Elsevier

Biological Psychiatry

Volume 69, Issue 10, 15 May 2011, Pages 967-973
Biological Psychiatry

Archival Report
Brain Network Connectivity in Individuals with Schizophrenia and Their Siblings

https://doi.org/10.1016/j.biopsych.2010.11.009Get rights and content

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Section snippets

Participants

The participants (Table 1) for this study were recruited through the Conte Center for the Neuroscience of Mental Disorders at Washington University School of Medicine in St. Louis and included: 1) probands who were individuals with DSM-IV schizophrenia (SCZ; n = 25); 2) the nonpsychotic siblings of individuals with schizophrenia (SCZ-SIB; n = 31); 3) healthy control subjects (CON; n = 15); and 4) the siblings of healthy control subjects (CON-SIB; n = 18). Siblings were full siblings, based on

Within-Network Connectivity

The within-network ANOVA included diagnostic group and sibling type as between-subject factors and network as a within-subject factor. This ANOVA revealed a trend level main effect of diagnostic group [F(1,85) = 3.34, p = .07], which reflected slightly lower within-network connectivity among SCZ and SCZ-SIB compared with CON and CON-SIB (Figure 2). We next examined whether specific regions within any of the networks showed reduced connectivity with its own network. To do so, we computed, for

Discussion

The goal of the current study was to examine differences in functional connectivity within and between known brain networks in patients with schizophrenia and their unaffected siblings to test the hypothesis that schizophrenia involves disruptions in the coordinated activity of brain regions. Our results suggest that both individuals with schizophrenia and their siblings have impaired brain connectivity and that these impairments are most prominent between networks compared with within

References (47)

  • C. Durisko et al.

    Functional activation in the cerebellum during working memory and simple speech tasks

    Cortex

    (2010)
  • J.A. Fiez

    Cerebellar contributions to cognition

    Neuron

    (1996)
  • E.T. Bullmore et al.

    The dysplastic net hypothesis: An integration of developmental and dysconnectivity theories of schizophrenia

    Schizophr Res

    (1997)
  • I. Feinberg

    Schizophrenia: Caused by a fault in programmed synaptic elimination during adolescence?

    J Psychiatr Res

    (1982)
  • J.X. Van Snellenberg et al.

    Functional neuroimaging of working memory in schizophrenia: Task performance as a moderating variable

    Neuropsychology

    (2006)
  • M.J. Minzenberg et al.

    Meta-analysis of 41 functional neuroimaging studies of executive function in schizophrenia

    Arch Gen Psychiatry

    (2009)
  • A.M. Achim et al.

    Episodic memory-related activation in schizophrenia: Meta-analysis

    Br J Psychiatry

    (2005)
  • J.D. Ragland et al.

    Prefrontal activation deficits during episodic memory in schizophrenia

    Am J Psychiatry

    (2009)
  • V.D. Calhoun et al.

    Functional brain networks in schizophrenia: A review

    Front Hum Neurosci

    (2009)
  • K.E. Stephan et al.

    Dysconnection in schizophrenia: From abnormal synaptic plasticity to failures of self-monitoring

    Schizophr Bull

    (2009)
  • N.C. Andreasen et al.

    “Cognitive dysmetria” as an integrative theory of schizophrenia: A dysfunction in cortical-subcortical-cerebellar circuitry?

    Schizophr Bull

    (1998)
  • J.S. Damoiseaux et al.

    Consistent resting-state networks across healthy subjects

    Proc Natl Acad Sci U S A

    (2006)
  • M.D. Fox et al.

    The human brain is intrinsically organized into dynamic, anticorrelated functional networks

    Proc Natl Acad Sci USA

    (2005)
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