BACKGROUND: Based on biological interactions between the serotonergic system and the brain-derived neurotrophic factor (BDNF), BDNF is a plausible candidate for a gene-gene-environment interaction moderating the interaction between the s/l- promoter polymorphism of the serotonin transporter (5-HTTLPR) and childhood abuse. We tested the hypothesis of a three-way interaction with respect to depressive symptoms. METHODS: 2035 Caucasian subjects from the Study of Health in Pomerania (German general population) completed the Beck Depression Inventory (BDI-II) and the Childhood Trauma Questionnaire. All subjects were genotyped for the BDNF Val66Met (rs6265) and the s/l 5-HTTLPR polymorphisms. RESULTS: Tobit regression analyses revealed a three-way-interaction between the three genotypes of 5-HTTLPR and the BDNF genotypes and overall childhood abuse for the BDI-II score (p=0.02). Emotional abuse carried the main effect of the interaction (p=0.008). The s/s genotype of the 5-HTTLPR exerted its negative impact on mental health after childhood abuse only in the presence of the BDNF Val/Val genotype but not in the presence of the BDNF Met allele. In contrast, the l allele of the 5-HTTLPR also emerged as a genetic risk factor for depression in carriers of one or two Met alleles. CONCLUSIONS: Our results point to a gene-gene-environment interaction that relevantly impacts on the role of the s/s genotype of the 5-HTTLPR in childhood abuse: Depending on the BDNF background (Val/Val versus Met allele) the s/s genotype showed either protective or risk properties with regard to depressive symptoms.
BACKGROUND: Based on biological interactions between the serotonergic system and the brain-derived neurotrophic factor (BDNF), BDNF is a plausible candidate for a gene-gene-environment interaction moderating the interaction between the s/l- promoter polymorphism of the serotonin transporter (5-HTTLPR) and childhood abuse. We tested the hypothesis of a three-way interaction with respect to depressive symptoms. METHODS: 2035 Caucasian subjects from the Study of Health in Pomerania (German general population) completed the Beck Depression Inventory (BDI-II) and the Childhood Trauma Questionnaire. All subjects were genotyped for the BDNF Val66Met (rs6265) and the s/l 5-HTTLPR polymorphisms. RESULTS: Tobit regression analyses revealed a three-way-interaction between the three genotypes of 5-HTTLPR and the BDNF genotypes and overall childhood abuse for the BDI-II score (p=0.02). Emotional abuse carried the main effect of the interaction (p=0.008). The s/s genotype of the 5-HTTLPR exerted its negative impact on mental health after childhood abuse only in the presence of the BDNF Val/Val genotype but not in the presence of the BDNF Met allele. In contrast, the l allele of the 5-HTTLPR also emerged as a genetic risk factor for depression in carriers of one or two Met alleles. CONCLUSIONS: Our results point to a gene-gene-environment interaction that relevantly impacts on the role of the s/s genotype of the 5-HTTLPR in childhood abuse: Depending on the BDNF background (Val/Val versus Met allele) the s/s genotype showed either protective or risk properties with regard to depressive symptoms.
Authors: Yin Ting Cheung; Raja B Khan; Wei Liu; Tara M Brinkman; Michelle N Edelmann; Wilburn E Reddick; Deqing Pei; Angela Panoskaltsis-Mortari; Deokumar Srivastava; Cheng Cheng; Leslie L Robison; Melissa M Hudson; Ching-Hon Pui; Kevin R Krull Journal: JAMA Oncol Date: 2018-07-12 Impact factor: 31.777
Authors: Blanca Gutiérrez; Juan Á Bellón; Margarita Rivera; Esther Molina; Michael King; Louise Marston; Francisco Torres-González; Berta Moreno-Küstner; Patricia Moreno-Peral; Emma Motrico; Carmen Montón-Franco; María J GildeGómez-Barragán; Marta Sánchez-Celaya; Miguel Á Díaz-Barreiros; Catalina Vicens; Juan de Dios Luna; Irwin Nazareth; Jorge Cervilla Journal: J Psychiatry Neurosci Date: 2015-05 Impact factor: 6.186
Authors: Janitza L Montalvo-Ortiz; Joel Gelernter; James Hudziak; Joan Kaufman Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2015-11-22 Impact factor: 3.568
Authors: Sandra Van der Auwera; Wouter J Peyrot; Yuri Milaneschi; Johannes Hertel; Bernhard Baune; Gerome Breen; Enda Byrne; Erin C Dunn; Helen Fisher; Georg Homuth; Douglas Levinson; Cathryn Lewis; Natalie Mills; Niamh Mullins; Matthias Nauck; Giorgio Pistis; Martin Preisig; Marcella Rietschel; Stephan Ripke; Patrick Sullivan; Alexander Teumer; Henry Völzke; Dorret I Boomsma; Naomi R Wray; Brenda Penninx; Hans Grabe Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2017-11-21 Impact factor: 3.568
Authors: Georg Schomerus; Katja Appel; Peter J Meffert; Melanie Luppa; Ronald M Andersen; Hans J Grabe; Sebastian E Baumeister Journal: Soc Psychiatry Psychiatr Epidemiol Date: 2012-12-25 Impact factor: 4.328