Disrupted sensorimotor and social-cognitive networks underlie symptoms in childhood-onset schizophrenia.
Schizophrenia is increasingly recognized as a neurodevelopmental disorder with altered connectivity among brain networks. In the current study we examined large-scale network interactions in childhood-onset schizophrenia, a severe form of the disease with salient genetic and neurobiological abnormalities. Using a data-driven analysis of resting-state functional magnetic resonance imaging fluctuations, we characterized data from 19 patients with schizophrenia and 26 typically developing controls, group matched for age, sex, handedness, and magnitude of head motion during scanning. This approach identified 26 regions with decreased functional correlations in schizophrenia compared to controls. These regions were found to organize into two function-related networks, the first with regions associated with social and higher-level cognitive processing, and the second with regions involved in somatosensory and motor processing. Analyses of across- and within-network regional interactions revealed pronounced across-network decreases in functional connectivity in the schizophrenia group, as well as a set of across-network relationships with overall negative coupling indicating competitive or opponent network dynamics. Critically, across-network decreases in functional connectivity in schizophrenia predicted the severity of positive symptoms in the disorder, such as hallucinations and delusions. By contrast, decreases in functional connectivity within the social-cognitive network of regions predicted the severity of negative symptoms, such as impoverished speech and flattened affect. These results point toward the role that abnormal integration of sensorimotor and social-cognitive processing may play in the pathophysiology and symptomatology of schizophrenia.
1 Child Psychiatry Branch, National Institute of Mental Health, NIH, Bethesda MD 20892, USA bermanr@mail.nih.gov.
Rebecca A
RA
Berman
2 Laboratory of Brain and Cognition, National Institute of Mental Health, NIH, Bethesda MD 20892, USA.
Stephen J
SJ
Gotts
1 Child Psychiatry Branch, National Institute of Mental Health, NIH, Bethesda MD 20892, USA.
Harrison M
HM
McAdams
1 Child Psychiatry Branch, National Institute of Mental Health, NIH, Bethesda MD 20892, USA.
Dede
D
Greenstein
1 Child Psychiatry Branch, National Institute of Mental Health, NIH, Bethesda MD 20892, USA.
Francois
F
Lalonde
1 Child Psychiatry Branch, National Institute of Mental Health, NIH, Bethesda MD 20892, USA.
Liv
L
Clasen
1 Child Psychiatry Branch, National Institute of Mental Health, NIH, Bethesda MD 20892, USA.
Rebecca E
RE
Watsky
1 Child Psychiatry Branch, National Institute of Mental Health, NIH, Bethesda MD 20892, USA.
Lorie
L
Shora
1 Child Psychiatry Branch, National Institute of Mental Health, NIH, Bethesda MD 20892, USA.
Anna E
AE
Ordonez
1 Child Psychiatry Branch, National Institute of Mental Health, NIH, Bethesda MD 20892, USA.
Armin
A
Raznahan
2 Laboratory of Brain and Cognition, National Institute of Mental Health, NIH, Bethesda MD 20892, USA.
Alex
A
Martin
1 Child Psychiatry Branch, National Institute of Mental Health, NIH, Bethesda MD 20892, USA.
Nitin
N
Gogtay
1 Child Psychiatry Branch, National Institute of Mental Health, NIH, Bethesda MD 20892, USA.
Judith
J
Rapoport
D000293:Adolescent; D001921:Brain / Q000503:physiopathology*; D016022:Case-Control Studies; D003071:Cognition; D017352:Echo-Planar Imaging; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D008297:Male; D009434:Neural Pathways / Q000503:physiopathology; D012561:Schizophrenia, Childhood / Q000175:diagnosis / Q000503:physiopathology* / Q000523:psychology*; D012919:Social Behavior; D055815:Young Adult
negative symptoms; neuropsychiatry: imaging; positive symptoms; psychosis; schizophrenia