Melbourne School of Psychological Sciences - Research Publications

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    Can antipsychotic dose reduction lead to better functional recovery in first-episode psychosis? A randomized controlled-trial of antipsychotic dose reduction. The reduce trial: Study protocol
    Weller, A ; Gleeson, J ; Alvarez-Jimenez, M ; McGorry, P ; Nelson, B ; Allott, K ; Bendall, S ; Bartholomeusz, C ; Koval, P ; Harrigan, S ; O'Donoghue, B ; Fornito, A ; Pantelis, C ; Amminger, GP ; Ratheesh, A ; Polari, A ; Wood, SJ ; van der El, K ; Ellinghaus, C ; Gates, J ; O'Connell, J ; Mueller, M ; Wunderink, L ; Killackey, E (WILEY, 2019-12)
    UNLABELLED: Antipsychotic medication has been the mainstay of treatment for psychotic illnesses for over 60 years. This has been associated with improvements in positive psychotic symptoms and a reduction in relapse rates. However, there has been little improvement in functional outcomes for people with psychosis. At the same time there is increasing evidence that medications contribute to life shortening metabolic and cardiovascular illnesses. There is also uncertainty as to the role played by antipsychotic medication in brain volume changes. AIM: The primary aim of the study is, in a population of young people with first-episode psychosis, to compare functional outcomes between an antipsychotic dose reduction strategy with evidence-based intensive recovery treatment (EBIRT) group (DRS+) and an antipsychotic maintenance treatment with EBIRT group (AMTx+) at 24-months follow-up. METHODS: Our single-blind randomized controlled trial, within a specialist early psychosis treatment setting, will test the whether the DRS+ group leads to better vocational and social recovery than, the AMTx+ group over a 2-year period in 180 remitted first-episode psychosis patients. Additionally, we will examine the effect of DRS+ vs AMTx+ on physical health, brain volume and cognitive functioning. This study will also determine whether the group receiving DRS+ will be no worse off in terms of psychotic relapses over 2 years follow-up. RESULTS: This paper presents the protocol, rationale and hypotheses for this study which commenced recruitment in July 2017. CONCLUSION: This study will provide evidence as to whether an antipsychotic dose-reduction recovery treatment leads to improved functioning and safer outcomes in first-episode psychosis patients. In addition, it will be the first-controlled experiment of the effect of exposure to antipsychotic maintenance treatment on brain volume changes in this population.
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    The Impact of Cannabis Use on Cognitive Functioning in Patients With Schizophrenia: A Meta-analysis of Existing Findings and New Data in a First-Episode Sample
    Yuecel, M ; Bora, E ; Lubman, DI ; Solowij, N ; Brewer, WJ ; Cotton, SM ; Conus, P ; Takagi, MJ ; Fornito, A ; Wood, SJ ; McGorry, PD ; Pantelis, C (OXFORD UNIV PRESS, 2012-03)
    Cannabis use is highly prevalent among people with schizophrenia, and coupled with impaired cognition, is thought to heighten the risk of illness onset. However, while heavy cannabis use has been associated with cognitive deficits in long-term users, studies among patients with schizophrenia have been contradictory. This article consists of 2 studies. In Study I, a meta-analysis of 10 studies comprising 572 patients with established schizophrenia (with and without comorbid cannabis use) was conducted. Patients with a history of cannabis use were found to have superior neuropsychological functioning. This finding was largely driven by studies that included patients with a lifetime history of cannabis use rather than current or recent use. In Study II, we examined the neuropsychological performance of 85 patients with first-episode psychosis (FEP) and 43 healthy nonusing controls. Relative to controls, FEP patients with a history of cannabis use (FEP + CANN; n = 59) displayed only selective neuropsychological impairments while those without a history (FEP - CANN; n = 26) displayed generalized deficits. When directly compared, FEP + CANN patients performed better on tests of visual memory, working memory, and executive functioning. Patients with early onset cannabis use had less neuropsychological impairment than patients with later onset use. Together, these findings suggest that patients with schizophrenia or FEP with a history of cannabis use have superior neuropsychological functioning compared with nonusing patients. This association between better cognitive performance and cannabis use in schizophrenia may be driven by a subgroup of "neurocognitively less impaired" patients, who only developed psychosis after a relatively early initiation into cannabis use.
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    Reduced parahippocampal cortical thickness in subjects at ultra-high risk for psychosis
    Tognin, S ; Riecher-Roessler, A ; Meisenzahl, EM ; Wood, SJ ; Hutton, C ; Borgwardt, SJ ; Koutsouleris, N ; Yung, AR ; Allen, P ; Phillips, LJ ; McGorry, PD ; Valli, I ; Velakoulis, D ; Nelson, B ; Woolley, J ; Pantelis, C ; McGuire, P ; Mechelli, A (CAMBRIDGE UNIV PRESS, 2014-02)
    BACKGROUND: Grey matter volume and cortical thickness represent two complementary aspects of brain structure. Several studies have described reductions in grey matter volume in people at ultra-high risk (UHR) of psychosis; however, little is known about cortical thickness in this group. The aim of the present study was to investigate cortical thickness alterations in UHR subjects and compare individuals who subsequently did and did not develop psychosis. METHOD: We examined magnetic resonance imaging data collected at four different scanning sites. The UHR subjects were followed up for at least 2 years. Subsequent to scanning, 50 UHR subjects developed psychosis and 117 did not. Cortical thickness was examined in regions previously identified as sites of neuroanatomical alterations in UHR subjects, using voxel-based cortical thickness. RESULTS: At baseline UHR subjects, compared with controls, showed reduced cortical thickness in the right parahippocampal gyrus (p < 0.05, familywise error corrected). There were no significant differences in cortical thickness between the UHR subjects who later developed psychosis and those who did not. CONCLUSIONS: These data suggest that UHR symptomatology is characterized by alterations in the thickness of the medial temporal cortex. We did not find evidence that the later progression to psychosis was linked to additional alterations in cortical thickness, although we cannot exclude the possibility that the study lacked sufficient power to detect such differences.
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    Volumetric Abnormalities Predating the Onset of Schizophrenia and Affective Psychoses: An MRI Study in Subjects at Ultrahigh Risk of Psychosis
    Dazzan, P ; Soulsby, B ; Mechelli, A ; Wood, SJ ; Velakoulis, D ; Phillips, LJ ; Yung, AR ; Chitnis, X ; Lin, A ; Murray, RM ; McGorry, PD ; McGuire, PK ; Pantelis, C (OXFORD UNIV PRESS, 2012-09)
    It remains unclear whether brain structural abnormalities observed before the onset of psychosis are specific to schizophrenia or are common to all psychotic disorders. This study aimed to measure regional gray matter volume prior to the onset of schizophreniform and of affective psychoses. We investigated 102 subjects at ultrahigh risk (UHR) of developing psychosis recruited from the Personal Assessment and Crisis Evaluation Clinic in Melbourne, Australia. Twenty-eight of these subjects developed psychosis subsequent to scanning: 19 schizophrenia, 7 affective psychoses, and 2 other psychoses. We examined regional gray matter volume using 1.5 mm thick, coronal, 1.5 Tesla magnetic resonance imaging and voxel-based morphometry methods of image analysis. Subjects were scanned at presentation and were followed up clinically for a minimum of 12 months, to detect later transition to psychosis. We found that both groups of subjects who subsequently developed psychosis (schizophrenia and affective psychosis) showed reductions in the frontal cortex relative to UHR subjects who did not develop psychosis. The subgroup that subsequently developed schizophrenia also showed smaller volumes in the parietal cortex and, at trend level, in the temporal cortex, whereas those who developed an affective psychosis had significantly smaller subgenual cingulate volumes. These preliminary findings suggest that volumetric abnormalities in UHR individuals developing schizophrenia vs affective psychoses comprise a combination of features that predate both disorders and others that may be specific to the nature of the subsequent disorder.