Genetic and environmental influences on pro-inflammatory monocytes in bipolar disorder: a twin study

Arch Gen Psychiatry. 2009 Sep;66(9):957-65. doi: 10.1001/archgenpsychiatry.2009.116.


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.

Publication types

  • Comparative Study
  • Twin Study

MeSH terms

  • Adult
  • Aged
  • Bipolar Disorder / blood
  • Bipolar Disorder / epidemiology
  • Bipolar Disorder / genetics*
  • Cyclic Nucleotide Phosphodiesterases, Type 4 / genetics
  • Diseases in Twins / blood
  • Diseases in Twins / epidemiology
  • Diseases in Twins / genetics
  • Environment
  • Female
  • Gene Expression / genetics*
  • Gene Expression Profiling / statistics & numerical data
  • Genetic Predisposition to Disease
  • Humans
  • Inflammation / genetics
  • Male
  • Middle Aged
  • Models, Genetic
  • Monocytes / metabolism
  • Monocytes / physiology*
  • Netherlands / epidemiology
  • Risk Factors
  • Twins, Dizygotic / genetics
  • Twins, Monozygotic / genetics


  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • PDE4B protein, human