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Abstract Objectives Studies have demonstrated that sex differences may play a crucial role in the alternations of brain structures in individuals with bipolar disorder, but findings are not consistent. The current study identified sex differences in brain structure and function among a large sample of individuals with bipolar I disorder (BD-I). Methods Structural and functional magnetic resonance imaging datasets were acquired from 105 individuals with BD-I (36 men and 69 women) and 210 healthy adults (72 men and 138 women). A general linear regression model was used for voxel-wise analysis of grey matter (GM) and functional connectivity. Age, sex, diagnosis, and sex-by-diagnosis interaction were defined as predictors. Results In GM, the left caudate (p p p = .003), right thalamus (p p = .015), and left middle/posterior cingulate gyrus (p = .022) exhibited sex-by-diagnosis interaction. Furthermore, by using these six brain regions as seeds, we observed sex-by-diagnosis interaction in the alteration of functional connectivity between the left thalamus and right angular gyrus (p = .019). Conclusions Our data revealed a sex-by-diagnosis interaction associated with structure and function of the limbic system in individuals with BD-I. These findings may serve as reference for future studies on the pathophysiology of bipolar disorder.
John Pollitt (Sat,) studied this question.