Polymorphic variation at the serotonin 1-A receptor gene is associated with comorbid depression and generalized anxiety

Background Serotonin 1-A receptors are key regulators of serotonin activity and their dysregulation might be implicated in the emergence of both major depression (MD) and generalized anxiety disorder (GAD). Previous studies have yielded inconclusive results as to whether the 5-HT1A receptor gene (HTR1A) has a role in the aetiology of MD and no study up to date has analysed this polymorphism on either pure MD or MD comorbid with GAD. Methods In this study, 1059 patients taking part in the PREDICT-Gene study were ascertained for Diagnostic and Statistical Manual of Mental Disorders-IV MD and GAD diagnoses using the Composite International Diagnostic Interview and the Primary Care Evaluation of Mental Disorders questionnaire, respectively. They were also genotyped for the C(-1019)G functional polymorphism at the promoter region of HTR1A gene. Results Genetic variability at HTR1A was significantly associated with MD [odds ratio (OR)=1.67; 95% confidence interval (CI)=1.14–2.44; P=0.008], although this effect disappeared after adjusting for GAD (OR=1.43; 95% CI=0.96–2.14; P=0.080). Similarly, a crude association between C(-1019)G polymorphism and GAD was found (OR=2.54; 95% CI=1.28–4.86; P=0.003), but these results became no longer significant after adjusting for MD (OR=1.97; 95% CI=0.99–3.91; P=0.050). However, a main effect of HTR1A G(-1019) allele on comorbid MD–GAD was found (OR=3.41; 95% CI=1.44–8.05; P=0.005) and it remained robust and statistically significant after adjusting by sex, age and family history of psychological problems (OR=2.82; 95% CI=1.18–6.77; P=0.020). Conclusion In our study, the HTR1A C(-1019)G polymorphism was found to be associated to the frequent clinical presentation of comorbid MD and GAD, suggesting a common genetic background for mixed depression and anxiety states. These findings should be considered as preliminary. Future replications in independent samples would be needed to confirm or discard such association.