Gene-expression analysis of clozapine treatment in whole blood of patients with psychosis

Psychiatr Genet. 2016 Oct;26(5):211-7. doi: 10.1097/YPG.0000000000000140.

Abstract

Objectives: Clozapine is an atypical antipsychotic primarily prescribed for treatment-resistant schizophrenia. We tested the specific effect of clozapine versus other drug treatments on whole-blood gene expression in a sample of patients with psychosis from the UK.

Methods: A total of 186 baseline whole-blood samples from individuals receiving treatment for established psychosis were analysed for gene expression on Illumina HumanHT-12.v4 BeadChips. After standard quality-control procedures, 152 samples remained, including 55 from individuals receiving clozapine. In a within-case study design, weighted gene correlation network analysis was used to identify modules of coexpressed genes. The influence of mood stabilizers, lithium carbonate/lithium citrate and sodium valproate was studied to identify their possible roles as confounders.

Results: Individuals receiving clozapine as their only antipsychotic (clozapine monotherapy) had a nominal association with one gene-expression module, whereas no significant change in gene expression was found for other drugs.

Conclusion: Overall, this study does not provide evidence that clozapine treatment induces medium to large different gene-expression patterns in human whole blood versus other antipsychotic treatments. This does not rule out the possibility of smaller effects as observed for other common antipsychotic treatments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents / blood
  • Antipsychotic Agents / pharmacology*
  • Clozapine / blood
  • Clozapine / pharmacology*
  • Female
  • Gene Expression / drug effects
  • Gene Expression Profiling
  • Humans
  • Male
  • Middle Aged
  • Psychotic Disorders / blood
  • Psychotic Disorders / drug therapy*
  • Psychotic Disorders / genetics*
  • Randomized Controlled Trials as Topic
  • Risperidone / therapeutic use
  • Schizophrenia / blood
  • Schizophrenia / drug therapy*
  • Schizophrenia / genetics*

Substances

  • Antipsychotic Agents
  • Clozapine
  • Risperidone