1. Rich-club connectivity and structural connectome organization in youth at clinical high-risk for psychosis and individuals with early illness schizophrenia.
- Author
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Hua JPY, Cummings J, Roach BJ, Fryer SL, Loewy RL, Stuart BK, Ford JM, Vinogradov S, and Mathalon DH
- Subjects
- Humans, Adolescent, Diffusion Tensor Imaging methods, Brain diagnostic imaging, Magnetic Resonance Imaging, Neural Pathways diagnostic imaging, Schizophrenia diagnostic imaging, Schizophrenia complications, Connectome methods, Antipsychotic Agents, Psychotic Disorders diagnostic imaging, Psychotic Disorders drug therapy, Psychotic Disorders complications
- Abstract
Brain dysconnectivity has been posited as a biological marker of schizophrenia. Emerging schizophrenia connectome research has focused on rich-club organization, a tendency for brain hubs to be highly-interconnected but disproportionately vulnerable to dysconnectivity. However, less is known about rich-club organization in individuals at clinical high-risk for psychosis (CHR-P) and how it compares with abnormalities early in schizophrenia (ESZ). Combining diffusion tensor imaging (DTI) and magnetic resonance imaging (MRI), we examined rich-club and global network organization in CHR-P (n = 41) and ESZ (n = 70) relative to healthy controls (HC; n = 74) after accounting for normal aging. To characterize rich-club regions, we examined rich-club MRI morphometry (thickness, surface area). We also examined connectome metric associations with symptom severity, antipsychotic dosage, and in CHR-P specifically, transition to a full-blown psychotic disorder. ESZ had fewer connections among rich-club regions (ps < .024) relative to HC and CHR-P, with this reduction specific to the rich-club even after accounting for other connections in ESZ relative to HC (ps < .048). There was also cortical thinning of rich-club regions in ESZ (ps < .013). In contrast, there was no strong evidence of global network organization differences among the three groups. Although connectome abnormalities were not present in CHR-P overall, CHR-P converters to psychosis (n = 9) had fewer connections among rich-club regions (ps < .037) and greater modularity (ps < .037) compared to CHR-P non-converters (n = 19). Lastly, symptom severity and antipsychotic dosage were not significantly associated with connectome metrics (ps < .012). Findings suggest that rich-club and connectome organization abnormalities are present early in schizophrenia and in CHR-P individuals who subsequently transition to psychosis., Competing Interests: Declaration of competing interest DHM received compensation as a consultant for Boehringer-Ingelheim, Cadent Therapeutics, Neurocrine Biosciences, Gilgamesh Pharma, Recognify Life Sciences, and Syndesi Therapeutics. The other authors report no conflict of interest. The other authors report no conflict of interest. JPYH, SLF, JMF, and DHM are United States Government employees. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government., (Published by Elsevier B.V.)
- Published
- 2023
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