Increased DNA methylation status of the serotonin receptor 5HTR1A gene promoter in schizophrenia and bipolar disorder

J Affect Disord. 2011 Aug;132(3):450-3. doi: 10.1016/j.jad.2011.03.018. Epub 2011 Mar 30.

Abstract

Background: Epigenetic changes may play a role in the etiology of psychotic diseases. It has been demonstrated that the serotonin receptor, 5HTR1A, is implicated in schizophrenia (SCZ) and bipolar disorder (BPD). The aim of this study was to investigate the methylation status of a promoter region of the 5HTR1A gene in BPD and SCZ patients.

Methods: Our study included 58 BPD and 40 SCZ (DSM-IV criteria) as well as 67 control subjects. DNA was extracted from blood leukocytes and high-resolution melt (HRM) method was used for analysis.

Results: Non-parametric analysis of variance (Kruskal-Wallis) within groups was significant: H=67.6; p<0.0001. The Mann-Whitney U-test showed increased methylation level in both BPD (Z=-7.4; p<0.0001) and SCZ (Z=4.2; p<0.0001) compared to controls. No effect either of age or gender by own, was observed. ANCOVA revealed a modest effect of age/gender covariance (F=3.99; p<0.048).

Limitation: We used a peripheral tissue. The relationship between methylation of blood and brain DNA is not well known. Data need to be replicated in a brain tissue.

Conclusion: We observed increased DNA methylation in the promoter region of the 5HTR1A gene of SCZ and BPD. This could explain the reported decrease of the receptor expression. The current study supports the growing interest of DNA methylation in psychopathology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bipolar Disorder / genetics*
  • Bipolar Disorder / metabolism
  • Brain / metabolism
  • Case-Control Studies
  • CpG Islands
  • DNA Methylation*
  • Diagnostic and Statistical Manual of Mental Disorders
  • Epigenesis, Genetic
  • Epigenomics
  • Female
  • Gene Expression
  • Genes
  • Genetic Predisposition to Disease
  • Humans
  • Leukocytes / metabolism
  • Male
  • Middle Aged
  • Promoter Regions, Genetic / genetics
  • Psychotic Disorders / genetics
  • Psychotic Disorders / metabolism
  • Receptor, Serotonin, 5-HT1A / genetics*
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Receptors, Serotonin / genetics
  • Receptors, Serotonin / metabolism
  • Schizophrenia / genetics*
  • Schizophrenia / metabolism
  • Young Adult

Substances

  • Receptors, Serotonin
  • Receptor, Serotonin, 5-HT1A