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Brain network connectivity in individuals with schizophrenia and their siblings.

ABSTRACT: Research on brain activity in schizophrenia has shown that changes in the function of any single region cannot explain the range of cognitive and affective impairments in this illness. Rather, neural circuits that support sensory, cognitive, and emotional processes are now being investigated as substrates for cognitive and affective impairments in schizophrenia, a shift in focus consistent with long-standing hypotheses about schizophrenia as a disconnection syndrome. Our goal was to further examine alterations in functional connectivity within and between the default mode network and three cognitive control networks (frontal-parietal, cingulo-opercular, and cerebellar) as a basis for such impairments.Resting state functional magnetic resonance imaging was collected from 40 individuals with DSM-IV-TR schizophrenia, 31 siblings of individuals with schizophrenia, 15 healthy control subjects, and 18 siblings of healthy control subjects while they rested quietly with their eyes closed. Connectivity metrics were compared between patients and control subjects for both within- and between-network connections and were used to predict clinical symptoms and cognitive function.Individuals with schizophrenia showed reduced distal and somewhat enhanced local connectivity between the cognitive control networks compared with control subjects. Additionally, greater connectivity between the frontal-parietal and cerebellar regions was robustly predictive of better cognitive performance across groups and predictive of fewer disorganization symptoms among patients.These results are consistent with the hypothesis that impairments of executive function and cognitive control result from disruption in the coordination of activity across brain networks and additionally suggest that these might reflect impairments in normal pattern of brain connectivity development.

SUBMITTER: Repovs G

PROVIDER: S-EPMC3081915 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Brain network connectivity in individuals with schizophrenia and their siblings.

Repovs Grega G Csernansky John G JG Barch Deanna M DM

Biological psychiatry 20101230 10

<h4>Background</h4>Research on brain activity in schizophrenia has shown that changes in the function of any single region cannot explain the range of cognitive and affective impairments in this illness. Rather, neural circuits that support sensory, cognitive, and emotional processes are now being investigated as substrates for cognitive and affective impairments in schizophrenia, a shift in focus consistent with long-standing hypotheses about schizophrenia as a disconnection syndrome. Our goal ...[more]

PMID: 21193174

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Project description:BACKGROUND:Altered structural network-connectivity has been reported in psychotic disorder but whether these alterations are associated with genetic vulnerability, and/or with phenotypic variation, has been less well examined. This study examined i) whether differences in network-connectivity exist between patients with psychotic disorder, siblings of patients with psychotic disorder and controls, and ii) whether network-connectivity alterations vary with (subclinical) symptomatology. METHODS:Network-connectivity measures (global efficiency (GE), density, local efficiency (LE), clustering coefficient (CC)) were derived from diffusion weighted imaging (DWI) and were compared between 85 patients with psychotic disorder, 93 siblings without psychotic disorder and 80 healthy comparison subjects using multilevel regression models. In patients, associations between Positive and Negative Syndrome Scale (PANSS) symptoms and topological measures were examined. In addition, interactions between subclinical psychopathology and sibling/healthy comparison subject status were examined in models of topological measures. RESULTS:While there was no main effect of group with respect to GE, density, LE and CC, siblings had a significantly higher CC compared to patients (B = 0.0039, p = .002). In patients, none of the PANSS symptom domains were significantly associated with any of the four network-connectivity measures. The two-way interaction between group and SIR-r positive score in the model of LE was significant (χ2 = 6.24, p = .01, df = 1). In the model of CC, the interactions between group and respectively SIS-r positive (χ2 = 5.59, p = .02, df = 1) and negative symptom scores (χ2 = 4.71, p = .03, df = 1) were significant. Stratified analysis showed that, in siblings, decreased LE and CC was significantly associated with increased SIS-r positive scores (LE: B = -0.0049, p = .003, CC: B = -0.0066, p = .01) and that decreased CC was significantly associated with increased SIS-r negative scores (B = -0.012, p = .003). There were no significant interactions between group and SIS-r scores in the models of GE and density. CONCLUSION:The findings indicate absence of structural network-connectivity alterations in individuals with psychotic disorder and in individuals at higher than average genetic risk for psychotic disorder, in comparison with healthy subjects. The differential subclinical symptom-network connectivity associations in siblings with respect to controls may be a sign of psychosis vulnerability in the siblings.

Dataset Information

Brain network connectivity in individuals with schizophrenia and their siblings.

Publications

Brain network connectivity in individuals with schizophrenia and their siblings.

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