Relationship between clinical features and inflammation-related monocyte gene expression in bipolar disorder - towards a better understanding of psychoimmunological interactions

Bipolar Disord. 2014 Mar;16(2):137-50. doi: 10.1111/bdi.12142. Epub 2013 Nov 29.


Objectives: Existing and previously published datasets were examined for associations between illness and treatment characteristics and monocyte pro-inflammatory gene expression in patients with bipolar disorder (BD). We hypothesized a priori that increased monocyte pro-inflammatory gene expression would be found more frequently in patients with a lifetime history of psychotic symptoms.

Methods: Monocyte quantitative polymerase chain reaction and symptom data from 64 patients with BD were collected from three Dutch studies. Regression analyses were performed to analyze the various associations between pro-inflammatory gene expression and clinical features, from which feature-expression heat maps were drawn.

Results: No associations were found between pro-inflammatory gene expression and lifetime psychotic symptoms, whereas a positive association was identified between subcluster 2 genes and manic symptoms. For several subcluster 1a genes, a negative association was found with age at onset. For most subcluster 2 genes, a positive association was found with the duration of illness. Current use of antidepressants and of anti-epileptic agents was associated with subcluster 2 gene expression, and current use of lithium and antipsychotic agents with subcluster 1a gene expression.

Conclusions: Our hypothesis that lifetime psychotic features would be associated with pro-inflammatory monocyte gene expression was not confirmed. In an explorative analysis we found: (i) a possible relationship between pro-inflammatory gene expression and manic symptomatology; (ii) a differential immune activation related to age at onset and duration of illness; and (iii) support for the concept of an immune suppressive action of some of the mood-regulating medications.

Keywords: bipolar disorder; gene expression; inflammation; monocyte; phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use
  • Bipolar Disorder / drug therapy
  • Bipolar Disorder / immunology
  • Bipolar Disorder / pathology*
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Female
  • Gene Expression / drug effects
  • Gene Expression / physiology*
  • Humans
  • Male
  • Middle Aged
  • Monocytes / drug effects
  • Monocytes / metabolism*
  • Psychiatric Status Rating Scales
  • Regression Analysis
  • Young Adult


  • Antidepressive Agents
  • Cytokines