Psychiatry - Research Publications

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    FRONTOSTRIATAL CONNECTIVITY IN TREATMENT-RESISTANT SCHIZOPHRENIA: RELATIONSHIP TO POSITIVE SYMPTOMS AND COGNITIVE FLEXIBILITY
    Cropley, V ; Ganella, E ; Wannan, C ; Zalesky, A ; Van Rheenen, T ; Bousman, C ; Everall, I ; Fornito, A ; Pantelis, C (OXFORD UNIV PRESS, 2018-04)
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    Exploring the moderating effects of dopaminergic polymorphisms and childhood adversity on brain morphology in schizophrenia-spectrum disorders
    Hoffmann, C ; Van Rheenen, TE ; Mancuso, SG ; Zalesky, A ; Bruggemann, J ; Lenroot, RK ; Sundram, S ; Weickert, CS ; Weickert, TW ; Pantelis, C ; Cropley, V ; Bousman, CA (ELSEVIER IRELAND LTD, 2018-11-30)
    Genetic and environmental etiologies may contribute to schizophrenia and its associated neurobiological profile. We examined the interaction between dopaminergic polymorphisms, childhood adversity and diagnosis (schizophrenia/schizoaffective disorder) on dopamine-related brain structures. Childhood adversity histories and structural MRI data were obtained from 249 (153 schizophrenia/schizoaffective, 96 controls) participants registered in the Australian Schizophrenia Research Bank. Polymorphisms in DRD2 and COMT were genotyped and a dopaminergic risk allelic load (RAL) was calculated. Regression analysis was used to test the main and interaction effects of RAL, childhood adversity and diagnosis on volumes of dopamine-related brain structures (caudate, putamen, nucleus accumbens, dorsolateral prefrontal cortex and hippocampus). A schizophrenia/schizoaffective diagnosis showed significant main effects on bilateral hippocampus, left dorsolateral prefrontal cortex and bilateral putamen volumes. RAL showed a significant main effect on left putamen volumes. Furthermore, across the whole sample, a significant two-way interaction between dopaminergic RAL and childhood adversity was found for left putamen volumes. No brain structure volumes were predicted by a three-way interaction that included diagnosis. Our finding suggests the left putamen may be particularly sensitive to dopaminergic gene-environment interactions regardless of diagnosis. However, larger studies are needed to assess whether these interactions are more or less pronounced in those with schizophrenia/schizoaffective disorders.
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    Deterioration of visuospatial associative memory following a first psychotic episode: a long-term follow-up study
    Wannan, CMJ ; Bartholomeusz, CF ; Cropley, VL ; Van Rheenen, TE ; Panayiotou, A ; Brewer, WJ ; Proffitt, TM ; Henry, L ; Harris, MG ; Velakoulis, D ; McGorry, P ; Pantelis, C ; Wood, SJ (CAMBRIDGE UNIV PRESS, 2018-01)
    BACKGROUND: Cognitive deficits are a core feature of schizophrenia, and impairments in most domains are thought to be stable over the course of the illness. However, cross-sectional evidence indicates that some areas of cognition, such as visuospatial associative memory, may be preserved in the early stages of psychosis, but become impaired in later established illness stages. This longitudinal study investigated change in visuospatial and verbal associative memory following psychosis onset. METHODS: In total 95 first-episode psychosis (FEP) patients and 63 healthy controls (HC) were assessed on neuropsychological tests at baseline, with 38 FEP and 22 HCs returning for follow-up assessment at 5-11 years. Visuospatial associative memory was assessed using the Cambridge Neuropsychological Test Automated Battery Visuospatial Paired-Associate Learning task, and verbal associative memory was assessed using Verbal Paired Associates subtest of the Wechsler Memory Scale - Revised. RESULTS: Visuospatial and verbal associative memory at baseline did not differ significantly between FEP patients and HCs. However, over follow-up, visuospatial associative memory deteriorated significantly for the FEP group, relative to healthy individuals. Conversely, verbal associative memory improved to a similar degree observed in HCs. In the FEP cohort, visuospatial (but not verbal) associative memory ability at baseline was associated with functional outcome at follow-up. CONCLUSIONS: Areas of cognition that develop prior to psychosis onset, such as visuospatial and verbal associative memory, may be preserved early in the illness. Later deterioration in visuospatial memory ability may relate to progressive structural and functional brain abnormalities that occurs following psychosis onset.
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    Cognitive abilities in first-degree relatives of individuals with bipolar disorder
    Calafiore, D ; Rossell, SL ; Van Rheenen, TE (ELSEVIER SCIENCE BV, 2018-01-01)
    BACKGROUND: Although the study of cognition in first degree relatives (FDRs) is not new, findings in this group are still somewhat inconsistent and much of the research examining FDR populations include individuals under the age of 25, who are arguably still at significant risk to go on to develop BD. The present study aimed to establish the value of cognitive performance as a genuine endophenotypic marker of familial risk for bipolar disorder (BD), by examining cognition in FDRs aged 25 years or older. METHODS: The current study compared the cognitive performance of 27 unaffected FDRs to 47 healthy controls (HCs) and 28 BD patients using the MATRICS Consensus Cognitive Battery (MCCB). RESULTS: Results indicated that FDRs had impaired verbal learning performance, as well as selective impairments on a measure of speed of processing; and a measure of spatial working memory compared to HC. LIMITATIONS: Limitations relate to the potential insensitivity of some of the tests in the MCCB for detecting cognitive deficits that have been previously noted in BD and FDR samples using other batteries. CONCLUSIONS: Findings from this study implicate verbal learning, processing speed and working memory performance as promising candidate endophenotypes of familial risk for BD.
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    Widespread Volumetric Reductions in Schizophrenia and Schizoaffective Patients Displaying Compromised Cognitive Abilities
    Van Rheenen, TE ; Cropley, V ; Zalesky, A ; Bousman, C ; Wells, R ; Bruggemann, J ; Sundram, S ; Weinberg, D ; Lenroot, RK ; Pereira, A ; Weickert, CS ; Weickert, TW ; Pantelis, C (OXFORD UNIV PRESS, 2018-05)
    OBJECTIVE: Progress toward understanding brain mechanisms in psychosis is hampered by failures to account for within-group heterogeneity that exists across neuropsychological domains. We recently identified distinct cognitive subgroups that might assist in identifying more biologically meaningful subtypes of psychosis. In the present study, we examined whether underlying structural brain abnormalities differentiate these cognitively derived subgroups. METHOD: 1.5T T1 weighted structural scans were acquired for 168 healthy controls and 220 patients with schizophrenia/schizoaffective disorder. Based on previous work, 47 patients were categorized as being cognitively compromised (impaired premorbid and current IQ), 100 as cognitively deteriorated (normal premorbid IQ, impaired current IQ), and 73 as putatively cognitively preserved (premorbid and current IQ within 1 SD of controls). Global, subcortical and cortical volume, thickness, and surface area measures were compared among groups. RESULTS: Whole cortex, subcortical, and regional volume and thickness reductions were evident in all subgroups compared to controls, with the largest effect sizes in the compromised group. This subgroup also showed abnormalities in regions not seen in the other patient groups, including smaller left superior and middle frontal areas, left anterior and inferior temporal areas and right lateral medial and inferior frontal, occipital lobe and superior temporal areas. CONCLUSIONS: This pattern of more prominent brain structural abnormalities in the group with the most marked cognitive impairments-both currently and putatively prior to illness onset, is consistent with the concept of schizophrenia as a progressive neurodevelopmental disorder. In this group, neurodevelopmental and neurodegenerative factors may be important for cognitive function.