Familial Risk for Schizophrenia vs Bipolar Disorder and Task-Based Neural Activation: A functional Magnetic Resonance Imaging Meta-Analysis

Abstract Background and Hypothesis Individuals at familial risk for developing schizophrenia (FRSZ) or bipolar disorder (FRBD) have shared and unique genetic risks. Few studies have compared neural activation between these two groups. Therefore, the present meta-analysis investigated functional brain similarities and differences between FRSZ and FRBD individuals. Study Design A systematic literature review was conducted of articles that compared FRSZ or FRBD individuals to healthy controls (31 FRSZ and 22 FRBD). Seed-based d mapping was used to conduct the meta-analysis. Analyses included comparisons of FRSZ to controls, FRBD to controls, and both relative groups to each other. Study Results Using a highly conservative family-wise error rate correction, there were no significant findings. Using a less conservative threshold, FRSZ compared to controls had lower activation in the left precuneus (Puncorrected = .02) across all studies and in the left middle frontal gyrus (Puncorrected = .03) in nonsocial cognition studies. FRBD compared to controls had lower activation in the left superior parietal gyrus (Puncorrected = .03) and right angular gyrus (Puncorrected = .03) in nonsocial cognition studies, and higher activation in the left superior frontal gyrus (Puncorrected = .01) in social tasks. Differences between FRSZ and FRBD were not significant. Conclusions There were few robust differences between FRSZ or FRBD compared to controls. This suggests only weak support for neural activation differences between individuals at genetic risk for schizophrenia or bipolar disorder and controls. The tentative findings observed were in different brain regions for FRSZ and FRBD, with no strong evidence for shared effects between schizophrenia and bipolar genetic risk on neural activation.