Rebecca E Watsky1, Stephen J Gotts2, Rebecca A Berman1, Harrison M McAdams1, Xueping Zhou1, Dede Greenstein1, Francois M Lalonde1, Peter Gochman1, Liv S Clasen1, Lorie Shora1, Anna E Ordóñez1, Nitin Gogtay1, Alex Martin2, Deanna M Barch3, Judith L Rapoport1, Siyuan Liu4. 1. Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, Building 10, Bethesda, MD 20892, USA. 2. Laboratory of Brain and Cognition, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, Building 10, Bethesda, MD 20892, USA. 3. Departments of Psychology, Psychiatry and Radiology, Washington University in St. Louis, One Brookings Drive, St. Louis, MO 63130, USA. 4. Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, Building 10, Bethesda, MD 20892, USA. Electronic address: siyuan.liu@nih.gov.
Abstract
BACKGROUND: Childhood-onset schizophrenia (COS) is a rare, severe form of the adult-onset disorder (AOS). Our previous resting-state fMRI study identified attenuated functional connectivity in COS compared with controls. Here, we ask whether COS and AOS patients and their siblings exhibit similar abnormalities of functional connectivity. METHODS: A whole-brain, data-driven approach was used to assess resting-state functional connectivity differences in COS (patients/siblings/controls, n: 26/28/33) and AOS (n: 19/28/30). There were no significant differences in age, sex, or head motion across groups in each dataset and as designed, the COS dataset has a significantly lower age than the AOS. RESULTS: Both COS and AOS patients showed decreased functional connectivity relative to controls among a wide set of brain regions (P<0.05, corrected), but their siblings did not. Decreased connectivity in COS and AOS patients showed no amplitude differences and was not modulated by age-at-onset or medication doses. Cluster analysis revealed that these regions fell into two large-scale networks: one sensorimotor network and one centered on default-mode network regions, but including higher-order cognitive areas only in COS. Decreased connectivity between these two networks was notable (P<0.05, corrected) for both patient groups. CONCLUSIONS: A shared pattern of attenuated functional connectivity was found in COS and AOS, supporting the continuity of childhood-onset and adult-onset schizophrenia. Connections were altered between sensorimotor areas and default-mode areas in both COS and AOS, suggesting potential abnormalities in processes of self-monitoring and sensory prediction. The absence of substantial dysconnectivity in siblings indicates that attenuation is state-related. Published by Elsevier B.V.
BACKGROUND: Childhood-onset schizophrenia (COS) is a rare, severe form of the adult-onset disorder (AOS). Our previous resting-state fMRI study identified attenuated functional connectivity in COS compared with controls. Here, we ask whether COS and AOSpatients and their siblings exhibit similar abnormalities of functional connectivity. METHODS: A whole-brain, data-driven approach was used to assess resting-state functional connectivity differences in COS (patients/siblings/controls, n: 26/28/33) and AOS (n: 19/28/30). There were no significant differences in age, sex, or head motion across groups in each dataset and as designed, the COS dataset has a significantly lower age than the AOS. RESULTS: Both COS and AOSpatients showed decreased functional connectivity relative to controls among a wide set of brain regions (P<0.05, corrected), but their siblings did not. Decreased connectivity in COS and AOSpatients showed no amplitude differences and was not modulated by age-at-onset or medication doses. Cluster analysis revealed that these regions fell into two large-scale networks: one sensorimotor network and one centered on default-mode network regions, but including higher-order cognitive areas only in COS. Decreased connectivity between these two networks was notable (P<0.05, corrected) for both patient groups. CONCLUSIONS: A shared pattern of attenuated functional connectivity was found in COS and AOS, supporting the continuity of childhood-onset and adult-onset schizophrenia. Connections were altered between sensorimotor areas and default-mode areas in both COS and AOS, suggesting potential abnormalities in processes of self-monitoring and sensory prediction. The absence of substantial dysconnectivity in siblings indicates that attenuation is state-related. Published by Elsevier B.V.
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