Genetic and Environmental Influences on Pro-Inflammatory Monocytes in Bipolar Disorder

Abstract

CONTEXT: A monocyte pro-inflammatory state has previously been reported in bipolar disorder (BD). OBJECTIVE: To determine the contribution of genetic and environmental influences on the association between monocyte pro-inflammatory state and BD. DESIGN: A quantitative polymerase chain reaction case-control study of monocytes in bipolar twins. Determination of the influence of additive genetic, common, and unique environmental factors by structural equation modeling (ACE). SETTING: Dutch academic research center. PARTICIPANTS: Eighteen monozygotic BD twin pairs, 23 dizygotic BD twin pairs, and 18 monozygotic and 16 dizygotic healthy twin pairs. MAIN OUTCOME MEASURES: Expression levels of monocytes in the previously reported coherent set of 19 genes (signature) reflecting the pro-inflammatory state. RESULTS: The familial occurrence of the association between the monocyte pro-inflammatory gene-expression signature and BD found in the within-trait/cross-twin correlations (twin correlations) was due to shared environmental factors (ie, both monozygotic and dizygotic ratios in twin correlations approximated 1; ACE modeling data: 94% [95% confidence interval, 53%-99%] explained by common [shared] environmental factors). Although most individual signature genes followed this pattern, there was a small subcluster of genes in which genetic influences could dominate. CONCLUSION: The association of the monocyte pro-inflammatory state with BD is primarily the result of a common shared environmental factor.