ORCID Profile
0000-0003-0485-8090
Current Organisations
The University of Sydney Brain and Mind Centre
,
The University of Sydney Faculty of Medicine and Health
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Biological Psychology (Neuropsychology, Psychopharmacology, Physiological Psychology) | Psychology
Expanding Knowledge in the Biological Sciences | Expanding Knowledge in Psychology and Cognitive Sciences |
Publisher: Elsevier BV
Date: 11-2019
DOI: 10.1016/J.CORTEX.2019.06.008
Abstract: To track neural correlates of naming performance with disease progression, we estimated key areas affected in nonfluent/agrammatic (nfvPPA) and logopenic (lvPPA) primary progressive aphasia variants over time and changes in naming correlates over time. Twenty-nine non-semantic PPA participants (17 nfvPPA and 12 lvPPA) were selected based upon current diagnostic criteria and PiB-PET status and conducted a confrontation-naming task and a structural MRI. Linear mixed-effect models implemented in FreeSurfer were used for tracking cortical thickness and epicenters of atrophy over time. Using averaged cortical thickness of epicenters and naming performance as variables of interest, two sets of multivariate analyses were conducted to compare atrophy progression and naming correlates across groups. While all PPA participants demonstrated naming deterioration and progressive cortical thinning in the left temporal lobe and the left inferior frontal gyrus, the lvPPA cohort showed greater naming deterioration and thinning in the left posterior inferior parietal cortex over time than it did the nfvPPA cohort. The multivariate analyses confirmed a widespread cortical thinning in lvPPA over time, but a more rapid thinning in the right superior frontal gyrus of nfvPPA participants. Impaired naming correlated with common cortical regions in both groups. These regions included the left anterior superior temporal gyrus and the posterior middle temporal gyrus, which was primarily affected in lvPPA. Non-semantic PPA variants initially present with separate epicenters of atrophy and different spatial-temporal patterns of neurodegeneration over time, but the common involvement in key cortical regions of the left temporal lobe accounts for naming deterioration in both groups.
Publisher: Elsevier BV
Date: 10-2017
Publisher: Oxford University Press (OUP)
Date: 27-10-2016
DOI: 10.1093/BRAIN/AWW263
Publisher: Elsevier BV
Date: 05-2017
DOI: 10.1016/J.NEUROIMAGE.2016.03.032
Abstract: Clinical differentiation between Alzheimer's disease (AD) and behavioural-variant frontotemporal dementia (bvFTD) is challenging due to overlapping clinical features at presentation. Whilst diagnostic criteria for both disorders incorporate evidence of frontal and temporal cortical atrophy, understanding of the progression of atrophy in these disorders is limited. This study aimed to elucidate common and disease-specific progressive changes in cortical and subcortical brain structures in AD and bvFTD. Forty-one AD, 37 bvFTD and 33 healthy controls underwent baseline MRI and of these longitudinal follow-up was obtained for 20AD and 20 bvFTD (1 to 4years). A total of 87 AD and 70 bvFTD consecutive scans were included in the study. The trajectories of progression in cortical and subcortical structures were identified with FreeSurfer and linear mixed effect modelling. The results uncovered cortical and subcortical disease-specific trajectories of neurodegeneration in AD and bvFTD. Specifically, direct comparisons between patient groups revealed that over time AD showed greater cortical atrophy in the inferior parietal and posterior cingulate cortex than bvFTD. Conversely, bvFTD patients showed greater atrophy in the striatum than AD over time. These results indicate that atrophy in the posterior cingulate and the striatum erges with disease progression in these dementia syndromes and may represent a potential diagnostic biomarker for tracking rates of progression of AD and bvFTD. These findings may help inform future drug trials by identifying appropriate outcome measures to quantify drug efficacy and their ability to modulate disease progression over time.
Publisher: BMJ
Date: 05-2017
Publisher: Elsevier BV
Date: 08-2020
Publisher: SAGE Publications
Date: 16-05-2018
Abstract: Hyperprolactinemia is a common side-effect of antipsychotics (APs), which may trigger serious secondary problems and compromise the adherence to treatment which is crucial for prognosis, especially in patients presenting with a first-episode of psychosis (FEP). We evaluated, in some cases for the first time, the effect of polymorphisms in multiple candidate genes on serum prolactin (PRL) levels in an AP-treated FEP cohort recruited in the multicenter PEPs study (Phenotype − genotype and environmental interaction Application of a predictive model in first psychotic episodes). PRL concentration was measured in serum from 222 patients. A total of 167 polymorphisms were selected in 23 genes. Genetic association analysis was performed in the whole s le and also in homogenous subgroups of patients treated with APs with a high (N = 101) or low risk (N = 95) of increasing PRL release, which showed significant differences in their PRL levels. After Bonferroni correction, polymorphisms in NTRK2, DRD2 and ACE genes were associated with PRL concentration. Our results give more support to the impact of DRD2, but also of other genes related to dopamine availability such as ACE. Moreover, this study provides the first evidence for the involvement of NTRK2, which suggests that pathways other than the ones related to dopamine or serotonin may participate in the AP-related PRL levels.
Publisher: Elsevier BV
Date: 05-2014
DOI: 10.1016/J.JAD.2014.02.034
Abstract: Most studies on the factors involved in the functional outcome of patients with bipolar disorder have identified subsyndromal depressive symptoms and cognitive impairment as key players. However, most studies are cross-sectional and very few have analyzed the interaction between cognition and subclinical depression. The present study aimed to identify the role of cognition, and particularly verbal memory, and subthreshold depressive symptoms in the functional outcome of patients with bipolar I and II disorder at one year follow-up. A confirmatory analysis was performed using the path analysis. A total of 111 euthymic patients were included to test the role of verbal memory as a mediator in the relationship of subthreshold depressive symptoms and functional outcome at one year follow-up. Measures of verbal memory, subthreshold depressive symptoms and functioning (at baseline, at 6 months and at one year follow-up) were gathered through the use of a neuropsychological assessment and validated clinical scales. The hypothesized mediation model displayed a good fit to data (Chi=0.393, df=2, p=0.625 RMSEA<0.001 with CI: 0.001-0.125 and CFI=1.00). Functional outcome at one year follow-up was predicted by the functional outcome at baseline, which in turn, was related to subthreshold depressive symptoms at baseline and to the verbal composite memory scores as a mediator variable. The results of this study prospectively confirm previous findings on the disabling role of subthreshold depressive symptoms and verbal memory impairment on psychosocial functioning. However, these results come from a s le with moderate to severe functional impairment hence, as a limitation, this may hinder the generalization of these results.
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1016/J.SCHRES.2014.08.017
Abstract: Schizoaffective patients can have neurocognitive deficits and default mode network dysfunction while being acutely ill. It remains unclear to what extent these abnormalities persist when they go into clinical remission. Memory and executive function were tested in 22 acutely ill schizoaffective patients they also underwent fMRI scanning during performance of the n-back working memory test. The same measures were obtained after they had been in remission for ≥ 2 months. Twenty-two matched healthy in iduals were also examined. In clinical remission, schizomanic patients showed an improvement of memory but not of executive function, while schizodepressive patients did not change in either domain. All schizoaffective patients in clinical remission showed memory and executive impairment compared to the controls. On fMRI, acutely ill schizomanic patients had reversible frontal hypo-activation when compared to clinical remission, while activation patterns in ill and remitted schizodepressive patients were similar. The whole group of schizoaffective patients in clinical remission showed a failure of de-activation in the medial frontal gyrus compared to the healthy controls. There was evidence for memory improvement and state dependent changes in activation in schizomanic patients across relapse and remission. Medial frontal failure of de-activation in remitted schizoaffective patients, which probably reflects default mode network dysfunction, appears to be a state independent feature of the illness.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 30-10-2017
Publisher: Elsevier BV
Date: 04-2022
DOI: 10.1016/J.CORTEX.2021.12.014
Abstract: The GGGGCC hexanucleotide repeat expansion in the non-coding region of the chromosome 9 open reading frame 72 gene (C9orf72) is the most common genetic cause of familial frontotemporal dementia (FTD). This study aims to clarify the patterns of cerebellar atrophy in FTD patients with and without a C9orf72 repeat expansion compared with healthy controls and determine whether associations between cerebellar atrophy and cognition differ between patient groups. Thirty C9orf72 repeat expansion-positive FTD patients, 30 C9orf72 repeat expansion-negative FTD patients, and 30 age-, sex-, and education-matched healthy controls underwent brain MRI and cognitive assessments. Patient groups were matched for clinical diagnosis, disease duration, general cognition, and disease severity. Compared with controls, the C9orf72 positive group showed cerebellar changes bilaterally involving the lobules V, VI, Crus I, Crus II, VIIb, VIIIa, left VIIIb, and right lobules I-IV. All these changes were localised within the regions affected in the C9orf72 negative group. No significant differences were found between patient groups. Correlation analyses with a liberal threshold found the cerebellar integrity to be associated with attention, language, and executive function in the C9orf72 positive group. In the C9orf72 negative group, these associations included attention, working memory, language, episodic memory, and executive function. This study clarifies the impact of C9orf72 repeat expansion on cerebellar integrity in FTD. The findings reveal overlapping patterns of cerebellar atrophy in C9orf72 positive and negative groups. The associations with cognitive functions suggest that the type of pathology linked with cerebellar atrophy is another relevant variable to consider in future studies.
Publisher: Springer Science and Business Media LLC
Date: 19-08-2019
DOI: 10.1007/S11065-019-09414-7
Abstract: Frontotemporal dementia (FTD) is a neurodegenerative brain disorder primarily affecting the frontal and/or temporal lobes. Three main subtypes have been recognized: behavioural-variant FTD (bvFTD), semantic dementia (SD), and progressive nonfluent aphasia (PNFA), each of which has a distinct clinical and cognitive profile. Although the role of the cerebellum in cognition is increasingly accepted, knowledge of cerebellar changes across neuroimaging modalities and their contribution to behavioural and cognitive changes in FTD syndromes is currently scant. We conducted an anatomical/activation likelihood estimation (ALE) meta-analysis in 53 neuroimaging studies (structural MRI: 42 positron emission tomography: 6 functional MRI: 4 single-photon emission computed tomography: 1) to identify the patterns of cerebellar changes and their relations to profiles of behavioural and cognitive deficits in FTD syndromes. Overall, widespread bilateral cerebellar changes were found in FTD and notably the patterns were subtype specific. In bvFTD, ALE peaks were identified in the bilateral Crus, left lobule VI, right lobules VIIb and VIIIb. In SD, focal cerebellar changes were located in the left Crus I and lobule VI. A separate ALE meta-analysis on PNFA studies was not performed due to the limited number of studies available. In addition, the ALE analysis indicated that bilateral Crus I and Crus II were associated with behavioural disruption and cognitive dysfunction. This ALE meta-analysis provides the quantification of the location and extent of cerebellar changes across the main FTD syndromes, which in turn provides evidence of cerebellar contributions to behavioural and cognitive changes in FTD. These results bring new insights into the mechanisms mediating FTD symptomatology.
Publisher: Springer Science and Business Media LLC
Date: 14-06-2018
DOI: 10.1007/S11682-018-9906-0
Abstract: Adults with severe traumatic brain injury (TBI) often suffer poor social cognition. Social cognition is complex, requiring verbal, non-verbal, auditory, visual and affective input and integration. While damage to focal temporal and frontal areas has been implicated in disorders of social cognition after TBI, the role of white matter pathology has not been examined. In this study 17 adults with chronic, severe TBI and 17 control participants underwent structural MRI scans and Diffusion Tensor Imaging. The Awareness of Social Inference Test (TASIT) was used to assess their ability to understand emotional states, thoughts, intentions and conversational meaning in everyday exchanges. Track-based spatial statistics were used to perform voxelwise analysis of Fractional Anisotropy (FA) and Mean Diffusivity (MD) of white matter tracts associated with poor social cognitive performance. FA suggested a wide range of tracts were implicated in poor TASIT performance including tracts known to mediate, auditory localisation (planum temporale) communication between nonverbal and verbal processes in general (corpus callosum) and in memory in particular (fornix) as well as tracts and structures associated with semantics and verbal recall (left temporal lobe and hippoc us), multimodal processing and integration (thalamus, external capsule, cerebellum) and with social cognition (orbitofrontal cortex, frontopolar cortex, right temporal lobe). Even when controlling for non-social cognition, the corpus callosum, fornix, bilateral thalamus, right external capsule and right temporal lobe remained significant contributors to social cognitive performance. This study highlights the importance of loss of white matter connectivity in producing complex social information processing deficits after TBI.
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.EURONEURO.2017.03.012
Abstract: Risperidone (R) is the most prescribed antipsychotic drug for patients with a first episode of psychosis (FEP). In a naturalistic cohort of chronic psychiatric inpatients, we demonstrated that clinicians adjust R dosage by CYP2D6 activity, despite being blinded to the genotype, which we described as an "intuitive pharmacogenetic" process. The aim of the present study is to replicate our previous findings of intuitive pharmacogenetic in a cohort of FEP patients using CYP2D6 phenotype extrapolated from genotypes. 70 FEP patients, under baseline treatment with R monotherapy were genotyped using the iPLEX® ADME PGx multiplex panel and TaqMan® Genotyping and Copy Number Assays. Plasma concentrations of R and its metabolite, 9-hydroxyrisperidone (9-OH), were determined. The predictive properties of those variables associated with R dosage were tested using a multiple linear regression model as well as regression trees. Significant differences in the mean daily dosage of R among CYP2D6 phenotypes were observed (Kruskal-Wallis test p=0.02): PM (4.00±2.3mg/mL), IM (4.56±2.44), EM (6.22±4.0mg/day) and UM (10.20±4.91mg/day). However, non-significant differences were observed in the R/9-OH ratio or in the Concentration/Dose ratio. Regression tree provided better estimations of R dosage than the multiple linear regression model (MAE=0.958 and R
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.SCHRES.2016.07.015
Abstract: A key finding underlying the continuum of psychosis concept is the presence of psychotic-like experiences (PLEs) in healthy subjects. However, it remains uncertain to what extent these experiences are related to the genetic risk for schizophrenia and how far they actually resemble attenuated forms of psychotic symptoms. Forty-nine adults with no history of mental illness in first-degree relatives and 59 siblings of patients with schizophrenia were rated on the psychosis section of the Computerized Diagnostic Interview Schedule IV (C DIS-IV) and the Rust Inventory of Schizotypal Cognitions (RISC). Those who rated positive on the CDIS-IV were re-interviewed using the lifetime version of the Present State Examination 9th edition (PSE-9) and the Structured interview for Schizotypy (SIS). Seventeen (34.69%) of the non-relatives and 22 (37.29%) of the relatives responded positively to one or more of the psychosis questions on the DIS. This difference was not significant. RISC scores were also similar between the groups. At follow-up interview with the PSE-9, 13/40 PLEs (32.50%) in the non-relatives were classified as possible or probable psychotic symptoms compared to 11/46 (23.91%) in the relatives. Using liberal symptom thresholds, 5 of those who attended the follow-up interview (2 non-relatives and 3 relatives) met SIS criteria for schizotypal personality disorder. Rates of PLEs, however considered, do not differ substantially between relatives and non-relatives of patients with schizophrenia. Only a minority of PLEs picked up by screening interviews resemble attenuated forms of psychotic symptoms.
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.SCHRES.2017.02.021
Abstract: This study aims to explore the gene-environment interaction hypothesis applied to pre-symptomatic neurodevelopmental phenotypes of first episode psychosis (FEP), that is, genetic factors might increase vulnerability to the effects of environmental adverse conditions occurring at later stages of development. We constructed a schematic 'two-hit' model, with Val/Val homozygosity for the catechol-O-methyltransferase (COMT) Val158Met polymorphism as the 'first hit' and history of obstetric complications and parental socioeconomic status as 'second hits'. Early adjustment, measured using the Premorbid Adjustment Scale, was considered the main outcome. The study population comprised 221 adolescents and adults with FEP and 191 sex- and age-matched controls. The interaction between the Val/Val COMT genotype and a positive history of obstetric complications plus low parental socioeconomic status was significantly associated with poorer early adjustment. These results were observed both in FEP in iduals and in controls, and remained significant after controlling for age, sex, and diagnosis. In iduals carrying Val/Val seem to be more sensitive to the synergistic effect of environmental factors acting early in neurodevelopment, which leads to vulnerability phenotypes such as impaired early adjustment.
Publisher: Wiley
Date: 13-05-2015
DOI: 10.1111/ACPS.12440
Abstract: Brain structural changes in schizoaffective disorder, and how far they resemble those seen in schizophrenia and bipolar disorder, have only been studied to a limited extent. Forty-five patients meeting DSM-IV and RDC criteria for schizoaffective disorder, groups of patients with 45 matched schizophrenia and bipolar disorder, and 45 matched healthy controls were examined using voxel-based morphometry (VBM). Analyses comparing each patient group with the healthy control subjects found that the patients with schizoaffective disorder and the patients with schizophrenia showed widespread and overlapping areas of significant volume reduction, but the patients with bipolar disorder did not. A subsequent analysis compared the combined group of patients with the controls followed by extraction of clusters. In regions where the patients differed significantly from the controls, no significant differences in mean volume between patients with schizoaffective disorder and patients with schizophrenia in any of five regions of volume reduction were found, but mean volumes in the patients with bipolar disorder were significantly smaller in three of five. The findings provide evidence that, in terms of structural gray matter brain abnormality, schizoaffective disorder resembles schizophrenia more than bipolar disorder.
Publisher: Cambridge University Press (CUP)
Date: 22-10-2019
DOI: 10.1017/S0033291719002794
Abstract: Social cognition has been associated with functional outcome in patients with first episode psychosis (FEP). Social cognition has also been associated with neurocognition and cognitive reserve. Although cognitive reserve, neurocognitive functioning, social cognition, and functional outcome are related, the direction of their associations is not clear. Therefore, the main aim of this study was to analyze the influence of social cognition as a mediator between cognitive reserve and cognitive domains on functioning in FEP both at baseline and at 2 years. The s le of the study was composed of 282 FEP patients followed up for 2 years. To analyze whether social cognition mediates the influence of cognitive reserve and cognitive domains on functioning, a path analysis was performed. The statistical significance of any mediation effects was evaluated by bootstrap analysis. At baseline, as neither cognitive reserve nor the cognitive domains studied were related to functioning, the conditions for mediation were not satisfied. Nevertheless, at 2 years of follow-up, social cognition acted as a mediator between cognitive reserve and functioning. Likewise, social cognition was a mediator between verbal memory and functional outcome. The results of the bootstrap analysis confirmed these significant mediations (95% bootstrapped CI (−10.215 to −0.337) and (−4.731 to −0.605) respectively). Cognitive reserve and neurocognition are related to functioning, and social cognition mediates in this relationship.
Publisher: Oxford University Press (OUP)
Date: 14-09-2015
Publisher: Physicians Postgraduate Press, Inc
Date: 27-12-2017
DOI: 10.4088/JCP.16M11122
Publisher: Cambridge University Press (CUP)
Date: 15-03-2012
Publisher: S. Karger AG
Date: 2013
DOI: 10.1159/000346654
Abstract: b i Background: /i /b Some functional imaging abnormalities found in bipolar disorder are state related, whereas others persist into euthymia. It is uncertain to what extent these latter changes may reflect continuing subsyndromal affective fluctuations and whether those can be modulated by therapeutic interventions. b i Method: /i /b We report functional magnetic resonance imaging (fMRI) findings during performance of the n-back working memory task in a bipolar patient who showed a marked improvement in subsyndromal affective symptoms after receiving eye movement desensitization and reprocessing (EMDR) therapy in the context of a clinical trial. b i Results: /i /b The patient's clinical improvement was accompanied by marked changes in functional imaging, as compared to 30 healthy subjects. fMRI changes were noted particularly in deactivation, with failure of deactivation in the medial frontal cortex partially normalizing after treatment. b i Conclusions: /i /b This case supports the potential therapeutic overall benefit of EMDR in traumatized bipolar patients and suggests a possible neurobiological mechanism of action: normalization of default mode network dysfunction.
Publisher: Elsevier BV
Date: 11-2012
DOI: 10.1016/J.BIOPSYCH.2012.04.035
Abstract: Genetic studies have found that the interleukin-1β gene (IL1B, 2q13) influences the risk for schizophrenia, but the underlying biological mechanisms of the association are still unclear. Investigation of the effects of genetic variability in this gene on brain function could provide more information about its role in the disorder. The present study examined the effects of a functional polymorphism at IL1B gene promoter (-511C/T rs16944) on brain correlates of working memory performance in schizophrenia. Forty-eight schizophrenia patients and 46 control subjects underwent functional magnetic resonance imaging while performing the n-back task. In the pooled s le, genetic variability at this locus was associated with differential brain activation in a bilateral frontal region including the dorsolateral prefrontal cortex. There was also a significant diagnosis × genotype interaction effect in an overlapping frontal region: the IL1B polymorphism did not affect activation in the control subjects in this area, but the schizophrenia patients who were T carriers showed significantly higher activation than the CC homozygotes. The findings support a role for IL1B variability in the dorsolateral prefrontal cortex dysfunction classically associated with schizophrenia.
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.SCHRES.2018.03.025
Abstract: Many studies having shown significant improvements in non-social and social cognitive performance in smoking FEP patients compared to non-smoking FEP patients. The findings are controversial. This study analyzed the effects of tobacco use on non-social and social cognitive function in a large group of FEP patients and a matched healthy control group. A s le of 335 patients with FEP and 253 healthy controls was ided into four subgroups: control tobacco users (CTU), control non-tobacco users (CNTU), patient tobacco users (PTU) and patient non-tobacco users (PNTU). Demographic variables, tobacco use variables (presence or absence, frequency and duration of tobacco use), neurocognitive (non-social) performance and social cognition were assessed. Comparison of 4 subgroups in non-social cognitive function revealed significant differences after controlling for covariables in executive functions (F=13.45 p≤0.001) and working memory domains (F=4.30 p=0.005). CTU and CNTU subgroups scored higher in all the domains compared to the PTU and the PNTU subgroups respectively. Social cognitive function was also significantly different within the four subgroups, with control subgroups showing better social cognition than patient subgroups. Significant differences in the executive functions domain were observed when comparing PTU and CTU groups (F=19.60 p≤0.001). No significant differences were revealed in the comparison between the patient groups. This large study suggests that tobacco use in FEP patients is not related to better non-social or social cognitive performance.
Publisher: Elsevier BV
Date: 04-2017
DOI: 10.1016/J.EURONEURO.2017.01.010
Abstract: We analyzed the efficacy of functional remediation, in a s le of patients with bipolar disorder who presented with subsyndromal symptoms. From a total s le of 239 patients with bipolar I and II disorder, according to DSM-IV-TR diagnostic criteria, entering a randomized clinical trial, those patients who presented with subsyndromal symptoms were selected based on a method already described by Berk and colleagues was applied. It consists of using the Clinical Global Impression-Bipolar version (CGI-BP) to establish the scores of the Hamilton Depression Rating Scale (HAM-D) and of the Young Mania Rating Scale (YMRS) that correspond with 1 in the CGI-BP. Functional outcome and mood symptoms were assessed at 6 and at 12-month follow-up. A total of 99 patients were selected for this post-hoc analysis, allocated as follows: functional remediation (n=33) psychoeducation (n=37) and treatment as usual (TAU,n=29). The repeated-measures analyses at 12-month follow-up revealed a significant group x time interaction in favour of the patients who received functional remediation when compared to psychoeducation and TAU (F=2.93 p=0.02) at improving psychosocial functioning. Finally, mood symptoms did not significantly change in any of the three groups at any time of follow-up, as shown by the non-significant group x time interaction effect in HAM-D scores (F=1.57 p=0.18) and YMRS scores (F=1.51 p=0.20). Bipolar patients with subsyndromal symptoms improve their functional outcome when exposed to functional remediation regardless of the persistence of mood symptomatology.
Publisher: Springer Science and Business Media LLC
Date: 12-2016
DOI: 10.1186/S13195-016-0219-5
Abstract: Progressive and relatively circumscribed loss of semantic knowledge, referred to as semantic dementia (SD) which falls under the broader umbrella of frontotemporal dementia, was officially identified as a clinical syndrome less than 50 years ago. Here, we review recent neuroimaging, pathological, and genetic research in SD. From a neuroimaging perspective, SD is characterised by hallmark asymmetrical atrophy of the anterior temporal pole and anterior fusiform gyrus, which is usually left lateralised. Functional magnetic resonance imaging (fMRI) studies have revealed widespread changes in connectivity, implicating the anterior temporal regions in semantic deficits in SD. Task-related fMRI have also demonstrated the relative preservation of frontal and parietal regions alongside preserved memory performance. In addition, recent longitudinal studies have demonstrated that, with disease progression, atrophy encroaches into the contralateral temporal pole and medial prefrontal cortices, which reflects emerging changes in behaviour and social cognition. Notably, unlike other frontotemporal dementia subtypes, recent research has demonstrated strong clinicopathological concordance in SD, with TDP43 type C as the most common pathological subtype. Moreover, an underlying genetic cause appears to be relatively rare in SD, with the majority of cases having a sporadic form of the disease. The relatively clear diagnosis, clinical course, and pathological homogeneity of SD make this syndrome a promising target for novel disease-modifying interventions. The development of neuroimaging markers of disease progression at the in idual level is an important area of research for future studies to address, in order to assist with this endeavour.
Publisher: Elsevier BV
Date: 06-2019
DOI: 10.1016/J.EURONEURO.2019.04.005
Abstract: Alterations of the endocannabinoid system (ECS) may play an important role in the development of schizophrenia and other psychotic disorders. Cannabis use is one of the environmental factors more repeatedly related to an increase the risk of developing a psychotic episode, while its use modifies the ECS normal function. In the present study we purposed to examine the gene by environment (GxE) interaction between 15 selected single nucleotide polymorphisms (SNPs) related to the ECS and cannabis use in a cohort of 321 patients with a first episode of psychosis (FEP) and 241 matched healthy controls. We found the fatty-acid amide hydrolase (FAAH) rs2295633 SNP genetic polymorphism was associated with a greater risk of presenting a FEP in subjects with relevant cannabis use, but not in subjects without a history of cannabis use. The probability of presenting a FEP was tenfold higher (OR: 10.69) in cannabis users who were homozygote carriers of the T allele of the FAAH rs2295633 SNP, compared to users of cannabis without this genotype. We also found that a higher a proportion of TT carriers of the FAAH rs2295633 SNP with a positive history of cannabis use was treated with high potency antipsychotic. This study has identified a GxE-environment interaction between a genetic polymorphism from the ECS and cannabis use involved in the risk of presenting a FEP. Although this preliminary data should be replicated with independent s les, our results highlight the importance of the pro-psychotic effects of exogenous cannabis use over the ECS in certain subjects.
Publisher: Wiley
Date: 05-05-2017
DOI: 10.1002/HBM.23627
Publisher: Elsevier BV
Date: 04-2018
Publisher: Elsevier BV
Date: 2021
Publisher: Royal College of Psychiatrists
Date: 07-2013
DOI: 10.1192/BJP.BP.112.114538
Abstract: The pathological basis of tar e dyskinesia is unknown. Although its clinical features implicate the basal ganglia, imaging studies have not found clear evidence that it is associated with volume changes in these or other brain structures. To determine, using voxel-based structural imaging, whether there are regions of grey matter volume change in people with schizophrenia who also have tar e dyskinesia compared with those without tar e dyskinesia. A total of 81 people with chronic schizophrenia, 32 with tar e dyskinesia and 49 without, were examined using magnetic resonance imaging (MRI) and whole-brain, optimised voxel-based morphometry. A comparison group of 61 healthy controls was also examined. Compared with those without tar e dyskinesia, patients with tar e dyskinesia showed a pattern of volume reductions in predominantly subcortical regions, including the basal ganglia and the thalamus. Within the basal ganglia, volume reductions were seen in the caudate nucleus, to a lesser extent in the putamen, and only marginally in the globus pallidus. The patients with tar e dyskinesia, but not those without, showed significant volume reductions in the basal ganglia compared with the healthy controls but both groups had smaller volumes than controls in other affected areas. The pathological process or processes that underlie the development of tar e dyskinesia are not just neurochemical in nature, but affect brain structure.
Publisher: Wiley
Date: 12-2022
DOI: 10.1002/ALZ.067557
Abstract: Previous reported sex differences on disease duration (DD) of frontotemporal dementia (FTD) have been inconsistent and lack the comparison between genetic and sporadic FTD. Our aim was to study the difference in disease duration between males and females in genetic and sporadic FTD. Mortality data was obtained from 61 deceased patients with genetic FTD (52% male) and 117 deceased patients with sporadic FTD (64% male) from the international FTD cohort previously reported by de Boer et al. , 2021. The age at symptom onset (AAO), age at death (AAD) and the DD (defined as the time between age at symptom onset and age at death) were compared between males and females in the genetic and sporadic FTD group using Mann Whitney U tests. Genetic FTD did not show significant sex differences in AAO, AAD and DD (p = 0.3, p = 0.3, p = 0.8 respectively, Figure 1). In sporadic FTD, the AAO and AAD did not significantly differ between males and females (p = 0.8 and p = 0.2 respectively). The DD in the sporadic FTD group was significantly shorter in females (median DD 7.0 years) in comparison to males (median DD 8.0 years, p = 0.01, Figure 2). In this study we show that females with sporadic FTD have a shorter disease duration than males whereas in genetic FTD the disease duration does not differ between sex. These findings suggest the existence of sex‐related differences in the disease course of sporadic FTD. We urge the need for international epidemiological FTD studies to further explore the role of sex in both genetic and sporadic FTD.
Publisher: Oxford University Press (OUP)
Date: 2020
DOI: 10.1093/BRAINCOMMS/FCAA194
Abstract: Mounting evidence suggests an association between cerebellar atrophy and cognitive impairment in the main frontotemporal dementia syndromes. In contrast, whether cerebellar atrophy is present in the motor syndromes associated with frontotemporal lobar degeneration (corticobasal syndrome and progressive supranuclear palsy) and the extent of its contribution to their cognitive profile remain poorly understood. The current study aimed to comprehensively chart profiles of cognitive impairment in relation to cerebellar atrophy in 49 dementia patients (corticobasal syndrome = 33 progressive supranuclear palsy = 16) compared to 33 age-, sex- and education-matched healthy controls. Relative to controls, corticobasal syndrome and progressive supranuclear palsy patients demonstrated characteristic cognitive impairment, spanning the majority of cognitive domains including attention and processing speed, language, working memory, and executive function with relative preservation of verbal and nonverbal memory. Voxel-based morphometry analysis revealed largely overlapping patterns of cerebellar atrophy in corticobasal syndrome and progressive supranuclear palsy relative to controls, primarily involving bilateral Crus II extending into adjacent lobules VIIb and VIIIa. After controlling for overall cerebral atrophy and disease duration, exploratory voxel-wise general linear model analysis revealed distinct cerebellar subregions differentially implicated across cognitive domains in each patient group. In corticobasal syndrome, reduction in grey matter intensity in the left Crus I was significantly correlated with executive dysfunction. In progressive supranuclear palsy, integrity of the vermis and adjacent right lobules I–IV was significantly associated with language performance. These results are consistent with the well-established role of Crus I in executive functions and provide further supporting evidence for vermal involvement in cognitive processing. The current study presents the first detailed exploration of the role of cerebellar atrophy in cognitive deficits in corticobasal syndrome and progressive supranuclear palsy, offering insights into the cerebellum’s contribution to cognitive processing even in neurodegenerative syndromes characterized by motor impairment.
Publisher: Wiley
Date: 03-05-2018
DOI: 10.1111/ACPS.12894
Abstract: The current investigation aimed at studying the sociodemographic, clinical, and neuropsychological variables related to functional outcome in a s le of euthymic patients with bipolar disorder(BD) presenting moderate-severe levels of functional impairment. Two-hundred and thirty-nine participants with BD disorders and with Functioning Assessment Short Test(FAST) scores equal or above 18 were administered a clinical and diagnostic interview, and the administration of mood measure scales and a comprehensive neuropsychological battery. Analyses involved preliminary Pearson bivariate correlations to identify sociodemographic and clinical variables associated with the FAST total score. Regarding neuropsychological variables, a principal component analysis (PCA) was performed to group the variables in orthogonal factors. Finally, a hierarchical multiple regression was run. The best fitting model for the variables associated with functioning was a linear combination of gender, age, estimated IQ, Hamilton Depression Rating Scale (HAM-D), number of previous manic episodes, Factor 1 and Factor 2 extracted from the PCA. The model, including all these previous variables, explained up to 29.4% of the observed variance. Male gender, older age, lower premorbid IQ, subdepressive symptoms, higher number of manic episodes, and lower performance in verbal memory, working memory, verbal fluency, and processing speed were associated with lower functioning in patients with BD.
Publisher: Royal College of Psychiatrists
Date: 2016
DOI: 10.1192/BJP.BP.114.162123
Abstract: Few randomised clinical trials have examined the efficacy of an intervention aimed at improving psychosocial functioning in bipolar disorder. To examine changes in psychosocial functioning in a group that has been enrolled in a functional remediation programme 1 year after baseline. This was a multicentre, randomised, rater-masked clinical trial comparing three patient groups: functional remediation, psychoeducation and treatment as usual over 1-year follow-up. The primary outcome was change in psychosocial functioning measured by means of the Functioning Assessment Short Test (FAST). Group×time effects for overall psychosocial functioning were examined using repeated-measures ANOVA (trial registration NCT01370668). There was a significant group×time interaction for overall psychosocial functioning, favouring patients in the functional remediation group ( F = 3.071, d.f. = 2, P = 0.049). Improvement in psychosocial functioning is maintained after 1-year follow-up in patients with bipolar disorder receiving functional remediation.
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.SCHRES.2017.06.032
Abstract: Patients with a first episode of psychosis (FEP) display a broad range of metabolic risk factors related to the development of erse medical comorbidities. Initial stages of these disorders are essential in understanding the increased vulnerability of developing cardiometabolic disturbances, associated with a reduced life expectancy. This study aimed to evaluate the metabolic profile of a cohort of patients with a FEP and its evolution during a two year follow-up, as well as the factors that influence the changes in their metabolic status. 16 participating centers from the PEPs Project recruited 335 subjects with a FEP and 253 matched healthy controls, aged 9-35years. We investigated a set of anthropometric measures, vital signs and laboratory data obtained from each participant over two years in a prospective, naturalistic study. From the beginning of the study the FEP group showed differences in the metabolic profile compared to the control group, together with a progressive worsening in the major part of the analyzed variables during the follow-up period, with higher rates of obesity and metabolic syndrome. Certain risk factors were related to determinate clinical variables such as male gender, the presence of affective symptoms or an early onset or to treatment variables such as the use of antipsychotic polypharmacy, antidepressants or mood stabilizers. Our results highlight the extremely high risk of patients at early phases of schizophrenia and other psychotic disorders of developing cardiovascular comorbidity and the fast worsening of the metabolic profile during the first two years.
Publisher: Wiley
Date: 30-12-2015
DOI: 10.1111/ACPS.12535
Abstract: Cognitive reserve (CR) is a concept that was postulated as a protective factor for some clinical symptoms after the observation that there is not a direct relationship between the degree of brain damage and its clinical manifestation. This study aimed to explore the association between CR and the main outcomes in bipolar disorder (BD): cognitive functions, psychosocial functioning and perceived quality of life. A s le of 224 euthymic bipolar patients was assessed with a neuropsychological battery, the Functioning Assessment Short Test and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). CR was calculated through three proxies: estimated premorbid Intelligent Quotient, educational level and occupational attainment. Relationships between CR and cognitive functions, psychosocial functioning and quality of life were assessed by multiple linear regression models. Higher CR was associated with better cognitive functioning (P < 0.001 in processing speed, working memory, verbal and visual memory, and executive function P = 0.026 in attention) and better psychosocial functioning (P = 0.008). For quality of life, CR was positively associated with the physical component of the SF-36 (P = 0.016) but negatively associated with the mental component (P = 0.004). The results suggest that CR may play an important role in the course and prognosis of bipolar patients and it should be considered in both clinical and research settings related to BD.
Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1016/J.SCHRES.2016.02.033
Abstract: Structural pathology in the hippoc us is well-documented in schizophrenia, but brain functional changes have not been consistently found. We used spatial navigation in a virtual reality environment, a task that is known to produce robust hippoc al activation in healthy subjects, to examine task-related activations and de-activations in the disorder. Twenty-seven DSM IV schizophrenia patients and 32 healthy controls underwent fMRI while they navigated to a goal through a virtual reality town. Activations and de-activations were examined at the whole brain level and also using a region-of-interest (ROI) in the hippoc us. Spatial navigation was associated with activation in the posterior hippoc us and parahippoc al gyrus plus widespread neocortical areas. The patients showed reduced activation compared to the controls in the left dorsolateral prefrontal cortex (DLPFC) and the left occipital/temporal cortex. No differences in hippoc al activation were seen either at the whole-brain level or in the ROI analysis. The patients showed failure of de-activation affecting some but not all subregions of the default mode network. Schizophrenia is associated with task-related hypoactivation in the DLPFC during spatial navigation, but not with functional changes in the hippoc us. The failure of de-activation also found adds to evidence for default mode network dysfunction in the disorder.
Publisher: Cambridge University Press (CUP)
Date: 21-10-2014
DOI: 10.1017/S0033291714002426
Abstract: Functional imaging studies in relatives of schizophrenic patients have had inconsistent findings, particularly with respect to altered dorsolateral prefrontal cortex activation. Some recent studies have also suggested that failure of deactivation may be seen. A total of 28 patients with schizophrenia, 28 of their siblings and 56 healthy controls underwent functional magnetic resonance imaging during performance of the n-back working memory task. An analysis of variance was fitted to in idual whole-brain maps from each set of patient–relative–matched pair of controls. Clusters of significant difference among the groups were then used as regions of interest to compare mean activations and deactivations among the groups. In all, five clusters of significant differences were found. The schizophrenic patients, but not the relatives, showed reduced activation compared with the controls in the lateral frontal cortex bilaterally, the left basal ganglia and the cerebellum. In contrast, both the patients and the relatives showed significant failure of deactivation compared with the healthy controls in the medial frontal cortex, with the relatives also showing less failure than the patients. Failure of deactivation was not associated with schizotypy scores or presence of psychotic-like experiences in the relatives. Both schizophrenic patients and their relatives show altered task-related deactivation in the medial frontal cortex. This in turn suggests that default mode network dysfunction may function as a trait marker for schizophrenia.
Publisher: IEEE
Date: 04-2018
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.SCHRES.2017.01.058
Abstract: Recent research demonstrates the heterogeneous etiology of psychotic disorders, where gen-environment (GxE) interaction plays a key role. Large genetic studies have linked many genetic variants with schizophrenia, but each variant is only associated with a small effect and the GxE interaction contribution has not been evaluated. The PEPs Project was designed to carefully collect a large amount of genetic and environmental exposure data of 335 FEP patients and 253 matched healthy controls.780single-nucleotide polymorphisms (from 159 candidate genes)and 16 environmental variables previously reported as the main psychosis non-genetic risk factors were analyzed together using entropy-based measures of information gain. Our analyses identified an interaction between nine SNPs and the exposition to the environmental risk factors of psychosis, showing a clear enrichment of genes linked to serotonin neurotransmission and neurodevelopmental processes. This study has allowed the identification of several GxE-environment interactions involved in the risk of presenting a FEP. Our results highlight the importance of serotonin neurotransmission interacting with certain environmental stimuli. The serotoninergic system may be playing a key role in the regulatory network of stress and other systems implicated in the emergence and development of psychotic disorders.
Publisher: Wiley
Date: 07-2018
DOI: 10.1002/ANA.25271
Abstract: Increasing evidence suggests that cerebellar damage impacts on cognitive functions. Frontotemporal dementias (FTDs) are neurodegenerative brain conditions, primarily affecting the frontal and/or temporal lobe. Three main phenotypes are recognized, each with a distinct clinical and cognitive profile: behavioral-variant FTD (bvFTD), semantic dementia (SD), and progressive nonfluent aphasia (PNFA). The severity of cerebellar changes and their relation to cognition in FTD, however, remain unclear. This study aimed to establish cerebellar gray matter changes on magnetic resonance imaging (MRI) and their relation to profiles of cognitive deficits in FTD subtypes. Ninety-six FTD patients (45 bvFTD, 28 SD, and 23 PNFA), meeting current clinical diagnostic criteria, and 35 age-, sex-, and education-matched controls underwent brain MRI and cognitive assessment. Cerebral and cerebellar gray matter integrity were investigated using voxel-based morphometry. Compared with controls, widespread bilateral cerebellar changes were observed in all FTD subtypes, with the greatest atrophy present in bvFTD. Significant associations were found between cerebellar integrity and cognitive performance in attention and working memory in bvFTD, visuospatial function in SD, and language-motor function in PNFA. Bilateral atrophy of crus and lobule VI were most commonly associated with cognitive deficits, irrespective of FTD phenotype. This study is the first to identify distinct patterns of cerebellar atrophy across FTD syndromes, which in turn relate to discrete cognitive dysfunctions, after accounting for the effect of cerebral atrophy. These findings extend our understanding of the cerebellum and point to its involvement across an array of processes beyond the domain of motor function. Ann Neurol 2018 :98-109.
Publisher: Elsevier BV
Date: 04-2018
DOI: 10.1016/J.RPSM.2015.12.002
Abstract: Eye movement desensitization and reprocessing (EMDR) is a relatively new psychotherapy that has gradually gained popularity for the treatment of post-traumatic stress disorder. In the present work, the standardised EMDR protocol is introduced, along with current hypotheses of its mechanism of action, as well as a critical review of the available literature on its clinical effectiveness in adult post-traumatic stress disorder. A systematic review of the published literature was performed using PubMed and PsycINFO databases with the keywords «eye movement desensitization and reprocessing» and «post-traumatic stress disorder» and its abbreviations «EMDR» and «PTSD». Fifteen randomised controlled trials of good methodological quality were selected. These studies compared EMDR with unspecific interventions, waiting lists, or specific therapies. Overall, the results of these studies suggest that EMDR is a useful, evidence-based tool for the treatment of post-traumatic stress disorder, in line with recent recommendations from different international health organisations.
Publisher: Oxford University Press (OUP)
Date: 25-01-2016
DOI: 10.1093/BRAIN/AWV387
Abstract: The typical presentation of semantic dementia is associated with marked, left predominant anterior temporal lobe atrophy and with changes in language. About 30% of in iduals, however, present with predominant right anterior temporal lobe atrophy, usually accompanied by behavioural changes and prosopagnosia. Here, we aimed to establish whether these initially distinct clinical presentations evolve into a similar syndrome at the neural and behavioural level. Thirty-one patients who presented with predominant anterior temporal lobe atrophy were included. Based on imaging, patients were categorized as either predominant left (n = 22) or right (n = 9) semantic dementia. Thirty-three Alzheimer's disease patients and 25 healthy controls were included for comparison. Participants completed the Addenbrooke's Cognitive Examination, a Face and Emotion Processing Battery and the Cambridge Behavioural Inventory, and underwent magnetic resonance imaging annually. Longitudinal neuroimaging analyses showed greater right temporal pole atrophy in left semantic dementia than Alzheimer's disease, whereas right semantic dementia showed greater orbitofrontal and left temporal lobe atrophy than Alzheimer's disease. Importantly, direct comparisons between semantic dementia groups revealed that over time, left semantic dementia showed progressive thinning in the right temporal pole, whereas right semantic dementia showed thinning in the orbitofrontal cortex and anterior cingulate. Behaviourally, longitudinal analyses revealed that general cognition declined in all patients. In contrast, patients with left and right semantic dementia showed greater emotion recognition decline than Alzheimer's disease. In addition, left semantic dementia showed greater motivation loss than Alzheimer's disease. Correlational analyses revealed that emotion recognition was associated with right temporal pole, right medial orbitofrontal and right fusiform integrity, while changes in motivation were associated with right temporal pole cortical thinning. While left and right semantic dementia show distinct profiles at presentation, both phenotypes develop deficits in emotion recognition and behaviour. These findings highlight the pervasive socio-emotional deficits in frontotemporal dementia, even in patients with an initial language presentation. These changes reflect right anterior temporal and orbitofrontal cortex degeneration, underscoring the role of these regions in social cognition and behaviour.
Publisher: Association for Computing Machinery (ACM)
Date: 02-01-2019
DOI: 10.1145/3290344
Abstract: Quantum computation is a topic of significant recent interest, with practical advances coming from both research and industry. A major challenge in quantum programming is dealing with errors (quantum noise) during execution. Because quantum resources (e.g., qubits) are scarce, classical error correction techniques applied at the level of the architecture are currently cost-prohibitive. But while this reality means that quantum programs are almost certain to have errors, there as yet exists no principled means to reason about erroneous behavior. This paper attempts to fill this gap by developing a semantics for erroneous quantum while-programs, as well as a logic for reasoning about them. This logic permits proving a property we have identified, called є-robustness, which characterizes possible “distance” between an ideal program and an erroneous one. We have proved the logic sound, and showed its utility on several case studies, notably: (1) analyzing the robustness of noisy versions of the quantum Bernoulli factory (QBF) and quantum walk (QW) (2) demonstrating the (in)effectiveness of different error correction schemes on single-qubit errors and (3) analyzing the robustness of a fault-tolerant version of QBF.
Publisher: Cambridge University Press (CUP)
Date: 07-07-2011
DOI: 10.1017/S0033291711001073
Abstract: It is not known whether first-episode psychosis is characterized by the same prefrontal cortex functional imaging abnormalities as chronic schizophrenia. Thirty patients with a first episode of non-affective functional psychosis and 28 healthy controls underwent functional magnetic resonance imaging (fMRI) during performance of the n-back working memory task. Voxel-based analyses of brain activations and deactivations were carried out and compared between groups. The connectivity of regions of significant difference between the patients and controls was also examined. The first-episode patients did not show significant prefrontal hypo- or hyperactivation compared to controls. However, they showed failure of deactivation in the medial frontal cortex. This area showed high levels of connectivity with the posterior cingulate gyrus recuneus and parts of the parietal cortex bilaterally. Failure of deactivation was significantly greater in first-episode patients who had or went on to acquire a DSM-IV diagnosis of schizophrenia than in those who did not, and in those who met RDC criteria for schizophrenia compared to those who did not. First-episode psychosis is not characterized by hypo- or hyperfrontality but instead by a failure of deactivation in the medial frontal cortex. The location and connectivity of this area suggest that it is part of the default mode network. The failure of deactivation seems to be particularly marked in first-episode patients who have, or progress to, schizophrenia.
Publisher: Oxford University Press (OUP)
Date: 06-2020
DOI: 10.1093/SCAN/NSAA085
Abstract: Negative and positive emotions are known to shape decision-making toward more or less impulsive responses, respectively. Decision-making and emotion processing are underpinned by shared brain regions including the ventromedial prefrontal cortex (vmPFC) and the amygdala. How these processes interact at the behavioral and brain levels is still unclear. We used a lesion model to address this question. Study participants included in iduals diagnosed with behavioral-variant frontotemporal dementia (bvFTD, n = 18), who typically present deficits in decision-making/emotion processing and atrophy of the vmPFC, in iduals with Alzheimer’s disease (AD, n = 12) who present with atrophy in limbic structures and age-matched healthy controls (CTRL, n = 15). Prior to each choice on the delay discounting task participants were cued with a positive, negative or neutral picture and asked to vividly imagine witnessing the event. As hypothesized, our findings showed that bvFTD patients were more impulsive than AD patients and CTRL and did not show any emotion-related modulation of delay discounting rate. In contrast, AD patients showed increased impulsivity when primed by negative emotion. This increased impulsivity was associated with reduced integrity of bilateral amygdala in AD but not in bvFTD. Altogether, our results indicate that decision-making and emotion interact at the level of the amygdala supporting findings from animal studies.
Publisher: Elsevier BV
Date: 04-2022
DOI: 10.1016/J.EURONEURO.2022.02.003
Abstract: Neurotrophins have been proposed to be involved in biological mechanisms which might underlie different clinical outcomes in schizophrenia. The aims of the present study were to examine the BDNF/NGF plasma levels in a cohort of first-episode schizophrenia (FES) patients in remission as potential biological predictors of relapse to study the associations between these neurotrophins and the symptomatology severity through different stages after a FES in two independent cohorts. 2EPs-Cohort: 69 first-episode in clinical remission were included. BDNF/NGF plasma levels and symptom severity were measured at enrollment and at 3-year or at the time of the second episode/relapse. FLAMM-PEPs-Cohort: 65 first-episodes were also included. BDNF/NGF and symptom severity were obtained at enrollment and 2-year follow-up. Symptomatology was assessed with the Marder-PANSS-Factor scores. Plasma neurotrophins did not differ significantly over time and neither BDNF/NGF were predictors of relapse. Besides, in remission stages, baseline BDNF levels showed significant correlations with both positive and negative symptoms (p<0.05) NGF, with negative symptomatology (p<0.01). Similarly, in the FLAMM-PEPs-Cohort, baseline BDNF/NGF levels showed significant correlations with negative symptoms (and not positive symptomatology) at follow-up (p<0.05). In both cohorts, lower levels correlated with higher symptom severity. Findings did not support a role for BDNF/NGF plasma levels as biomarkers of relapse in FES patients. Nevertheless, baseline BDNF/NGF may lead to be considered potentially useful biomarkers of long-term severity in schizophrenia and of the underlying illness traits, specially of negative symptomatology severity. More longitudinal studies in FES s les and adding a control group are warranted to replicate these findings.
Publisher: Frontiers Media SA
Date: 07-11-2017
Publisher: Springer Science and Business Media LLC
Date: 21-11-2017
DOI: 10.1007/S00406-017-0857-Z
Abstract: In idual changes over time in cognition in patients with psychotic disorders have been studied very little, especially in the case of first episode psychosis (FEP). We aimed to establish whether change in in idual trajectories in cognition over 2 years of a s le of 159 FEP patients was reliable and clinically significant, using the reliable change index (RCI) and clinically significant change (CSC) methods. We also studied a s le of 151 matched healthy controls. Patients and controls were assessed with a set of neuropsychological tests, as well as premorbid, clinical and functionality measures. We analysed the course of cognitive measures over time, using analysis of variance, and the in idual trajectories in the cognitive measures with the regression-based RCI (RCI
Publisher: Elsevier BV
Date: 04-2017
DOI: 10.1016/J.PSYCHRES.2017.01.045
Abstract: Although an interaction between COMT Val158Met and BDNF Val66Met polymorphisms with cannabis use has been proposed with respect to the risk of psychosis emergence, findings remain inconclusive. The aim of the present study was to evaluate the different possible associations between these polymorphisms and early cannabis use and the age at the first episode of psychosis. The relationship between age at psychosis onset and COMT Val158Met and BDNF Val66Met polymorphisms with early cannabis use as well as those factors associated with early cannabis use were investigated. Among 260 Caucasian first-episode psychosis patients, early cannabis use and the presence of the met-allele from the BDNF Val66Met polymorphism were significantly associated with age at psychosis onset. Furthermore, early cannabis use was significantly associated with male gender in the logistic regression analysis. These findings provide evidence of the important role of early cannabis use and the Val66Met BDNF polymorphism on age at psychosis onset and they point out to sex-specific differences in cannabis use patterns.
Publisher: Elsevier BV
Date: 11-2013
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.NEUROPSYCHOLOGIA.2017.03.014
Abstract: Compromised autobiographical memory (ABM) retrieval is well established in dementia, attributable to degeneration of a core memory brain network. It remains unclear, however, how the progressive spread of atrophy with advancing disease severity impacts ABM retrieval across life epochs. To this end, we conducted a longitudinal study of recent and remote ABM in Alzheimer's disease (AD, n =11), and a frontotemporal lobar degeneration group (FTD, n =13) comprising 7 behavioral variant FTD and 6 semantic dementia patients, in comparison with 23 healthy older Controls. Patients were re-assessed approximately one year following their initial visit and underwent repeat testing and brain imaging. Linear mixed modeling neuroimaging analyses explored disease-specific cortical changes driving ABM alterations over time. AD patients showed comparable ABM profiles across assessment periods however, follow-up performance correlated strongly with lateral temporal lobe integrity. In contrast, recent ABMs were disproportionately disrupted at follow-up relative to baseline in the FTD group, attributable to cortical thinning in posterior brain regions, including the right posterior cingulate cortex. Our findings offer new insights regarding the potential time-specific role of discrete cortical regions in ABM retrieval and the differential fate of formerly evocative memories with advancing disease severity in dementia syndromes.
Publisher: Elsevier BV
Date: 10-2019
Publisher: Cambridge University Press (CUP)
Date: 21-09-2015
DOI: 10.1017/S0033291715001713
Abstract: Functional remediation is a novel intervention with demonstrated efficacy at improving functional outcome in euthymic bipolar patients. However, in a previous trial no significant changes in neurocognitive measures were detected. The objective of the present analysis was to test the efficacy of this therapy in the enhancement of neuropsychological functions in a subgroup of neurocognitively impaired bipolar patients. A total of 188 out of 239 DSM-IV euthymic bipolar patients performing below two standard deviations from the mean of normative data in any neurocognitive test were included in this subanalysis. Repeated-measures analyses of variance were conducted to assess the impact of the treatment arms [functional remediation, psychoeducation, or treatment as usual (TAU)] on participants’ neurocognitive and functional outcomes in the subgroup of neurocognitively impaired patients. Patients receiving functional remediation ( n = 56) showed an improvement on delayed free recall when compared with the TAU ( n = 63) and psychoeducation ( n = 69) groups as shown by the group × time interaction at 6-month follow-up [ F 2,158 = 3.37, degrees of freedom (df) = 2, p = 0.037]. However, Tukey post-hoc analyses revealed that functional remediation was only superior when compared with TAU ( p = 0.04), but not with psychoeducation ( p = 0.10). Finally, the patients in the functional remediation group also benefited from the treatment in terms of functional outcome ( F 2,158 = 4.26, df = 2, p = 0.016). Functional remediation is effective at improving verbal memory and psychosocial functioning in a s le of neurocognitively impaired bipolar patients at 6-month follow-up. Neurocognitive enhancement may be one of the active ingredients of this novel intervention, and, specifically, verbal memory appears to be the most sensitive function that improves with functional remediation.
Publisher: Future Medicine Ltd
Date: 12-2017
Publisher: Georg Thieme Verlag KG
Date: 16-05-2013
Abstract: Agitation is a severe clinical state which represents a therapeutic challenge and often forms part of manic or mixed episodes. Therapeutic options for acute mania have been limited for many years to lithium and typical antipsychotics. Besides anticonvulsants, atypical antipsychotics have been increasingly introduced in the last decade after proving their efficacy in this indication. To avoid intramuscular administration and excessive sedation, a therapeutic contact to the often agitated patient is required. De-escalation techniques can be helpful in this respect but also reduce aggressive behaviour on the ward, improve compliance, reduce relapse rates and lead to a better outcome in the long-term course of the illness. Therefore, a basic knowledge about de-escalation techniques in acute manic patients is an important clinical tool which will be critically reviewed. Furthermore, the efficacy and tolerability of atypical antipsychotics in acute mania, such as olanzapine, zotepine, risperidone, quetiapine, ziprasidone, aripiprazole, paliperidone and asenapine are discussed.
Publisher: Oxford University Press (OUP)
Date: 04-03-2020
Abstract: The behavioural variant of frontotemporal dementia (bvFTD) is a frequent cause of early-onset dementia. The diagnosis of bvFTD remains challenging because of the limited accuracy of neuroimaging in the early disease stages and the absence of molecular biomarkers, and therefore relies predominantly on clinical assessment. BvFTD shows significant symptomatic overlap with non-degenerative primary psychiatric disorders including major depressive disorder, bipolar disorder, schizophrenia, obsessive-compulsive disorder, autism spectrum disorders and even personality disorders. To date, ∼50% of patients with bvFTD receive a prior psychiatric diagnosis, and average diagnostic delay is up to 5–6 years from symptom onset. It is also not uncommon for patients with primary psychiatric disorders to be wrongly diagnosed with bvFTD. The Neuropsychiatric International Consortium for Frontotemporal Dementia was recently established to determine the current best clinical practice and set up an international collaboration to share a common dataset for future research. The goal of the present paper was to review the existing literature on the diagnosis of bvFTD and its differential diagnosis with primary psychiatric disorders to provide consensus recommendations on the clinical assessment. A systematic literature search with a narrative review was performed to determine all bvFTD-related diagnostic evidence for the following topics: bvFTD history taking, psychiatric assessment, clinical scales, physical and neurological examination, bedside cognitive tests, neuropsychological assessment, social cognition, structural neuroimaging, functional neuroimaging, CSF and genetic testing. For each topic, responsible team members proposed a set of minimal requirements, optimal clinical recommendations, and tools requiring further research or those that should be developed. Recommendations were listed if they reached a ≥ 85% expert consensus based on an online survey among all consortium participants. New recommendations include performing at least one formal social cognition test in the standard neuropsychological battery for bvFTD. We emphasize the importance of 3D-T1 brain MRI with a standardized review protocol including validated visual atrophy rating scales, and to consider volumetric analyses if available. We clarify the role of 18F-fluorodeoxyglucose PET for the exclusion of bvFTD when normal, whereas non-specific regional metabolism abnormalities should not be over-interpreted in the case of a psychiatric differential diagnosis. We highlight the potential role of serum or CSF neurofilament light chain to differentiate bvFTD from primary psychiatric disorders. Finally, based on the increasing literature and clinical experience, the consortium determined that screening for C9orf72 mutation should be performed in all possible robable bvFTD cases or suspected cases with strong psychiatric features.
Publisher: American Psychiatric Association Publishing
Date: 08-2013
DOI: 10.1176/APPI.AJP.2012.12070971
Abstract: OBJECTIVE The authors sought to assess the efficacy of functional remediation, a novel intervention program, on functional improvement in a s le of euthymic patients with bipolar disorder. METHOD In a multicenter, randomized, rater-blind clinical trial involving 239 outpatients with DSM-IV bipolar disorder, functional remediation (N=77) was compared with psychoeducation (N=82) and treatment as usual (N=80) over 21 weeks. Pharmacological treatment was kept stable in all three groups. The primary outcome measure was improvement in global psychosocial functioning, measured blindly as the mean change in score on the Functioning Assessment Short Test from baseline to endpoint. RESULTS At the end of the study, 183 patients completed the treatment phase. Repeated-measures analysis revealed significant functional improvement from baseline to endpoint over the 21 weeks of treatment (last observation carried forward), suggesting an interaction between treatment assignment and time. Tukey's post hoc tests revealed that functional remediation differed significantly from treatment as usual, but not from psychoeducation. CONCLUSIONS Functional remediation, a novel group intervention, showed efficacy in improving the functional outcome of a s le of euthymic bipolar patients as compared with treatment as usual.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-07-2017
DOI: 10.1212/WNL.0000000000004215
Abstract: To identify distinct behavioral phenotypes of behavioral-variant frontotemporal dementia (bvFTD) and to elucidate differences in functional, neuroimaging, and progression to residential care placement. Eighty-eight patients with bvFTD were included in a cluster analysis applying levels of disinhibition and apathy (Cambridge Behavioural Inventory-Revised) to identify phenotypic subgroups. Between-group (Kruskal-Wallis, Mann-Whitney U ) functional differences (Disability Assessment for Dementia) and time to residential care placement (survival analyses) were examined. Cortical thickness differences (whole-brain MRI) were analyzed in patients with bvFTD vs healthy controls (n = 30) and between phenotypic subgroups. Four phenotypic subgroups were identified: primary severe apathy (n = 26), severe apathy and disinhibition (n = 26), mild apathy and disinhibition (n = 27), and primary severe disinhibition (n = 9). Patients with severely apathetic phenotypes were more functionally impaired and had more extensive brain atrophy than those with mild apathy or severe disinhibition alone. Further imaging analyses indicated that the right middle temporal region is critical for the development of disinhibition, an association that remains with disease progression and in the context of severe apathy. Finally, no difference in time to residential care admission was found between phenotypes. This study reveals that different clinical behavioral phenotypes of bvFTD have differing profiles of functional decline and distinct patterns of associated cortical changes. These findings emphasize the importance of apathy in functional impairment, highlight the role of the right temporal region in disinhibition, and suggest that disability may be a sensitive outcome measure for treatments targeting reduction of apathy. These phenotypes could also support understanding of prognosis and clinical management.
Publisher: Wiley
Date: 14-08-2018
DOI: 10.1111/ACPS.12949
Abstract: Cognitive reserve (CR) refers to the brain's capacity to cope with pathology in order to minimize the symptoms. CR is associated with different outcomes in severe mental illness. This study aimed to analyze the impact of CR according to the diagnosis of first-episode affective or non-affective psychosis (FEP). A total of 247 FEP patients (211 non-affective and 36 affective) and 205 healthy controls were enrolled. To assess CR, common proxies have been integrated (premorbid IQ education-occupation leisure activities). The groups were ided into high and low CR. In non-affective patients, those with high CR were older, had higher socioeconomic status (SES), shorter duration of untreated psychosis, and a later age of onset. They also showed greater performance in most cognitive domains. In affective patients, those with a greater CR showed a higher SES, better functioning, and greater verbal memory performance. CR plays a differential role in the outcome of psychoses according to the diagnosis. Specifically, in order to address the needs of non-affective patients with low CR, cognitive rehabilitation treatments will need to be 'enriched' by adding pro-cognitive pharmacological agents or using more sophisticated approaches. However, a functional remediation therapy may be of choice for those with an affective psychosis and low CR.
Publisher: S. Karger AG
Date: 2014
DOI: 10.1159/000356972
Abstract: b i Objective: /i /b The present study examined whole-brain structural abnormalities in schizophrenia, with a special focus on the anterior and posterior cingulate cortex (ACC, PCC) as this is an understudied issue in schizophrenia. b i Method: /i /b Whole-brain voxel-based morphometry analyses of gray matter (GM) and white matter (WM) were performed to detect volumetric differences between 14 patients with schizophrenia and 14 healthy controls matched for age, sex, educational level and parents' educational level. We examined within-group GM and WM correlations and completed the analysis with measurements of sulci in medial cortical areas. b i Results: /i /b Compared with the healthy controls, the schizophrenic patients showed significant decreases in GM volumes in the ACC and PCC, and in neighboring WM regions such as the corpus callosum and the fimbriae of the fornix. Moreover, the patient group also displayed a negative correlation between volumes of GM and WM in the ACC. Finally, the patients showed significantly reduced volumes in the right cingulate sulci and left inferior frontal sulci. b i Conclusion: /i /b Our results replicate typical brain-structural abnormalities with new findings in the medial prefrontal cortex, suggested to be a key region in this disorder.
Publisher: Elsevier BV
Date: 10-2017
Publisher: Cambridge University Press (CUP)
Date: 2014
Publisher: Cambridge University Press (CUP)
Date: 10-2016
DOI: 10.1016/J.EURPSY.2016.04.011
Abstract: A functional polymorphism of the brain-derived neurotrophic factor gene ( BDNF ) Val66Met has been associated with cognitive function and symptom severity in patients with schizophrenia. It has been suggested that the Val66Met polymorphism has a role as a modulator in a range of clinical features of the illness, including symptoms severity, therapeutic responsiveness, age of onset, brain morphology and cognitive function. However, little work has been done in first-episode schizophrenia (FES) spectrum disorders. The objective of this study is to investigate the association of the BDNF Val66Met polymorphism on cognitive function and clinical symptomatology in FES patients. Using a cross-sectional design in a cohort of 204 patients with FES or a schizophrenia spectrum disorder and 204 healthy matched controls, we performed BDNF Val66Met genotyping and tested its relationship with cognitive testing (attention, working memory, learning/verbal memory and reasoning roblem-solving) and assessment of clinical symptom severity. There was no significant influence of the BDNF allele frequency on cognitive factor scores in either patients or controls. An augmented severity of negative symptoms was found in FES patients that carried the Met allele. The results of this study suggest that in patients with a first-episode of schizophrenia or a schizophrenia spectrum disorder, the BDNF Val66Met polymorphism does not exert an influence on cognitive functioning, but is associated with negative symptoms severity. BDNF may serve as suitable marker of negative symptomatology severity in FES patients within the schizophrenia spectrum.
Publisher: Wiley
Date: 13-03-2019
DOI: 10.1111/BDI.12766
Publisher: Frontiers Media SA
Date: 13-08-2018
Publisher: Elsevier BV
Date: 2017
Publisher: Springer Science and Business Media LLC
Date: 27-03-2023
DOI: 10.1186/S40478-023-01544-7
Abstract: Heterozygous mutations in the GRN gene and hexanucleotide repeat expansions in C9orf72 are the two most common genetic causes of Frontotemporal Dementia (FTD) with TDP-43 protein inclusions. The triggers for neurodegeneration in FTD with GRN (FTD- GRN ) or C9orf72 (FTD- C9orf72 ) gene abnormalities are unknown, although evidence from mouse and cell culture models suggests that GRN mutations disrupt lysosomal lipid catabolism. To determine how brain lipid metabolism is affected in familial FTD with TDP-43 inclusions, and how this is related to myelin and lysosomal markers, we undertook comprehensive lipidomic analysis, enzyme activity assays, and western blotting on grey and white matter s les from the heavily-affected frontal lobe and less-affected parietal lobe of FTD- GRN cases, FTD- C9orf72 cases, and age-matched neurologically-normal controls. Substantial loss of myelin-enriched sphingolipids (sulfatide, galactosylceramide, sphingomyelin) and myelin proteins was observed in frontal white matter of FTD- GRN cases. A less-pronounced, yet statistically significant, loss of sphingolipids was also observed in FTD- C9orf7 2. FTD- GRN was distinguished from FTD- C9orf72 and control cases by increased acylcarnitines in frontal grey matter and marked accumulation of cholesterol esters in both frontal and parietal white matter, indicative of myelin break-down. Both FTD- GRN and FTD- C9orf72 cases showed significantly increased lysosomal and phagocytic protein markers, however galactocerebrosidase activity, required for lysosomal catabolism of galactosylceramide and sulfatide, was selectively increased in FTD- GRN . We conclude that both C9orf72 and GRN mutations are associated with disrupted lysosomal homeostasis and white matter lipid loss, but GRN mutations cause a more pronounced disruption to myelin lipid metabolism. Our findings support the hypothesis that hyperactive myelin lipid catabolism is a driver of gliosis and neurodegeneration in FTD- GRN . Since FTD- GRN is associated with white matter hyperintensities by MRI, our data provides important biochemical evidence supporting the use of MRI measures of white matter integrity in the diagnosis and management of FTD.
Publisher: Elsevier BV
Date: 09-2014
DOI: 10.1016/J.PSYCHRES.2014.05.012
Abstract: Traumatic events are frequent in bipolar patients and can worsen the course of the disease. Psychotherapeutic interventions for these events have not been studied so far. Twenty DSM-IV bipolar I and II patients with subsyndromal mood symptoms and a history of traumatic events were randomly assigned to Eye Movement Desensitization and Reprocessing therapy (n=10) or treatment as usual (n=10). The treatment group received between 14 and 18 Eye Movement Desensitization and Reprocessing sessions during 12 weeks. Evaluations of affective symptoms, symptoms of trauma and trauma impact were carried out by a blind rater at baseline, 2 weeks, 5 weeks, 8 weeks, 12 weeks and at 24 weeks follow-up. Patients in the treatment group showed a statistically significant improvement in depressive and hypomanic symptoms, symptoms of trauma and trauma impact compared to the treatment as usual group after intervention. This effect was only partly maintained in trauma impact at the 24 weeks follow-up visit. One patient dropped from Eye Movement Desensitization and Reprocessing group whereas four from the treatment as usual group. This pilot study suggests that Eye Movement Desensitization and Reprocessing therapy may be an effective and safe intervention to treat subsyndromal mood and trauma symptoms in traumatized bipolar patients.
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.SCHRES.2017.01.047
Abstract: This study aimed to investigate the course of negative symptoms and its stability over a two-year period following a first-episode schizophrenia (FES) and the possible predictors of higher severity in this symptomatology after this period. In this longitudinal two-year prospective follow-up study we included 268 patients with a FES, according to DSM-IV. Analysis of variance was conducted in patients who completed the full follow-up to study changes in negative symptoms over three visits. Regression analyses were conducted to show correlates and potential predictors of negative symptoms at two-year follow-up. There was a significant effect for time in negative symptomatology, which was less severe at one-year follow-up after a FES and remained stable up to two years (Time 1>Time 2>Time 3) F(2,151)=20.45, p<0.001. Poorer premorbid adjustment (p=0.01) and higher negative symptoms at baseline (p<0.001) made a significant contribution to the changes in the negative symptoms severity at two-years after a FES (R We found a reduction in the negative symptomatology at one-year after a FES. This change remained stable at two-year. Our results suggested that the presence of this symptomatology early in the course of the illness, together with a poorer premorbid adjustment, predict more severe negative symptoms at mid-term outcome.
Publisher: Public Library of Science (PLoS)
Date: 11-08-2016
Publisher: Elsevier BV
Date: 10-2017
Publisher: Elsevier BV
Date: 10-2017
Publisher: Elsevier BV
Date: 06-2022
DOI: 10.1016/J.SCHRES.2022.05.005
Abstract: Network analysis is an important conceptual and analytical approach in mental health research. However, few studies have used network analysis to examine the structure of cognitive performance in psychotic disorders. We examined the network structure of the cognitive scores of a s le of 207 first-episode psychosis (FEP) patients and 188 healthy controls. Participants were assessed using a battery of 10 neuropsychological tests. Fourteen cognitive scores encompassing six cognitive domains and premorbid IQ were selected to perform the network analysis. Many similarities were found in the network structure of FEP patients and healthy controls. Verbal memory, attention, working memory and executive function nodes were the most central nodes in the network. Nodes in both groups corresponding to the same tests tended to be strongly connected. Verbal memory, attention, working memory and executive function were central dimensions in the cognitive network of FEP patients and controls. These results suggest that the interplay between these core dimensions is essential for demands to solve complex tasks, and these interactions may guide the aims of cognitive rehabilitation. Network analysis of cognitive dimensions might have therapeutic implications that deserve further research.
Publisher: Elsevier BV
Date: 10-2017
Publisher: Wiley
Date: 28-08-2019
DOI: 10.1002/ACN3.50869
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.JAD.2018.06.005
Abstract: This study aimed to assess (1) whether there were clinical, neuropsychological and functional differences between and within affective and non-affective psychoses at baseline and two years-follow-up and (2) to explore clinical and neuropsychological predictors of psychosocial functioning in the whole s le. This is a subanalysis from a multicentre, naturalistic, longitudinal prospective study ('Phenotype-genotype and environmental interaction. Application of a predictive model in first psychotic episodes'). The s le consisted of 192 patients with a first psychotic episode (FEP): 142 with non-affective psychoses and 50 with affective psychoses. Student t-tests, paired t-tests, Pearson correlations, ANOVAs and regression analyses were performed. At baseline, the groups differed in perseverative errors (WCST), Premorbid Adjustment Scale (PAS), family history of psychiatric disorder, negative (PANSS) and manic symptoms (YMRS). At two years follow-up, the groups differed in all the PANSS subscales and in depressive symptoms assessed by the MADRS. When the whole s le was considered, the regression model which best explained the estimated variance in functioning at follow-up (41%) was composed by PANSS total score and verbal fluency assessed by the FAS (COWAT). We found clinical and neurocognitive differences at baseline which decreased in the follow-up. Reduced performances at baseline in executive functions in combination with symptom severity (PANSS) were predictors of FEP patients' poor functional outcome.
Publisher: S. Karger AG
Date: 2017
DOI: 10.1159/000478852
Abstract: b i Background/Aims: /i /b Although some patients with primary progressive aphasia (PPA) exhibit novel or improved skills after the onset of dementia, these changes have yet to be quantified. Therefore, this study systematically explored and identified the emergence of positive behaviours after dementia onset. b i Methods: /i /b This study included 48 carers of patients with PPA: 12 nonfluent/agrammatic PPA (nfvPPA), 22 semantic variant PPA (svPPA), and 14 logopenic variant PPA (lvPPA). The presence and frequency of positive behaviour changes after dementia onset were established using the Hypersensory and Social/Emotional Scale (HSS). b i Results: /i /b Scores on Sensitivity to Details, Visuospatial Activities, and Music Activities differed significantly among the groups. More specifically, svPPA was associated with increased visuospatial activity, but only in the mild stage of the disease nfvPPA was associated with increased visuospatial activity and decreased music activity, while lvPPA exhibited the reverse profile. b i Conclusions: /i /b The results demonstrate that subsets of PPA patients show novel or increased positive behaviours following dementia onset, and differences among subtypes may be helpful for improving diagnostic accuracy. Additionally, harnessing these skills may improve the quality of life of both patients and carers.
Publisher: Elsevier BV
Date: 05-2022
DOI: 10.1016/J.SCHRES.2021.06.031
Abstract: An altered sense of self-awareness and agency has been proposed to underlie symptoms of schizophrenia. In this study, we used the enfacement illusion paradigm - in which perception of another person's face leads to changes in perception of one's own peri-personal space - to examine the brain correlates of the sense of agency and its potential disruption in schizophrenia. Thirty-three schizophrenic patients and 27 healthy controls underwent fMRI scanning during performance of a task designed to elicit the enfacement illusion. Activations were examined using whole-brain analysis and also in an a priori identified region of interest (ROI) in the temporoparietal junction (TPJ), a region that has been described as involved in self/other differentiation and sense of agency. Both groups showed a pattern of cortical activation involving the pre and postcentral cortex, Rolandic operculum, insula, parietal, temporal and occipital cortex bilaterally as well as TPJ (but only right-side in patients). Examination of the TPJ ROI revealed significantly reduced activation on the left in the patients that was associated with poorer insight. The findings suggest brain functional abnormality in schizophrenia related to the formation or maintenance of processes related to self and/or agency. Decreased function in the TPJ may have a role in the impaired insight seen in patients with the disorder.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 30-03-2021
DOI: 10.1212/WNL.0000000000011638
Abstract: To test the hypothesis that white matter hyperintensities (WMH) in behavioral-variant frontotemporal dementia (bvFTD) and Alzheimer disease (AD) are associated with disease variables such as disease severity, cortical atrophy, and cognition, we conducted a cross-sectional brain MRI study with volumetric and voxel-wise analyses. A total of 129 patients (64 bvFTD, 65 AD) and 66 controls underwent high-resolution brain MRI and clinical and neuropsychological examination. Genetic screening was conducted in 124 cases (54 bvFTD, 44 AD, 26 controls) and postmortem pathology was available in 18 cases (13 bvFTD, 5 AD). WMH were extracted using an automated segmentation algorithm and analyses of total volumes and spatial distribution were conducted. Group differences in total WMH volume and associations with vascular risk and disease severity were examined. Syndrome-specific voxel-wise associations between WMH, cortical atrophy, and performance across different cognitive domains were assessed. Total WMH volumes were larger in patients with bvFTD than patients with AD and controls. In bvFTD, WMH volumes were associated with disease severity but not vascular risk. Patients with bvFTD and patients with AD showed distinct spatial patterns of WMH that mirrored characteristic patterns of cortical atrophy. Regional WMH load correlated with worse cognitive performance in discrete cognitive domains. WMH-related cognitive impairments were shared between syndromes, with additional associations found in bvFTD. Increased WMH are common in patients with bvFTD and patients with AD. Our findings suggest that WMH are partly independent of vascular pathology and associated with the neurodegenerative process. WMH occur in processes independent of and related to cortical atrophy. Furthermore, increased WMH in different regions contributes to cognitive deficits.
Publisher: Oxford University Press (OUP)
Date: 17-07-2015
Publisher: Cambridge University Press (CUP)
Date: 14-01-2018
DOI: 10.1017/S0033291717003774
Abstract: Cognitive deficits are a core feature of early stages in schizophrenia. However, the extent to which antipsychotic (AP) have a deleterious effect on cognitive performance remains under debate. We aim to investigate whether anticholinergic loadings and dose of AP drugs in first episode of psychosis (FEP) in advanced phase of remission are associated with cognitive impairment and the differences between premorbid intellectual quotient (IQ) subgroups. Two hundred and sixty-six patients participated. The primary outcomes were cognitive dimensions, dopaminergic/anticholinergic load of AP [in chlorpromazine equivalents (Eq-CPZ) and the Anticholinergic Risk Scale (ARS), respectively]. Impairments in processing speed, verbal memory and global cognition were significantly associated with high Eq-CPZ and verbal impairment with high ARS score. Moreover, this effect was higher in the low IQ subgroup. Clinicians should be aware of the potential cognitive impairment associated with AP in advanced remission FEP, particularly in lower premorbid IQ patients.
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1016/J.JAD.2015.07.020
Abstract: Midline brain abnormalities might increase susceptibility to both first-episode and chronic mental disorder. Evidence of cavum vergae (CV) abnormality in mental disorders is scarce. The presence of CV was assessed by a researcher blind to clinical information in a cross-disorder s le of 639 patients with mood and psychotic disorders and in 223 healthy controls. Homogeneous magnetic resonance imaging methods of acquisition and assessment were applied. Seven out of 639 patients with mood or psychotic disorders were detected with CV which corresponds to a prevalence of 1.1%. There were no concurrent cases of CV in the healthy control group. Identified cases which are briefly described were diagnosed from bipolar I disorder (n=2), delusional disorder (n=1), brief psychotic disorder (n=1) and schizoaffective disorder (n=3). Patients with CV had descriptively lower current IQ, executive functioning and memory scores in relation to patients without CV but this was not statistically significant. Effects of medication and lack of statistical power of the CV patient group. Midline brain abnormalities, such as CV, might represent an unspecific risk factor for the development of severe mental disorders.
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.NEUROSCIENCE.2017.06.029
Abstract: Functional imaging studies have implicated the hippoc us and parahippoc al gyrus in cue-guided spatial navigation, but also many other regions. Furthermore, little is known about de-activations that take place during performance of navigation tasks, something that is of interest given that the hippoc us is a component of the default mode network, which de-activates during attention-demanding tasks. In this study 22 healthy subjects underwent whole-brain functional Magnetic Resonance Imaging (fMRI) while they navigated toward a previously learned goal in a virtual reality environment. At a threshold of p<0.05 corrected, the subjects showed a pattern of widespread cortical activations, including the parahippoc al and retrosplenial cortex and also parts of the frontal, temporal and occipital cortex. Hippoc al activation, however, was restricted to the posterior portion of the structure bilaterally. De-activations were seen in the medial frontal cortex and other regions of the default mode network, but not in the posterior cingulate cortex recuneus. The findings support the involvement of the hippoc us in cue-guided navigation, but suggest that its posterior regions are particularly important. Cue-guided spatial navigation is associated with de-activation in some but not all parts of the default mode network.
Publisher: Springer Science and Business Media LLC
Date: 14-03-2023
DOI: 10.1007/S00415-023-11638-W
Abstract: Characterisation of the clinical profile of behavioural-variant frontotemporal dementia (bvFTD) has predominantly been based on Western s les. Some small studies have suggested that the clinical profile may differ in culturally and linguistically erse populations. Additionally, there is evidence that patients from non-English speaking backgrounds may have more cognitive reserve, allowing them to tolerate more disease pathology before clinical symptoms emerge. This study aims to characterise the clinical profiles of patients with bvFTD from culturally erse backgrounds. BvFTD patients were classified as Australian-born (Australian) or Culturally and Linguistically Diverse-English-speaking (CALD-English) and Culturally and Linguistically Diverse-Language Other Than English (CALD-LOTE). Clinical features, cognitive test performance and cognitive reserve were compared between groups. Voxel-based morphometry was used to examine the neural correlates of cognitive reserve. 107 patients with bvFTD (53 Australian, 36 CALD-English, 18 CALD-LOTE) and 51 controls were included. Analysis of neuropsychiatric features revealed more elation in Australian patients compared to CALD-English patients, with trends for CALD-LOTE patients to report more irritability. CALD-LOTE patients also had higher cognitive reserve and showed relatively greater verbal than non-verbal cognitive impairment. Neuroimaging analyses revealed that higher cognitive reserve was associated with lower integrity in the frontal–temporal regions associated with typical disease pathology in bvFTD. Our findings support the hypothesis that cognitive reserve may delay early cognitive decline in culturally and linguistically erse patients, although these patients may still show poor verbal performance due to cultural testing biases. Clinically, these results highlight the need to consider cultural and linguistic background to inform the assessment of dementia.
Publisher: Wiley
Date: 12-2019
Publisher: Oxford University Press (OUP)
Date: 17-04-2018
Publisher: Springer Science and Business Media LLC
Date: 04-04-2017
Publisher: Springer Science and Business Media LLC
Date: 21-03-2016
DOI: 10.1007/S11682-016-9535-4
Abstract: Schizophrenia is considered a disorder of abnormal brain connectivity. Although whole brain maps of averaged bivariate voxel correlations have been successfully applied to study connectivity abnormalities in schizophrenia these maps do not adequately explore the multivariate nature of brain connectivity. Here we adapt a novel method for high-dimensional regression (supervised principal component regression) to estimate brain maps of multivariate non redundant connectivity (NRC) from resting functional Magnetic Resonance Imaging (fMRI) data of 116 patients with schizophrenia and 122 matched controls. Disorder related differences in NRC involved caudate hyper-connectivity and hypo-connectivity of several cortical areas such as the dorsal cingulate, the cuneus and the right postcentral cortex. These abnormalities were coupled with abnormalities in the litude of signal fluctuations and, to a minor extent, with differences in the dimensionality of connectivity patterns as quantified by the number of supervised principal components. Second level seed correlation analyses linked the observed abnormalities to an additional set of brain regions relevant to schizophrenia such as the thalamus and the temporal cortex. The non redundant connectivity maps proposed here are a new tool that will complement the information provided by other already available voxel based whole brain connectivity measures.
Publisher: SAGE Publications
Date: 11-07-2017
Abstract: The profile of grey matter abnormalities and related white-matter pathology in schizoaffective disorder has only been studied to a limited extent. The aim of this study was to identify grey- and white-matter abnormalities in patients with schizoaffective disorder using complementary structural imaging techniques. Forty-five patients meeting Diagnostic and Statistical Manual of Mental Disorders–Fourth Edition criteria and Research Diagnostic Criteria for schizoaffective disorder and 45 matched healthy controls underwent structural-T1 and diffusion magnetic resonance imaging to enable surface-based brain morphometry and diffusion tensor imaging analyses. Analyses were conducted to determine group differences in cortical volume, cortical thickness and surface area, as well as in fractional anisotropy and mean diffusivity. At a threshold of p = 0.05 corrected, all measures revealed significant differences between patients and controls at the group level. Spatial overlap of abnormalities was observed across the various structural neuroimaging measures. In grey matter, patients with schizoaffective disorder showed abnormalities in the frontal and temporal lobes, striatum, fusiform, cuneus, precuneus, lingual and limbic regions. White-matter abnormalities were identified in tracts connecting these areas, including the corpus callosum, superior and inferior longitudinal fasciculi, anterior thalamic radiation, uncinate fasciculus and cingulum bundle. The spatial overlap of abnormalities across the different imaging techniques suggests widespread and consistent brain pathology in schizoaffective disorder. The abnormalities were mainly detected in areas that have commonly been reported to be abnormal in schizophrenia, and to some extent in bipolar disorder, which may explain the clinical and aetiological overlap in these disorders.
Publisher: Wiley
Date: 17-02-2022
DOI: 10.1002/GPS.5692
Abstract: Abnormal beliefs and delusions have been reported in some people with dementia, however, the prevalence of delusions, and their neurocognitive basis has been underexplored. This study aimed to examine the presence, severity, content and neural correlates of delusions in a large, well‐characterised cohort of dementia patients using a transdiagnostic, cross‐sectional approach. Four‐hundred and eighty‐seven people with dementia were recruited: 102 Alzheimer's disease, 136 behavioural‐variant frontotemporal dementia, 154 primary progressive aphasia, 29 motor neurone disease, 46 corticobasal syndrome, 20 progressive supranuclear palsy. All patients underwent neuropsychological assessment and brain magnetic resonance imaging, and the Neuropsychiatric Inventory was conducted with an informant, by an experienced clinician. In our cohort, 48/487 patients (10.8%) had delusions. A diagnosis of behavioural‐variant frontotemporal dementia (18.4%) and Alzheimer's disease (11.8%) were associated with increased risk of delusions. A positive gene mutation was observed in 11/27 people with delusions. In iduals with frequent delusions performed worse on the Addenbrooke's Cognitive Examination ( p = 0.035), particularly on the orientation/attention ( p = 0.022) and memory ( p = 0.013) subtests. Voxel‐based morphometry analyses found that increased delusional psychopathology was associated with reduced integrity of the right middle frontal gyrus, right planum temporale and left anterior temporal pole. Our results demonstrate that delusions are relatively common in dementia and uncover a unique cognitive and neural profile associated with the manifestation of delusions. Clinically, delusions may lead to delayed or misdiagnosis. Our results shed light on how to identify in iduals at risk of neuropsychiatric features of dementia, a crucial first step to enable targeted symptom management.
Publisher: Springer Science and Business Media LLC
Date: 14-02-2022
DOI: 10.1038/S41598-022-05687-W
Abstract: As a global health emergency, the rapid spread of the novel coronavirus disease (COVID-19) led to the implementation of widespread restrictions (e.g., quarantine, physical/social distancing measures). However, while these restrictions reduce the viral spread of COVID-19, they may exacerbate behavioural and cognitive symptoms in dementia patients and increase pressure on caregiving. Here, we aimed to assess the impact of COVID-19 and related restrictions on both carers and people living with dementia across the world. We conducted an international survey (Australia, Germany, Spain, and the Netherlands) to assess the impact of COVID-19 on carers and people living with dementia. People with dementia experienced worsened neuropsychiatric symptoms since the outbreak of COVID-19, most commonly, depression, apathy, delusions, anxiety, irritability, and agitation. Regression analyses revealed that limited understanding of the COVID-19 situation and not living with the carer was associated with worsened neuropsychiatric symptoms. Carers also reported a decline in their own mental health, increased stress and reduced social networks as a result of COVID-19 and related restrictions. Regression analyses revealed uncertainty about the future and loneliness were associated with worsened carer mental health. Findings from this study will inform strategies for the development of support services and compassionate protocols that meet the evolving needs of those living with dementia and their carers.
Location: France
Location: Australia
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: Australia
Start Date: 2021
End Date: 2023
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2021
End Date: 2023
Funder: Australian Research Council
View Funded ActivityStart Date: 2021
End Date: 12-2024
Amount: $382,865.00
Funder: Australian Research Council
View Funded Activity