Psychiatry - Research Publications
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ItemEffects of NRG1 and DAOA genetic variation on transition to psychosis in individuals at ultra-high risk for psychosis(NATURE PUBLISHING GROUP, 2013-04)Prospective studies have suggested genetic variation in the neuregulin 1 (NRG1) and D-amino-acid oxidase activator (DAOA) genes may assist in differentiating high-risk individuals who will or will not transition to psychosis. In a prospective cohort (follow-up=2.4-14.9 years) of 225 individuals at ultra-high risk (UHR) for psychosis, we assessed haplotype-tagging single-nucleotide polymorphisms (htSNPs) spanning NRG1 and DAOA for their association with transition to psychosis, using Cox regression analysis. Two NRG1 htSNPs (rs12155594 and rs4281084) predicted transition to psychosis. Carriers of the rs12155594 T/T or T/C genotype had a 2.34 (95% confidence interval (CI)=1.37-4.00) times greater risk of transition compared with C/C carriers. For every rs4281084 A-allele the risk of transition increased by 1.55 (95% CI=1.05-2.27). For every additional rs4281084-A and/or rs12155594-T allele carried the risk increased ∼1.5-fold, with 71.4% of those carrying a combination of 3 of these alleles transitioning to psychosis. None of the assessed DAOA htSNPs were associated with transition. Our findings suggest NRG1 genetic variation may improve our ability to identify UHR individuals at risk for transition to psychosis.
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ItemNeurocognitive predictors of transition to psychosis: medium- to long-term findings from a sample at ultra-high risk for psychosis(CAMBRIDGE UNIV PRESS, 2013-11)BACKGROUND: Individuals at ultra-high risk (UHR) for psychosis show reduced neurocognitive performance across domains but it is unclear which reductions are associated with transition to frank psychosis. The aim of this study was to investigate differences in baseline neurocognitive performance between UHR participants with (UHR-P) and without transition to psychosis (UHR-NP) and a healthy control (HC) group and examine neurocognitive predictors of transition over the medium to long term. METHOD: A sample of 325 UHR participants recruited consecutively from the Personal Assessment and Crisis Evaluation (PACE) Clinic in Melbourne and 66 HCs completed a neurocognitive assessment at baseline. The UHR group was followed up between 2.39 and 14.86 (median = 6.45) years later. Cox regression was used to investigate candidate neurocognitive predictors of psychosis onset. RESULTS: The UHR group performed more poorly than the HC group across a range of neurocognitive domains but only performance on digit symbol coding and picture completion differed between the groups. The risk of transition was only significantly associated with poorer performance on visual reproduction [hazard ratio (HR) 0.919, 95% confidence interval (CI) 0.876-0.965, p = 0.001] and matrix reasoning (HR 0.938, 95% CI 0.883-0.996, p = 0.037). These remained significant even after controlling for psychopathology at baseline. CONCLUSIONS: This study is the longest follow-up of an UHR sample to date. UHR status was associated with poorer neurocognitive performance compared to HCs on some tasks. Cognition at identification as UHR was not a strong predictor of risk for transition to psychosis. The results suggests the need to include more experimental paradigms that isolate discrete cognitive processes to better understand neurocognition at this early stage of illness.
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ItemSulcogyral patterns and morphological abnormalities of the orbitofrontal cortex in psychosis(PERGAMON-ELSEVIER SCIENCE LTD, 2013-07-01)Three types of OFC sulcogyral patterns have been identified in the general population. The distribution of these three types has been found altered in individuals at genetic risk of psychosis, first episode psychosis (FEP) and chronic schizophrenia. The aim of this study was to replicate and extend previous research by additionally investigating: intermediate and posterior orbital sulci, cortical thickness, and degree of gyrification/folding of the OFC, in a large sample of FEP patients and healthy controls. OFC pattern type was classified based on a method previously devised, using T1-weighted magnetic resonance images. Cortical thickness and local gyrification indices were calculated using FreeSurfer. Occurrence of Type I pattern was decreased and Type II pattern was increased in FEP patients for the right hemisphere. Interestingly, controls displayed an OFC pattern type distribution that was disparate to that previously reported. Significantly fewer intermediate orbital sulci were observed in the left hemisphere of patients. Grey matter thickness of orbitofrontal sulci was reduced bilaterally, and left hemisphere reductions were related to OFC pattern type in patients. There was no relationship between pattern type and degree of OFC gyrification. An interaction was found between the number of intermediate orbital sulci and OFC gyrification; however this group difference was specific to only the small subsample of people with three intermediate orbital sulci. Given that cortical folding is largely determined by birth, our findings suggest that Type II pattern may be a neurodevelopmental risk marker while Type I pattern may be somewhat protective. This finding, along with compromised orbitofrontal sulci thickness, may reflect early abnormalities in cortical development and point toward a possible endophenotypic risk marker of schizophrenia-spectrum disorders.
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ItemCognitive precursors of severe mental disorders(PSYCHOLOGY PRESS, 2013-01-01)