Psychiatry - Research Publications
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ItemHuman amygdala volume is predicted by common DNA variation in the stathmin and serotonin transporter genes(NATURE PUBLISHING GROUP, 2013-07)Despite the relevance of changes in amygdala volume to psychiatric illnesses and its heritability in both health and disease, the influence of common genetic variation on amygdala morphology remains largely unexplored. In the present study, we investigated the influence of a number of novel genetic variants on amygdala volume in 139 neurologically healthy individuals of European descent. Amygdala volume was significantly associated with allelic variation in the stathmin (STMN1) and serotonin transporter (SLC6A4) genes, which have been linked to healthy and disordered affective processing. These results were replicated across both manual and automated methods of amygdala parcellation, although manual tracing showed stronger effects, providing a cautionary note to studies relying on automated parcellation methods. Future studies will need to determine whether amygdala volume mediates the impact of stathmin and serotonin transporter gene variants on normal and dysfunctional emotion processing.
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ItemStructural and Functional Imaging Studies in Chronic Cannabis Users: A Systematic Review of Adolescent and Adult Findings(PUBLIC LIBRARY SCIENCE, 2013-02-04)BACKGROUND: The growing concern about cannabis use, the most commonly used illicit drug worldwide, has led to a significant increase in the number of human studies using neuroimaging techniques to determine the effect of cannabis on brain structure and function. We conducted a systematic review to assess the evidence of the impact of chronic cannabis use on brain structure and function in adults and adolescents. METHODS: Papers published until August 2012 were included from EMBASE, Medline, PubMed and LILACS databases following a comprehensive search strategy and pre-determined set of criteria for article selection. Only neuroimaging studies involving chronic cannabis users with a matched control group were considered. RESULTS: One hundred and forty-two studies were identified, of which 43 met the established criteria. Eight studies were in adolescent population. Neuroimaging studies provide evidence of morphological brain alterations in both population groups, particularly in the medial temporal and frontal cortices, as well as the cerebellum. These effects may be related to the amount of cannabis exposure. Functional neuroimaging studies suggest different patterns of resting global and brain activity during the performance of several cognitive tasks both in adolescents and adults, which may indicate compensatory effects in response to chronic cannabis exposure. LIMITATIONS: However, the results pointed out methodological limitations of the work conducted to date and considerable heterogeneity in the findings. CONCLUSION: Chronic cannabis use may alter brain structure and function in adult and adolescent population. Further studies should consider the use of convergent methodology, prospective large samples involving adolescent to adulthood subjects, and data-sharing initiatives.
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ItemTask-related deactivation and functional connectivity of the subgenual cingulate cortex in major depressive disorder.(Frontiers Media SA, 2012)BACKGROUND: Major depressive disorder is associated with functional alterations in activity and resting-state connectivity of the extended medial frontal network. In this study we aimed to examine how task-related medial network activity and connectivity were affected in depression. METHODS: 18 patients with major depressive disorder, aged 15- to 24-years-old, were matched with 19 healthy control participants. We characterized task-related activations and deactivations while participants engaged with an executive-control task (the multi-source interference task, MSIT). We used a psycho-physiological interactions approach to examine functional connectivity changes with subgenual anterior cingulate cortex. Voxel-wise statistical maps for each analysis were compared between the patient and control groups. RESULTS: There were no differences between groups in their behavioral performances on the MSIT task, and nor in patterns of activation and deactivation. Assessment of functional connectivity with the subgenual cingulate showed that depressed patients did not demonstrate the same reduction in functional connectivity with the ventral striatum during task performance, but that they showed greater reduction in functional connectivity with adjacent ventromedial frontal cortex. The magnitude of this latter connectivity change predicted the relative activation of task-relevant executive-control regions in depressed patients. CONCLUSION: The study reinforces the importance of the subgenual cingulate cortex for depression, and demonstrates how dysfunctional connectivity with ventral brain regions might influence executive-attentional processes.
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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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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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ItemA systematic review of diffusion weighted MRI studies of white matter microstructure in adolescent substance users(PERGAMON-ELSEVIER SCIENCE LTD, 2013-09)Recent studies using diffusion weighted magnetic resonance imaging (DW-MRI) have provided evidence of abnormal white matter microstructure in adults with substance use disorders (SUDs). While there is a growing body of research using DW-MRI to examine the impact of heavy substance use during adolescence, this literature has not been systematically reviewed. Online databases were searched for DW-MRI studies of adolescent substance users, and 10 studies fulfilled the inclusion and exclusion criteria. We identified consistent evidence for abnormal white matter microstructure in neocortical association pathways as well as in projection and thalamic pathways. Dose-dependent relationships between DW-MRI measures and patterns of substance use were also observed. The consistency of these findings with DW-MRI research in adults suggests that white matter microstructure is impacted in the early stages of heavy substance use. However, given the largely cross-sectional nature of the available data, important questions remain regarding the extent to which white matter abnormalities are a consequence of adolescent exposure to alcohol and other drugs of abuse or reflect pre-existing differences that increase risk for SUDs.
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ItemReduced orbitofrontal cortical thickness in male adolescents with internet addiction(BIOMED CENTRAL LTD, 2013-03-12)BACKGROUND: The orbitofrontal cortex (OFC) has consistently been implicated in the pathology of both drug and behavioral addictions. However, no study to date has examined OFC thickness in internet addiction. In the current study, we investigated the existence of differences in cortical thickness of the OFC in adolescents with internet addiction. On the basis of recently proposed theoretical models of addiction, we predicted a reduction of thickness in the OFC of internet addicted individuals. FINDINGS: Participants were 15 male adolescents diagnosed as having internet addiction and 15 male healthy comparison subjects. Brain magnetic resonance images were acquired on a 3T MRI and group differences in cortical thickness were analyzed using FreeSurfer. Our results confirmed that male adolescents with internet addiction have significantly decreased cortical thickness in the right lateral OFC (p<0.05). CONCLUSION: This finding supports the view that the OFC alterations in adolescents with internet addiction reflect a shared neurobiological marker of addiction-related disorders in general.
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ItemNo Preview AvailableEffect of long-term cannabis use on axonal fibre connectivity(OXFORD UNIV PRESS, 2012-07)Cannabis use typically begins during adolescence and early adulthood, a period when cannabinoid receptors are still abundant in white matter pathways across the brain. However, few studies to date have explored the impact of regular cannabis use on white matter structure, with no previous studies examining its impact on axonal connectivity. The aim of this study was to examine axonal fibre pathways across the brain for evidence of microstructural alterations associated with long-term cannabis use and to test whether age of regular cannabis use is associated with severity of any microstructural change. To this end, diffusion-weighted magnetic resonance imaging and brain connectivity mapping techniques were performed in 59 cannabis users with longstanding histories of heavy use and 33 matched controls. Axonal connectivity was found to be impaired in the right fimbria of the hippocampus (fornix), splenium of the corpus callosum and commissural fibres. Radial and axial diffusivity in these pathways were associated with the age at which regular cannabis use commenced. Our findings indicate long-term cannabis use is hazardous to the white matter of the developing brain. Delaying the age at which regular use begins may minimize the severity of microstructural impairment.
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ItemNo Preview AvailableFunctional Connectivity in Brain Networks Underlying Cognitive Control in Chronic Cannabis Users(NATURE PUBLISHING GROUP, 2012-07)The long-term effect of regular cannabis use on brain function underlying cognitive control remains equivocal. Cognitive control abilities are thought to have a major role in everyday functioning, and their dysfunction has been implicated in the maintenance of maladaptive drug-taking patterns. In this study, the Multi-Source Interference Task was employed alongside functional magnetic resonance imaging and psychophysiological interaction methods to investigate functional interactions between brain regions underlying cognitive control. Current cannabis users with a history of greater than 10 years of daily or near-daily cannabis smoking (n=21) were compared with age, gender, and IQ-matched non-using controls (n=21). No differences in behavioral performance or magnitude of task-related brain activations were evident between the groups. However, greater connectivity between the prefrontal cortex and the occipitoparietal cortex was evident in cannabis users, as compared with controls, as cognitive control demands increased. The magnitude of this connectivity was positively associated with age of onset and lifetime exposure to cannabis. These findings suggest that brain regions responsible for coordinating behavioral control have an increased influence on the direction and switching of attention in cannabis users, and that these changes may have a compensatory role in mitigating cannabis-related impairments in cognitive control or perceptual processes.
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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.