The risk for major depression conferred by childhood maltreatment is multiplied by BDNF and SERT genetic vulnerability: a replication study

The risk for major depression conferred by childhood maltreatment is multiplied by BDNF and SERT genetic vulnerability: a replication study

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J Psychiatry Neurosci 2015;40(3):187-196

Blanca Gutiérrez, PhD; Juan Ángel Bellón, MD, PhD; Margarita Rivera, PhD; Esther Molina, PhD; Michael King, MD, PhD; Louise Marston, PhD; Francisco Torres-González, MD, PhD; Berta Moreno-Küstner, PhD; Patricia Moreno-Peral, PhD; Emma Motrico, PhD; Carmen Montón-Franco, MD, PhD; María Josefa GildeGómez-Barragán, MD, PhD; Marta Sánchez-Celaya, MD, PhD; Miguel Ángel Díaz-Barreiros, MD, PhD; Catalina Vicens, MD, PhD; Juan de Dios Luna, PhD; Irwin Nazareth, MD, PhD; Jorge Cervilla, MD, PhD

Abstract

Background: There is limited evidence for a moderating role of both serotonin transporter (SERT) and brain-derived neurotrophic factor (BDNF) genes on the risk for major depression (MD) developing after childhood maltreatment. However, research on this topic remains inconclusive, and there is a lack of data from longitudinal studies with large and representative population samples. Our study aimed to clarify whether, in the presence of previous childhood maltreatment, individuals carrying low functional alleles for both SERT 5-HTTLPR and BDNF Val66Met polymorphisms had a higher risk for MD.

Methods: We explored 2- and 3-way gene (SERT and BDNF) × environment (childhood maltreatment) interactions in a large sample of Spanish adults who were followed up over a 3-year period and assessed in person for both DSM-IV MD and exposure to childhood maltreatment.

Results: Our study included 2679 participants. Those with both the 5-HTTLPR s allele and the BDNF Met allele showed the highest risk of MD if they had previously experienced emotional (z = 2.08, p = 0.037), sexual (z = 2.19, p = 0.029) or any kind of childhood abuse (z = 2.37, p = 0.018). These 3-way interactions remained significant regardless of whether the 5-HTTLPR triallelic or the 5-HTTLPR biallelic polymorphisms were included in the analyses.

Limitations: Retrospective assessment of childhood maltreatment may have resulted in a moderate degree of recall bias.

Conclusion: Our results confirm that the risk of depression conferred by childhood maltreatment is modified by variation at both SERT and BDNF genes.


Submitted Apr. 4, 2014; Revised July 30, 2014, Sept. 3, 2014; Accepted Sept. 24, 2014; Early-released Dec. 16, 2014

Acknowledgements: The authors thank all participants for agreeing to provide a biological sample and all interviewers for their work. This is a collaborative study between two Andalusian research groups (PSYBAM-CTS628 and SAMSERAP Málaga-CTS582) and the group of Mental Health Sciences at UCL, United Kingdom. Spanish groups are members of 2 different research frameworks funded by the Spanish Ministry of Science and Innovation (i.e. the Spanish Centre for Biomedical Research in Mental Health [CIBERSAM](CB07/09) and the Spanish Network of Primary Care Research [redIAPP] (RD06/0018). The PREDICT-gene study was partially funded by a grant of the Spanish Ministry of Science and Innovation (SAF-2006- 07192). The PredictD–Europe study was funded by a grant from The European Commission (QL4-CT2002- 00683). The PredictD–Spain study was funded by grants from the Spanish Ministry of Health (PI04/1980, PI0/41771, PI04/2450 and PI06/1442) and the Andalusian Council of Health (05/403, 06/278 and 08/0194).

Affiliations: Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM-University of Granada), Spain (Gutiérrez, Rivera, Molina, Torres-González, Cervilla); Institute of Neurosciences Federico Olóriz, Centro de Investigación Biomédica, University of Granada, Spain (Gutiérrez, Molina, Cervilla); Department of Psychiatry, School of Medicine, University of Granada, Spain (Gutiérrez, Torres- González, Cervilla); MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, King´s College London, United Kingdom (Gutiérrez, Rivera, Cervilla); Centro de Salud El Palo, Departamento de Medicina Preventiva y Salud Pública, Universidad de Málaga, Spain (Bellón); Unidad de Investigación del Distrito de Atención Primaria de Málaga (redIAPP, grupo SAMSERAP), Spain (Bellón, Moreno-Peral); Mental Health Sciences, Faculty of Brain Sciences, UCL, UK (King, Nazareth); Research Department of Primary Care and Population Health, UCL, UK (Marston); Departamento Personalidad, Evaluación y Tratamiento Psicológico, Grupo GAP, Facultad de Psicología, Universidad de Málaga, Spain (Moreno-Küstner); Universidad Loyola Andalucía and Departamento de Psicología Evolutiva y de la Educación de la Universidad de Sevilla, Sevilla, Spain (Motrico); Centro de Salud Casablanca (redIAPP, grupo Aragón), Departamento de Medicina y Psiquiatría, Universidad de Zaragoza, Spain (Montón-Franco); Unidad Docente de Medicina Familiar y Comunitaria de La Rioja, Servicio Riojano de la Salud, Logroño, La Rioja, Spain (GildeGómez-Barragán); Directora Continuidad Asistencial Hospital Universitario Infanta Sofía, Madrid ( Sánchez-Celaya); Centro de Salud Vecindario, Gerencia de Atención Primaria de Gran Canaria, Servicio Canario de Salud, Las Palmas, Spain (Díaz-Barreiros); Centro de Salud son Serra-La Vileta, Unidad Docente de Medicina Familiar y Comunitaria de Mallorca, Instituto Balear de la Salud (redIAPP, grupo Baleares), Palma de Mallorca, Illes Balears, Spain (Vicens); Departamento de Bioestadística, Universidad de Granada, Spain (de Dios Luna); Hospital Universitario Clínico San Cecilio, Granada, Spain (Cervilla).

Competing interests: None declared.

Contributors: B. Gutiérrez, J. Bellón, M. Rivera, E. Molina, M. King, F. Torres-González, B. Moreno, P. Moreno-Peral, E. Motrico, C. Montón- Franco, M. GildeGómez-Barragán, M. Sánchez-Celaya, M. Díaz-Barreiros, C. Vicens, L. Juan-de-Dios, I. Nazareth and J. Cevilla designed the study. B. Gutiérrez, J. Bellón, M. Rivera, E. Molina, M. King, F. Torres-González, B. Moreno, P. Moreno-Peral, E. Motrico, C. Montón- Franco, M. GildeGómez-Barragán, M. Sánchez-Celaya, M. Díaz-Barreiros, C. Vicens, I. Nazareth and J. Cevilla acquired the data, which B. Gutiérrez, J. Bellón, M. Rivera, E. Molina, M. King, L. Marston, L. Juan-de-Dios, I. Nazareth and J. Cevilla analyzed. B. Gutiérrez, J. Bellón, M. King, L. Marston, I. Nazareth and J. Cevilla wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.140097

Correspondence to: B. Gutiérrez, CIBERSAM-Universidad de Granada, Instituto de Neurociencias Federico Olóriz, Centro de Investigación Biomédica (CIBM), Universidad de Granada, Avda. Conocimiento s/n, 18100 Armilla, Granada, Spain; blancag@ugr.es