Tina Behdinan1, George Foussias2, Anne L Wheeler3, Laura Stefanik3, Daniel Felsky1, Gary Remington2, Tarek K Rajji2, M Mallar Chakravarty4, Aristotle N Voineskos5. 1. Kimel Family Translational Imaging-Genetics Research Lab, Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada; Institute of Medical Science, University of Toronto, 27 King's College Circle, Toronto, ON M5S, Canada. 2. Institute of Medical Science, University of Toronto, 27 King's College Circle, Toronto, ON M5S, Canada; Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada; Department of Psychiatry, University of Toronto, 27 King's College Circle, Toronto, ON, M5S, Canada. 3. Kimel Family Translational Imaging-Genetics Research Lab, Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada. 4. Cerebral Imaging Centre, Douglas Mental Health University Institute, Verdun, QC, Canada; Department of Psychiatry, McGill University, Montreal, QC, Canada. 5. Kimel Family Translational Imaging-Genetics Research Lab, Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada; Institute of Medical Science, University of Toronto, 27 King's College Circle, Toronto, ON M5S, Canada; Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada; Department of Psychiatry, University of Toronto, 27 King's College Circle, Toronto, ON, M5S, Canada. Electronic address: Aristotle.Voineskos@camh.ca.
Abstract
PURPOSE: Studies show that deficit syndrome schizophrenia patients, characterized by primary negative symptoms and poor functional outcome, have impairment in specific neural circuits. We assessed whether these same neural circuits are directly linked to functional outcomes across schizophrenia patients. METHODS: T1- and diffusion-weighted MR images were obtained for schizophrenia (n=30) and matched healthy control participants (n=30). Negative symptoms and functional outcome were assessed at baseline and 6-month follow-up. Cortical thickness and tract-wise fractional anisotropy (FA) were compared between groups. To assess relationships of neuroimaging measures with functional outcome, principal component analysis (PCA) was performed on tract-wise FA values and components were entered into a multiple regression model for schizophrenia participants. RESULTS: Consistent with the literature, schizophrenia participants showed frontotemporal reductions in cortical thickness and tract-wise FA compared to controls. The top two components from PCA explained 71% of the variance in tract-wise FA values. The second component (associated with inferior longitudinal and arcuate fasciculus FA) was significantly correlated with functional outcome (baseline: β=0.54, p=0.03; follow-up: β=0.74, p=0.047); further analysis revealed this effect was mediated by negative symptoms. Post-hoc network analysis revealed increased cortical coupling between right inferior frontal and supramarginal gyri (connected by the arcuate fasciculus) in schizophrenia participants with poorer functional outcome. CONCLUSIONS: Our findings indicate that impairment in the same neural circuitry susceptible in deficit syndrome schizophrenia predicts functional outcome in a continuous manner in schizophrenia participants. This relationship was mediated by negative symptom burden. Our findings provide novel evidence for brain-based biomarkers of longitudinal functional outcome in people with schizophrenia.
PURPOSE: Studies show that deficit syndrome schizophreniapatients, characterized by primary negative symptoms and poor functional outcome, have impairment in specific neural circuits. We assessed whether these same neural circuits are directly linked to functional outcomes across schizophreniapatients. METHODS: T1- and diffusion-weighted MR images were obtained for schizophrenia (n=30) and matched healthy control participants (n=30). Negative symptoms and functional outcome were assessed at baseline and 6-month follow-up. Cortical thickness and tract-wise fractional anisotropy (FA) were compared between groups. To assess relationships of neuroimaging measures with functional outcome, principal component analysis (PCA) was performed on tract-wise FA values and components were entered into a multiple regression model for schizophreniaparticipants. RESULTS: Consistent with the literature, schizophreniaparticipants showed frontotemporal reductions in cortical thickness and tract-wise FA compared to controls. The top two components from PCA explained 71% of the variance in tract-wise FA values. The second component (associated with inferior longitudinal and arcuate fasciculus FA) was significantly correlated with functional outcome (baseline: β=0.54, p=0.03; follow-up: β=0.74, p=0.047); further analysis revealed this effect was mediated by negative symptoms. Post-hoc network analysis revealed increased cortical coupling between right inferior frontal and supramarginal gyri (connected by the arcuate fasciculus) in schizophreniaparticipants with poorer functional outcome. CONCLUSIONS: Our findings indicate that impairment in the same neural circuitry susceptible in deficit syndrome schizophrenia predicts functional outcome in a continuous manner in schizophreniaparticipants. This relationship was mediated by negative symptom burden. Our findings provide novel evidence for brain-based biomarkers of longitudinal functional outcome in people with schizophrenia.
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