Psychiatry - Research Publications
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ItemGenetic Influences on Cost-Efficient Organization of Human Cortical Functional Networks(SOC NEUROSCIENCE, 2011-03-02)The human cerebral cortex is a complex network of functionally specialized regions interconnected by axonal fibers, but the organizational principles underlying cortical connectivity remain unknown. Here, we report evidence that one such principle for functional cortical networks involves finding a balance between maximizing communication efficiency and minimizing connection cost, referred to as optimization of network cost-efficiency. We measured spontaneous fluctuations of the blood oxygenation level-dependent signal using functional magnetic resonance imaging in healthy monozygotic (16 pairs) and dizygotic (13 pairs) twins and characterized cost-efficient properties of brain network functional connectivity between 1041 distinct cortical regions. At the global network level, 60% of the interindividual variance in cost-efficiency of cortical functional networks was attributable to additive genetic effects. Regionally, significant genetic effects were observed throughout the cortex in a largely bilateral pattern, including bilateral posterior cingulate and medial prefrontal cortices, dorsolateral prefrontal and superior parietal cortices, and lateral temporal and inferomedial occipital regions. Genetic effects were stronger for cost-efficiency than for other metrics considered, and were more clearly significant in functional networks operating in the 0.09-0.18 Hz frequency interval than at higher or lower frequencies. These findings are consistent with the hypothesis that brain networks evolved to satisfy competitive selection criteria of maximizing efficiency and minimizing cost, and that optimization of network cost-efficiency represents an important principle for the brain's functional organization.
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ItemS166. EFFECTIVE CONNECTIVITY OF FRONTOSTRIATAL SYSTEMS IN FIRST-EPISODE PSYCHOSIS(Oxford University Press (OUP), 2020-05-18)Abstract Background Neuroimaging studies have found dysconnectivity of frontostriatal circuits across a broad spectrum of psychotic symptoms. However, it is unknown whether dysconnectivity within frontostriatal circuits originates from disrupted bottom-up or top-down control signaling within these systems. Here, we used dynamic causal modelling (DCM) to examine the effective connectivity of frontostriatal systems in first-episode psychosis (FEP). Methods A total of 55 FEP patients (26 males; mean [SD] age = 19.24 [2.89]) and 24 healthy controls (15 males; mean [SD] age = 21.83 [1.93]) underwent a resting-state functional magnetic resonance imaging protocol. Biologically plausible connections between eight left hemisphere regions encompassing the dorsal and ventral frontostriatal systems were modelled using spectral DCM. The regions comprise dorsolateral prefrontal cortex, ventromedial prefrontal cortex, anterior hippocampus, amygdala, dorsal caudate, nucleus accumbens, thalamus, and the midbrain. Effective connectivity between groups were assessed using a parametric Bayesian model. Associations between effective connectivity parameters and positive symptoms, measured by the Brief Psychiatric Rating Scale positive subscale, was assessed in the patient group in a separate Bayesian general linear model. Results DCM shows evidence for differences in effective connectivity between patients and healthy controls, namely in the bottom-down connections distributed in the frontostriatal system encompassing the hippocampus, amygdala, striatum, and midbrain. Compared to healthy controls, patients also demonstrated increased disinhibition of the midbrain. In patients, positive symptoms are associated with increased top-down connections to the midbrain. Outgoing connection from the midbrain to the nucleus accumbens is also increased in association with positive symptoms. Discussion Aberrant top-down connectivity in the frontostriatal system in patients is consistent with top-down dysregulation of dopamine function in FEP, as dopaminergic activity in the midbrain is proposed to be under the control of higher brain areas. In patients, increased self-inhibition of the midbrain, as well as symptom associations in both ingoing and outgoing connections of this region, are congruous with hyperactivity of the midbrain as proposed by the dopamine dysregulation hypothesis. Here, we demonstrate that mathematical models of brain imaging signals can be used to identify the key disruptions driving brain circuit dysfunction, identifying new targets for treatment.
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ItemNo Preview AvailableCan 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(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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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 AvailableAltered Striatal Functional Connectivity in Subjects With an At-Risk Mental State for Psychosis(OXFORD UNIV PRESS, 2014-07)Recent functional imaging work in individuals experiencing an at-risk mental state (ARMS) for psychosis has implicated dorsal striatal abnormalities in the emergence of psychotic symptoms, contrasting with earlier findings implicating the ventral striatum. Our aims here were to characterize putative dorsal and ventral striatal circuit-level abnormalities in ARMS individuals using resting-state functional magnetic resonance imaging (fMRI) and to investigate their relationship to positive psychotic symptoms. Resting-state fMRI was acquired in 74 ARMS subjects and 35 matched healthy controls. An established method for mapping ventral and dorsal striatal functional connectivity was used to examine corticostriatal functional integrity. Positive psychotic symptoms were assessed using the Comprehensive Assessment of At-Risk Mental State and the Positive and Negative Syndrome Scale. Compared with healthy controls, ARMS subjects showed reductions in functional connectivity between the dorsal caudate and right dorsolateral prefrontal cortex, left rostral medial prefrontal cortex, and thalamus, and between the dorsal putamen and left thalamic and lenticular nuclei. ARMS subjects also showed increased functional connectivity between the ventral putamen and the insula, frontal operculum, and superior temporal gyrus bilaterally. No differences in ventral striatal (ie, nucleus accumbens) functional connectivity were found. Altered functional connectivity in corticostriatal circuits were significantly correlated with positive psychotic symptoms. Together, these results suggest that risk for psychosis is mediated by a complex interplay of alterations in both dorsal and ventral corticostriatal systems.