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

Molina, Esthera; Cervilla, Jorgea,b; Rivera, Margaritaa,g; Torres, Franciscoa; Bellón, Juan Ángelc; Moreno, Bertad; King, Michaele; Nazareth, Irwinf; Gutiérrez, Blancaa

doi: 10.1097/YPG.0b013e3283457a48
Original Articles

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.

aCIBERSAM, University of Granada, Section of Psychiatry, Institute of Neurosciences, Biomedical Research Centre (CIBM)

bMental Health Unit, ‘San Cecilio’ University Hospital, Granada

cDepartment of Preventive Medicine, University of Malaga, ‘El Palo’ Primary Care Centre, Primary Care Research Unit (redIAPP, grupo SAMSERAP)

dDepartment of Personality, Assessment and Psychological Treatment, University of Malaga (redIAPP, grupo SAMSERAP), Málaga, Spain

eDepartment of Mental Health Sciences, University College London, Royal Free Campus

fResearch Department of Primary Care and Population Health, University College London and MRC General Practice Research Framework

gMRC SGDP Centre, Institute of Psychiatry, King's College London, London, UK

Correspondence to Blanca Gutiérrez, PhD, Section of Psychiatry and Institute of Neurosciences, School of Medicine, University of Granada, Avda. Madrid 11, Granada 18012, Spain Tel: +34 958242075; fax: +34 958240730; e-mail:

Received May 14, 2010

Accepted December 8, 2010

© 2011 Lippincott Williams & Wilkins, Inc.