Disruption of Cortical Association Networks in Schizophrenia and Psychotic Bipolar Disorder

Justin T. Baker, Avram J. Holmes, Grace A. Masters, B. T. Thomas Yeo, Fenna Krienen, Randy L. Buckner, Dost Öngür
2014 JAMA psychiatry  
D elusions, hallucinations, and formal thought disorder, as seen in a range of psychotic disorders (including schizophrenia, schizoaffective disorder, and psychotic bipolar disorder), are widely assumed to result from breakdown in information processing across large-scale distributed brain networks. Multiple brain networks have been implicated in the functional deficits observed in schizophrenia and bipolar disorder. Recent attention has focused on abnormalities in the default network, which is
more » ... implicated in processing internal stimuli and representations of the self. Default network abnormalities have been discovered in a range of neuropsychiatric conditions, raising the possibility that this dysfunction could represent a common substrate for mental illness. 1,2 However, other systems are also affected in schizophrenia, with abnormalities in the dorsolateral prefrontal cortex perhaps the best characterized, 3-8 supporting the notion that multiple brain networks are functioning abnormally in psychotic disorders. Despite much progress, it remains unclear whether a single organizing principle underlies network abnormalities in psychotic disorders. For example, does brain network dysfunction occur piecemeal in schizophrenia and bipolar disorder because of a shared but broadly distributed mechanism, or is it better explained by damage to key control systems? 9,10 The frontoparietal control network spans portions of the dorsolateral prefrontal cortex, dorsomedial prefrontal cortex, lateral IMPORTANCE Psychotic disorders (including schizophrenia, schizoaffective disorder, and psychotic bipolar disorder) are devastating illnesses characterized by breakdown in the integration of information processing. Recent advances in neuroimaging allow for the estimation of brain networks on the basis of intrinsic functional connectivity, but the specific network abnormalities in psychotic disorders are poorly understood. OBJECTIVE To compare intrinsic functional connectivity across the cerebral cortex in patients with schizophrenia spectrum disorders or psychotic bipolar disorder and healthy controls. DESIGN, SETTING, AND PARTICIPANTS We studied 100 patients from an academic psychiatric hospital (28 patients with schizophrenia, 32 patients with schizoaffective disorder, and 40 patients with bipolar disorder with psychosis) and 100 healthy controls matched for age, sex, race, handedness, and scan quality from December 2009 to October 2011. MAIN OUTCOMES AND MEASURES Functional connectivity profiles across 122 regions that covered the entire cerebral cortex. RESULTS Relative to the healthy controls, individuals with a psychotic illness had disruption across several brain networks, with preferential reductions in functional connectivity within the frontoparietal control network (P < .05, corrected for family-wise error rate). This functionally defined network includes portions of the dorsolateral prefrontal cortex, posteromedial prefrontal cortex, lateral parietal cortex, and posterior temporal cortex. This effect was seen across diagnoses and persisted after matching patients and controls on the basis of scan quality. CONCLUSIONS AND RELEVANCE Our study results support the view that cortical information processing is disrupted in psychosis and provides new evidence that disruptions within the frontoparietal control network may be a shared feature across both schizophrenia and affective psychosis. regional pairs within control A, within control B, and between control A and control B were compared between controls (n = 100), patients with bipolar disorder (n = 40), and patients with schizophrenia or schizoaffective disorder (n = 60). As observed at the psychotic disorders group level, mean correlation among regions of the frontoparietal control B network was significantly greater (P < .01) in healthy participants (r = 0.494) than in patients with bipolar disorder with psychosis (r = 0.405) or patients with schizophrenia or schizoaffective disorder (r = 0.411; Figure 5 ). The pattern of frontoparietal network disruption displayed consistency across the patient groups ( Figure 5 ; for full grid, see eFigure 5 in the Supplement). We did not discover any significant relationships in a series of demographic and clinical variables and our findings (see eMaterials in the Supplement). assisted with participant recruitment, clinical assessment, and scanning. Subjects were provided monetary compensation for their participation.
doi:10.1001/jamapsychiatry.2013.3469 pmid:24306091 pmcid:PMC4435541 fatcat:mmomfa73tbh7djs2ufxyky7mui