PMID- 23481907 OWN - NLM STAT- MEDLINE DCOM- 20140424 LR - 20180816 IS - 1873-7862 (Electronic) IS - 0924-977X (Linking) VI - 23 IP - 10 DP - 2013 Oct TI - Three-way interaction effect of 5-HTTLPR, BDNF Val66Met, and childhood adversity on depression: a replication study. PG - 1300-6 LID - S0924-977X(13)00049-7 [pii] LID - 10.1016/j.euroneuro.2013.01.010 [doi] AB - Both the serotonin transporter linked promoter region (5-HTTLPR) and the brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms have been shown to interact with unfavourable environment in relation to depression symptoms and to depression diagnosis. Several attempts have been made to study a three-way interaction effect of these factors on depression, however with contradictory results. We aimed to test the hypothesis of a three-way interaction effect and to attempt at replication in an independent population-based sample. Family maltreatment, sexual abuse and depression were self-reported by an adolescent population-based cohort (N=1393) from the county of Vastmanland, Sweden. DNA was isolated from saliva, and used for genotyping of the 5-HTTLPR and BDNF Val66Met polymorphisms. Neither 5-HTTLPR or BDNF genotypes separately, nor in interaction with each other had any relation to depression, however in an environment adjusted model a two-way interaction and a three-way interaction effect was found. Both 5-HTTLPR and BDNF Val66Met interacted with unfavourable environment in relation to depressive symptoms (Adj R(2)=0.19). Depressive symptoms and depression were more common among carriers of either the ss/sl+Val/Val or the ll+Met genotypes in the presence of early-life adversities. This three-way effect was more pronounced among girls. The current study, with a virtually similar set-up compared to previous studies, can partially confirm previous findings and their generalizability. The study also shows the importance of genetic plasticity in individuals with different environmental exposure, for different phenotypic expression. CI - Copyright (c) 2013 Elsevier B.V. and ECNP. All rights reserved. FAU - Comasco, Erika AU - Comasco E AD - Department of Neuroscience, Unit of Pharmacology, Uppsala University, BMC, Box 593S-751 24 Uppsala, Sweden. FAU - Aslund, Cecilia AU - Aslund C FAU - Oreland, Lars AU - Oreland L FAU - Nilsson, Kent W AU - Nilsson KW LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130306 PL - Netherlands TA - Eur Neuropsychopharmacol JT - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology JID - 9111390 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (SLC6A4 protein, human) RN - 0 (Serotonin Plasma Membrane Transport Proteins) RN - 7171WSG8A2 (BDNF protein, human) SB - IM MH - Adolescent MH - Adolescent Development MH - Alleles MH - Amino Acid Substitution MH - Brain-Derived Neurotrophic Factor/*genetics/metabolism MH - Child MH - Child Abuse/psychology MH - *Child Development MH - Cohort Studies MH - Depression/etiology/*genetics/metabolism MH - Diagnostic and Statistical Manual of Mental Disorders MH - Female MH - *Gene-Environment Interaction MH - Genetic Association Studies MH - Humans MH - Male MH - *Polymorphism, Genetic MH - Promoter Regions, Genetic MH - Serotonin Plasma Membrane Transport Proteins/*genetics/metabolism MH - Stress, Physiological MH - Stress, Psychological/*physiopathology MH - Sweden OTO - NOTNLM OT - Adolescents OT - Brain-derived neurotrophic factor OT - Depression OT - Maltreatment OT - Serotonin transporter OT - Sexual abuse EDAT- 2013/03/14 06:00 MHDA- 2014/04/25 06:00 CRDT- 2013/03/14 06:00 PHST- 2012/12/20 00:00 [received] PHST- 2013/01/08 00:00 [revised] PHST- 2013/01/27 00:00 [accepted] PHST- 2013/03/14 06:00 [entrez] PHST- 2013/03/14 06:00 [pubmed] PHST- 2014/04/25 06:00 [medline] AID - S0924-977X(13)00049-7 [pii] AID - 10.1016/j.euroneuro.2013.01.010 [doi] PST - ppublish SO - Eur Neuropsychopharmacol. 2013 Oct;23(10):1300-6. doi: 10.1016/j.euroneuro.2013.01.010. Epub 2013 Mar 6.