Investigation of serotonergic receptors and transporter genes in vulnerability of depression, anxiety and neuroticism. A human population study.

Abstract

Background

Depression and related phenotypes, such as anxiety and neuroticism thought to have common genetic background.  The malfunction of the serotonergic system is likely to play an important role in the aetiology of these phenotypes, with compelling evidence coming from animal and human studies.  However, recent studies indicated that other factors should be investigated, such as environmental stress.

Aim

To investigate the role of the serotonergic gene variants (HTR1A-7 and SERT) in interaction with each other and other factors, such as stressful events in development of depression and related phenotypes.

Method

Using two large independent Caucasian cohorts, haplotype tagging SNPs and detailed questionnaires about psychiatric phenotypes as well as background information.

 Results

My study confirmed the importance of stressful life events in depression and anxiety modulated via the 5-HT1A and 5-HT1B autoreceptor, but not via the SERT. I found evidence for epistatic interaction between HTR2A and SERT genes and between different subunits of the HT3 gene which may contribute towards the depressive phenotype. Finally, certain alleles of SNPs in other serotonergic receptors (5-HT4 and 5-HT) were also associated with depression, anxiety and neuroticism however this association was weak.

Duration of the project

4 years (Sept 2006 - Sept 2010)