Resting State Functional Connectivity of Emotion Regulation Circuits in Schizophrenia and Bipolar Disorder

Background: Schizophrenia and bipolar disorder are debilitating mental illnesses that share core difficulties of emotional disturbance and impulsivity. Neurobiological models of emotion regulation critically involve a complex coordination of the brain’s limbic structures and frontal areas, and animal research has identified regions of frontal cortex which directly connect to key inhibitors of the limbic system. However, further research is needed to investigate whether these direct connections facilitate emotion regulation in humans. Our research investigates whether disruptions within these frontolimbic circuits may underlie emotion regulation difficulties, as observed in patients of schizophrenia and bipolar disorder. Methods: Using resting state fMRI data from patients of schizophrenia (n=185), bipolar disorder (n=152), and healthy controls (n=691), we calculated functional connectivity between the amygdala, posterior orbitofrontal cortex (pOFC), and portions of the ventromedial prefrontal cortex (vmPFC). Group-level connectivity differences between diagnostic groups were then assessed using GLM designs. Results: We identified significant decreases in resting state functional connectivity occurring between the amygdala and vmPFC, and between the vmPFC and pOFC, in patients of schizophrenia relative to healthy controls. Subsequent analyses correlating edge strength in the schizophrenia group to measures of impulse control and suicidality did not reach significance. No significant differences in connectivity were identified in contrasts between healthy controls and bipolar disorder, or between bipolar disorder and schizophrenia. Conclusion: Our findings are consistent with the interpretation of schizophrenia as a disconnection disorder, and support the notion that frontolimbic circuits are functionally altered in schizophrenia