Psychological Medicine

Original Articles

Early adversity and 5-HTT/BDNF genes: new evidence of gene–environment interactions on depressive symptoms in a general population

M. Aguileraa1, B. Ariasa1, M. Wichersa2, N. Barrantes-Vidala3, J. Moyaa4, H. Villaa4, J. van Osa2, M. I. Ibáñeza4, M. A. Ruipéreza4, G. Orteta4 and L. Fañanása1 c1

a1 Unitat d'Antropologia, Departament Biologia Animal, Facultat de Biologia, Universitat de Barcelona and Institut de Biomedicina de la Universitat de Barcelona (IBUB) and CIBER de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Spain

a2 Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, Maastricht, The Netherlands

a3 Departament de Psicologia Clínica i de la Salut, Facultat de Psicologia, Universitat Autònoma de Barcelona and CIBER Salud Mental, Instituto de Salud Carlos III, Barcelona, Spain

a4 Departament de Psicologia Bàsica, Clínica i Psicobiologia, Facultat de Ciències Humanes i Socials, Universitat Jaume I, Spain


Background Adverse childhood experiences have been described as one of the major environmental risk factors for depressive disorder. Similarly, the deleterious impact of early traumatic experiences on depression seems to be moderated by individual genetic variability. Serotonin transporter (5-HTT) and brain-derived neurotrophic factor (BDNF) modulate the effect of childhood adversity on adult depression, although inconsistencies across studies have been found. Moreover, the gene×environment (G×E) interaction concerning the different types of childhood adversity remains poorly understood. The aim of this study was to analyse the putative interaction between the 5-HTT gene (5-HTTLPR polymorphism), the BDNF gene (Val66Met polymorphism) and childhood adversity in accounting for adult depressive symptoms.

Method A sample of 534 healthy individuals filled in self-report questionnaires of depressive symptomatology [the Symptom Check List 90 Revised (SCL-90-R)] and different types of childhood adversities [the Childhood Trauma Questionnaire (CTQ)]. The 5-HTTLPR polymorphism (5-HTT gene) and the Val66Met polymorphism (BDNF gene) were genotyped in the whole sample.

Results Total childhood adversity (β=0.27, p<0.001), childhood sexual abuse (CSA; β=0.17, p<0.001), childhood emotional abuse (β=0.27, p<0.001) and childhood emotional neglect (β=0.22, p<0.001) had an impact on adult depressive symptoms. CSA had a greater impact on depressive symptoms in Met allele carriers of the BDNF gene than in the Val/Val group (F=5.87, p<0.0001), and in S carriers of the 5-HTTLPR polymorphism (5-HTT gene) (F=5.80, p<0.0001).

Conclusions Childhood adversity per se predicted higher levels of adult depressive symptoms. In addition, BDNF Val66Met and 5-HTTLPR polymorphisms seemed to moderate the effect of CSA on adult depressive symptoms.

(Received July 23 2008)

(Revised October 20 2008)

(Accepted January 07 2009)

(Online publication February 12 2009)


c1 Address for correspondence: Dr L. Fañanás, Unitat d'Antropologia, Departament Biologia Animal, Facultat Biologia, Universitat de Barcelona, Av. Diagonal 645, 08028 Barcelona, Spain. (Email: