Psychiatry - Research Publications
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ItemNo Preview AvailableWhite matter pathology in schizophrenia(Springer Nature, 2020-01-01)Significant effort has been devoted to characterizing white matter pathology in patients with schizophrenia and its impact on brain connectivity (Samartzis et al., J Neuroimaging 24(2):101-10, 2014; Fusar-Poli et al., Neurosci Biobehav Rev 37(8):1680-91, 2013; Bora et al., Schizophr Res 127(1):46-57, 2011). This is particularly important in light of the disconnection hypothesis-a key etiological theory of schizophrenia suggesting that symptoms arise from a failure of integration between distinct brain regions (Friston, Schizophr Res 30(2):115-25, 1998). In this chapter, we focus on neuroimaging evidence demonstrating structural white matter alterations in schizophrenia. Key questions addressed include: what methods are sensitive to the pathophysiology of schizophrenia? What is the evidence that white matter pathology emerges prior to or near to the onset of psychosis? Is the trajectory of white matter pathology stable or, alternatively, a dynamic process, with progressive changes evident over the course of illness? What are the limitations of these studies? How does neuroimaging evidence relate to micro- and meso-structural white matter findings?.
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ItemConnectome analysis with diffusion MRI in idiopathic Parkinson's disease: Evaluation using multi-shell, multi-tissue, constrained spherical deconvolution(ELSEVIER SCI LTD, 2018)Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects extensive regions of the central nervous system. In this work, we evaluated the structural connectome of patients with PD, as mapped by diffusion-weighted MRI tractography and a multi-shell, multi-tissue (MSMT) constrained spherical deconvolution (CSD) method to increase the precision of tractography at tissue interfaces. The connectome was mapped with probabilistic MSMT-CSD in 21 patients with PD and in 21 age- and gender-matched controls. Mapping was also performed by deterministic single-shell, single tissue (SSST)-CSD tracking and probabilistic SSST-CSD tracking for comparison. A support vector machine was trained to predict diagnosis based on a linear combination of graph metrics. We showed that probabilistic MSMT-CSD could detect significantly reduced global strength, efficiency, clustering, and small-worldness, and increased global path length in patients with PD relative to healthy controls; by contrast, probabilistic SSST-CSD only detected the difference in global strength and small-worldness. In patients with PD, probabilistic MSMT-CSD also detected a significant reduction in local efficiency and detected clustering in the motor, frontal temporoparietal associative, limbic, basal ganglia, and thalamic areas. The network-based statistic identified a subnetwork of reduced connectivity by MSMT-CSD and probabilistic SSST-CSD in patients with PD, involving key components of the cortico-basal ganglia-thalamocortical network. Finally, probabilistic MSMT-CSD had superior diagnostic accuracy compared with conventional probabilistic SSST-CSD and deterministic SSST-CSD tracking. In conclusion, probabilistic MSMT-CSD detected a greater extent of connectome pathology in patients with PD, including those with cortico-basal ganglia-thalamocortical network disruptions. Connectome analysis based on probabilistic MSMT-CSD may be useful when evaluating the extent of white matter connectivity disruptions in PD.
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ItemPET imaging of putative microglial activation in individuals at ultra-high risk for psychosis, recently diagnosed and chronically ill with schizophrenia(NATURE PUBLISHING GROUP, 2017-08-29)We examined putative microglial activation as a function of illness course in schizophrenia. Microglial activity was quantified using [11C](R)-(1-[2-chrorophynyl]-N-methyl-N-[1-methylpropyl]-3 isoquinoline carboxamide (11C-(R)-PK11195) positron emission tomography (PET) in: (i) 10 individuals at ultra-high risk (UHR) of psychosis; (ii) 18 patients recently diagnosed with schizophrenia; (iii) 15 patients chronically ill with schizophrenia; and, (iv) 27 age-matched healthy controls. Regional-binding potential (BPND) was calculated using the simplified reference-tissue model with four alternative reference inputs. The UHR, recent-onset and chronic patient groups were compared to age-matched healthy control groups to examine between-group BPND differences in 6 regions: dorsal frontal, orbital frontal, anterior cingulate, medial temporal, thalamus and insula. Correlation analysis tested for BPND associations with gray matter volume, peripheral cytokines and clinical variables. The null hypothesis of equality in BPND between patients (UHR, recent-onset and chronic) and respective healthy control groups (younger and older) was not rejected for any group comparison or region. Across all subjects, BPND was positively correlated to age in the thalamus (r=0.43, P=0.008, false discovery rate). No correlations with regional gray matter, peripheral cytokine levels or clinical symptoms were detected. We therefore found no evidence of microglial activation in groups of individuals at high risk, recently diagnosed or chronically ill with schizophrenia. While the possibility of 11C-(R)-PK11195-binding differences in certain patient subgroups remains, the patient cohorts in our study, who also displayed normal peripheral cytokine profiles, do not substantiate the assumption of microglial activation in schizophrenia as a regular and defining feature, as measured by 11C-(R)-PK11195 BPND.
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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.