Psychiatry - Research Publications
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ItemDivergent effects of first-generation and second-generation antipsychotics on cortical thickness in first-episode psychosis(CAMBRIDGE UNIV PRESS, 2015-02)BACKGROUND: Whether there are differential effects of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) on the brain is currently debated. Although some studies report that FGAs reduce grey matter more than SGAs, others do not, and research to date is limited by a focus on schizophrenia spectrum disorders. To address this limitation, this study investigated the effects of medication in patients being treated for first-episode schizophrenia or affective psychoses. METHOD: Cortical thickness was compared between 52 first-episode psychosis patients separated into diagnostic (i.e. schizophrenia or affective psychosis) and medication (i.e. FGA and SGA) subgroups. Patients in each group were also compared to age- and sex-matched healthy controls (n = 28). A whole-brain cortical thickness interaction analysis of medication and diagnosis was then performed. Correlations between cortical thickness with antipsychotic dose and psychotic symptoms were examined. RESULTS: The effects of medication and diagnosis did not interact, suggesting independent effects. Compared with controls, diagnostic differences were found in frontal, parietal and temporal regions. Decreased thickness in FGA-treated versus SGA-treated groups was found in a large frontoparietal region (p < 0.001, corrected). Comparisons with healthy controls revealed decreased cortical thickness in the FGA group whereas the SGA group showed increases in addition to decreases. In FGA-treated patients cortical thinning was associated with higher negative symptoms whereas increased cortical thickness in the SGA-treated group was associated with lower positive symptoms. CONCLUSIONS: Our results suggest that FGA and SGA treatments have divergent effects on cortical thickness during the first episode of psychosis that are independent from changes due to illness.
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ItemNo Preview AvailableAbnormal white matter integrity in synthetic cannabinoid users(ELSEVIER SCIENCE BV, 2016-11)Synthetic cannabinoids have become increasingly popular in the last few years especially among adolescents and young adults. However, no previous studies have assessed the effects of synthetic cannabinoids on the structure of the human brain. Understanding the harms of synthetic cannabinoid use on brain structure is therefore crucial given its increasing use. Diffusion tensor imaging (DTI) was performed in 22 patients who used synthetic cannabinoids more than five times a week for at least 1 year and 18 healthy controls. Fractional anisotropy (FA) was significantly reduced in the cannabinoid group compared to controls in a cluster of white matter voxels spanning the left temporal lobe, subcortical structures and brainstem. This cluster was predominantly traversed by the inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, fornix, cingulum-hippocampus and corticospinal tracts. Long-term use of synthetic cannabinoids is associated with white matter abnormalities in adolescents and young adults. Disturbed brain connectivity in synthetic cannabinoid users may underlie cognitive impairment and vulnerability to psychosis.
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ItemNo Preview AvailableThe 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(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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ItemNo Preview AvailableCognitive deficits in youth with familial and clinical high risk to psychosis: a systematic review and meta-analysis(WILEY, 2014-07)OBJECTIVE: It is likely that cognitive deficits are vulnerability markers for developing schizophrenia, as these deficits are already well-established findings in first-episode psychosis. Studies at-risk adolescents and young adults are likely to provide information about cognitive deficits that predate the onset of the illness. METHOD: We conducted meta-analyses of studies comparing familial-high risk (FHR) or ultra-high risk (UHR; n = 2113) and healthy controls (n = 1748) in youth studies in which the mean age was between 15 and 29. RESULTS: Compared with controls, high risk subjects were impaired in each domain in both UHR (d = 0.34-0.71) and FHR (d = 0.24-0.81). Heterogeneity of effect sizes across studies was modest, increasing confidence to the findings of the current meta-analysis (I(2) = 0-0.18%). In both risk paradigms, co-occurrence of genetic risk with attenuated symptoms was associated with more severe cognitive dysfunction. In UHR, later transition to psychosis was associated with more severe cognitive deficits in all domains (d = 0.31-0.49) except sustained attention. However, cognitive impairment has a limited capacity to predict the outcome of high-risk patients. CONCLUSION: Cognitive deficits are already evident in adolescents and young adults who have familial or clinical risk for psychosis. Longitudinal developmental studies are important to reveal timing and trajectory of emergence of such deficits.
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ItemNo Preview AvailableMeta-analysis of Cognitive Impairment in First-Episode Bipolar Disorder: Comparison With First-Episode Schizophrenia and Healthy Controls(OXFORD UNIV PRESS, 2015-09)Neurocognitive deficits are evident both in established schizophrenia and bipolar disorder (BP). However, it has been suggested that schizophrenia, but not BP, is characterized by neurodevelopmental abnormalities that can lead to cognitive deficits at the earliest stages of the illness. The aim of this meta-analytic review was to compare neurocognitive deficits in first-episode BP (FEBP) with healthy controls and first-episode schizophrenia (FES) patients. The current meta-analysis included a total of 22 adult studies and involved comparisons of 533 FEBP patients with 1417 healthy controls and 605 FEBP and 822 FES patients. FEBP patients were significantly impaired in all cognitive domains (d = 0.26-0.80) and individual tasks (d = 0.22-0.66) investigated. FES patients significantly underperformed FEBP patients in most cognitive domains (d = 0.05-0.63) and on individual tasks (d = 0.13-0.77). Neuropsychological impairment, which is comparable to chronic BP, was evident in FEBP. Similar to chronic patients, cognitive functions in FEBP lie intermediate between FES and healthy controls. Neurodevelopmental factors are likely to play a significant role not only in schizophrenia but also in BP.
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ItemCognitive impairment in euthymic major depressive disorder: a meta-analysis(CAMBRIDGE UNIV PRESS, 2013-10)BACKGROUND: There is evidence to suggest that cognitive deficits might persist beyond the acute stages of illness in major depressive disorder (MDD). However, the findings are somewhat inconsistent across the individual studies conducted to date. Our aim was to conduct a systematic review and meta-analysis of existing studies that have examined cognition in euthymic MDD patients. METHOD: Following a systematic search across several publication databases, meta-analyses were conducted for 27 empirical studies that compared euthymic adult MDD patients (895 participants) and healthy controls (997 participants) across a range of cognitive domains. The influence of demographic variables and confounding factors, including age of onset and recurrent episodes, was examined. RESULTS: Compared with healthy controls, euthymic MDD patients were characterized by significantly poorer cognitive functions. However, the magnitude of observed deficits, with the exception of inhibitory control, were generally modest when late-onset cases were excuded. Late-onset cases demonstrated significantly more pronounced deficits in verbal memory, speed of information processing and some executive functions. CONCLUSIONS: Cognitive deficits, especially poor response inhibition, are likely to be persistent features, at least of some forms, of adult-onset MDD. More studies are necessary to examine cognitive dysfunction in remitted psychotic, melancholic and bipolar spectrum MDD. Cognitive deficits overall appear to be more common among patients with late-onset depression, supporting the theories suggesting that possible vascular and neurodegenerative factors play a role in a substantial number of these patients.
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ItemNo Preview AvailableBrain functional connectivity during induced sadness in patients with obsessive-compulsive disorder(CMA-CANADIAN MEDICAL ASSOC, 2012-07)BACKGROUND: Obsessive-compulsive disorder (OCD) is associated with a range of emotional abnormalities linked to its defining symptoms, comorbid illnesses and cognitive deficits. The aim of this preliminary study was to examine functional changes in the brain that are associated with experimentally induced sad mood in patients with OCD compared with healthy controls in a frontolimbic circuit relevant to both OCD and mood regulation. METHODS: Participants underwent a validated sad mood induction procedure during functional magnetic resonance imaging. Analyses focused on mapping changes in the functional connectivity of the subgenual anterior cingulate cortex (ACC) within and between the 2 groups in response to successfully induced sadness. RESULTS: We enrolled 11 patients with OCD and 10 age-, sex- and IQ-matched controls in our study. Unlike controls, patients with OCD did not demonstrate predicted increases in functional connectivity between the subgenual ACC and other frontal regions during mood induction. Instead, patients demonstrated heightened connectivity between the subgenual ACC and ventral caudate/nucleus accumbens region and the hypothalamus. LIMITATIONS: Our study included a small, partially medicated patient cohort that precluded our ability to investigate sex or drug effects, evaluate behavioural differences between the groups and perform a whole-brain analysis. CONCLUSION: The ventral striatum and ventral frontal cortex were distinctly and differentially modulated in their connectivity with the subgenual ACC during the experience of sad mood in patients with OCD. These results suggest that, in patients with OCD, induced sadness appears to have provoked a primary subcortical component of the hypothesized "OCD circuit," which may offer insights into why OCD symptoms tend to develop and worsen during disturbed emotional states.
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