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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ItemDelusional Misidentification Syndromes in Obsessive-Compulsive Disorder(SPRINGER, 2013-06)Delusional misidentification syndromes (DMS) have been rarely reported in patients with conditions other than schizophrenia-related disorders, diffuse brain disease (dementia) and focal neurological illness. In this report, we describe DMS (i.e. Capgras and Fregoli syndromes) in two patients with severe and treatment resistant obsessive-compulsive disorder (OCD), one with paranoid personality disorder (PPD) and the other with a pervasive developmental disorder (PDD) not otherwise specified. While our findings highlight an interesting phenomenon (the occurrence of DMS in OCD), it is presently unclear whether this association is rare or underreported. Misidentification syndromes might be the ultimate result of a combination of obsessive fears and preexisting cognitive bias/deficits, such as mistrustfulness (in PPD) or poor theory of mind (in PDD).
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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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ItemA magnetic resonance imaging study of hippocampal, amygdala and subgenual prefrontal cortex volumes in major depression subtypes: Melancholic versus psychotic depression(ELSEVIER, 2013)BACKGROUND: Volumetric studies examining brain structure in depression subtypes are limited and inconclusive. The aim of the current study was to compare the volumes of brain regions previously implicated in depression among patients with melancholic major depressive disorder (MDD), patients with psychotic MDD and normal controls. METHODS: Twenty two patients with melancholic MDD, 17 with psychotic MDD and 18 normal controls were included in the study. Hippocampal (HV), amygdala (AV), anterior (ASCV) and posterior (PSCV) subgenual cortex volumes were measured on magnetic resonance volumetric images. RESULTS: There were no volumetric differences between patients with melancholic and psychotic subgroups. We identified larger AVs and smaller left ASCVs in both patient groups compared to controls with medium to large effect sizes. Regression analysis revealed that AVs were predicted by the presence of depression, late depression-onset, insomnia and left hippocampal tail volume in patients, but not in controls. There were no differences in HVs, right ASCVs and PSCVs across the 3 groups. LIMITATIONS: Small sample size, a possible inclusion of paracingulate gyrus in ASCV and PSCV tracings, significant differences in education level and medication status are discussed as limitations. CONCLUSIONS: Diagnostically delineated melancholic and psychotic MDD patients do not differ in medial temporal and cingulate volumes. However, significant volumetric differences were detected between both patient-groups and controls.