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A Twin Study

Roos C. Padmos, MD; G. Caroline M. Van Baal, PhD; Ronald Vonk, MD; Annemarie J. M. Wijkhuijs, BSc; René S. Kahn, MD, PhD; Willem A. Nolen, MD, PhD; Hemmo A. Drexhage, MD, PhD

Arch Gen Psychiatry. 2009;66(9):957-965.

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.

Author Affiliations: Department of Immunology, Erasmus Medical Center, Rotterdam (Drs Padmos and Drexhage and Ms Wijkhuijs); Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht (Drs Van Baal and Kahn); Reinier van Arkel Group, ’s-Hertogenbosch (Dr Vonk); and Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen (Dr Nolen), the Netherlands.

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