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Original Investigation
June 2017

Transdiagnostic Associations Between Functional Brain Network Integrity and Cognition

Author Affiliations
  • 1Department of Psychological and Brain Sciences, Washington University, St Louis, Missouri
  • 2Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri
  • 3Department of Psychiatry and Pediatrics, University of Texas Southwestern Medical Center, Dallas
  • 4Departments of Psychiatry and Neurobiology, Yale University, New Haven, Connecticut
  • 5Olin Research Center, Institute of Living, Hartford, Connecticut
  • 6Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, Massachusetts
  • 7Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
  • 8Department of Psychiatry, University of Cincinnati, Cincinnati, Ohio
  • 9BioImaging Research Center, Department of Psychology, University of Georgia, Athens
  • 10BioImaging Research Center, Department of Neuroscience, University of Georgia, Athens
  • 11Department of Biomedical Engineering, Washington University, St Louis, Missouri
  • 12Department of Psychology, Rosalind Franklin University of Medicine and Science, Chicago, Illinois
  • 13Department of Radiology, Washington University School of Medicine, St Louis, Missouri
JAMA Psychiatry. 2017;74(6):605-613. doi:10.1001/jamapsychiatry.2017.0669
Key Points

Questions  Is the efficiency of the cingulo-opercular network and frontoparietal network reduced across multiple psychotic disorders, and does lower efficiency predict impairments in generalized cognitive ability?

Findings  In this case-control study, cingulo-opercular network but not frontoparietal network efficiency was significantly reduced in patients with schizophrenia, schizoaffective disorder, and psychotic bipolar disorder compared with healthy control individuals. Lower cingulo-opercular network global efficiency was associated with worse general cognitive ability and mediates the association between psychotic disorder status and cognitive function.

Meaning  Reduced efficiency of information transfer within the cingulo-opercular network is a shared vulnerability across multiple psychotic disorders and represents a common mechanism that contributes to the generalized cognitive deficit.


Importance  Cognitive impairment occurs across the psychosis spectrum and is associated with functional outcome. However, it is unknown whether these shared manifestations of cognitive dysfunction across diagnostic categories also reflect shared neurobiological mechanisms or whether the source of impairment differs.

Objective  To examine whether the general cognitive deficit observed across psychotic disorders is similarly associated with functional integrity of 2 brain networks widely implicated in supporting many cognitive domains.

Design, Setting, and Participants  A total of 201 healthy control participants and 375 patients with psychotic disorders from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium were studied from September 29, 2007, to May 31, 2011. The B-SNIP recruited healthy controls and stable outpatients from 6 sites: Baltimore, Maryland; Boston, Massachusetts; Chicago, Illinois; Dallas, Texas; Detroit, Michigan; and Hartford, Connecticut. All participants underwent cognitive testing and resting-state functional magnetic resonance imaging. Data analysis was performed from April 28, 2015, to February 21, 2017.

Main Outcomes and Measures  The Brief Assessment of Cognition in Schizophrenia was used to measure cognitive ability. A principal axis factor analysis on the Brief Assessment of Cognition in Schizophrenia battery yielded a single factor (54% variance explained) that served as the measure of general cognitive ability. Functional network integrity measures included global and local efficiency of the whole brain, cingulo-opercular network (CON), frontoparietal network, and auditory network and exploratory analyses of all networks from the Power atlas. Group differences in network measures, associations between cognition and network measures, and mediation models were tested.

Results  The final sample for the current study included 201 healthy controls, 143 patients with schizophrenia, 103 patients with schizoaffective disorder, and 129 patients with psychotic bipolar disorder (mean [SD] age, 35.1 [12.0] years; 281 male [48.8%] and 295 female [51.2%]; 181 white [31.4%], 348 black [60.4%], and 47 other [8.2%]). Patients with schizophrenia (Cohen d = 0.36, P < .001) and psychotic bipolar disorder (Cohen d = 0.33, P = .002) had significantly reduced CON global efficiency compared with healthy controls. All patients with psychotic disorders had significantly reduced CON local efficiency, but the clinical groups did not differ from one another. The CON global efficiency was significantly associated with general cognitive ability across all groups (β = 0.099, P = .009) and significantly mediated the association between psychotic disorder status and general cognition (β = −0.037; 95% CI, −0.076 to −0.014). Subcortical network global efficiency was also significantly reduced in psychotic disorders (F3,587 = 4.01, P = .008) and positively predicted cognitive ability (β = 0.094, P = .009).

Conclusions and Relevance  These findings provide evidence that reduced CON and subcortical network efficiency play a role in the general cognitive deficit observed across the psychosis spectrum. They provide new support for the dimensional hypothesis that a shared neurobiological mechanism underlies cognitive impairment in psychotic disorders.