The International Journal of Neuropsychopharmacology

Research Article

Epistasis between 5-HTTLPR and ADRA2B polymorphisms influences attentional bias for emotional information in healthy volunteers

Kris H. Naudtsa1, Ruben T. Azevedoa2, Anthony S. Davida2, Kees van Heeringena3 and Ayana A. Gibbsa2a4 c1

a1 Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, King's College London, King's Health Partners, London, UK

a2 Department of Psychosis Studies, Institute of Psychiatry, King's College London, King's Health Partners, London, UK

a3 Department of Psychiatry and Medical Psychology, Ghent University, Ghent, Belgium

a4 Division of Clinical Medicine, Brighton and Sussex Medical School, Falmer, Brighton, UK


Individual differences in emotional processing are likely to contribute to vulnerability and resilience to emotional disorders such as depression and anxiety. Genetic variation is known to contribute to these differences but they remain incompletely understood. The serotonin transporter (5-HTTLPR) and α2B-adrenergic autoreceptor (ADRA2B) insertion/deletion polymorphisms impact on two separate but interacting monaminergic signalling mechanisms that have been implicated in both emotional processing and emotional disorders. Recent studies suggest that the 5-HTTLPR s allele is associated with a negative attentional bias and an increased risk of emotional disorders. However, such complex behavioural traits are likely to exhibit polygenicity, including epistasis. This study examined the contribution of the 5-HTTLPR and ADRA2B insertion/deletion polymorphisms to attentional biases for aversive information in 94 healthy male volunteers and found evidence of a significant epistatic effect (p<0.001). Specifically, in the presence of the 5-HTTLPR s allele, the attentional bias for aversive information was attenuated by possession of the ADRA2B deletion variant whereas in the absence of the s allele, the bias was enhanced. These data identify a cognitive mechanism linking genotype-dependent serotonergic and noradrenergic signalling that is likely to have implications for the development of cognitive markers for depression/anxiety as well as therapeutic drug effects and personalized approaches to treatment.

(Received June 10 2011)

(Reviewed July 07 2011)

(Revised July 14 2011)

(Accepted July 20 2011)

(Online publication August 19 2011)


c1 Address for correspondence: Dr A. A. Gibbs, Clinical Imaging Sciences Centre, University of Sussex, Falmer, Brighton BN1 9RR, UK. Tel.: 01273876702 Fax: 01273877548 Email: