Shared intermediate phenotypes for schizophrenia and bipolar disorder: Neuroanatomical features of subtypes distinguished by executive dysfunction

Background: Shared genetic vulnerability for schizophrenia and bipolar disorder may be associated with common neuroanatomical features. In view of the evidence for working memory dysfunction as a candidate intermediate phenotype for both disorders, we explored neuroanatomical distinctions between subtypes defined according to working memory (n-back task) performance. Methods: We analyzed T1-weighted MRI scans for patients with schizophrenia-spectrum disorder, bipolar-I disorder (BD-I) and healthy controls. The VBM8 toolbox was used to assess differences in grey and white matter volume across traditional diagnostic groups (schizophrenia v. BD-I). Subsequently, groups were defined as “executively spared” (ES) based on the achievement of greater than 50% accuracy in the 2-back task performance (comparable to performance in the control group) or “executively deficit” (ED) based on the achievement of less than 50% accuracy. Results: Our study included 40 patients with schizophrenia-spectrum disorders, 30 patients with BD-I and 34 controls. Both the schizophrenia and BD-I groups showed grey matter volume reductions relative to the control group, but not relative to each other. The ED subtype (n = 32 [10 BD-I, 22 schizophrenia]) showed grey matter volume reductions in the bilateral superior and medial frontal gyri, right inferior opercular gyri and hippocampus relative to controls. The ES subtype (n = 38 [20 BD-I, 18 schizophrenia]) showed grey matter volume reductions in the right precuneus and left superior and medial orbital frontal gyri relative to controls. The ED subtype showed grey matter volume reduction in the right inferior frontal and precentral gyri relative to the ES subtype. There were no significant differences in white matter volume in any group comparisons. Limitations: This analysis was limited by small sample sizes. Further, insufficient numbers were available to assess a control-deficit comparison group. We were unable to assess the effects of mood stabilizer dose on brain structure. Conclusion: Neuroanatomical commonalities are evident among patients with schizophrenia-spectrum disorders and BD-I with working memory deficits. Reduced inferior frontal lobe volume may mediate cognitive deficits shared across the psychosis–mood spectrum.