, others did not detail the target EF constructs to be assessed by the VR paradigm, and there was often incomplete reporting of results. Further, cybersickness was assessed by only four of the 19 studies. he authors propose several recommendations to improve the theory and practice of VR assessments of EF. A key conclusion is the critical need to address the methodological and psychometric properties during the development of these assessments to ensure their validity and reliability. Furthermore, we suggest an increased focus on potential adverse effects such as cybersickness. Future research should consider the integration of biosensors into VR systems, and the potential of VR in assessing spatial navigation. While VR assessments show promising potential, their adoption must be systematic and validated to ensure their utility in real-world applications.
Publisher: Elsevier BV
Date: 06-2008
Publisher: Elsevier BV
Date: 08-2009
DOI: 10.1016/J.PNPBP.2009.05.020
Abstract: Brain morphologic changes of limbic-cortical regions have been reported in major depressive disorder (MDD). However, it remains largely unknown whether MDD is associated with abnormalities in midline brain structures, which play a critical role in limbic-cortical connectivity, and whether such changes reflect state or trait markers of the disorder. We used magnetic resonance imaging to investigate the length of the adhesio interthalamica (AI) and cavum septum pellucidum (CSP) in 29 currently depressed patients, 27 remitted depressed patients, and 33 age- and gender-matched healthy control subjects. The currently depressed patients had a significantly shorter AI compared with controls, but there was no difference in the AI length between the remitted patients and controls. The AI length in the overall patient group was negatively correlated with the severity of symptoms of "loss of interest" at the time of scanning. Furthermore, the patients with co-morbid anxiety disorders tended to have a shorter AI compared with those without. The CSP length and prevalence of a large CSP (>or=6 mm) did not differ between the groups. Although a comprehensive investigation of medication effects was not possible due to incomplete medication data, these findings suggest that a shorter length of the AI may be associated with state-related brain changes in major depression rather than a stable marker of illness vulnerability. Whether the AI length exhibits ongoing changes across the course of the illness remains to be determined in longitudinal studies.
Publisher: Elsevier BV
Date: 06-2010
DOI: 10.1016/J.JAD.2009.08.022
Abstract: Functional abnormalities of the superior temporal gyrus (STG) have been implicated in the pathophysiology of bipolar disorder, but magnetic resonance imaging (MRI) studies of this region have yielded inconsistent findings. We used MRI to examine the volumes of the STG and its gray matter subregions [planum polare (PP), Heschl gyrus (HG), planum temporale (PT), and lateral STG (rostral and caudal regions)] in 26 patients with established bipolar I disorder (8 males and 18 females, mean age=38.4 years) and 24 age and gender-matched healthy controls (7 males and 17 females, mean age=38.7 years). Bipolar patients had significantly smaller volumes of the PT and caudal STG compared with controls in the left hemisphere. The STG white matter volume did not differ between the groups. There was no association between the STG volume and number of manic/depressive episodes, family history, or clinical subtype (i.e., psychotic and nonpsychotic), but daily dosage of lithium treatment at the time of scanning was positively correlated with right PP and right rostral STG volumes. Entire clinical data (e.g., lifetime medication, symptomatology) were not available. These findings implicate a role for the STG gray matter, especially its left posterior regions, in the neurobiology of bipolar disorder. Our findings may also support the notion of lithium-induced gray matter expansion.
Publisher: Elsevier BV
Date: 11-2006
DOI: 10.1016/J.PSCYCHRESNS.2006.02.006
Abstract: Reports of abnormal activation of the dorsolateral prefrontal cortex (dlPFC) are common in functional neuroimaging studies of schizophrenia, although very few have examined brain activity in patients close to the onset of illness. In this H(2)(15)O PET study, eight young male patients with first-episode schizophreniform psychosis and age-matched control subjects performed a version of the Stroop task that we have previously shown to engage the middle-frontal gyrus. At the time of testing, patients were antipsychotic-naïve and were scanned within 1 week of initial contact with our clinical program. All patients received a later diagnosis of schizophrenia 6 months after participating in the study. Whole-brain (within-group) and region-of-interest (between-group) analyses were carried out and data underwent spatial reproducibility testing. Compared with healthy subjects, patients showed significantly greater reaction-time (RT) interference but normal RT accuracy on the Stroop task. This pattern correlated with significant under-activation of the posterior left middle-frontal gyri in the patient versus control group. These findings support an emerging model of impaired cognitive control in schizophrenia and suggest that there is significant dysfunction of the dlPFC close to the onset of illness that may coincide with, or be modulated by, the transition-to-illness phase.
Publisher: CMA Joule Inc.
Date: 2011
DOI: 10.1503/JPN.100082
Publisher: American Psychiatric Association Publishing
Date: 2015
DOI: 10.1176/APPI.NEUROPSYCH.13080184
Abstract: In a chart review of patients with obsessive-compulsive disorder (OCD) attending a university clinic, ECT was prescribed for five subjects (1.2%), only because of severe intervening manic (N=1) or depressive episodes (N=4). Although affective symptoms improved in four of the five patients, OCD symptoms remained unchanged (N=3) or transiently worsened (N=2).
Publisher: Elsevier BV
Date: 04-2011
DOI: 10.1016/J.SCHRES.2010.12.020
Abstract: Despite an increasing number of published voxel based morphometry studies of schizophrenia, there has been no adequate attempt to examine gray (GM) and white matter (WM) abnormalities and the heterogeneity of published findings. In the current article, we used a coordinate based meta-analysis technique to simultaneously examine GM and WM abnormalities in schizophrenia and to assess the effects of gender, chronicity, negative symptoms and other clinical variables. 79 studies meeting our inclusion criteria were included in the meta-analysis. Schizophrenia was associated with GM reductions in the bilateral insula/inferior frontal cortex, superior temporal gyrus, anterior cingulate gyrus/medial frontal cortex, thalamus and left amygdala. In WM analyses of volumetric and diffusion-weighted images, schizophrenia was associated with decreased FA and/or WM in interhemispheric fibers, anterior thalamic radiation, inferior longitudinal fasciculi, inferior frontal occipital fasciculi, cingulum and fornix. Male gender, chronic illness and negative symptoms were associated with more severe GM abnormalities and illness chronicity was associated with more severe WM deficits. The meta-analyses revealed overlapping GM and WM structural findings in schizophrenia, characterized by bilateral anterior cortical, limbic and subcortical GM abnormalities, and WM changes in regions including tracts that connect these structures within and between hemispheres. However, the available findings are biased towards characteristics of schizophrenia s les with poor prognosis.
Publisher: American Medical Association (AMA)
Date: 02-2009
DOI: 10.1001/ARCHGENPSYCHIATRY.2008.522
Abstract: Although drug cues reliably activate the brain's reward system, studies rarely examine how the processing of drug stimuli compares with natural reinforcers or relates to clinical outcomes. To determine hedonic responses to natural and drug reinforcers in long-term heroin users and to examine the utility of these responses in predicting future heroin use. Prospective design examining experiential, expressive, reflex modulation, and cortical/attentional responses to opiate-related and affective stimuli. The opiate-dependent group was reassessed a median of 6 months after testing to determine their level of heroin use during the intervening period. Community drug and alcohol services and a clinical research facility. Thirty-three opiate-dependent in iduals (mean age, 31.6 years) with stabilized opiate-substitution pharmacotherapy and 19 sex- and age-matched healthy non-drug users (mean age, 30 years). Self-ratings, facial electromyography, startle-elicited postauricular reflex, and event-related potentials combined with measures of heroin use at baseline and follow-up. Relative to the control group, the opiate-dependent group rated pleasant pictures as less arousing and showed increased corrugator activity, less postauricular potentiation, and decreased startle-elicited P300 attenuation while viewing pleasant pictures. The opiate-dependent group rated the drug-related pictures as more pleasant and arousing, and demonstrated greater startle-elicited P300 attenuation while viewing them. Although a startle-elicited P300 litude response to pleasant (relative to drug-related) pictures significantly predicted regular (at least weekly) heroin use at follow-up, subjective valence ratings of pleasant pictures remained the superior predictor of use after controlling for baseline craving and heroin use. Heroin users demonstrated reduced responsiveness to natural reinforcers across a range of psychophysiological measures. Subjective rating of pleasant pictures robustly predicted future heroin use. Our findings highlight the importance of targeting anhedonic symptoms within clinical treatment settings.
Publisher: Informa UK Limited
Date: 20-02-2016
DOI: 10.1080/15374416.2014.987381
Abstract: This study examined whether development of two forms of cognitive control (proactive and reactive) between early and midadolescence was associated with the onset of major depressive disorder (MDD) during the same period and if it prospectively predicted MDD onset between mid- and late adolescence. Adolescents (N = 165) completed 3 waves of assessments, at 12 (T1), 16 (T2), and 18 (T3) years of age. Diagnostic interviews were conducted at each time point to identify three groups of adolescents: "early MDD," those who developed MDD between early (T1) and mid- (T2) adolescence (n = 23) "late MDD," those who developed MDD between mid- (T2) and late (T3) adolescence (n = 20) and "controls," those who did not develop MDD (n = 122). A modified Stroop task was completed at T1 and T2 to examine development of proactive and reactive cognitive control. Adolescents with early MDD exhibited significant declines in reactive control, as well as a trend level decline for proactive control, during this period compared to controls. No significant differences in reactive or proactive control were identified in adolescents with late MDD compared to controls, but they did exhibit significant improvements in proactive control compared to those with early MDD. These findings suggest that normative maturation of reactive, and possibly proactive, cognitive control abilities are impaired in adolescents who develop MDD between early and midadolescence. This has implications for understanding the mechanisms underlying certain forms of behavioral dysregulation that are commonly seen in MDD.
Publisher: Oxford University Press (OUP)
Date: 28-11-2014
DOI: 10.1093/SCAN/NSS126
Publisher: Frontiers Media SA
Date: 2012
Publisher: Wiley
Date: 07-2010
DOI: 10.1111/J.1465-3362.2009.00162.X
Abstract: Inhalant abuse among adolescents is a significant health concern in many countries however, limited research has explored whether the intoxication experience differs between commonly used inhalants. The aim of the present study was to examine how exposure to different types of paints (chrome vs. non-chrome) were experienced by adolescent users. Sixteen adolescent (aged 15-19 years) regular inhalant users completed a semistructured questionnaire enquiring about their inhalant use. Participants were ided into two groups based on paint colour preference [chrome paints (n = 10) and non-chrome paints (n = 6)] and were compared using appropriate statistical tests. Relative to non-chrome users, the chrome-using group were more likely to report deliberately inhaling to experience altered perceptions (such as visual and auditory hallucinations). In addition, a significantly greater proportion of chrome users reported that the perceptual alterations they experienced after sniffing paint differed between paint colours, with chrome colours being associated with more vivid hallucinations. While both chrome and non-chrome users reported a comparable level of pleasure from paint sniffing, chrome paint users were more likely to be motivated by the potential to hallucinate. Our findings suggest that the type of inhalant used is an important consideration that may have relevance to clinical treatment.
Publisher: Physicians Postgraduate Press, Inc
Date: 23-09-2015
DOI: 10.4088/JCP.14L09499
Publisher: Elsevier BV
Date: 05-2013
Publisher: Wiley
Date: 11-05-2008
DOI: 10.1002/HBM.20381
Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1016/J.BIOPSYCH.2015.11.013
Abstract: The past few decades have seen a marked change in the composition of commonly smoked cannabis. These changes primarily involve an increase of the psychoactive compound ∆(9)-tetrahydrocannabinol (THC) and a decrease of the potentially therapeutic compound cannabidiol (CBD). This altered composition of cannabis may be linked to persistent neuroanatomic alterations typically seen in regular cannabis users. In this review, we summarize recent findings from human structural neuroimaging investigations. We examine whether neuroanatomic alterations are 1) consistently observed in s les of regular cannabis users, particularly in cannabinoid receptor-high areas, which are vulnerable to the effects of high circulating levels of THC, and 2) associated either with greater levels of cannabis use (e.g., higher dosage, longer duration, and earlier age of onset) or with distinct cannabinoid compounds (i.e., THC and CBD). Across the 31 studies selected for inclusion in this review, neuroanatomic alterations emerged across regions that are high in cannabinoid receptors (i.e., hippoc us, prefrontal cortex, amygdala, cerebellum). Greater dose and earlier age of onset were associated with these alterations. Preliminary evidence shows that THC exacerbates, whereas CBD protects from, such harmful effects. Methodologic differences in the quantification of levels of cannabis use prevent accurate assessment of cannabis exposure and direct comparison of findings across studies. Consequently, the field lacks large "consortium-style" data sets that can be used to develop reliable neurobiological models of cannabis-related harm, recovery, and protection. To move the field forward, we encourage a coordinated approach and suggest the urgent development of consensus-based guidelines to accurately and comprehensively quantify cannabis use and exposure in human studies.
Publisher: Elsevier BV
Date: 06-2009
DOI: 10.1016/J.NEUBIOREV.2009.01.002
Abstract: Interest in the early phase of psychotic disorders has risen dramatically in recent years. Neurobiological investigations have focused specifically on identifying brain changes associated with the onset of psychosis. The link between these neurobiological findings and the complex phenomenology of the early psychosis period is not well understood. In this article, we re-cast some of these observations, primarily from neuroimaging studies, in the context of phenomenological models of "the self" and disturbance thereof in psychotic illness. Specifically, we argue that disturbance of the basic or minimal self ("ipseity"), as articulated in phenomenological literature, may be associated with abnormalities in midline cortical structures as observed in neuroimaging studies of pre-onset and early psychotic patients. These findings are discussed with regards to current ideas on the neural basis of self-referential mental activity, including the notion of a putative "default-mode" of brain function, and its relation to distinguishing between self- and other-generated stimuli. Further empirical work examining the relationship between neurobiological and phenomenological variables may be of value in identifying risk markers for psychosis onset.
Publisher: EDITORA SCIENTIFIC
Date: 06-2010
Publisher: Oxford University Press (OUP)
Date: 04-06-2012
DOI: 10.1093/BRAIN/AWS136
Publisher: Elsevier BV
Date: 06-2010
DOI: 10.1016/J.BIOPSYCH.2010.01.020
Abstract: We conducted a meta-analysis of gray matter abnormalities in bipolar disorder (BD) using voxel-based morphometry studies to help clarify the structural abnormalities underpinning this condition. A systematic review was conducted for voxel-based morphometry studies of patients with BD. Meta-analyses of gray matter differences between BD and control subjects were undertaken using "signed differential mapping," a novel method that, in contrast to previously used techniques, allows inclusion of negative findings and ensures that single studies do not exert undue influence on the results. Meta-regression and subgroup analyses were used to examine the effect of moderator variables on gray matter abnormalities. A total of 21 studies comparing gray matter volumes of 660 BD patients and 770 healthy control subjects were included. Gray matter reduction in left rostral anterior cingulate cortex (ACC) and right fronto-insular cortex was associated with BD. Fronto-insular cortex abnormality was not evident in early phases of the illness. In chronic patients, longer duration of illness was associated with increased gray matter in a cluster that included basal ganglia, subgenual ACC, and amygdala. Lithium treatment was associated with enlargement of ACC gray matter volumes, which overlapped with the region where gray matter was reduced in BD. The most robust gray matter reductions in BD occur in anterior limbic regions, which may be related to the executive control and emotional processing abnormalities seen in this patient population. Clinical factors such as illness duration and lithium treatment also impact on case-control comparisons of gray matter volume.
Publisher: Elsevier BV
Date: 02-2008
DOI: 10.1016/J.PSCYCHRESNS.2007.06.004
Abstract: Abnormalities of the anterior cingulate cortex (ACC) are thought to be involved in the pathophysiology of bipolar disorder, but structural Magnetic Resonance Imaging (MRI) studies have reported variable findings. Reasons for this include a failure to consider variability in regional cortical folding patterns and a reliance on relatively coarse measures (e.g., volume) to index anatomical change. We sought to overcome these limitations by combining a novel protocol for parcellating the ACC and adjacent paracingulate cortex (PaC) that accounts for inter-in idual variations in sulcal and gyral morphology with a cortical surface-based approach that allowed calculation of regional grey matter volume, surface area and cortical thickness in 24 patients with bipolar I disorder and 24 matched controls. No changes in grey matter volume or surface area were identified in any region, but patients did show significant reductions in cortical thickness in the left rostral PaC and right dorsal PaC that were not attributable to group differences in cortical folding patterns. These findings suggest that bipolar disorder is associated with more pronounced changes in the PaC, and that reliance on volumetric measures alone may obscure more subtle differences.
Publisher: Elsevier BV
Date: 04-2009
DOI: 10.1016/J.PSCYCHRESNS.2008.06.006
Abstract: Major depressive disorder (MDD) has been associated with increased pituitary gland volume (PGV), which is thought to reflect stress-related dysregulation related to hypothalamic-pituitary-adrenal (HPA) axis activity. However, it is unclear whether PGV alteration reflects a "dynamic" change related to current mood instability or if it is a stable marker of illness vulnerability. In this study we investigated PGV in currently depressed patients (cMDD) (n=31), remitted depressed patients (rMDD) (n=31) and healthy controls (n=33), using 1.5 Tesla magnetic resonance imaging (MRI). The groups were matched for age and gender. We found no significant PGV, intra-cranial volume (ICV) or whole brain volume (WBV) differences between cMDD patients, rMDD patients and healthy controls. Furthermore, PGV was not correlated with clinical features of depression (e.g., age of onset number of episodes and scores on subscales of the Beck Depression Inventory, the Positive Affect and Negative Affect Scale, and the Mood and Anxiety Symptom Questionnaire). In conclusion, PGV does not appear to be a marker of current or past MDD in adult patients.
Publisher: Elsevier BV
Date: 04-2009
DOI: 10.1016/J.PSCYCHRESNS.2008.06.005
Abstract: There is evidence that anterior cingulate cortex (ACC) function is related to in idual differences in temperament. An important question regards how early such brain-behavior associations emerge. We examined the relationship between cortical folding patterns of the ACC, which are functionally relevant and primarily determined by birth, and in idual differences in four core temperament dimensions (Effortful Control, Negative Affectivity, Surgency, and Affiliation). Magnetic resonance imaging was used to classify 153 (81 male) early adolescents as displaying a leftward asymmetric, rightward asymmetric, or symmetric pattern of ACC folding, as indexed by the incidence and extent of the paracingulate sulcus (PCS). A leftward asymmetric pattern of ACC folding was associated with significantly higher temperamental Effortful Control and lower Negative Affectivity than a rightward asymmetric pattern. Further, this difference was significant only for males. Across males and females, a symmetric pattern was associated with higher temperamental Affiliation than was a rightward asymmetric pattern of ACC folding. These findings suggest that early neurodevelopmental processes contribute to in idual differences in temperament. They also illustrate sexual dimorphisms in the neural underpinnings of temperament.
Publisher: Oxford University Press (OUP)
Date: 14-09-2011
DOI: 10.1093/SCAN/NSR049
Publisher: Elsevier BV
Date: 10-2008
DOI: 10.1016/J.PNPBP.2008.07.007
Abstract: Abnormal neurodevelopment in midline structures such as the adhesio interthalamica (AI) has been reported in psychotic disorders, but it is unknown whether in iduals at risk for the disorder share the AI findings observed in patients with florid psychosis. Magnetic resonance imaging of 162 patients with first-episode psychosis (FEP), 89 patients with chronic schizophrenia, 135 in iduals at ultra high-risk (UHR) of psychosis (of whom 39 later developed psychosis), and 87 healthy controls were used to investigate the length and prevalence of the AI. The relation of the AI length to lateral ventricular enlargement was also explored. The patients with FEP and chronic schizophrenia as well as UHR in iduals had a shorter AI than the controls, but there was no difference in the AI findings between the UHR in iduals who did and did not subsequently develop psychosis. There was a negative correlation between the AI length and lateral ventricular volume in all the diagnostic groups. The absence of the AI was more common in the chronic schizophrenia patients when compared with all other groups. These results support the notion that the AI absence or shorter length could be a neurodevelopmental marker related to vulnerability to psychopathology, but also suggest that schizophrenia patients may manifest progressive brain changes related to ongoing atrophy of the AI after the onset.
Publisher: Informa Healthcare
Date: 28-04-2014
DOI: 10.1517/14656566.2014.914493
Abstract: Since the recognition of the effectiveness of clomipramine in treating obsessive-compulsive disorder (OCD), a number of recent empirical studies have confirmed a key role of the serotonergic (5-HT) system in the pathophysiology of OCD. The current study presents a review of the existing double-blind studies testing 5-HT antidepressants in OCD. A systematic review was performed to identify double-blind, placebo-controlled, randomized clinical trials investigating the efficacy of antidepressants with marked 5-HT effects [clomipramine, selective serotonin reuptake inhibitors (SSRIs), venlafaxine, desvenlafaxine, duloxetine, mirtazapine, agomelatine, vortioxetine and vilazodone] in the short-term treatment of OCD. The search provided 29 studies investigating eight different 5-HT antidepressants. While the findings show reliable efficacy of clomipramine and SSRIs in the treatment of OCD symptoms, no double-blind studies were identified investigating the efficacy of desvenlafaxine, duloxetine, mirtazapine, agomelatine, vortioxetine or vilazodone. While our results support the effectiveness of older antidepressants with marked 5-HT effects in OCD, it also suggests that newer agents should be tested more comprehensively.
Publisher: Wiley
Date: 10-09-2012
Publisher: SAGE Publications
Date: 08-2003
DOI: 10.1046/J.1440-1614.2003.01193.X
Abstract: Objective: The evidence from structural imaging studies supports the notion that schizophrenia arises from an early abnormality in brain development. In this paper we review the timing of structural changes in schizophrenia and argue that schizophrenia is a neurodevelopmental disorder with limited progressive brain changes occurring during the evolution and early phase of psychosis. Method: The available cross-sectional and longitudinal studies are reviewed, along with data from our own research. Results: The current literature, including our own data, suggests that structural brain changes are apparent premorbidly, consistent with a neurodevelopmental lesion. These are prominent in frontal and cingulate regions, and appear related to premorbid neuropsychological deficits in executive function. However, there appear to be additional brain changes over the transition to illness and beyond. Conclusions: We propose first, that an early neurodevelopmental insult interacts with either normal or abnormal postpubertal brain maturation to produce further (late neurodevelopmental) brain structural and functional changes and second, that the effect of such neurodevelopmental lesions will have different consequences for functions that normally develop early in life, such as memory, compared with functions developing later, such as executive functions. A model is presented suggesting that the structural and functional abnormalities in schizophrenia can be understood as a consequence of the neurodevelopmental stage at which brain changes occur.
Publisher: Elsevier BV
Date: 03-2009
DOI: 10.1016/J.NEUBIOREV.2008.10.010
Abstract: Recent animal and human studies suggest that the dorsal anterior cingulate cortex (dACC) and its related subcortical structures including nucleus accumbens (NAc) are in the center of a brain network that determines and pursues the best option from available alternatives. Specifically, the involvement of the dACC network in decision-making can be categorized under two broad processes of evaluation and execution. The former aims to determine the most cost-effective option while the latter aims to attain the preferred option. The present article reviews neural and molecular findings to show that the dopamine system might modulate this dACC network at multiple levels to optimize both processes. Several lines of evidence suggest that the dopamine system has a bimodal effect, allows the network to compare different representations in the evaluation phase, and focuses the network on the preferred representation in the execution phase. This is apparently achieved by modulating other neurotransmission systems and by transmitting different signals via D1 vs. D2 receptor subtypes and phasic vs. tonic firing.
Publisher: Wiley
Date: 24-08-2007
DOI: 10.1111/J.1600-0447.2007.01069.X
Abstract: Anterior cingulate cortex (ACC) abnormalities are commonly reported in studies of patients with bipolar disorder (BD), but it is unclear whether these precede or follow illness onset. We investigated the evidence for early neurodevelopmental anomalies in the ACC and adjacent paracingulate cortex (PaC) of BD patients by studying cortical folding patterns of the region. Magnetic resonance images were acquired from 54 BD patients and 116 healthy controls. Cortical folding patterns were assessed by classifying the incidence of the paracingulate sulcus (PCS) and interruptions in the course of the cingulate sulcus (CS). Patients were significantly less likely to show a PCS bilaterally. There were no differences in the frequency of CS interruptions. The bilateral reduction observed in our patient s le implicates aberrant pre- or peri-natal developmental processes. To our knowledge, this is the first in vivo evidence for early neurodevelopmental anomaly of the ACC/PaC region in BD.
Publisher: Wiley
Date: 23-01-2016
DOI: 10.1111/CDEV.12480
Abstract: Few studies have directly examined whether cognitive control can moderate the influence of temperamental positive and negative affective traits on adolescent risk-taking behavior. Using a combined multimethod, latent variable approach to the assessment of adolescent risk-taking behavior and cognitive control, this study examined whether cognitive control moderates the influence of temperamental surgency and frustration on risk-taking behavior in a s le of 177 adolescents (Mage = 16.12 years, SD = 0.69). As predicted, there was a significant interaction between cognitive control and frustration, but not between cognitive control and surgency, in predicting risk-taking behavior. These findings have important implications and suggest that the determinants of adolescent risk taking depend on the valence of the affective motivation for risk-taking behavior.
Publisher: Elsevier BV
Date: 06-2009
DOI: 10.1016/J.JAD.2008.10.010
Abstract: The corpus callosum enables the efficient linking of the two cerebral hemispheres. Reductions in the size of the anterior callosum have been described in geriatric depression, although findings in young adults have been much more equivocal. Data was acquired in 26 currently depressed (mean age 32.15 years, 5/26 male) and 28 remitted non-geriatric adults (mean age 36.36 years, 7/28 male), and 32 control subjects (mean age 34.41 years, 11/32 male). The total area, length and curvature of the callosum, and regional thickness along 39 points, from a mid-sagittal T1-weighted magnetic resonance image were compared across the groups. Total area, length and curvature did not differ between the groups. The currently-depressed group showed expansions in the thickness of the posterior body and isthmus when compared to controls this was not seen in remitted patients. Similar expansions were seen when comorbidly anxious patients were compared to depressed patients without anxiety. There was no difference between melancholic and non-melancholic patients, and medication status did not affect the results. Currently-depressed patients showed higher rates of co-morbid anxiety and medication usage than remitted patients, although in the depression group as a whole there was no difference between medicated and unmedicated patients. The corpus callosum shows expansions in regions connecting frontal, temporal and parietal regions in currently depressed patients only, suggestive of state-related changes in white matter in major depression that may reflect the effects of state-related factors on white matter structure.
Publisher: Royal College of Psychiatrists
Date: 05-2009
DOI: 10.1192/BJP.BP.107.049205
Abstract: The anterior cingulate cortex is frequently implicated in the pathophysiology of bipolar disorder, but magnetic resonance imaging (MRI) studies have reported variable findings owing to a reliance on patient s les with chronic illness and to limited appreciation of the region's heterogeneity. To characterise anterior cingulate cortex abnormalities in patients with bipolar disorder experiencing their first episode of psychosis while accounting for regional anatomical variability. Grey matter volume, surface area and cortical thickness were measured in six anterior cingulate cortex subregions per hemisphere using MRI scans acquired from 26 patients with bipolar I disorder experiencing first-episode psychosis and 26 healthy controls matched for age, gender and regional morphological variability. Relative to controls, male patients displayed increased thickness in the right subcallosal limbic anterior cingulate cortex. No significant differences were identified in females for grey matter volume or surface area measures. The findings were not attributable to medication effects. These data suggest that first-episode psychosis in bipolar disorder is associated with a gender-specific, right-lateralised thickness increase in anterior cingulate cortex subregions known to play a role in regulating physiological stress responses.
Publisher: Cambridge University Press (CUP)
Date: 21-01-2009
Publisher: Elsevier BV
Date: 07-2011
DOI: 10.1016/J.BIOPSYCHO.2011.05.003
Abstract: Sex differences in emotional processes represent some of the most robust sex stereotypes worldwide. However, empirical support for these stereotypes is lacking, especially from research utilizing objective measures, such as neuroimaging methodologies. We conducted a selective review of functional neuroimaging studies that have empirically tested for sex differences in the association between brain function and emotional processes (including perception, reactivity, regulation and experience). Evidence was found for marked sex differences in the neural mechanisms underlying emotional processes, and in most cases suggested that males and females use different strategies during emotional processing, which may lead to sex differences in the observed (or subjectively reported) emotional process. We discuss how these findings may offer insight into the mechanisms underlying sex differences in emotional behaviors, and outline a number of methodological considerations for future research. Importantly, results suggest that sex differences should not be ignored in research investigating the neurobiology of emotion.
Publisher: SAGE Publications
Date: 11-10-2013
Abstract: High doses of opiate substitution pharmacotherapy are associated with greater treatment retention and lower illicit drug consumption, although the neurobiological bases of these benefits are poorly understood. Dysfunction of the anterior cingulate cortex (ACC) is associated with greater addiction severity and mood dysregulation in opiate users, such that the beneficial effects of substitution pharmacotherapy may relate to normalisation of ACC function. This study aimed to investigate the differential impact of methadone compared with buprenorphine on dorsal ACC biochemistry. A secondary aim was to explore the differential effects of methadone and buprenorphine on dorsal ACC biochemistry in relation to depressive symptoms. Twenty-four heroin-dependent in iduals stabilised on methadone ( n=10) or buprenorphine ( n=14) and 24 healthy controls were scanned using proton Magnetic Resonance Spectroscopy and compared for metabolite concentrations of N-acetylaspartate, glutamate/glutamine, and myo-inositol. (1) Methadone was associated with normalisation of dorsal ACC biochemistry (increased N-acetylaspartate and glutamate/glutamine levels, and decreased myo-inositol levels) in a dose-dependent manner (2) buprenorphine-treated in iduals had higher myo-inositol and glutamate/glutamine levels than methadone-treated patients in the right dorsal ACC and (3) myo-inositol levels were positively correlated with depressive symptoms in participants stabilised on buprenorphine. These findings point to a beneficial role of high-dose methadone on dorsal ACC biochemistry, and suggest a link between elevated myo-inositol levels and depressive symptoms in the context of buprenorphine treatment.
Publisher: Elsevier BV
Date: 08-2016
DOI: 10.1016/J.APPET.2016.04.002
Abstract: This study was aimed to investigate if treatment-related success in weight loss (i.e., reductions of BMI and fat percentage) is linked to significant changes in choice evoked brain activity in adolescents with excess weight. Sixteen adolescents with excess weight (age range: 12-18 BMI range: 22-36) performed the Risky-Gains Task during functional Magnetic Resonance Imaging (fMRI) both before and after a 12-week weight loss intervention. Success in weight loss was selectively associated with increased activation in the anterior insula. We concluded that adolescents with the greatest increases in activation of the insula-related interoceptive neural circuitry also show greater reductions in BMI and fat mass.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2013
Publisher: SAGE Publications
Date: 2009
DOI: 10.1080/00048670903107534
Abstract: Objective: Callosal structural and functional alterations have been demonstrated in a range of neuropsychiatric illnesses, including bipolar disorder, but no study has examined regional callosal thickness in this phenotype. The aim of the present study was therefore to examine callosal size and shape in a well-defined group of bipolar affective disorder patients and controls. Methods: The participants included 24 patients with DSM-IV bipolar I disorder and 24 matched healthy controls. The corpus callosum was extracted from mid-callosal images from T1-weighted magnetic resonance imaging scans on all participants, and callosal area, length, bending angle and regional callosal thickness measures were computed from these images. Results: The callosum was thinner in the bipolar group overall, with a disproportionately reduced thickness in the splenium. Psychotic and non-psychotic patients did not differ, although patients without a family history of mood disorders had a thinner callosum. Conclusion: Callosal reductions are present in established bipolar disorder, and affect posterior regions more than anterior regions. This may reflect a primary disturbance to myelination, or a secondary effect of grey matter changes.
Publisher: Informa UK Limited
Date: 2007
Publisher: Elsevier BV
Date: 03-2012
DOI: 10.1016/J.JANXDIS.2011.12.001
Abstract: We evaluated whether traumatic events are associated with a distinctive pattern of socio-demographic and clinical features of obsessive-compulsive disorder (OCD). We compared socio-demographic and clinical features of 106 patients developing OCD after post-traumatic stress disorder (PTSD termed post-traumatic OCD), 41 patients developing OCD before PTSD (pre-traumatic OCD), and 810 OCD patients without any history of PTSD (non-traumatic OCD) using multinomial logistic regression analysis. A later age at onset of OCD, self-mutilation disorder, history of suicide plans, panic disorder with agoraphobia, and compulsive buying disorder were independently related to post-traumatic OCD. In contrast, earlier age at OCD onset, alcohol-related disorders, contamination-washing symptoms, and self-mutilation disorder were all independently associated with pre-traumatic OCD. In addition, patients with post-traumatic OCD without a previous history of obsessive-compulsive symptoms (OCS) showed lower educational levels, greater rates of contamination-washing symptoms, and more severe miscellaneous symptoms as compared to post-traumatic OCD patients with a history of OCS.
Publisher: American Medical Association (AMA)
Date: 02-06-2008
DOI: 10.1001/ARCHPSYC.65.6.694
Abstract: Cannabis is the most widely used illicit drug in the developed world. Despite this, there is a paucity of research examining its long-term effect on the human brain. To determine whether long-term heavy cannabis use is associated with gross anatomical abnormalities in 2 cannabinoid receptor-rich regions of the brain, the hippoc us and the amygdala. Cross-sectional design using high-resolution (3-T) structural magnetic resonance imaging. Participants were recruited from the general community and underwent imaging at a hospital research facility. Fifteen carefully selected long-term (>10 years) and heavy (>5 joints daily) cannabis-using men (mean age, 39.8 years mean duration of regular use, 19.7 years) with no history of polydrug abuse or neurologic/mental disorder and 16 matched nonusing control subjects (mean age, 36.4 years). Volumetric measures of the hippoc us and the amygdala combined with measures of cannabis use. Subthreshold psychotic symptoms and verbal learning ability were also measured. Cannabis users had bilaterally reduced hippoc al and amygdala volumes (P = .001), with a relatively (and significantly [P = .02]) greater magnitude of reduction in the former (12.0% vs 7.1%). Left hemisphere hippoc al volume was inversely associated with cumulative exposure to cannabis during the previous 10 years (P = .01) and subthreshold positive psychotic symptoms (P < .001). Positive symptom scores were also associated with cumulative exposure to cannabis (P = .048). Although cannabis users performed significantly worse than controls on verbal learning (P < .001), this did not correlate with regional brain volumes in either group. These results provide new evidence of exposure-related structural abnormalities in the hippoc us and amygdala in long-term heavy cannabis users and corroborate similar findings in the animal literature. These findings indicate that heavy daily cannabis use across protracted periods exerts harmful effects on brain tissue and mental health.
Publisher: Royal College of Psychiatrists
Date: 12-2009
DOI: 10.1192/BJP.BP.108.055731
Abstract: Cognitive functioning in affective psychosis and schizoaffective disorder is much less studied compared with schizophrenia. To quantitatively undertake a meta-analysis of the available data that directly compares cognitive functioning across schizophrenia, schizoaffective disorder and affective psychosis. Following a thorough literature review, 31 studies that compared the performances of people with schizophrenia (1979 participants) with that of those with affective psychosis or schizoaffective disorder (1314 participants) were included. To determine the effect of demographic and clinical confounders, meta-regression and subgroup analyses were conducted. In 6 of 12 cognitive domains, people with schizophrenia performed worse than people with schizoaffective disorder or affective psychosis. However, the between-group differences were small and the distribution of effect sizes showed substantial heterogeneity. The between-group differences were driven by a higher percentage of males, more severe negative symptoms and younger age at onset of illness in the schizophrenia s les. Neuropsychological data do not provide evidence for categorical differences between schizophrenia and other groups. However, a subgroup of in iduals with schizophrenia who have more severe negative symptoms may be cognitively more impaired than those with affective psychosis/schizoaffective disorder.
Publisher: American Psychological Association (APA)
Date: 2000
Publisher: Elsevier BV
Date: 08-2017
Publisher: CMA Joule Inc.
Date: 11-2010
DOI: 10.1503/JPN.090177
Publisher: Springer Science and Business Media LLC
Date: 28-04-2023
DOI: 10.1007/S10899-023-10206-1
Abstract: This study investigated whether there was community support for prominent gambling harm reduction policies, as well as perceived responsibility for electronic gambling machine (EGM) related harm in an Australian s le (n = 906). Using a randomised experimental design, we also explored whether these outcomes were influenced by three alternative explanations for EGM-related harm: a brain-based account of gambling addiction, an account that highlighted the intentional design of the gambling environment focused on the “losses disguised as wins” (LDWs), and a media release advocating against further government intervention in the gambling sector. We observed clear majority support for most policies presented, including mandatory pre-commitment, self-exclusion, and a $1 limit on EGM bets. A substantial majority of participants agreed that in iduals, governments, and industry should be held responsible for EGM-related harm. Participants presented with the explanation of LDWs attributed greater responsibility for gambling-related harm to industry and government, less agreement that electronic gambling machines are fair, and more agreement that EGMs are likely to mislead or deceive consumers. There was some limited evidence of greater support for policy intervention in this group, including a blanket ban of EGMs, clinical treatment funded by gambling taxes, mass media c aigns, and mandatory pre-commitment for EGMs. We found no evidence that a brain-based account of gambling addiction substantially undermined support for policy intervention. We predicted that the information about LDWs and the brain-based account of EGM related harm would soften attributions of personal responsibility for gambling harm. Our results did not support either of these predictions.
Publisher: Wiley
Date: 03-11-2011
DOI: 10.1111/J.1465-3362.2010.00256.X
Abstract: Inhalants are frequently among the first drugs abused by adolescents however, little is known about how chronic inhalant abuse affects cognition (e.g. executive functioning). Several studies have examined cognitive deficits among inhalant users however, no study has thoroughly addressed the confounding issues frequently associated with inhalant users (e.g. polysubstance use). The aim of the current study was to examine possible deficits in cognitive control among young, regular inhalant users and explore the relationship between inhalant use and executive functioning. Three groups (n = 19) of young people (aged 14-24) were recruited: an inhalant-using group, a drug-using control group and a community control group. The inhalant and drug-using controls were matched on demographic, clinical and substance use measures. All three groups were matched on age, sex and education. Cognitive control was assessed using Stroop and Go/No-Go tasks. There were no significant differences in performance between the groups on any measure. However, three measures (incongruent reaction times and congruent errors for the Stroop and omission errors for the Go/No-Go) were significantly correlated with inhalant use measures, suggesting inhalant use was associated with poorer performance. The lack of significant differences between the groups is surprising however, it raises important questions regarding cognitive deficits among chronic inhalant users. Further longitudinal studies using well-matched control participants are required to delineate the nature and timing of cognitive and neurobiological pathology among adolescent inhalant users.
Publisher: Wiley
Date: 26-09-2007
DOI: 10.1111/J.1600-0447.2006.00902.X
Abstract: Anterior cingulate (ACC) hypo-activity is commonly observed in chronically ill schizophrenia patients. However, it is unclear whether this is secondary to persistent illness and/or medication. We examined eight antipsychotic-naïve first-episode patients and matched healthy controls undergoing PET scanning while performing the Stroop task. Group-averaged and single-subject analyses showed ACC activation in both controls and patients, albeit in different sub-regions (paracingulate and cingulate respectively). A direct comparison revealed relative under-activity of the left paracingulate cortex in patients. These findings suggest that the more pervasive hypo-activation observed in chronic patients may be secondary to persistent illness and/or medication.
Publisher: Wiley
Date: 04-03-2016
DOI: 10.1002/HBM.23154
Publisher: Cambridge University Press (CUP)
Date: 2016
DOI: 10.1016/J.EURPSY.2015.09.460
Abstract: Cognitive deficits have been reported during the early stages of bipolar disorder however, the role of medication on such deficits remains unclear. The aim of this study was to compare the effects of lithium and quetiapine monotherapy on cognitive performance in people following first episode mania. The design was a single-blind, randomised controlled trial on a cohort of 61 participants following first episode mania. Participants received either lithium or quetiapine monotherapy as maintenance treatment over a 12-month follow-up period. The groups were compared on performance outcomes using an extensive cognitive assessment battery conducted at baseline, month 3 and month 12 follow-up time-points. There was a significant interaction between group and time in phonemic fluency at the 3-month and 12-month endpoints, reflecting greater improvements in performance in lithium-treated participants relative to quetiapine-treated participants. After controlling for multiple comparisons, there were no other significant interactions between group and time for other measures of cognition. Although the effects of lithium and quetiapine treatment were similar for most cognitive domains, the findings imply that early initiation of lithium treatment may benefit the trajectory of cognition, specifically verbal fluency in young people with bipolar disorder. Given that cognition is a major symptomatic domain of bipolar disorder and has substantive effects on general functioning, the ability to influence the trajectory of cognitive change is of considerable clinical importance.
Publisher: Elsevier BV
Date: 03-2013
DOI: 10.1016/J.NEUBIOREV.2013.01.003
Abstract: Longitudinal studies of biological domains in bipolar disorder (BD) are crucial in determining if such baseline changes are progressive. We reviewed reported studies of longitudinal brain structural/functional magnetic resonance imaging (MRI) and neuropsychological changes in BD through November 2012. Longitudinal brain structural MRI studies suggest cortical and subcortical abnormalities within networks subserving emotional regulation. There is evidence of neuroprogressive loss of gray matter volume in prefrontal and anterior cingulate cortex and the subgenual region, with less consistent findings in temporal and subcortical regions. Abnormal amygdala neurodevelopment is noted in adolescent onset BD and possible changes in hippoc us require further evaluation. The fewer reported longitudinal functional MRI studies suggest neurobiological changes in activation patterns involving fronto-limbic circuitry which relate to different illness phase and mood states. Early onset pediatric/adolescent BD may signify a more malignant course of illness in which extensive and executive neurocognitive deficits are found early and may persist, with some potential for improvement during remission and perhaps with treatment. Future studies should include larger s les, combine investigational modalities, incorporate genetic profiles, consider standardization of assessments and collaborative ventures across institutions, selection of more homogeneous subgroups and track neurobiological changes longer to clarify trajectories of changes.
Publisher: Springer Science and Business Media LLC
Date: 31-05-2011
DOI: 10.1038/MP.2011.62
Publisher: Elsevier BV
Date: 07-2016
DOI: 10.1016/J.ADDBEH.2016.02.011
Abstract: Several factors are associated with an increased risk of adolescent problem gambling, including positive gambling attitudes, higher levels of gambling involvement, ineffective coping strategies and unhelpful parenting practices. It is less clear, however, how these factors interact or influence each other in the development of problem gambling behavior during adolescence. The aim of the current study was to simultaneously explore these predictors, with a particular focus on the extent to which coping skills and parenting styles may moderate the expected association between gambling involvement and gambling problems. Participants were 612 high school students. The data were analyzed using a zero-inflated Poisson (ZIP) regression model, controlling for gender. Although several variables predicted the number of symptoms associated with problem gambling, none of them predicted the probability of displaying any problem gambling. Gambling involvement fully mediated the relationship between positive gambling attitudes and gambling problem severity. There was a significant relationship between gambling involvement and problems at any level of problem focused coping, reference to others and inconsistent discipline. However, adaptive coping styles employed by adolescents and consistent disciplinary practices by parents were buffers of gambling problems at low levels of adolescent gambling involvement, but failed to protect adolescents when their gambling involvement was high. These findings indicate that research exploring the development of gambling problems is required and imply that coping and parenting interventions may have particular utility for adolescents who are at risk of development gambling problems but who are not gambling frequently.
Publisher: Wiley
Date: 10-09-2009
DOI: 10.1111/J.1600-0447.2009.01414.X
Abstract: The aim of this study was to critically review the literature in order to determine if Theory of Mind (ToM) impairment can be considered a trait-marker for schizophrenia spectrum disorders and bipolar disorder (BD). After a thorough literature search, we reviewed the empirical studies investigating ToM impairments in remitted schizophrenia patients, first episode patients, subjects at high-risk (HR) for psychosis and first-degree relatives of schizophrenia patients. Studies investigating ToM impairment in other schizophrenia spectrum conditions, affective psychosis and BD were also reviewed. ToM abnormalities exist at onset and continue throughout the course of schizophrenia, persist into remission, and while less severe, are apparent in HR populations. Mentalizing impairments are also observed in other forms of psychotic illness and BD. Mentalizing impairment in schizophrenia spectrum disorders and BD might reflect underlying general cognitive deficits and residual symptom expression, rather than representing a specific trait-marker.
Publisher: SAGE Publications
Date: 19-07-2016
Abstract: Cognitive deficits are apparent in the early stages of bipolar disorder however, the timing and trajectory of cognitive functioning following a first episode of mania remains unclear. The aim of this study was to assess the trajectory of cognitive functioning in people following a first episode of mania over a 12-month period, relative to healthy controls. The cohort included 61 participants who had recently stabilised from a first treated manic episode, and 21 demographically similar healthy controls. These groups were compared on changes observed over time using an extensive cognitive battery, over a 12-month follow-up period. A significant group by time interaction was observed in one measure of processing speed (Trail Making Test – part A,) and immediate verbal memory (Rey Auditory Verbal Learning Test – trial 1), with an improved performance in people following a first episode of mania relative to healthy controls. On the contrary, there was a significant group by time interaction observed on another processing speed task pertaining to focussed reaction time (Go/No-Go, missed go responses), with first episode of mania participants performing significantly slower in comparison with healthy controls. Furthermore, a significant group by time interaction was observed in inhibitory effortful control (Stroop effect), in which healthy controls showed an improvement over time relative to first episode of mania participants. There were no other significant interactions of group by time related to other measures of cognition over the 12-month period. Our findings revealed cognitive change in processing speed, immediate memory and one measure of executive functioning over a 12-month period in first episode of mania participants relative to healthy controls. There was no evidence of change over time for all other cognitive domains. Further studies focussed on the at-risk period, subgroup analysis, and the effects of medication on the cognitive trajectory following first episode of mania are needed.
Publisher: Wiley
Date: 25-08-2004
DOI: 10.1111/J.1360-0443.2004.00808.X
Abstract: Addiction has been conceptualized as a shift from controlled experimentation to uncontrolled, compulsive patterns of use. Current neurobiological models of addiction emphasize changes within the brain's reward system, such that drugs of abuse 'hijack' this system and bias behaviour towards further drug use. While this model explains the involuntary nature of craving and the motivational drive to continue drug use, it does not explain fully why some addicted in iduals are unable to control their drug use when faced with potentially disastrous consequences. In this review, we argue that such maladaptive and uncontrolled behaviour is underpinned by a failure of the brain's inhibitory control mechanisms. Relevant neuroimaging, neuropsychological and clinical studies are reviewed, along with data from our own research. The current literature suggests that in addition to the brain's reward system, two frontal cortical regions (anterior cingulate and orbitofrontal cortices), critical in inhibitory control over reward-related behaviour, are dysfunctional in addicted in iduals. These same regions have been implicated in other compulsive conditions characterized by deficits in inhibitory control over maladaptive behaviours, such as obsessive-compulsive disorder. We propose that in chronically addicted in iduals, maladaptive behaviours and high relapse rates may be better conceptualized as being 'compulsive' in nature as a result of dysfunction within inhibitory brain circuitry, particularly during symptomatic states. This model may help to explain why some addicts lose control over their drug use, and engage in repetitive self-destructive patterns of drug-seeking and drug-taking that takes place at the expense of other important activities. This model may also have clinical utility, as it allows for the adoption of treatments effective in other disorders of inhibitory dysregulation.
Publisher: Elsevier BV
Date: 03-2014
DOI: 10.1016/J.SCHRES.2014.01.041
Abstract: A shallow olfactory sulcus has been reported in schizophrenia, possibly reflecting abnormal forebrain development during early gestation. However, it remains unclear whether this anomaly exists prior to the onset of psychosis and/or differs according to illness stage. In the current study, magnetic resonance imaging was used to investigate the length and depth of the olfactory sulcus in 135 ultra high-risk (UHR) in iduals [of whom 52 later developed psychosis (UHR-P) and 83 did not (UHR-NP)], 162 patients with first-episode psychosis (FEP), 89 patients with chronic schizophrenia, and 87 healthy controls. While there was no group difference in the length of the sulcus, UHR-P subjects had significantly shallower olfactory sulcus at baseline as compared with UHR-NP and control subjects. The depth of this sulcus became increasingly more superficial as one moved from UHR-P subjects to FEP patients to chronic schizophrenia patients. Finally, the depth of the olfactory sulcus in the UHR-P subjects was negatively correlated with the severity of negative symptoms. These findings suggest that the altered depth of the olfactory sulcus, which exists before psychosis onset, could be predictive of transition to psychosis, but also suggest ongoing changes of the sulcus morphology during the course of the illness.
Publisher: Elsevier BV
Date: 02-2010
DOI: 10.1016/J.PNPBP.2009.10.005
Abstract: The superior temporal gyrus (STG), especially its lateral portion, and temporal pole (TP) both play a central role in emotional processing, but it remains largely unknown whether patients with major depressive disorder (MDD) exhibit morphologic changes in these regions. We delineated the STG subregions [planum polare (PP), Heschl gyrus (HG), planum temporale (PT), rostral STG, and caudal STG] and TP using magnetic resonance imaging in 29 currently depressed patients (mean age=32.5 years, 7 males), 27 remitted depressed patients (mean age=35.1 years, 9 males), and 33 age- and gender-matched healthy control subjects (mean age=34.0 years, 12 males). Both current and remitted MDD patients showed a significant volume reduction of the left PT and bilateral caudal STG as compared with healthy controls. The TP volume did not differ between the groups. The right PT volume was negatively correlated with total score on the Beck Depression Inventory in the MDD patients as a whole. Medication, presence of melancholia, and comorbidity with anxiety disorders did not affect the TP and STG volumes. These findings suggest that the volume reduction of the STG, but not the TP, may represent enduring brain changes in MDD even after recovery from depression, but right STG volume may also be related to the severity of depressive symptoms.
Publisher: Society for Neuroscience
Date: 02-03-2011
DOI: 10.1523/JNEUROSCI.4858-10.2011
Abstract: The human cerebral cortex is a complex network of functionally specialized regions interconnected by axonal fibers, but the organizational principles underlying cortical connectivity remain unknown. Here, we report evidence that one such principle for functional cortical networks involves finding a balance between maximizing communication efficiency and minimizing connection cost, referred to as optimization of network cost-efficiency. We measured spontaneous fluctuations of the blood oxygenation level-dependent signal using functional magnetic resonance imaging in healthy monozygotic (16 pairs) and dizygotic (13 pairs) twins and characterized cost-efficient properties of brain network functional connectivity between 1041 distinct cortical regions. At the global network level, 60% of the interin idual variance in cost-efficiency of cortical functional networks was attributable to additive genetic effects. Regionally, significant genetic effects were observed throughout the cortex in a largely bilateral pattern, including bilateral posterior cingulate and medial prefrontal cortices, dorsolateral prefrontal and superior parietal cortices, and lateral temporal and inferomedial occipital regions. Genetic effects were stronger for cost-efficiency than for other metrics considered, and were more clearly significant in functional networks operating in the 0.09–0.18 Hz frequency interval than at higher or lower frequencies. These findings are consistent with the hypothesis that brain networks evolved to satisfy competitive selection criteria of maximizing efficiency and minimizing cost, and that optimization of network cost-efficiency represents an important principle for the brain's functional organization.
Publisher: Springer Science and Business Media LLC
Date: 08-08-2016
DOI: 10.1007/S00213-016-4398-3
Abstract: Conflicting evidence exists on the effects of cannabis use on brain white matter integrity. The extant literature has exclusively focused on younger cannabis users, with no studies s ling older cannabis users. We recruited a s le with a broad age range to examine the integrity of major white matter tracts in association with cannabis use parameters and neurodevelopmental stage. Regular cannabis users (n = 56) and non-users (n = 20) with a mean age of 32 (range 18-55 years) underwent structural and diffusion MRI scans. White matter was examined using voxel-based statistics and via probabilistic tract reconstruction. The integrity of tracts was assessed using average fractional anisotropy, axial diffusivity and radial diffusivity. Diffusion measures were compared between users and non-users and as group-by-age interactions. Correlations between diffusion measures and age of onset, duration, frequency and dose of current cannabis use were examined. Cannabis users overall had lower fractional anisotropy than healthy non-users in the forceps minor tract only (p = .015, partial eta = 0.07), with no voxel-wise differences observed. Younger users showed predominantly reduced axial diffusivity, whereas older users had higher radial diffusivity in widespread tracts. Higher axial diffusivity was associated with duration of cannabis use in the cingulum angular bundle (beta = 5.00 × 10(-5), p = .003). Isolated higher AD in older cannabis users was also observed. The findings suggest that exogenous cannabinoids alter normal brain maturation, with differing effects at various neurodevelopmental stages of life. These age-related differences are posited to account for the disparate results described in the literature.
Publisher: Wiley
Date: 17-12-2007
Publisher: Elsevier BV
Date: 02-2005
DOI: 10.1016/J.PSCYCHRESNS.2004.11.007
Abstract: Functional imaging and neuropsychological data suggest that interconnected brain structures including the orbito-frontal cortex (OFC), anterior cingulate cortex (ACC) and caudate nucleus (CN) are involved in the pathophysiology of obsessive-compulsive disorder (OCD), but structural imaging studies investigating these regions have yielded inconclusive results. This may be due to inconsistencies in the identification of anatomical boundaries and methodologies utilised (i.e. automated vs. manual tracing). This magnetic resonance imaging study used manual tracing to measure volumes of selected brain regions (OFC, ACC and CN) in OCD patients and compared them with s les of healthy (HC) and psychiatric (schizophrenia SCZ) controls (n=18 in each group). Concurrently, automated voxel-based analysis was also used to detect subtle differences in cerebral grey and white matter. For the OCD vs. HC comparison, there were no significant volumetric differences detected using the manual or the automated method (although the latter revealed a deficit in the subcortical white matter of the right temporal region). A direct comparison of the two patient groups showed no significant differences using the manual method. However, a moderate effect size was detected for OFC grey matter (reduced in SCZ), which was supported by findings of reduced OFC volume in the automated analysis. Automated analyses also showed reduced volumes in the dorsal (white matter) and ventral ACC (grey and white matter), as well as the left posterior cingulate (grey and white matter) in SCZ. The findings suggest that in contrast to findings in SCZ, there are very few (if any) gross structural anomalies in OCD.
Publisher: Wiley
Date: 12-11-2011
DOI: 10.1111/J.1469-7610.2010.02337.X
Abstract: Early adolescence is a critical time for the development of both internalizing and externalizing disorders. We aimed to investigate whether pituitary volume, an index of hypothalamic-pituitary-adrenal (HPA) axis function, represents a vulnerability factor for the emergence of internalizing and externalizing symptoms during adolescence using a prospective, longitudinal design. One hundred and fifty-five adolescents completed 3T structural magnetic resonance imaging (MRI), symptom rating scales and a diagnostic interview during early adolescence (M age 12.6 years, SD .5 years) symptom rating scales were re-administered approximately three years later (M age 15.2 years). The volume of the pituitary gland was estimated by manually delineating its structure on MR images. The degree to which pituitary volumes prospectively predicted change in internalizing and externalizing symptoms across the two time-points was assessed using hierarchal linear regression, after controlling for the influence of gender, age, pubertal stage and intracranial volume. Larger pituitary volumes prospectively predicted an increase in internalizing, but not externalizing, symptoms from early adolescence to mid-adolescence. This study provides the first evidence that increased pituitary volume might represent a specific vulnerability marker for the development of internalizing symptoms during early to mid-adolescence.
Publisher: Elsevier BV
Date: 03-2010
DOI: 10.1016/J.JAD.2009.06.003
Abstract: Functional neuroimaging studies have implicated the insular cortex in emotional processing, including the evaluation of one's own emotion, as well as in the neurobiology of major depressive disorder (MDD). Nevertheless, it remains largely unknown whether MDD patients exhibit morphologic changes of the insular cortex, and whether such changes reflect state or trait markers of the disorder. We delineated the anterior and posterior insular cortices using magnetic resonance imaging in 29 currently depressed patients (mean age=32.5 years, 7 males), 27 remitted depressed patients (mean age=35.1 years, 9 males), and 33 age- and gender-matched healthy control subjects (mean age=34.0 years, 12 males). Both current and remitted MDD patients showed significant volume reduction of the left anterior insular cortex as compared with healthy controls, but there was no group difference in the posterior insular cortex volume. Insular volumes did not correlate with the severity of depressive symptoms. Furthermore, the presence of melancholia and co-morbidity with anxiety disorders did not affect insular cortex volumes. Although there was no difference in the insular cortex volume between medicated and unmedicated patients, a comprehensive investigation of medication effects was not possible, as complete data (e.g., dose, duration) were not available. These findings suggest that the morphologic abnormality of the anterior insular cortex, which plays a major role in introspection and emotional control, may be a trait-related marker of vulnerability to major depression, supporting the notion that MDD involves pathological alterations of limbic and related cortical structures.
Publisher: SAGE Publications
Date: 11-2007
Abstract: Early onset substance use has consistently been associated with increased risk for a range of adverse outcomes in late adolescence and early adulthood. However, the mechanisms that underlie this relationship are not fully understood. Recent advances in developmental neuro-science, together with emerging literature on early onset substance use, suggest that the adolescent brain may be more vulnerable to the effects of addictive substances because of the extensive neuromaturational processes that are occurring during this period. Such findings are suggestive of disrupted developmental trajectories in early onset users, although there is growing evidence that high-risk youths have premorbid neurobiological vulnerabilities. Prospective studies investigating neurobiological correlates and sequelae of early adolescent drug use are urgently required to inform appropriate public health responses.
Publisher: Wiley
Date: 18-07-2019
DOI: 10.1111/ADB.12652
Abstract: Cannabis use is highly prevalent and often considered to be relatively harmless. Nonetheless, a subset of regular cannabis users may develop dependence, experiencing poorer quality of life and greater mental health problems relative to non-dependent users. The neuroanatomy characterizing cannabis use versus dependence is poorly understood. We aimed to delineate the contributing role of cannabis use and dependence on morphology of the hippoc us, one of the most consistently altered brain regions in cannabis users, in a large multi-site dataset aggregated across four research sites. We compared hippoc al volume and vertex-level hippoc al shape differences (1) between 121 non-using controls and 140 cannabis users (2) between 106 controls, 50 non-dependent users and 70 dependent users and (3) between a subset of 41 controls, 41 non-dependent users and 41 dependent users, matched on s le characteristics and cannabis use pattern (onset age and dosage). Cannabis users did not differ from controls in hippoc al volume or shape. However, cannabis-dependent users had significantly smaller right and left hippoc i relative to controls and non-dependent users, irrespective of cannabis dosage. Shape analysis indicated localized deflations in the superior-medial body of the hippoc us. Our findings support neuroscientific theories postulating dependence-specific neuroadaptations in cannabis users. Future efforts should uncover the neurobiological risk and liabilities separating dependent and non-dependent use of cannabis.
Publisher: Wiley
Date: 03-12-2008
DOI: 10.1002/MDS.21725
Abstract: We describe one male and one female patient who each developed childhood/adolescent obsessive-compulsive disorder as a prelude to the development of a typical picture of chorea-acanthocytosis (ChAc). In each patient, the caudate nucleus showed dramatic atrophy. The role of the caudate in compulsive phenomena, and the predilection for neurological disorders with onset in adolescence to present as major mental illness, is discussed. On the basis of the current evidence and previous findings, we suggest that ChAc can be understood as a disorder whose clinical presentation reflects an interaction between the disease process and the in idual's neurodevelopmental stage with both initial interrupted neurodevelopment, and supervening neurodegeneration.
Publisher: Wiley
Date: 05-2008
DOI: 10.1038/BJP.2008.76
Publisher: Elsevier BV
Date: 09-2009
DOI: 10.1016/J.JAD.2008.11.021
Abstract: While there is evidence to suggest that major depressive disorder (MDD) is associated with structural brain abnormalities, the precise nature of these abnormalities remains unclear. To review recent structural magnetic resonance imaging (MRI) research findings in MDD while considering the potential influence of key clinical and demographic variables. A selective review of all T1-weighted structural MRI studies published between 2000 and 2007 in adult s les of MDD patients. Volumetric reductions of the hippoc us, basal ganglia and OFC and SGPFC are consistently found in MDD patients, with more persistent forms of MDD (e.g., multiple episodes or repeated relapses, longer illness duration) being associated with greater impact on regional brain volumes. Gender, medication, stage of illness, and family history all affect the nature of the findings in a regionally specific manner. Overall, differences between the s les in factors such as illness severity, medication, gender and family history of mental illness makes difficult to identify their confounding effects on the observed neuroanatomical changes. Also, the tracing protocols used for particular brain regions were different amongst the reviewed studies, making difficult to compare their findings. The data support the notion that MDD involves pathological alterations of limbic and cortical structures, and that they are generally more apparent in patients with more severe or persistent forms of the illness.
Publisher: Oxford University Press (OUP)
Date: 12-03-2014
DOI: 10.1093/SCAN/NST013
Publisher: Elsevier BV
Date: 06-2015
DOI: 10.1016/J.JANXDIS.2015.04.004
Abstract: We assessed correlates of obsessive-compulsive (OCPD), schizotypal (SPD) and borderline (BPD) personality disorders in 110 obsessive-compulsive disorder (OCD) patients. We found OCD patients with OCPD (20.9%) to exhibit higher rates of hoarding and bipolar disorders, increased severity of hoarding and symmetry, lower prevalence of unacceptable thoughts involving sex and religion and less non-planning impulsivity. Conversely, OCD patients with SPD (13.6%) displayed more frequently bipolar disorder, increased severity of depression and OCD neutralization, greater prevalence of "low-order" behaviors (i.e., touching), lower low-planning impulsivity and greater "behavioral" compulsivity. Finally, in exploratory analyses, OCD patients with BPD (21.8%) exhibited lower education, higher rates of several comorbid psychiatric disorders, greater frequency of compulsions involving interpersonal domains (e.g. reassurance seeking), increased severity of depression, anxiety and OCD dimensions other than symmetry and hoarding, more motor and non-planning impulsivity, and greater "cognitive" compulsivity. These findings highlight the importance of assessing personality disorders in OCD s les.
Publisher: SAGE Publications
Date: 22-11-2014
Abstract: There is growing evidence that anhedonia is a commonly experienced symptom among substance-using populations. This systematic review synthesises findings across a range of substances to address questions regarding the time course of anhedonia, how anhedonia relates to other symptoms of substance dependence and whether it is similarly prevalent across all addictive drugs. A literature search was conducted on PubMed, PsycINFO and MEDLINE, yielding 32 studies that used self-report measures of anhedonia among participants with a history of a substance abuse, dependence or long-term daily use of addictive substances. Findings from these studies indicate that anhedonia (1) is elevated in s les dependent on a range of substances (2) typically appears as a consequence of substance abuse or dependence, and diminishes with abstinence and (3) predicts increased drug cravings and the likelihood of relapse in those attempting abstinence. The common experience of anhedonia in substance-dependent populations, and its relationship to relapse, emphasises the importance of developing therapeutic interventions that specifically target anhedonia in the treatment of all substance use disorders.
Location: Australia
Start Date: 2016
End Date: 2017
Funder: Department of Industry, Innovation and Science
View Funded ActivityStart Date: 2017
End Date: 2021
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2011
End Date: 2013
Funder: National Council for Scientific and Technological Development & Foundation for Research Support
View Funded ActivityStart Date: 2011
End Date: 2013
Funder: Australian Research Council
View Funded ActivityStart Date: 2008
End Date: 2011
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2012
End Date: 2016
Funder: National Health and Medical Research Council
View Funded Activity