Blanca Gutiérrez1, Juan Á Bellón2, Margarita Rivera3, Esther Molina4, Michael King5, Louise Marston6, Francisco Torres-González7, Berta Moreno-Küstner8, Patricia Moreno-Peral9, Emma Motrico10, Carmen Montón-Franco11, María J GildeGómez-Barragán12, Marta Sánchez-Celaya13, Miguel Á Díaz-Barreiros14, Catalina Vicens15, Juan de Dios Luna16, Irwin Nazareth5, Jorge Cervilla17. 1. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM-University of Granada), the Institute of Neurosciences Federico Olóriz, Centro de Investigación Biomédica, the Department of Psychiatry, School of Medicine, University of Granada, Spain, and the MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, King´s College London, United Kingdom. 2. Centro de Salud El Palo. Departamento de Medicina Preventiva y Salud Pública. Universidad de Málaga and the Unidad de Investigación del Distrito de Atención Primaria de Málaga (redIAPP, grupo SAMSERAP), Spain. 3. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM-University of Granada), Spain, and the MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, King´s College London, United Kingdom. 4. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM-University of Granada) and the Institute of Neurosciences Federico Olóriz, Centro de Investigación Biomédica, University of Granada, Spain. 5. Mental Health Sciences, Faculty of Brain Sciences, UCL, UK. 6. Research Department of Primary Care and Population Health, UCL, UK. 7. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM-University of Granada), and the Department of Psychiatry, School of Medicine, University of Granada, Spain. 8. Dpto. Personalidad, Evaluación y Tratamiento Psicológico, Grupo GAP. Facultad de Psicología, Universidad de Málaga, Spain. 9. Unidad de Investigación del Distrito de Atención Primaria de Málaga (redIAPP, grupo SAMSERAP), Spain. 10. Universidad Loyola Andalucía and Departamento de Psicología Evolutiva y de la Educación de la Universidad de Sevilla, Sevilla, Spain. 11. Centro de Salud Casablanca. (redIAPP, grupo Aragón) Departamento de Medicina y Psiquiatría. Universidad de Zaragoza, Spain. 12. Unidad Docente de Medicina Familiar y Comunitaria de La Rioja. Servicio Riojano de la Salud, Logroño, La Rioja. Spain. 13. Directora Continuidad Asistencial Hospital Universitario Infanta Sofía, Madrid. 14. Centro de Salud Vecindario, Gerencia de Atención Primaria de Gran Canaria, Servicio Canario de Salud, Las Palmas, Spain. 15. 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. 16. Departamento de Bioestadística, Universidad de Granada, Spain. 17. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM-University of Granada), the Institute of Neurosciences Federico Olóriz, Centro de Investigación Biomédica, University of Granada, the Department of Psychiatry, School of Medicine, University of Granada, Hospital Universitario Clínico San Cecilio, the Granada, Spain, and the MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, King´s College London, United Kingdom.
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.
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.
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