Reported structural abnormalities of patients with bipolar disorder (BD) are inconsistent and the use of psychotropic medication is one of the sources of heterogeneity. A fairly small number of morphometric studies have involved comparison of BD on different mood stabilizers. Here in this study, we aimed to investigate the cortical thickness and subcortical volumes in euthymic BD patients on lithium and valproate and healthy controls (HC), and to elucidate the relationship between the use of medication and brain structure variations. We acquired structural magnetic resonance imaging data from 35 BD patients (19/valproate;16/lithium) and 30 HC subjects. Cortical thickness was compared in multiple locations across the continuous cortical surface, and subcortical volumes were compared on a structure-by-structure basis. Group analyses revealed widespread thinning of the prefrontal cortex in BD. Compared with BD on valproate, BD on lithium showed significant increased cortical thickness of the left rostral middle frontal cortex and right superior frontal cortex, while cortical thickness was not significantly different between BD on lithium and HC in the bilateral rostral middle frontal cortex. Moreover, no significant difference was observed in subcortical volume. Limitations of this study comprise the possible effect of other psychotropic drugs, small sample size and the cross-sectional design. Therefore, the results suggest medication-related neurobiological difference between BD patients on different mood stabilizers, but no casual role can be proposed. Our findings provided new evidence about the effects of psychotropic medication upon neuroanatomy in BD, and could help to explain the inconsistency of existing studies as well as contribute to the extraction of reliable neuroimaging biomarkers in BD.

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