ORCID Profile
0000-0003-0029-1525
Current Organisation
University of Melbourne
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Research Topics
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Complementary and Alternative Medicine | Nuclear Medicine | Biological Psychology (Neuropsychology, Psychopharmacology, Physiological Psychology) | Complementary and Alternative Medicine not elsewhere classified
ANZSRC Socio-Economic Objective (SEO)
Nutrition | Behaviour and Health | Preventive Medicine | Health Status (e.g. Indicators of Well-Being) |
Related Links
Publications
Neuregulin-1 (NRG1) polymorphisms linked with psychosis transition are associated with enlarged lateral ventricles and white matter disruption in schizophrenia.
Publisher: Cambridge University Press (CUP)
Date: 22-08-2017
DOI: 10.1017/S0033291717002173
Abstract: Two single-nucleotide polymorphisms (SNPs) (rs4281084 and rs12155594) within the neuregulin-1 (NRG1) gene have been associated with psychosis transition. However, the neurobiological changes associated with these SNPs remain unclear. We aimed to determine what relationship these two SNPs have on lateral ventricular volume and white matter integrity, as abnormalities in these brain structures are some of the most consistent in schizophrenia. Structural ( n = 370) and diffusion ( n = 465) magnetic resonance imaging data were obtained from affected and unaffected in iduals predominantly of European descent. The SNPs rs4281084, rs12155594, and their combined allelic load were examined for their effects on lateral ventricular volume, fractional anisotropy (FA) as well as axial (AD) and radial (RD) diffusivity. Additional exploratory analyses assessed NRG1 effects on gray matter volume, cortical thickness, and surface area throughout the brain. In iduals with a schizophrenia age of onset ⩽25 and a combined allelic load ⩾3 NRG1 risk alleles had significantly larger right (up to 50%, p adj = 0.01) and left (up to 45%, p adj = 0.05) lateral ventricle volumes compared with those with allelic loads of less than three. Furthermore, carriers of three or more risk alleles, regardless of age of onset and case status, had significantly reduced FA and elevated RD but stable AD in the frontal cortex compared with those carrying fewer than three risk alleles. Our findings build on a growing body of research supporting the functional importance of genetic variation within the NRG1 gene and complement previous findings implicating the rs4281084 and rs12155594 SNPs as markers for psychosis transition.
Investigation of peripheral complement factors across stages of psychosis
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.SCHRES.2018.11.035
Abstract: The complement cascade has been proposed to contribute to the pathogenesis of schizophrenia. However, it remains unclear whether peripheral complement levels differ in cases compared to controls, change over the course of illness and whether they are associated with current symptomatology. This study aimed to: i) investigate whether peripheral complement protein levels are altered at different stages of illness, and ii) identify patterns among complement protein levels that predict clinical symptoms. Complement factors C1q, C3 and C4 were quantified in 183 participants [n = 83 Healthy Controls (HC), n = 10 Ultra-High Risk (UHR) for psychosis, n = 40 First Episode Psychosis (FEP), n = 50 Chronic schizophrenia] using Multiplex ELISA. Permutation-based t-tests were used to assess between-group differences in complement protein levels at each of the three illness stages, relative to age- and gender-matched healthy controls. Canonical correlation analysis was used to identify patterns of complement protein levels that correlated with clinical symptoms. C4 was significantly increased in chronic schizophrenia patients, while C3 and C4 were significantly increased in UHR patients. There were no differences in C1q, C3 and C4 in FEP patients when adjusting for BMI. A molecular pattern of increased C4 and decreased C3 was associated with positive and negative symptom severity in the pooled patient s le. Our findings indicate that peripheral complement concentration is increased across specific stages of psychosis and its imbalance may be associated with symptom severity. Given the small s le size of the UHR group, these findings should be regarded as exploratory, requiring replication.
Small effect of dopamine release and no effect of dopamine depletion on [18F]fallypride binding in healthy humans
Publisher: Wiley
Date: 2008
DOI: 10.1002/SYN.20506
Abstract: Molecular imaging has been used to estimate both drug-induced and tonic dopamine release in the striatum and most recently extrastriatal areas of healthy humans. However, to date, studies of drug-induced and tonic dopamine release have not been performed in the same subjects. This study performed positron emission tomography (PET) with [18F]fallypride in healthy subjects to assess (1) the reproducibility of [18F]fallypride and (2) both D- hetamine-induced and alpha-methyl-p-tyrosine (AMPT)-induced changes in dopamin release on [(18)F]fallypride binding in striatal and extrastriatal areas. Subjects underwent [18F]fallypride PET studies at baseline and following oral D- hetamine administration (0.5 mg/kg) and oral AMPT administration (3 g/70 kg/day over 44 h). Binding potential (BP) (BP(ND)) of [18F]fallypride was calculated in striatal and extrastriatal areas using a reference region method. Percent change in regional BP(ND) was computed and correlated with change in cognition and mood. Test-retest variability of [18F]fallypride was low in both striatal and extrastriatal regions. D-Amphetamine significantly decreased BP(ND) by 8-14% in striatal sub isions, caudate, putamen, substantia nigra, medial orbitofrontal cortex, and medial temporal cortex. Correlation between change in BP(ND) and verbal fluency was seen in the thalamus and substantia nigra. In contrast, depletion of endogenous dopamine with AMPT did not effect [18F]fallypride BP(ND) in both striatum and extrastriatal regions. These findings indicate that [18F]fallypride is useful for measuring hetamine-induced dopamine release, but may be unreliable for estimating tonic dopamine levels, in striatum and extrastriatal regions of healthy humans.
Evidence for network-based cortical thickness reductions in schizophrenia
Publisher: American Psychiatric Association Publishing
Date: 07-2019
DOI: 10.1176/APPI.AJP.2019.18040380
Abstract: Cortical thickness reductions in schizophrenia are irregularly distributed across multiple loci. The authors hypothesized that cortical connectivity networks would explain the distribution of cortical thickness reductions across the cortex, and, specifically, that cortico-cortical connectivity between loci with these reductions would be exceptionally strong and form an interconnected network. This hypothesis was tested in three cross-sectional schizophrenia cohorts: first-episode psychosis, chronic schizophrenia, and treatment-resistant schizophrenia. Structural brain images were acquired for 70 patients with first-episode psychosis, 153 patients with chronic schizophrenia, and 47 patients with treatment-resistant schizophrenia and in matching healthy control groups (N=57, N=168, and N=54, respectively). Cortical thickness was compared between the patient and respective control groups at 148 regions spanning the cortex. Structural connectivity strength between pairs of cortical regions was quantified with structural covariance analysis. Connectivity strength between regions with cortical thickness reductions was compared with connectivity strength between 5,000 sets of randomly chosen regions to establish whether regions with reductions were interconnected more strongly than would be expected by chance. Significant (false discovery rate corrected) and widespread cortical thickness reductions were found in the chronic schizophrenia (79 regions) and treatment-resistant schizophrenia (106 regions) groups, with more circumscribed reductions in the first-episode psychosis group (34 regions). Cortical thickness reductions with the largest effect sizes were found in frontal, temporal, cingulate, and insular regions. In all cohorts, both the patient and healthy control groups showed significantly increased structural covariance between regions with cortical thickness reductions compared with randomly selected regions. Brain network architecture can explain the irregular topographic distribution of cortical thickness reductions in schizophrenia. This finding, replicated in three distinct schizophrenia cohorts, suggests that the effect is robust and independent of illness stage.
Fragility and volatility of structural hubs in the human connectome
Publisher: Springer Science and Business Media LLC
Date: 23-07-2018
DOI: 10.1038/S41593-018-0188-Z
Abstract: Brain structure reflects the influence of evolutionary processes that pit the costs of its anatomical wiring against the computational advantages conferred by its complexity. We show that cost-neutral 'mutations' of the human connectome almost inevitably degrade its complexity and disconnect high-strength connections to prefrontal network hubs. Conversely, restoring the peripheral location and strong connectivity of empirically observed hubs confers a wiring cost that the brain appears to minimize. Progressive cost-neutral randomization yields daughter networks that differ substantially from one another and results in a topologically unstable phenomenon consistent with a phase transition in complex systems. The fragility of hubs to disconnection shows a significant association with the acceleration of gray matter loss in schizophrenia. Together with effects on wiring cost, we suggest that fragile prefrontal hub connections and topological volatility act as evolutionary influences on brain networks whose optimal set point may be perturbed in neuropsychiatric disorders.
Functional Connectivity of Corticostriatal Circuitry and Psychosis-Like Experiences in the General Community
Publisher: Cold Spring Harbor Laboratory
Date: 07-10-2018
DOI: 10.1101/437376
Abstract: Psychotic symptoms are proposed lie on a continuum, ranging from isolated psychosis-like experiences (PLEs) in non-clinical populations to frank disorder. Here, we investigate neurobiological correlates of this symptomatologic continuum by examining whether functional connectivity of dorsal corticostriatal circuitry, which is disrupted in patients and high-risk in iduals, is associated with the severity of subclinical PLEs. A community s le of 672 adults with no history of psychiatric or neurological illnesses completed a battery of seven questionnaires spanning various PLE domains. Principal component analysis (PCA) estimated major dimensions of PLEs from the questionnaires. PCA dimension scores were then correlated with whole-brain voxelwise functional connectivity (FC) maps of the striatum in a subset of 353 participants who completed a resting-state neuroimaging protocol. PCA identified two dimensions of PLEs accounting for 62.57% of variance in the measures, corresponding to positive and negative PLEs. Reduced FC between the dorsal striatum and prefrontal cortex correlated with higher positive PLEs. Negative PLEs correlated with increased FC between the dorsal striatum and visual and sensorimotor areas. In the ventral corticostriatal system, positive and negative PLEs were both associated with FC between the ventro-rostral putamen and sensorimotor cortices. Consistent with past findings in patients and high-risk in iduals, subthreshold positive symptomatology is associated with reduced FC of the dorsal circuit. These findings suggest that the connectivity of this circuit tracks the expression of psychotic phenomena across a broad spectrum of severity, extending from the subclinical domain to clinical diagnosis.
UN Decade on Ecosystem Restoration 2021–2030—What Chance for Success in Restoring Coastal Ecosystems?
Publisher: Frontiers Media SA
Date: 20-02-2020
Addressing Challenges in the Application of Animal Movement Ecology to Aquatic Conservation and Management
Publisher: Frontiers Media SA
Date: 16-03-2017
Effects of cigarette smoking on cortical thickness in major depressive disorder
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.JPSYCHIRES.2016.09.009
Abstract: Findings of surface-based morphometry studies in major depressive disorder (MDD) are still inconsistent. Given that cigarette smoking is highly prevalent in MDD and has documented negative effects on the brain, it is possible that some of the inconsistencies may be partly explained by cigarette use. The aim of the current study was to examine the influence of cigarette smoking on brain structure in MDD. 50 MDD patients (25 smokers and 25 non-smokers) and 22 age, education, gender and BMI matched non-smoker healthy controls underwent structural magnetic resonance imaging. Thickness and area of the cortex were measured using surface-based morphometry implemented with Freesurfer (v5.3.0). The non-smoker MDD patients had significantly increased cortical thickness, including in the left temporal cortex (p < 0.001), right insular cortex (p = 0.033) and left pre- and postcentral gyrus (p = 0.045), compared to healthy controls. We also found decreased cortical thickness in MDD patients who smoked compared to non-smoking patients in regions that overlapped with the regions found to be increased in non-smoking patients in comparison to controls. Non-smoker MDD patients had increased surface area in the right lateral occipital cortex (p = 0.009). We did not find any region where cortical thickness or surface area significantly differed between controls and either smoker MDD patients or all MDD patients. The findings of the current study suggest that cigarette smoking is associated with cortical thinning in regions found to be increased in patients with MDD. However, these results should be considered preliminary due to methodological limitations.
Caspase-2 protects against oxidative stress in vivo
Publisher: Springer Science and Business Media LLC
Date: 22-12-2014
DOI: 10.1038/ONC.2014.413
Abstract: Caspase-2 belongs to the caspase family of cysteine proteases with established roles in apoptosis. Recently, caspase-2 has been implicated in nonapoptotic functions including maintenance of genomic stability and tumor suppression. Our previous studies demonstrated that caspase-2 also regulates cellular redox status and delays the onset of several ageing-related traits. In the current study, we tested stress tolerance ability in caspase-2-deficient (Casp2(-/-)) mice by challenging both young and old mice with a low dose of the potent reactive oxygen species (ROS) generator, PQ that primarily affects lungs. In both groups of mice, PQ induced pulmonary damage. However, the lesions in caspase-2 knockout mice were consistently and reproducibly more severe than those in wild-type (WT) mice. Furthermore, serum interleukin (IL)-1β and IL-6 levels were higher in PQ-exposed aged Casp2(-/-) mice indicating increased inflammation. Interestingly, livers from Casp2(-/-) mice displayed karyomegaly, a feature commonly associated with ageing and aneuploidy. Given that Casp2(-/-) mice show impaired antioxidant defense, we tested oxidative damage in these mice. Protein oxidation significantly increased in PQ-injected old Casp2(-/-) mice. Moreover, FoxO1, SOD2 and Nrf2 expression levels were reduced and induction of superoxide dismutase (SOD) and glutathione peroxidase activity was not observed in PQ-treated Casp2(-/-) mice. Strong c-Jun amino-terminal kinase (JNK) activation was observed in Casp2(-/-) mice, indicative of increased stress. Together, our data strongly suggest that caspase-2 deficiency leads to increased cellular stress largely because these mice fail to respond to oxidative stress by upregulating their antioxidant defense mechanism. This makes the mice more vulnerable to exogenous challenges and may partly explain the shorter lifespan of Casp2(-/-) mice.
Effects of 2G and 3G mobile phones on performance and electrophysiology in adolescents, young adults and older adults
Publisher: Elsevier BV
Date: 11-2011
DOI: 10.1016/J.CLINPH.2011.04.006
Abstract: This study examined sensory and cognitive processing in adolescents, young adults and older adults, when exposed to 2nd (2G) and 3rd (3G) generation mobile phone signals. Tests employed were the auditory 3-stimulus oddball and the N-back. Forty-one 13-15 year olds, forty-two 19-40 year olds and twenty 55-70 year olds were tested using a double-blind cross-over design, where each participant received Sham, 2G and 3G exposures, separated by at least 4 days. 3-Stimulus oddball task: Behavioural: accuracy and reaction time of responses to targets were not affected by exposure. Electrophysiological: augmented N1 was found in the 2G condition (independent of age group). N-back task: Behavioural: the combined groups performed less accurately during the 3G exposure (compared to Sham), with post hoc tests finding this effect separately in the adolescents only. Electrophysiological: delayed ERD/ERS responses of the alpha power were found in both 3G and 2G conditions (compared to Sham independent of age group). Employing tasks tailored to each in idual's ability level, this study provides support for an effect of acute 2G and 3G exposure on human cognitive function. The subtlety of mobile phone effect on cognition in our study suggests that it is important to account for in idual differences in future mobile phone research.
Associations Between Neighborhood Disadvantage, Resting-State Functional Connectivity, and Behavior in the Adolescent Brain Cognitive Development Study: The Moderating Role of Positive Family and School Environments.
Publisher: Elsevier BV
Date: 09-2021
Synthesis and Evaluation in Monkey of Two Sensitive 11C-Labeled Aryloxyanilide Ligands for Imaging Brain Peripheral Benzodiazepine Receptors In Vivo
Publisher: American Chemical Society (ACS)
Date: 08-12-2007
DOI: 10.1021/JM0707370
Abstract: We sought to develop (11)C-labeled ligands for sensitive imaging of brain peripheral benzodiazepine receptors (PBR) in vivo. Two aryloxyanilides with high affinity for PBR were identified and synthesized, namely, N-acetyl- N-(2-methoxycarbonylbenzyl)-2-phenoxyaniline ( 3, PBR01) and N-(2-methoxybenzyl)- N-(4-phenoxypyridin-3-yl)acetamide ( 10, PBR28). 3 was hydrolyzed to 4, which was esterified with [ (11)C]iodomethane to provide [ (11)C] 3. The O-desmethyl analogue of 10 was converted into [ (11)C] 10 with [ (11)C]iodomethane. [ (11)C] 3 and [ (11)C] 10 were each injected into monkey to assess their brain kinetics with positron emission tomography (PET). After administration of either radioligand there was moderately high brain uptake of radioactivity. Receptor blocking and displacement experiments showed that a high proportion of this radioactivity was bound specifically to PBR. In monkey and rat, 3 and 10 were rapidly metabolized by ester hydrolysis and N-debenzylation, respectively, each to a single polar radiometabolite. [ (11)C] 3 and [ (11)C] 10 are effective for imaging PBR in monkey brain. [ (11)C] 10 especially warrants further evaluation in human subjects.
Downregulation of plasma SELENBP1 protein in patients with recent-onset schizophrenia
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.PNPBP.2018.03.010
Abstract: Upregulation of selenium binding protein 1 (SELENBP1) mRNA expression has been reported in schizophrenia, primarily in the dorsolateral prefrontal cortex. However, peripheral blood studies are limited and results are inconsistent. In this study, we examined SELENBP1 mRNA expression in whole blood and protein expression in plasma from patients with recent-onset schizophrenia (n = 30), treatment-resistant schizophrenia (n = 71) and healthy controls (n = 57). We also examined the effects of SELENBP1 genetic variation on gene and protein expression. We found lower SELENBP1 plasma protein levels in patients with recent-onset schizophrenia (p = 0.042) but not in treatment-resistant schizophrenia (p = 0.81). Measurement of peripheral mRNA levels showed no difference between treatment-resistant schizophrenia and healthy controls (p = 0.234) but clozapine plasma levels (p = 0.036) and duration of illness (p = 0.028) were positively correlated with mRNA levels. Genetic variation was not associated with mRNA or protein expression. Our data represent the first peripheral proteomic study of SELENBP1 in schizophrenia and suggest that plasma SELENBP1 protein is downregulated in patients with recent-onset schizophrenia.
Differential involvement of hippocampal subfields in Niemann-Pick type C disease: a case–control study
Publisher: Springer Science and Business Media LLC
Date: 19-06-2021
DOI: 10.1007/S11011-021-00782-9
Abstract: Hippoc al brain regions are strongly implicated in Niemann Pick type C disease (NPC), but little is known regarding distinct subregions of the hippoc al complex and whether these are equally or differentially affected. To address this gap, we compared volumes of five hippoc al subfields between NPC and healthy in iduals using MRI. To this end, 9 adult-onset NPC cases and 9 age- and gender-matched controls underwent a 3 T T1-weighted MRI scan. Gray matter volumes of the cornu ammonis (CA1, CA2 and CA3), dentate gyrus (DG), subiculum, entorhinal cortex and hippoc al-amygdalar transition area were calculated by integrating MRI-based image intensities with microscopically defined cytoarchitectonic probabilities. Compared to healthy controls, NPC patients showed smaller volumes of the CA1-3 and DG regions bilaterally, with the greatest difference localized to the left DG (Cohen's d = 1.993, p = 0.008). No significant associations were shown between hippoc al subfield volumes and key clinical features of NPC, including disease duration, symptom severity and psychosis. The pattern of hippoc al subregional atrophy in NPC differs from those seen in other dementias, which may indicate unique cytoarchitectural vulnerabilities in this earlier-onset disorder. Future MRI studies of hippoc al subfields may clarify its potential as a biomarker of neurodegeneration in NPC.
Widespread Volumetric Reductions in Schizophrenia and Schizoaffective Patients Displaying Compromised Cognitive Abilities
Publisher: Oxford University Press (OUP)
Date: 21-08-2017
Association of Structural Magnetic Resonance Imaging Measures With Psychosis Onset in Individuals at Clinical High Risk for Developing Psychosis
Publisher: American Medical Association (AMA)
Date: 07-2021
In Vivo 7-Tesla MRI Investigation of Brain Iron and Its Metabolic Correlates in Chronic Schizophrenia
Publisher: Springer Science and Business Media LLC
Date: 26-10-2022
DOI: 10.1038/S41537-022-00293-1
Abstract: Brain iron is central to dopaminergic neurotransmission, a key component in schizophrenia pathology. Iron can also generate oxidative stress, which is one proposed mechanism for gray matter volume reduction in schizophrenia. The role of brain iron in schizophrenia and its potential link to oxidative stress has not been previously examined. In this study, we used 7-Tesla MRI quantitative susceptibility mapping (QSM), magnetic resonance spectroscopy (MRS), and structural T 1 imaging in 12 in iduals with chronic schizophrenia and 14 healthy age-matched controls. In schizophrenia, there were higher QSM values in bilateral putamen and higher concentrations of phosphocreatine and lactate in caudal anterior cingulate cortex (caCC). Network-based correlation analysis of QSM across corticostriatal pathways as well as the correlation between QSM, MRS, and volume, showed distinct patterns between groups. This study introduces increased iron in the putamen in schizophrenia in addition to network-wide disturbances of iron and metabolic status.
Systematic Review: Quantitative Susceptibility Mapping (QSM) of Brain Iron Profile in Neurodegenerative Diseases
Publisher: Frontiers Media SA
Date: 18-02-2021
DOI: 10.3389/FNINS.2021.618435
Abstract: Iron has been increasingly implicated in the pathology of neurodegenerative diseases. In the past decade, development of the new magnetic resonance imaging technique, quantitative susceptibility mapping (QSM), has enabled for the more comprehensive investigation of iron distribution in the brain. The aim of this systematic review was to provide a synthesis of the findings from existing QSM studies in neurodegenerative diseases. We identified 80 records by searching MEDLINE, Embase, Scopus, and PsycInfo databases. The disorders investigated in these studies included Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Wilson's disease, Huntington's disease, Friedreich's ataxia, spinocerebellar ataxia, Fabry disease, myotonic dystrophy, pantothenate-kinase-associated neurodegeneration, and mitochondrial membrane protein-associated neurodegeneration. As a general pattern, QSM revealed increased magnetic susceptibility (suggestive of increased iron content) in the brain regions associated with the pathology of each disorder, such as the amygdala and caudate nucleus in Alzheimer's disease, the substantia nigra in Parkinson's disease, motor cortex in amyotrophic lateral sclerosis, basal ganglia in Huntington's disease, and cerebellar dentate nucleus in Friedreich's ataxia. Furthermore, the increased magnetic susceptibility correlated with disease duration and severity of clinical features in some disorders. Although the number of studies is still limited in most of the neurodegenerative diseases, the existing evidence suggests that QSM can be a promising tool in the investigation of neurodegeneration.
Using longitudinal imaging to map the ‘relapse signature’ of schizophrenia and other psychoses
Publisher: Cambridge University Press (CUP)
Date: 22-05-2014
DOI: 10.1017/S2045796014000341
Abstract: Brain imaging studies in schizophrenia have typically involved single assessment and cross-sectional designs, while longitudinal studies rarely incorporate more than two time points. While informative, these studies do not adequately capture potential trajectories of neurobiological change, particularly in the context of a changing clinical picture. We propose that the analysis of brain trajectories using multiple time points may inform our understanding of the illness and the effect of treatment. This paper makes the case for frequent serial neuroimaging across the course of schizophrenia psychoses and its application to active illness epsiodes to provide a detailed examination of psychosis relapse and remission.
Neighborhood disadvantage and longitudinal brain-predicted-age trajectory during adolescence
Publisher: Elsevier BV
Date: 10-2021
Imaging of neuroinflammation in adult Niemann-Pick type C disease
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 24-03-2020
DOI: 10.1212/WNL.0000000000009287
Abstract: To test the hypothesis that neuroinflammation is a key process in adult Niemann-Pick type C (NPC) disease, we undertook PET scanning utilizing a ligand binding activated microglia on 9 patients and 9 age- and sex-matched controls. We scanned all participants with the PET radioligand 11 C-(R)-PK-11195 and undertook structural MRI to measure gray matter volume and white matter fractional anisotropy (FA). We found increased binding of 11 C-(R)-PK-11195 in total white matter compared to controls ( p 0.01), but not in gray matter regions, and this did not correlate with illness severity or duration. Gray matter was reduced in the thalamus ( p 0.0001) in patients, who also showed widespread reductions in FA across the brain compared to controls ( p 0.001). A significant correlation between 11 C-(R)-PK11195 binding and FA was shown ( p = 0.002), driven by the NPC patient group. Our findings suggest that neuroinflammation—particularly in white matter—may underpin some structural and degenerative changes in patients with NPC.
Brain-Predicted Age Associates With Psychopathology Dimensions in Youths
Publisher: Elsevier BV
Date: 04-2021
Predicting individual improvement in schizophrenia symptom severity at 1-year follow-up: Comparison of connectomic, structural, and clinical predictors
Publisher: Wiley
Date: 29-05-2020
DOI: 10.1002/HBM.25020
Microglial activation and progressive brain changes in schizophrenia
Publisher: Wiley
Date: 08-01-2016
DOI: 10.1111/BPH.13364
The impact of premorbid and current intellect in schizophrenia
Publisher: Springer Science and Business Media LLC
Date: 04-11-2015
Abstract: Cognitive heterogeneity among people with schizophrenia has been defined on the basis of premorbid and current intelligence quotient (IQ) estimates. In a relatively large, community cohort, we aimed to independently replicate and extend cognitive subtyping work by determining the extent of symptom severity and functional deficits in each group. A total of 635 healthy controls and 534 patients with a diagnosis of schizophrenia or schizoaffective disorder were recruited through the Australian Schizophrenia Research Bank. Patients were classified into cognitive subgroups on the basis of the Wechsler Test of Adult Reading (a premorbid IQ estimate) and current overall cognitive abilities into preserved, deteriorated, and compromised groups using both clinical and empirical ( k -means clustering) methods. Additional cognitive, functional, and symptom outcomes were compared among the resulting groups. A total of 157 patients (29%) classified as ‘preserved’ performed within one s.d. of control means in all cognitive domains. Patients classified as ‘deteriorated’ ( n =239, 44%) performed more than one s.d. below control means in all cognitive domains except estimated premorbid IQ and current visuospatial abilities. A separate 138 patients (26%), classified as ‘compromised,’ performed more than one s.d. below control means in all cognitive domains and displayed greater impairment than other groups on symptom and functional measures. In the present study, we independently replicated our previous cognitive classifications of people with schizophrenia. In addition, we extended previous work by demonstrating worse functional outcomes and symptom severity in the compromised group.
Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group
Publisher: Springer Science and Business Media LLC
Date: 17-10-2017
DOI: 10.1038/MP.2017.170
Neuroanatomical Predictors of Functional Outcome in Individuals at Ultra-High Risk for Psychosis
Publisher: Oxford University Press (OUP)
Date: 07-2017
Complement proteins are elevated in blood serum but not CSF in clinical high-risk and antipsychotic-naïve first-episode psychosis
Publisher: Elsevier BV
Date: 10-2023
The Impact of Childhood Adversity on Cognitive Development in Schizophrenia
Publisher: Oxford University Press (OUP)
Date: 03-05-2020
Abstract: Childhood adversity, such as physical, sexual, and verbal abuse, as well as neglect and family conflict, is a risk factor for schizophrenia. Such adversity can lead to disruptions of cognitive function during development, undermining intellectual capabilities and academic achievement. Schizophrenia is a neurodevelopmental disorder that is associated with cognitive impairments that may become evident during childhood. The Australian Schizophrenia Research Bank database comprises a large community cohort (N = 1169) in which we previously identified 3 distinct cognitive groups among people with schizophrenia: (1) Compromised, current, and estimated premorbid cognitive impairment (2) Deteriorated, substantial decline from estimated premorbid function and (3) Preserved, performing in the normal cognitive range without decline. The compromised group displayed the worst functional and symptom outcomes. Here, we extend our previous work by assessing the relationship among these categories of cognitive abilities and reported childhood adversity in 836 patients and healthy controls. Exploratory factor analysis of the Childhood Adversity Questionnaire revealed 3 factors (lack of parental involvement overt abuse family breakdown and hardship). People with schizophrenia reported significantly more childhood adversity than healthy controls on all items and factors. People with schizophrenia in the compromised group reported significantly more lack of parental involvement and family breakdown and hardship and lower socioeconomic status than those in the deteriorated group. The cognitive groups were not related to family history of psychosis. These findings identify specific social and family factors that impact cognition, highlighting the important role of these factors in the development of cognitive and functional abilities in schizophrenia.
A randomized controlled trial investigating the effect of Pycnogenol and Bacopa CDRI08 herbal medicines on cognitive, cardiovascular, and biochemical functioning in cognitively healthy elderly people: The Australian Research Council Longevity Intervention (ARCLI) study protocol (ANZCTR12611000487910)
Publisher: Springer Science and Business Media LLC
Date: 06-03-2012
Delayed Development of Brain Connectivity in Adolescents With Schizophrenia and Their Unaffected Siblings
Publisher: American Medical Association (AMA)
Date: 09-2015
DOI: 10.1001/JAMAPSYCHIATRY.2015.0226
Abstract: Abnormalities in structural brain connectivity have been observed in patients with schizophrenia. Mapping these abnormalities longitudinally and understanding their genetic risk via sibship studies will provide crucial insight into progressive developmental changes associated with schizophrenia. To identify corticocortical connections exhibiting an altered developmental trajectory in adolescents with childhood-onset schizophrenia (COS) and to determine whether similar alterations are found in patients' unaffected siblings. Using prospective structural brain magnetic resonance imaging, large-scale corticocortical connectivity was mapped from ages 12 to 24 years in 109 patients with COS (272 images), 86 of their unaffected siblings (184 images), and 102 healthy controls (262 images) over a 20-year period beginning January 1, 1991, through April 30, 2011, as part of the ongoing COS study at the National Institute of Mental Health. Structural connectivity between pairs of cortical regions was estimated using a validated technique based on across-subject covariation in magnetic resonance imaging-derived cortical thickness measurements. Compared with normally developing controls, significant left-hemisphere occipitotemporal deficits in cortical thickness correlations were found in patients with COS as well as their healthy siblings (P < .05). Deficits in siblings normalized by mid-adolescence, whereas patients with COS showed significantly longer maturational delays, with cortical thickness correlations between the left temporal lobe and left occipital cortex not showing evidence of development until early adulthood. The normalization of deficits with age in patients with COS correlated with improvement in symptoms. Compared with controls, left-hemisphere occipitotemporal thickness correlations in a subgroup of patients with high positive symptoms were significantly reduced from age 14 to 18 years (P < .05) however, other patients with low positive symptoms showed no significant deficits. Delayed maturation of occipitotemporal connectivity appears to be a trait marker in patients with COS, with a milder endophenotype in unaffected siblings associated with resilience to developing schizophrenia. These findings indicate genetically influenced and connection-specific developmental abnormalities in the schizophrenia connectome, and lead to the hypothesis that visual hallucinations in patients with COS may be because of delayed development of the inferior longitudinal fasciculus, a prominent occipitotemporal fiber.
Individual deviations from normative models of brain structure in a large cross-sectional schizophrenia cohort
Publisher: Springer Science and Business Media LLC
Date: 22-09-2021
Valuation system connectivity is correlated with poly-drug use in young adults
Publisher: Elsevier BV
Date: 12-2021
DOI: 10.1016/J.NEURES.2021.06.006
Abstract: Poly-drug consumption contributes to fatal overdose in more than half of all poly-drug users. Analyzing decision-making networks may give insight into the motivations behind poly-drug use. We correlated average functional connectivity of the valuation system (VS), executive control system (ECS) and valuation-control complex (VCC) in a large population s le (n = 992) with drug use behaviour. VS connectivity is correlated with sedative use, ECS connectivity is separately correlated with hallucinogens and opiates. Network connectivity is also correlated with drug use via two-way interactions with other substances including alcohol and tobacco. These preliminary findings can contribute to our understanding of the common combinations of substance co-use and associated neural patterns.
Elevated ubiquitinated proteins in brain and blood of individuals with schizophrenia
Publisher: Springer Science and Business Media LLC
Date: 19-02-2019
DOI: 10.1038/S41598-019-38490-1
Abstract: Dysregulation of the ubiquitin proteasome system (UPS) has been linked to schizophrenia but it is not clear if this dysregulation is detectable in both brain and blood. We examined free mono-ubiquitin, ubiquitinated proteins, catalytic ubiquitination, and proteasome activities in frozen postmortem OFC tissue from 76 (38 schizophrenia, 38 control) matched in iduals, as well as erythrocytes from 181 living participants, who comprised 30 in iduals with recent onset schizophrenia (mean illness duration = 1 year), 63 in iduals with ‘treatment-resistant’ schizophrenia (mean illness duration = 17 years), and 88 age-matched participants without major psychiatric illness. Ubiquitinated protein levels were elevated in postmortem OFC in schizophrenia compared to controls (p = .001, AUC = 74.2%). Similarly, in iduals with ‘treatment-resistant’ schizophrenia had higher levels of ubiquitinated proteins in erythrocytes compared to those with recent onset schizophrenia (p 0.001, AUC = 65.5%) and controls (p 0.001, AUC = 69.4%). The results could not be better explained by changes in proteasome activity, demographic, medication, or tissue factors. Our results suggest that ubiquitinated protein formation may be abnormal in both the brain and erythrocytes of those with schizophrenia, particularly in the later stages or specific sub-groups of the illness. A derangement in protein ubiquitination may be linked to pathogenesis or neurotoxicity in schizophrenia, and its manifestation in the blood may have prognostic utility.
Exploring the moderating effects of dopaminergic polymorphisms and childhood adversity on brain morphology in schizophrenia-spectrum disorders
Publisher: Elsevier BV
Date: 11-2018
Quantification of brain phosphodiesterase 4 in rat with (R)-[11C]Rolipram-PET
Publisher: Elsevier BV
Date: 07-2005
DOI: 10.1016/J.NEUROIMAGE.2005.03.017
Abstract: Phosphodiesterase 4 (PDE4) catabolizes the second messenger 3', 5'-cyclic adenosine monophosphate and may play a critical role in brain diseases. Our aim was to quantify PDE4 in rats with positron emission tomography (PET). High (n = 6) and low specific activity (SA) (n = 2) higher affinity ((R)-[(11)C]rolipram) and high SA lower affinity ((S)-[(11)C]rolipram) (n = 2) enantiomers were intravenously administered to Sprague-Dawley rats. Brain data were acquired using the ATLAS PET scanner and reconstructed using the 3D-ordered subset expectation maximization algorithm. Arterial s les were taken to measure unmetabolized [(11)C]rolipram. Total distribution volumes (V(T)') were calculated using a 1-tissue compartment (1C) and an unconstrained 2-tissue compartment (2C) model. High SA R experiments showed later and greater brain uptake, and slower washout than low SA R and S experiments. In all regions and in all experiments, the 2C model gave significantly better fitting than the 1C model. The poor fitting by the latter caused underestimation of V(T)' by 19-31%. The 2C model identified V(T)' reasonably well with coefficients of variation less than 10%. V(T)' values by this model were 16.4-29.2 mL/cm(3) in high SA R, 2.9-3.5 in low SA R, and 3.1-3.7 in S experiments. Specific binding of (R)-[(11)C]rolipram was accurately measured in living rats. In high SA R experiments, approximately 86% of V(T)' was specific binding. Distribution and changes of PDE4 in animal models can now be studied by measuring V(T)' of high SA (R)-[(11)C]rolipram.
Functional Connectivity of Corticostriatal Circuitry and Psychosis-like Experiences in the General Community
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.BIOPSYCH.2019.02.013
Abstract: Psychotic symptoms are proposed to lie on a continuum, ranging from isolated psychosis-like experiences (PLEs) in nonclinical populations to frank disorder. Here, we investigated the neurobiological correlates of this continuum by examining whether functional connectivity of dorsal corticostriatal circuitry, which is disrupted in psychosis patients and in iduals at high risk for psychosis, is associated with the severity of subclinical PLEs. A community s le of 672 adults with no history of psychiatric or neurological illnesses completed a battery of seven questionnaires spanning various PLE domains. Principal component analysis of 12 subscales taken from seven questionnaires was used to estimate major dimensions of PLEs. Dimension scores from principal component analysis were then correlated with whole-brain voxelwise functional connectivity maps of the dorsal striatum in a subset of 353 participants who completed a resting-state neuroimaging protocol. Principal component analysis identified two dimensions of PLEs that accounted for 62.57% of variance in the measures, corresponding to positive (i.e., subthreshold delusions and hallucinations) and negative (i.e., subthreshold social and physical anhedonia) symptom-like PLEs. Reduced functional connectivity between the dorsal striatum and prefrontal and motor cortices correlated with more severe positive PLEs. Increased functional connectivity between the dorsal striatum and motor cortex was associated with more severe negative PLEs. Consistent with past findings in patients and in iduals at high risk for psychosis, subthreshold positive symptomatology is associated with reduced functional connectivity of the dorsal circuit. This finding suggests that the connectivity of this circuit tracks the expression of psychotic phenomena across a broad spectrum of severity, extending from the subclinical domain to clinical diagnosis.
Reliability and Predictive Validity of a Consensus-Based Risk Assessment Tool
Publisher: Informa UK Limited
Date: 05-09-2008
Brain charts for the human lifespan
Publisher: Cold Spring Harbor Laboratory
Date: 10-06-2021
DOI: 10.1101/2021.06.08.447489
Abstract: Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify in idual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight 1 . Here, we built an interactive resource to benchmark brain morphology, www.brainchart.io , derived from any current or future s le of magnetic resonance imaging (MRI) data. With the goal of basing these reference charts on the largest and most inclusive dataset available, we aggregated 123,984 MRI scans from 101,457 participants aged from 115 days post-conception through 100 postnatal years, across more than 100 primary research studies. Cerebrum tissue volumes and other global or regional MRI metrics were quantified by centile scores, relative to non-linear trajectories 2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones 3 showed high stability of in idual centile scores over longitudinal assessments and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared to non-centiled MRI phenotypes, and provided a standardised measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In sum, brain charts are an essential first step towards robust quantification of in idual deviations from normative trajectories in multiple, commonly-used neuroimaging phenotypes. Our collaborative study proves the principle that brain charts are achievable on a global scale over the entire lifespan, and applicable to analysis of erse developmental and clinical effects on human brain structure. Furthermore, we provide open resources to support future advances towards adoption of brain charts as standards for quantitative benchmarking of typical or atypical brain MRI scans.
Disruptions in white matter microstructure associated with impaired visual associative memory in schizophrenia-spectrum illness
Publisher: Springer Science and Business Media LLC
Date: 24-09-2021
DOI: 10.1007/S00406-021-01333-0
Abstract: Episodic memory ability relies on hippoc al-prefrontal connectivity. However, few studies have examined relationships between memory performance and white matter (WM) microstructure in hippoc al-prefrontal pathways in schizophrenia-spectrum disorder (SSDs). Here, we investigated these relationships in in iduals with first-episode psychosis (FEP) and chronic schizophrenia-spectrum disorders (SSDs) using tractography analysis designed to interrogate the microstructure of WM tracts in the hippoc al-prefrontal pathway. Measures of WM microstructure (fractional anisotropy [FA], radial diffusivity [RD], and axial diffusivity [AD]) were obtained for 47 in iduals with chronic SSDs, 28 FEP in iduals, 52 older healthy controls, and 27 younger healthy controls. Tractography analysis was performed between the hippoc us and three targets involved in hippoc al-prefrontal connectivity (thalamus, amygdala, nucleus accumbens). Measures of WM microstructure were then examined in relation to episodic memory performance separately across each group. Both those with FEP and chronic SSDs demonstrated impaired episodic memory performance. However, abnormal WM microstructure was only observed in in iduals with chronic SSDs. Abnormal WM microstructure in the hippoc al-thalamic pathway in the right hemisphere was associated with poorer memory performance in in iduals with chronic SSDs. These findings suggest that disruptions in WM microstructure in the hippoc al-prefrontal pathway may contribute to memory impairments in in iduals with chronic SSDs but not FEP.
Systematic review protocol: Quantitative susceptibility mapping of brain iron accumulation in neurodegenerative diseases
Publisher: Cold Spring Harbor Laboratory
Date: 19-02-2020
DOI: 10.1101/2020.02.18.20022608
Abstract: Iron has been found to play an important role in neurodegeneration. Quantitative susceptibility mapping (QSM) is a relatively new – and the most accurate - MRI technique available for assessment of iron deposition in the brain. There is a rapidly growing number of studies using QSM to investigate brain iron distribution in neurodegenerative diseases including but not limited to Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis, Huntington disease and Wilson’s disease. These studies have shown increased iron deposition in the brain regions that are associated with the pathology of the disease. Additionally, QSM is found to be accurate in differential diagnosis of neurodegenerative diseases where clinical presentations are indistinguishable. Structural changes evidenced by QSM are reported to precede the onset of clinical manifestation of neurodegenerative diseases suggesting its benefit in early diagnosis. To our knowledge, no systematic review of QSM findings in neurodegenerative diseases has been published before. A systematic synthesis and conclusion of the existing evidence can improve our understanding of the pathophysiology of neurodegeneration, describe the clinical and research utility of QSM, and point out the direction for future studies in neuropsychiatric disorders. This document is a systematic review protocol developed in accordance with Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) guideline. This protocol is prepared as a guide for conducting a systematic review of studies investigating brain iron and microstructural changes in neurodegenerative diseases using quantitative susceptibility mapping (QSM). This protocol has also been submitted to Prospective Register of Systematic Reviews (PROSPERO) for registration. By publishing this protocol, we aim to enhance clarity and transparency of our systematic review and minimise the risk of bias in the process of its development.
Brain-predicted age associates with psychopathology dimensions in youth
Publisher: Cold Spring Harbor Laboratory
Date: 14-06-2020
DOI: 10.1101/2020.06.13.149658
Abstract: This study aims to investigate whether dimensional constructs of psychopathology relate to advanced, attenuated or normal patterns of brain development, and to determine whether these constructs share common neurodevelopmental profiles. Psychiatric symptom ratings from 9312 youths (8-21 years) were parsed into 7 independent dimensions of clinical psychopathology representing conduct, anxiety, obsessive-compulsive, attention, depression, bipolar, and psychosis symptoms. Using a subset of this cohort with structural MRI ( n =1313), a normative model of brain morphology was established and the model was then applied to predict the age of youth with clinical symptoms. We investigated whether the deviation of brain-predicted age from true chronological age, called the brain age gap, explained in idual variation in each psychopathology dimension. In idual variation in the brain age gap significantly associated with clinical dimensions representing psychosis ( t =3.16, p =0.0016), obsessive-compulsive symptoms ( t =2.5, p =0.01), and general psychopathology ( t =4.08, p .0001). Greater symptom severity along these dimensions was associated with brain morphology that appeared older than expected for typically developing youth of the same age. Psychopathology dimensions clustered into two modules based on shared brain loci where putative accelerated neurodevelopment was most prominent. Patterns of morphological development were accelerated in frontal cortices for depression, psychosis and conduct symptoms (Module I), whereas acceleration was most evident in subcortex and insula for the remaining dimensions (Module II). Our findings suggest that advanced brain development, particularly in frontal cortex and subcortical nuclei, underpins clinical psychosis and obsessive-compulsive symptoms in youth. Psychopathology dimensions share common neural substrates, despite representing clinically independent symptom profiles.
Investigation of structural brain correlates of neurological soft signs in individuals at ultra-high risk for psychosis
Publisher: Springer Science and Business Media LLC
Date: 31-08-2021
DOI: 10.1007/S00406-021-01300-9
Abstract: Increased severity of neurological soft signs (NSS) in schizophrenia have been associated with abnormal brain morphology in cerebello-thalamo-cortical structures, but it is unclear whether similar structures underlie NSS prior to the onset of psychosis. The present study investigated the relationship between severity of NSS and grey matter volume (GMV) in in iduals at ultra-high risk for psychosis (UHR) stratified for later conversion to psychosis. Structural T1-weighted MRI scans were obtained from 56 antipsychotic-naïve UHR in iduals and 35 healthy controls (HC). The UHR in iduals had follow-up data (mean follow-up: 5.2 years) to ascertain clinical outcome. Using whole-brain voxel-based morphometry, the relationship between NSS and GMV at baseline was assessed in UHR, HC, as well as in iduals who later transitioned (UHR-P, n = 25) and did not transition (UHR-NP, n = 31) to psychosis. NSS total and subscale scores except motor coordination were significantly higher in UHR compared to HC. Higher signs were also found in UHR-P, but not UHR-NP. Total NSS was not associated with GMV in the whole s le or in each group. However, in UHR-P in iduals, greater deficits in sensory integration was associated with lower GMV in the left cerebellum, right insula, and right middle frontal gyrus. In conclusion, NSS are present in UHR in iduals, particularly those who later transitioned to a psychotic disorder. While these signs show little overall variation with GMV, the association of sensory integration deficits with lower GMV in UHR-P suggests that certain brain areas may be implicated in the development of specific neurological abnormalities in the psychosis prodrome.
The effects of a muscarinic receptor 1 gene variant on cortical thickness and surface area in schizophrenia.
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.PSCYCHRESNS.2018.08.014
Abstract: In iduals with schizophrenia who are homozygous at the c.267C>A single nucleotide polymorphism (rs2067477) within the cholinergic muscarinic M1 receptor gene have been reported to perform less well on the Wisconsin Card Sorting Test and demonstrate reduced grey matter volume in the right precentral gyrus. We investigated if rs2067477 genotype variation influenced cortical thickness and cortical surface area in a s le of 176 schizophrenia/schizoaffective disorder patients using FreeSurfer. We were unable to detect any significant changes to either surface-based measure of brain structure across genotype. Future studies should expand the focus and include SNPs that are in linkage disequilibrium with rs2067477.
Characterization of facial emotion recognition in bipolar disorder: Focus on emotion mislabelling and neutral expressions
Publisher: Wiley
Date: 11-11-2021
DOI: 10.1111/JNP.12267
Abstract: Increasing evidence suggests that facial emotion recognition is impaired in bipolar disorder (BD). However, patient–control differences are small owing to ceiling effects on the tasks used to assess them. The extant literature is also limited by a relative absence of attention towards identifying patterns of emotion misattribution or understanding whether neutral faces are mislabelled in the same way as ones displaying emotion. We addressed these limitations by comparing facial emotion recognition performance in BD patients and healthy controls on a novel and challenging task. Thirty‐four outpatients with BD I and 32 demographically matched healthy controls completed a facial emotion recognition task requiring the labelling of neutral and emotive faces displayed at low emotional intensities. Results indicated that BD patients were significantly less accurate at labelling faces than healthy controls, particularly if they displayed fear or neutral expressions. There were no between‐group differences in response times or patterns of emotion mislabelling, with both groups confusing sad and neutral faces, although BD patients also mislabelled sad faces as angry. Task performance did not significantly correlate with mood symptom severity in the BD group. These findings suggest that facial emotion recognition impairments in BD extend to neutral face recognition. Emotion misattribution occurs in a similar, albeit exaggerated manner in patients with BD compared to healthy controls. Future behavioural and neuroimaging research should reconsider the use of neutral faces as baseline stimuli in their task designs.
Structural neuroimaging across early-stage psychosis: Aberrations in neurobiological trajectories and implications for the staging model
Publisher: SAGE Publications
Date: 12-10-2017
Abstract: This review critically examines the structural neuroimaging evidence in psychotic illness, with a focus on longitudinal imaging across the first-episode psychosis and ultra-high-risk of psychosis illness stages. A thorough search of the literature involving specifically longitudinal neuroimaging in early illness stages of psychosis was conducted. The evidence supporting abnormalities in brain morphology and altered neurodevelopmental trajectories is discussed in the context of a clinical staging model. In general, grey matter (and, to a lesser extent, white matter) declines across multiple frontal, temporal (especially superior regions), insular and parietal regions during the first episode of psychosis, which has a steeper trajectory than that of age-matched healthy counterparts. Although the ultra-high-risk of psychosis literature is considerably mixed, evidence indicates that certain volumetric structural aberrations predate psychotic illness onset (e.g. prefrontal cortex thinning), while other abnormalities present in ultra-high-risk of psychosis populations are potentially non-psychosis-specific (e.g. hippoc al volume reductions). We highlight the advantages of longitudinal designs, discuss the implications such studies have on clinical staging and provide directions for future research.
Access to new cancer medicines in Australia
Publisher: Springer Science and Business Media LLC
Date: 07-04-2016
Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium
Publisher: Elsevier BV
Date: 11-2018
Impaired olfactory ability associated with larger left hippocampus and rectus volumes at earliest stages of schizophrenia: A sign of neuroinflammation?
Publisher: Elsevier BV
Date: 07-2020
Gradients of striatal function in antipsychotic-free first-episode psychosis and schizotypy.
Publisher: Springer Science and Business Media LLC
Date: 18-04-2023
DOI: 10.1038/S41398-023-02417-2
Abstract: Both psychotic illness and subclinical psychosis-like experiences (PLEs) have been associated with cortico-striatal dysfunction. This work has largely relied on a discrete parcellation of the striatum into distinct functional areas, but recent evidence suggests that the striatum comprises multiple overlapping and smoothly varying gradients (i.e., modes) of functional organization. Here, we investigated two of these functional connectivity modes, previously associated with variations in the topographic patterning of cortico-striatal connectivity (first-order gradient), and dopaminergic innervation of the striatum (second-order gradient), and assessed continuities in striatal function from subclinical to clinical domains. We applied connectopic mapping to resting-state fMRI data to obtain the first-order and second-order striatal connectivity modes in two distinct s les: (1) 56 antipsychotic-free patients (26 females) with first-episode psychosis (FEP) and 27 healthy controls (17 females) and (2) a community-based cohort of 377 healthy in iduals (213 females) comprehensively assessed for subclinical PLEs and schizotypy. The first-order “cortico-striatal” and second-order “dopaminergic” connectivity gradients were significantly different in FEP patients compared to controls bilaterally. In the independent s le of healthy in iduals, variations in the left first-order “cortico-striatal” connectivity gradient were associated with inter-in idual differences in a factor capturing general schizotypy and PLE severity. The presumed cortico-striatal connectivity gradient was implicated in both subclinical and clinical cohorts, suggesting that variations in its organization may represent a neurobiological trait marker across the psychosis continuum. Disruption of the presumed dopaminergic gradient was only noticeable in patients, suggesting that neurotransmitter dysfunction may be more apparent to clinical illness.
Effective Connectivity and Dopaminergic Function of Fronto-Striato-Thalamic Circuitry in First-Episode Psychosis, Established Schizophrenia, and Healthy Controls
Publisher: Cold Spring Harbor Laboratory
Date: 15-03-2021
DOI: 10.1101/2021.03.11.21253426
Abstract: Dysfunction of fronto-striato-thalamic (FST) circuits is thought to contribute to dopaminergic dysfunction and symptom onset in psychosis, but it remains unclear whether this dysfunction is driven by aberrant bottom-up subcortical signaling or impaired top-down cortical regulation. Here, we used spectral dynamic causal modelling (DCM) of resting-state functional magnetic resonance imaging (fMRI) to characterize the effective connectivity of dorsal and ventral FST circuits in a s le of 46 antipsychotic-naïve first-episode psychosis (FEP) patients and 23 controls and an independent s le of 36 patients with established schizophrenia (SCZ) patients and 100 controls. We found that midbrain and thalamic connectivity were implicated across both patient groups. Dysconnectivity in FEP patients was mainly restricted to the subcortex, with positive symptom severity being associated with midbrain connectivity. Dysconnectivity between the cortex and subcortical systems was only apparent in SCZ patients. In another independent s le of 33 healthy in iduals who underwent concurrent fMRI and [ 18 F]DOPA positron emission tomography, we found that striatal dopamine synthesis capacity was associated with the effective connectivity of nigrostriatal and striatothalamic pathways, implicating similar circuits as those associated with psychotic symptom severity in patients. Our findings thus indicate that subcortical dysconnectivity is salient in the early stages of psychosis, that cortical dysfunction may emerge later in the illness, and that nigrostriatal and striatothalamic signaling are closely related to striatal dopamine synthesis capacity, which is a robust risk marker for psychosis.
Increased peripheral inflammation in schizophrenia is associated with worse cognitive performance and related cortical thickness reductions.
Publisher: Springer Science and Business Media LLC
Date: 24-03-2021
DOI: 10.1007/S00406-021-01237-Z
Abstract: While the biological substrates of brain and behavioural changes in persons with schizophrenia remain unclear, increasing evidence implicates that inflammation is involved. In schizophrenia, including first-episode psychosis and anti-psychotic naïve patients, there are numerous reports of increased peripheral inflammation, cognitive deficits and neuropathologies such as cortical thinning. Research defining the relationship between inflammation and schizophrenia symptomatology and neuropathology is needed. Therefore, we analysed the level of C-reactive protein (CRP), a peripheral inflammation marker, and its relationship with cognitive functioning in a cohort of 644 controls and 499 schizophrenia patients. In a subset of in iduals who underwent MRI scanning (99 controls and 194 schizophrenia cases), we tested if serum CRP was associated with cortical thickness. CRP was significantly increased in schizophrenia patients compared to controls, co-varying for age, sex, overweight/obesity and diabetes (p < 0.006E-10). In schizophrenia, increased CRP was mildly associated with worse performance in attention, controlling for age, sex and education (R =- 0.15, p = 0.001). Further, increased CRP was associated with reduced cortical thickness in three regions related to attention: the caudal middle frontal, the pars opercularis and the posterior cingulate cortices, which remained significant after controlling for multiple comparisons (all p < 0.05). Together, these findings indicate that increased peripheral inflammation is associated with deficits in cognitive function and brain structure in schizophrenia, especially reduced attention and reduced cortical thickness in associated brain regions. Using CRP as a biomarker of peripheral inflammation in persons with schizophrenia may help to identify vulnerable patients and those that may benefit from adjunctive anti-inflammatory treatments.
Molecular Imaging of the Dopaminergic System and its Association with Human Cognitive Function
Publisher: Elsevier BV
Date: 05-2006
DOI: 10.1016/J.BIOPSYCH.2006.03.004
Abstract: Molecular imaging with positron emission tomography (PET) and single photon emission computed tomography (SPECT) has recently been used to examine dopamine (DA) function and its relationship with cognition in human subjects. This article will review PET and SPECT studies that have explored the relationship between cognitive processes and components of the DA system (pre-, intra-, and postsynaptic) in healthy and patient populations such as Parkinson's disease (PD), schizophrenia, Huntington's disease, and aging. It is demonstrated that DA activity modulates a range of frontal executive-type cognitive processes such as working memory, attentional functioning, and sequential organization, and alterations of DA within the fronto-striato-thalamic circuits might contribute to the cognitive impairments observed in PD, schizophrenia, and normal aging. Although associations between DA and cognitive measures need to be considered within the context of fronto-striato-thalamic circuitry, it is suggested that striatal (especially caudate) DA activity, particularly via D2 receptors, might be important for response inhibition, temporal organization of material, and motor performance, whereas cortical DA transmission via D1 receptors might be important for maintaining and representing on-going behavior.
Brain morphology is differentially impacted by peripheral cytokines in schizophrenia-spectrum disorder
Publisher: Elsevier BV
Date: 07-2021
DOI: 10.1016/J.BBI.2021.04.002
Abstract: Deficits in brain morphology are one of the most widely replicated neuropathological features in schizophrenia-spectrum disorder (SSD), although their biological underpinnings remain unclear. Despite the existence of hypotheses by which peripheral inflammation may impact brain structure, few studies have examined this relationship in SSD. This study aimed to establish the relationship between peripheral markers of inflammation and brain morphology and determine whether such relationships differed across healthy controls and in iduals with first episode psychosis (FEP) and chronic schizophrenia. A panel of 13 pro- and anti-inflammatory cytokines were quantified from serum in 175 participants [n = 84 Healthy Controls (HC), n = 40 FEP, n = 51 Chronic SCZ]. We first performed a series of permutation tests to identify the cytokines most consistently associated with brain structural regions. Using moderation analysis, we then determined the extent to which in idual variation in select cytokines, and their interaction with diagnostic status, predicted variation in brain structure. We found significant interactions between cytokine level and diagnosis on brain structure. Diagnostic status significantly moderated the relationship of IFNγ, IL4, IL5 and IL13 with frontal thickness, and of IFNγ and IL5 and total cortical volume. Specifically, frontal thickness was positively associated with IFNγ, IL4, IL5 and IL13 cytokine levels in the healthy control group, whereas pro-inflammatory cytokines IFNγ and IL5 were associated with lower total cortical volume in the FEP group. Our findings suggest that while there were no relationships detected in chronic schizophrenia, the relationship between peripheral inflammatory markers and select brain regions are differentially impacted in FEP and healthy controls. Longitudinal investigations are required to determine whether the relationship between brain structure and peripheral inflammation changes over time.
Investigation of Brain Iron in Niemann-Pick Type C: A 7T Quantitative Susceptibility Mapping Study
Publisher: American Society of Neuroradiology (ASNR)
Date: 22-06-2023
DOI: 10.3174/AJNR.A7894
Neuroanatomical heterogeneity and homogeneity in individuals at clinical high risk for psychosis
Publisher: Springer Science and Business Media LLC
Date: 26-07-2022
DOI: 10.1038/S41398-022-02057-Y
Abstract: In iduals at Clinical High Risk for Psychosis (CHR-P) demonstrate heterogeneity in clinical profiles and outcome features. However, the extent of neuroanatomical heterogeneity in the CHR-P state is largely undetermined. We aimed to quantify the neuroanatomical heterogeneity in structural magnetic resonance imaging measures of cortical surface area (SA), cortical thickness (CT), subcortical volume (SV), and intracranial volume (ICV) in CHR-P in iduals compared with healthy controls (HC), and in relation to subsequent transition to a first episode of psychosis. The ENIGMA CHR-P consortium applied a harmonised analysis to neuroimaging data across 29 international sites, including 1579 CHR-P in iduals and 1243 HC, offering the largest pooled CHR-P neuroimaging dataset to date. Regional heterogeneity was indexed with the Variability Ratio (VR) and Coefficient of Variation (CV) ratio applied at the group level. Personalised estimates of heterogeneity of SA, CT and SV brain profiles were indexed with the novel Person-Based Similarity Index (PBSI), with two complementary applications. First, to assess the extent of within-diagnosis similarity or ergence of neuroanatomical profiles between in iduals. Second, using a normative modelling approach, to assess the ‘normativeness’ of neuroanatomical profiles in in iduals at CHR-P. CHR-P in iduals demonstrated no greater regional heterogeneity after applying FDR corrections. However, PBSI scores indicated significantly greater neuroanatomical ergence in global SA, CT and SV profiles in CHR-P in iduals compared with HC. Normative PBSI analysis identified 11 CHR-P in iduals (0.70%) with marked deviation ( .5 SD) in SA, 118 (7.47%) in CT and 161 (10.20%) in SV. Psychosis transition was not significantly associated with any measure of heterogeneity. Overall, our examination of neuroanatomical heterogeneity within the CHR-P state indicated greater ergence in neuroanatomical profiles at an in idual level, irrespective of psychosis conversion. Further large-scale investigations are required of those who demonstrate marked deviation.
An Interleukin-1 beta (IL1B) haplotype linked with psychosis transition is associated with IL1B gene expression and brain structure
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.SCHRES.2018.09.008
Abstract: We investigated IL1B genetic variation previously associated with risk for transition to psychosis for its association with gene expression in human post-mortem dorsolateral prefrontal cortex (DLPFC) from 74 (37 schizophrenia, 37 control) in iduals and brain structure in 92 (44 schizophrenia, 48 control) living in iduals. The IL1B A-G-T 'risk for psychosis transition' haplotype (rs16944|rs4848306|rs12621220) was associated with upregulation of IL1B mRNA expression in the DLPFC as well as reduced total grey matter and left middle frontal volumes and enlarged left lateral ventricular volume. Our results suggest IL1B genetic variation may confer psychosis risk via elevated mRNA expression and/or brain structure abnormalities.
Deterioration of visuospatial associative memory following a first psychotic episode: A long-term follow-up study
Publisher: Cambridge University Press (CUP)
Date: 19-06-2018
DOI: 10.1017/S003329171700157X
Abstract: Cognitive deficits are a core feature of schizophrenia, and impairments in most domains are thought to be stable over the course of the illness. However, cross-sectional evidence indicates that some areas of cognition, such as visuospatial associative memory, may be preserved in the early stages of psychosis, but become impaired in later established illness stages. This longitudinal study investigated change in visuospatial and verbal associative memory following psychosis onset. In total 95 first-episode psychosis (FEP) patients and 63 healthy controls (HC) were assessed on neuropsychological tests at baseline, with 38 FEP and 22 HCs returning for follow-up assessment at 5–11 years. Visuospatial associative memory was assessed using the Cambridge Neuropsychological Test Automated Battery Visuospatial Paired-Associate Learning task, and verbal associative memory was assessed using Verbal Paired Associates subtest of the Wechsler Memory Scale - Revised. Visuospatial and verbal associative memory at baseline did not differ significantly between FEP patients and HCs. However, over follow-up, visuospatial associative memory deteriorated significantly for the FEP group, relative to healthy in iduals. Conversely, verbal associative memory improved to a similar degree observed in HCs. In the FEP cohort, visuospatial (but not verbal) associative memory ability at baseline was associated with functional outcome at follow-up. Areas of cognition that develop prior to psychosis onset, such as visuospatial and verbal associative memory, may be preserved early in the illness. Later deterioration in visuospatial memory ability may relate to progressive structural and functional brain abnormalities that occurs following psychosis onset.
Differentiating the effect of antipsychotic medication and illness on brain volume reductions in first-episode psychosis: A Longitudinal, Randomised, Triple-blind, Placebo-controlled MRI Study.
Publisher: Springer Science and Business Media LLC
Date: 26-02-2021
DOI: 10.1038/S41386-021-00980-0
Abstract: Changes in brain volume are a common finding in Magnetic Resonance Imaging (MRI) studies of people with psychosis and numerous longitudinal studies suggest that volume deficits progress with illness duration. However, a major unresolved question concerns whether these changes are driven by the underlying illness or represent iatrogenic effects of antipsychotic medication. In this study, 62 antipsychotic-naïve patients with first-episode psychosis (FEP) received either a second-generation antipsychotic (risperidone or paliperidone) or a placebo pill over a treatment period of 6 months. Both FEP groups received intensive psychosocial therapy. A healthy control group ( n = 27) was also recruited. Structural MRI scans were obtained at baseline, 3 months and 12 months. Our primary aim was to differentiate illness-related brain volume changes from medication-related changes within the first 3 months of treatment. We secondarily investigated long-term effects at the 12-month timepoint. From baseline to 3 months, we observed a significant group x time interaction in the pallidum ( p 0.05 FWE-corrected), such that patients receiving antipsychotic medication showed increased volume, patients on placebo showed decreased volume, and healthy controls showed no change. Across the entire patient s le, a greater increase in pallidal grey matter volume over 3 months was associated with a greater reduction in symptom severity. Our findings indicate that psychotic illness and antipsychotic exposure exert distinct and spatially distributed effects on brain volume. Our results align with prior work in suggesting that the therapeutic efficacy of antipsychotic medications may be primarily mediated through their effects on the basal ganglia.
The activity and connectivity of the facial emotion processing neural circuitry in bipolar disorder: a systematic review
Publisher: Elsevier BV
Date: 2021
Development of morning–eveningness in adolescence: implications for brain development and psychopathology
Publisher: Wiley
Date: 03-11-2023
DOI: 10.1111/JCPP.13718
Abstract: Morning–evening preference is defined as an in idual's preference for a morning‐ or evening‐oriented rhythm. Across adolescence, a preference for eveningness becomes more predominant. Although eveningness is cross‐sectionally associated with internalizing and externalizing psychopathology, few studies have examined developmental changes in eveningness and its potential biological substrates. Here, we investigated the longitudinal relationships among the trajectory of eveningness preference, internalizing and externalizing psychopathology and white matter development, across adolescence. Two‐hundred and nine adolescents (49% male) were assessed longitudinally at four separate time points between 12 and 19 years of age. Morning–evening preference and internalizing and externalizing symptoms were assessed at each time point. Diffusion‐weighted images were acquired on a subset of participants at the final two time points to estimate changes in global mean fractional anisotropy (FA). Linear mixed models were performed to estimate the change in eveningness over time. A series of linear regression models assessed the influence of change in eveningness on psychopathology and white matter development at age 19. Across the s le, a preference for eveningness became more predominant by 19 years of age. Greater in idual‐level change towards eveningness significantly predicted greater severity in externalizing, but not internalizing, symptoms at 19 years of age. In contrast, change in psychopathology from 12 to 19 years of age was not associated with morning–eveningness at age 19. A change towards eveningness predicted an attenuated increase in FA between 17 and 19 years of age. This study suggests that developmental changes in morning–evening preference may predict both neurodevelopmental and psychological outcomes in adolescents.
Pre- and post-synaptic dopamine imaging and its relation with frontostriatal cognitive function in Parkinson disease: PET studies with [11C]NNC 112 and [18F]FDOPA
Publisher: Elsevier BV
Date: 07-2008
DOI: 10.1016/J.PSCYCHRESNS.2007.11.003
Abstract: Frontostriatal cognitive dysfunction is common in Parkinson disease (PD), but the explanation for its heterogeneous expressions remains unclear. This study examined the dopamine system within the frontostriatal circuitry with positron emission tomography (PET) to investigate pre- and post-synaptic dopamine function in relation to the executive processes in PD. Fifteen non-demented PD patients and 14 healthy controls underwent [(18)F]FDOPA (for dopamine synthesis) and [(11)C]NNC 112 (for D(1) receptors) PET scans and cognitive testing. Parametric images of [(18)F]FDOPA uptake (K(i)) and [(11)C]NNC 112 binding potential (BP(ND)) were calculated using reference tissue models. Group differences in K(i) and BP(ND) were assessed with both volume of interest and statistical parametric mapping, and were correlated with cognitive tests. Measurement of [(18)F]FDOPA uptake in cerebral cortex was questionable because of higher K(i) values in white than adjacent gray matter. These paradoxical results were likely to be caused by violations of the reference tissue model assumption rendering interpretation of cortical [(18)F]FDOPA uptake in PD difficult. We found no regional differences in D(1) receptor density between controls and PD, and no overall differences in frontostriatal performance. Although D(1) receptor density did not relate to frontostriatal cognition, K(i) decreases in the putamen predicted performance on the Wisconsin Card Sorting Test in PD only. These results suggest that striatal dopamine denervation may contribute to some frontostriatal cognitive impairment in moderate stage PD.
Hippocampal subfields and visuospatial associative memory across stages of schizophrenia-spectrum disorder
Publisher: Cambridge University Press (CUP)
Date: 04-12-2019
DOI: 10.1017/S0033291718003458
Abstract: While previous studies have identified relationships between hippoc al volumes and memory performance in schizophrenia, these relationships are not apparent in healthy in iduals. Further, few studies have examined the role of hippoc al subfields in illness-related memory deficits, and no study has examined potential differences across varying illness stages. The current study aimed to investigate whether in iduals with early and established psychosis exhibited differential relationships between visuospatial associative memory and hippoc al subfield volumes. Measurements of visuospatial associative memory performance and grey matter volume were obtained from 52 in iduals with a chronic schizophrenia-spectrum disorder, 28 youth with recent-onset psychosis, 52 older healthy controls, and 28 younger healthy controls. Both chronic and recent-onset patients had impaired visuospatial associative memory performance, however, only chronic patients showed hippoc al subfield volume loss. Both chronic and recent-onset patients demonstrated relationships between visuospatial associative memory performance and hippoc al subfield volumes in the CA4/dentate gyrus and the stratum that were not observed in older healthy controls. There were no group by volume interactions when chronic and recent-onset patients were compared. The current study extends the findings of previous studies by identifying particular hippoc al subfields, including the hippoc al stratum layers and the dentate gyrus, that appear to be related to visuospatial associative memory ability in in iduals with both chronic and first-episode psychosis.
Differentiating the Effect of Medication and Illness on Brain Volume Reductions in First-Episode Psychosis: A Longitudinal, Randomized, Triple-blind, Placebo-controlled MRI Study
Publisher: Cold Spring Harbor Laboratory
Date: 23-03-2020
DOI: 10.1101/2020.03.18.20038471
Abstract: Changes in brain volume are a common finding in Magnetic Resonance Imaging (MRI) studies of people with psychosis and numerous longitudinal studies suggest that volume deficits progress with illness duration. However, a major unresolved question concerns whether these changes are driven by the underlying illness or represent iatrogenic effects of antipsychotic medication. Here, we report MRI findings from a triple-blind randomised placebo-controlled study where 62 antipsychotic-naïve patients with first episode psychosis (FEP) received either an atypical antipsychotic or a placebo pill over a treatment period of 6 months. Both FEP groups received intensive psychosocial therapy. A healthy control group (n=27) was also recruited. Structural MRI scans were obtained at baseline, 3-months and 12- months. Our primary aim was to differentiate illness-related brain volume changes from medication-related changes within the first 3 months of treatment. We secondarily investigated long-term effects at the 12-month timepoint. From baseline to 3 months, we observed a significant group x time interaction in the pallidum (p 0.05 FWE-corrected), such that patients receiving antipsychotic medication showed increased volume, patients on placebo showed decreased volume, and healthy controls showed no change. In patients, a greater increase in pallidal grey matter volume over 3 months was associated with a greater reduction in symptom severity. We additionally found preliminary evidence for illness- related volume reductions in prefrontal cortices at 12 months and medication-related volume reductions in cerebellum at both 3-months and 12-months. Our findings indicate that psychotic illness and antipsychotic exposure exert distinct and spatially distributed effects on brain volume. Our results align with prior work in suggesting that the therapeutic efficacy of antipsychotic medications may be primarily mediated through their effects on the basal ganglia.
Does coffee enriched with chlorogenic acids improve mood and cognition after acute administration in healthy elderly? A pilot study
Publisher: Springer Science and Business Media LLC
Date: 20-07-2012
DOI: 10.1007/S00213-011-2395-0
Abstract: Caffeine exerts positive effects on cognitive and behavioral processes, especially in sub-optimal conditions when arousal is low. Apart from caffeine, coffee contains other compounds including the phenolic compounds ferulic acid, caffeic acid, and the chlorogenic acids, which have purported antioxidant properties. The chlorogenic acids are the most abundant family of compounds found in coffee, yet their effects on cognition and mood have not been investigated. This study aims to ascertain whether a coffee rich in chlorogenic acid modulates brain function. The present pilot study examined the acute effects of decaffeinated coffee with regular chlorogenic acid content and decaffeinated coffee with high chlorogenic acid content on mood and cognitive processes, as measured by behavioral tasks and event-related potentials (ERPs). Performance and ERP responses to a battery of cognitive tasks were recorded at baseline and following the equivalent of three cups of coffee in a randomized, double-blind, crossover study of 39 healthy older participants. Compared with the decaffeinated coffee with regular chlorogenic acid and placebo, caffeinated coffee showed a robust positive effect on higher-level mood and attention processes. To a lesser extent, the decaffeinated coffee high in chlorogenic acid also improved some mood and behavioral measures, relative to regular decaffeinated coffee. Our pilot results suggest that non-caffeine compounds in coffee such as the chlorogenic acids may be capable of exerting some acute behavioral effects, thus warranting further investigation.
The impact of smoking status on cognition and brain morphology in schizophrenia spectrum disorders
Publisher: Cambridge University Press (CUP)
Date: 14-01-2022
DOI: 10.1017/S0033291720005152
Abstract: Cigarette smoking is associated with worse cognition and decreased cortical volume and thickness in healthy cohorts. Chronic cigarette smoking is prevalent in schizophrenia spectrum disorders (SSD), but the effects of smoking status on the brain and cognition in SSD are not clear. This study aimed to understand whether cognitive performance and brain morphology differed between smoking and non-smoking in iduals with SSD compared to healthy controls. Data were obtained from the Australian Schizophrenia Research Bank. Cognitive functioning was measured in 299 controls and 455 SSD patients. Cortical volume, thickness and surface area data were analysed from T1-weighted structural scans obtained in a subset of the s le ( n = 82 controls, n = 201 SSD). Associations between smoking status (cigarette smoker/non-smoker), cognition and brain morphology were tested using analyses of covariance, including diagnosis as a moderator. No smoking by diagnosis interactions were evident, and no significant differences were revealed between smokers and non-smokers across any of the variables measured, with the exception of a significantly thinner left posterior cingulate in smokers compared to non-smokers. Several main effects of smoking in the cognitive, volume and thickness analyses were initially significant but did not survive false discovery rate (FDR) correction. Despite the general absence of significant FDR-corrected findings, trend-level effects suggest the possibility that subtle smoking-related effects exist but were not uncovered due to low statistical power. An investigation of this topic is encouraged to confirm and expand on our findings.
High-resolution connectomic fingerprints: Mapping neural identity and behavior
Publisher: Elsevier BV
Date: 04-2021
The effects of a muscarinic receptor 1 gene variant on executive and non-executive cognition in schizophrenia spectrum disorders
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.PSYCHRES.2019.01.032
Abstract: In iduals with schizophrenia who are homozygous at the c.267C > A (rs2067477) single nucleotide polymorphism within the muscarinic M1 receptor gene have been reported to perform less well on the Wisconsin Card Sorting Test (WCST). We investigated if rs2067477 genotype variation influenced WCST performance and non-executive cognition cross-diagnostically in a s le of 147 schizophrenia spectrum participants (SSD) and 294 healthy controls. We were unable to detect any significant differences in executive and non-executive cognitive performance across genotype. A broader genetic focus should be considered when investigating the association between the muscarinic system and cognition in SSD.
Resting-state functional brain networks in first-episode psychosis: A 12-month follow-up study
Publisher: SAGE Publications
Date: 27-05-2018
Abstract: Schizophrenia is increasingly conceived as a disorder of brain network connectivity and organization. However, reports of network abnormalities during the early illness stage of psychosis are mixed. This study adopted a data-driven whole-brain approach to investigate functional connectivity and network architecture in a first-episode psychosis cohort relative to healthy controls and whether functional network properties changed abnormally over a 12-month period in first-episode psychosis. Resting-state functional connectivity was performed at two time points. At baseline, 29 first-episode psychosis in iduals and 30 healthy controls were assessed, and at 12 months, 14 first-episode psychosis in iduals and 20 healthy controls completed follow-up. Whole-brain resting-state functional connectivity networks were mapped for each in idual and analyzed using graph theory to investigate whether network abnormalities associated with first-episode psychosis were evident and whether functional network properties changed abnormally over 12 months relative to controls. This study found no evidence of abnormal resting-state functional connectivity or topology in first-episode psychosis in iduals relative to healthy controls at baseline or at 12-months follow-up. Furthermore, longitudinal changes in network properties over a 12-month period did not significantly differ between first-episode psychosis in iduals and healthy control. Network measures did not significantly correlate with symptomatology, duration of illness or antipsychotic medication. This is the first study to show unaffected resting-state functional connectivity and topology in the early psychosis stage of illness. In light of previous literature, this suggests that a subgroup of first-episode psychosis in iduals who have a neurotypical resting-state functional connectivity and topology may exist. Our preliminary longitudinal analyses indicate that there also does not appear to be deterioration in these network properties over a 12-month period. Future research in a larger s le is necessary to confirm our longitudinal findings.
Cognitive reserve attenuates age-related cognitive decline in the context of putatively accelerated brain ageing in schizophrenia-spectrum disorders
Publisher: Cambridge University Press (CUP)
Date: 09-07-2020
DOI: 10.1017/S0033291719001417
Abstract: In schizophrenia, relative stability in the magnitude of cognitive deficits across age and illness duration is inconsistent with the evidence of accelerated deterioration in brain regions known to support these functions. These discrepant brain–cognition outcomes may be explained by variability in cognitive reserve (CR), which in neurological disorders has been shown to buffer against brain pathology and minimize its impact on cognitive or clinical indicators of illness. Age-related change in fluid reasoning, working memory and frontal brain volume, area and thickness were mapped using regression analysis in 214 in iduals with schizophrenia or schizoaffective disorder and 168 healthy controls. In patients, these changes were modelled as a function of CR. Patients showed exaggerated age-related decline in brain structure, but not fluid reasoning compared to controls. In the patient group, no moderation of age-related brain structural change by CR was evident. However, age-related cognitive change was moderated by CR, such that only patients with low CR showed evidence of exaggerated fluid reasoning decline that paralleled the exaggerated age-related deterioration of underpinning brain structures seen in all patients . In schizophrenia-spectrum illness, CR may negate ageing effects on fluid reasoning by buffering against pathologically exaggerated structural brain deterioration through some form of compensation. CR may represent an important modifier that could explain inconsistencies in brain structure – cognition outcomes in the extant literature.
A Systematic Review of Cognition-Brain Morphology Relationships on the Schizophrenia-Bipolar Disorder Spectrum
Publisher: Oxford University Press (OUP)
Date: 07-06-2021
Abstract: The nature of the relationship between cognition and brain morphology in schizophrenia-spectrum disorders (SSD) and bipolar disorder (BD) is uncertain. This review aimed to address this, by providing a comprehensive systematic investigation of links between several cognitive domains and brain volume, cortical thickness, and cortical surface area in SSD and BD patients across early and established illness stages. An initial search of PubMed and Scopus databases resulted in 1486 articles, of which 124 met inclusion criteria and were reviewed in detail. The majority of studies focused on SSD, while those of BD were scarce. Replicated evidence for specific regions associated with indices of cognition was minimal, however for several cognitive domains, the frontal and temporal regions were broadly implicated across both recent-onset and established SSD, and to a lesser extent BD. Collectively, the findings of this review emphasize the significance of both frontal and temporal regions for some domains of cognition in SSD, while highlighting the need for future BD-related studies on this topic.
Linking Cortical and Connectional Pathology in Schizophrenia
Publisher: Oxford University Press (OUP)
Date: 12-09-2019
Examining the cognitive effects of a special extract of Bacopa monniera (CDRI08: Keenmnd): A review of ten years of research at Swinburne University
Publisher: Frontiers Media SA
Date: 11-06-2013
DOI: 10.18433/J35G6M
Abstract: Bacopa monniera (EBm), an Indian aquatic herb, has been used in traditional Ayurvedic medicine for centuries for indications related to memory and inflammation. More recently specific extracts of EBm have emerged that have been subjected to rigorous in vitro, animal and now human clinical trials. In this paper we discuss some of these studies with special reference to mechanisms and efficacy of a special extract of Bacopa (CDRI08). Studies using this extract indicate that CDRI08 has several modes of action on the human brain. Promising indications for use in humans include improving cognition in the elderly and in patients with neurodegenerative disorders.
Investigation of orbitofrontal sulcogyral pattern in chronic schizophrenia
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1016/J.PSCYCHRESNS.2015.09.001
Abstract: Abnormalities of orbitofrontal cortex (OFC) pattern type distribution have been associated with schizophrenia-spectrum disorders. We investigated OFC pattern type in a large s le of chronic schizophrenia patients and healthy controls. We found an increased frequency of Type II but no difference in Type I or III folding pattern in the schizophrenia group in comparison to controls. Further large studies are required to investigate the diagnostic specificity of altered OFC pattern type and to confirm the distribution of pattern type in the normal population.
White matter connectivity disruptions in early and chronic schizophrenia
Publisher: Cambridge University Press (CUP)
Date: 22-05-2017
DOI: 10.1017/S0033291717001313
Abstract: White matter disruptions in schizophrenia have been widely reported, but it remains unclear whether these abnormalities differ between illness stages. We mapped the connectome in patients with recently diagnosed and chronic schizophrenia and investigated the extent and overlap of white matter connectivity disruptions between these illness stages. Diffusion-weighted magnetic resonance images were acquired in recent-onset ( n = 19) and chronic patients ( n = 45) with schizophrenia, as well as age-matched controls ( n = 87). Whole-brain fiber tracking was performed to quantify the strength of white matter connections. Connections were tested for significant streamline count reductions in recent-onset and chronic groups, relative to separate age-matched controls. Permutation tests were used to assess whether disrupted connections significantly overlapped between chronic and recent-onset patients. Linear regression was performed to test whether connectivity was strongest in controls, weakest in chronic patients, and midway between these extremities in recent-onset patients (controls recent-onset chronic). Compared with controls, chronic patients displayed a widespread network of connectivity disruptions ( p 0.01). In contrast, connectivity reductions were circumscribed to the anterior fibers of the corpus callosum in recent-onset patients ( p 0.01). A significant proportion of disrupted connections in recent-onset patients (86%) coincided with disrupted connections in chronic patients ( p 0.01). Linear regression revealed that chronic patients displayed reduced connectivity relative to controls, while recent-onset patients showed an intermediate reduction compared with chronic patients ( p 0.01). Connectome pathology in recent-onset patients with schizophrenia is confined to select tracts within a more extensive network of white matter connectivity disruptions found in chronic illness. These findings may suggest a trajectory of progressive deterioration of connectivity in schizophrenia.
Accelerated gray and white matter deterioration with age in schizophrenia
Publisher: American Psychiatric Association Publishing
Date: 03-2017
Functional Connectivity in Antipsychotic-Treated and Antipsychotic-Naive Patients with First-Episode Psychosis and Low Risk of Self-harm or Aggression: A Secondary Analysis of a Randomized Clinical Trial
Publisher: American Medical Association (AMA)
Date: 09-2021
Brain morphology does not clearly map to cognition in individuals on the bipolar-schizophrenia-spectrum: a cross-diagnostic study of cognitive subgroups
Publisher: Elsevier BV
Date: 02-2021
The effect of a muscarinic receptor 1 gene variant on grey matter volume in schizophrenia
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1016/J.PSCYCHRESNS.2015.09.004
Abstract: Previous research has demonstrated that in iduals with schizophrenia who are homozygous at the c.267C>A single nucleotide polymorphism (rs2067477) within the cholinergic muscarinic M1 receptor (CHRM1) perform less well on the Wisconsin Card Sorting Test (WCST) than those who are heterozygous. This study sought to determine whether variation in the rs2067477 genotype was associated with differential changes in brain structure. Data from 227 patients with established schizophrenia or schizoaffective disorder were obtained from the Australian Schizophrenia Research Bank. Whole-brain voxel-based morphometry was performed to compare regional grey matter volume (GMV) between the 267C/C (N=191) and 267C/A (N=36) groups. Secondary analyses tested for an effect of genotype on cognition (the WCST was not available). In iduals who were homozygous (267C/C) demonstrated significantly reduced GMV in the right precentral gyrus compared to those who were heterozygous (267C/A). These preliminary results suggest that the rs2067477 genotype is associated with brain structure in the right precentral gyrus in in iduals with schizophrenia/schizoaffective disorder. Future studies are required to replicate these results and directly link the volumetric reductions with specific cognitive processes.
Widespread decrease of nicotinic acetylcholine receptors in Parkinson's disease
Publisher: Wiley
Date: 22-12-2005
DOI: 10.1002/ANA.20688
Increased power by harmonizing structural MRI site differences with the ComBat batch adjustment method in ENIGMA
Publisher: Elsevier BV
Date: 09-2020
Baseline grey matter volume of non-transitioned ultra high risk for psychosis individuals with and without attenuated psychotic symptoms at long-term follow-up
Publisher: Elsevier BV
Date: 06-2016
DOI: 10.1016/J.SCHRES.2015.05.014
Abstract: Two thirds of in iduals identified as ultra-high risk (UHR) for psychosis do not transition to psychosis over the medium to long-term (non-transition UHR-NT). Nevertheless, many of these in iduals have persistent attenuated psychotic symptoms (APS). The current study examined whether there were differences in baseline grey matter volume (i.e. at initial identification as UHR) in UHR-NT in iduals whom had APS compared to those without APS (No-APS) at medium to long-term follow-up. Participants were help-seeking in iduals who were identified as being at UHR for psychosis between 2 and 12years previously (mean=7.5). The s le consisted of 109 participants who underwent a Magnetic Resonance Imaging scan at baseline and who had not been observed to develop a psychotic disorder over the follow-up period (UHR-NT). Using voxel-based morphometry, baseline grey matter volume (GMV) was compared between participants with (N=30) and without (N=79) APS at follow-up. At baseline, the APS and No-APS groups were clinically indistinguishable. At follow-up, the APS group had significantly worse symptoms and impaired functioning. In iduals with APS had reduced baseline GMV in frontal, temporal, posterior and cingulate regions compared to those without APS at follow-up. Reduced GMV was associated with more severe positive, negative and depressive symptoms and lower global functioning in the combined UHR-NT cohort. These associations were independent of later APS outcome. This study found that differences in regional GMV are discernible at an early stage of UHR and may be specific to in iduals who have APS and psychopathology at follow-up. Our findings suggest that lower GMV at baseline may confer neurobiological risk for later APS and/or increased psychopathology while the absence of these structural abnormalities might be protective.
Genetic variation in glutamatergic genes moderates the effects of childhood adversity on brain volume and IQ in treatment-resistant schizophrenia
Publisher: Springer Science and Business Media LLC
Date: 14-09-2023
White Matter Disruptions in Schizophrenia Are Spatially Widespread and Topologically Converge on Brain Network Hubs
Publisher: Oxford University Press (OUP)
Date: 17-08-2017
PET imaging of putative microglial activation in individuals at ultra-high risk for psychosis, recently diagnosed and chronically ill with schizophrenia
Publisher: Springer Science and Business Media LLC
Date: 29-08-2017
DOI: 10.1038/TP.2017.193
Associations Between Delay Discounting and Connectivity of the Valuation-control System in Healthy Young Adults
Publisher: Elsevier BV
Date: 2021
Cognitive validation of cross-diagnostic cognitive subgroups on the schizophrenia-bipolar spectrum
Publisher: Elsevier BV
Date: 04-2020
Related Organisations
Related Funding Activities
Linkage Projects - Grant ID: LP110100410
Start Date: 2011
End Date: 10-2011
Amount: $173,826.00
Funder: Australian Research Council
View Funded Activity