Heterogeneity of Outcomes and Network Connectivity in Early-Stage Psychosis: A Longitudinal Study |
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Authors: | Shi Yu Chan Roscoe Brady Melissa Hwang Amy Higgins Kathryn Nielsen Dost
ngür Mei-Hua Hall |
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Institution: | 1. Schizophrenia and Bipolar Disorder Research Program, McLean Hospital, Belmont, MA;2. Psychosis Neurobiology Laboratory, McLean Hospital, Belmont, MA;3. Department of Psychiatry, Harvard Medical School, Boston, MA;4. Department of Psychiatry, Beth Israel Deaconess Medical Center and Massachusetts Mental Health Center, Boston, MA |
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Abstract: | Imaging studies in psychotic disorders typically examine cross-sectional relationships between magnetic resonance imaging (MRI) signals and diagnosis or symptoms. We sought to examine changes in network connectivity identified using resting-state functional MRI (fMRI) corresponding to divergent functional recovery trajectories and relapse in early-stage psychosis (ESP). Prior studies have linked schizophrenia to hyperconnectivity in the default mode network (DMN). Given the correlations between the DMN and behavioral impairments in psychosis, we hypothesized that dynamic changes in DMN connectivity reflect the heterogeneity of outcomes in ESP. Longitudinal data were collected from 66 ESP patients and 20 healthy controls. Longitudinal cluster analysis identified subgroups of patients with similar trajectories in terms of symptom severity and functional outcomes. DMN connectivity was measured in a subset of patients (n = 36) longitudinally over 2 scans separated by a mean of 12 months. We then compared connectivity between patients and controls, and among the different outcome trajectory subgroups. Among ESP participants, 4 subgroups were empirically identified corresponding to: “Poor,” “Middle,” “Catch-up,” and “Good” trajectory outcomes in the complete dataset (n = 36), and an independent replication (n = 30). DMN connectivity changes differed significantly between functional subgroups (F3,32 = 6.06, P-FDR corrected = .01); DMN connectivity increased over time in the “Poor” outcome cluster (β = +0.145) but decreased over time in the “Catch-up” cluster (β = −0.212). DMN connectivity is dynamic and correlates with a change in functional status over time in ESP. This approach identifies a brain-based marker that reflects important neurobiological processes required to sustain functional recovery. |
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Keywords: | default mode network early-stage psychosis trajectory analysis functional outcomes fMRI heterogeneity |
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