title: Childhood maternal care is associated with DNA methylation of the genes for brain-derived neurotrophic factor (BDNF) and oxytocin receptor (OXTR) in peripheral blood cells in adult men and women.
abstract: In adults, reporting low and high maternal care in childhood, we compared DNA methylation in two stress-associated genes (two target sequences in the oxytocin receptor gene, OXTR; one in the brain-derived neurotrophic factor gene, BDNF) in peripheral whole blood, in a cross-sectional study (University of Basel, Switzerland) during 2007-2008. We recruited 89 participants scoring < 27 (n = 47, 36 women) or > 33 (n = 42, 35 women) on the maternal care subscale of the Parental Bonding Instrument (PBI) at a previous assessment of a larger group (N = 709, range PBI maternal care = 0-36, age range = 19-66 years; median 24 years). 85 participants gave blood for DNA methylation analyses (Sequenom(R) EpiTYPER, San Diego, CA) and cell count (Sysmex PocH-100i™, Kobe, Japan). Mixed model statistical analysis showed greater DNA methylation in the low versus high maternal care group, in the BDNF target sequence [Likelihood-Ratio (1) = 4.47; p = 0.035] and in one OXTR target sequence Likelihood-Ratio (1) = 4.33; p = 0.037], but not the second OXTR target sequence [Likelihood-Ratio (1) < 0.001; p = 0.995). Mediation analyses indicated that differential blood cell count did not explain associations between low maternal care and BDNF (estimate = -0.005, 95% CI = -0.025 to 0.015; p = 0.626) or OXTR DNA methylation (estimate = -0.015, 95% CI = -0.038 to 0.008; p = 0.192). Hence, low maternal care in childhood was associated with greater DNA methylation in an OXTR and a BDNF target sequence in blood cells in adulthood. Although the study has limitations (cross-sectional, a wide age range, only three target sequences in two genes studied, small effects, uncertain relevance of changes in blood cells to gene methylation in brain), the findings may indicate components of the epiphenotype from early life stress.
authors.affiliation: a Department of Psychology, Division of Clinical Psychology and Epidemiology , University of Basel , Basel , Switzerland .|b National Center of Competence in Research (NCCR), Swiss Etiological Study of Adjustment and Mental Health (sesam), University of Basel , Switzerland .|c Douglas Mental Health University Institute, McGill University , Montréal , Canada .
authors.forename: Eva
authors.initials: E
authors.lastname: Unternaehrer
authors.affiliation: a Department of Psychology, Division of Clinical Psychology and Epidemiology , University of Basel , Basel , Switzerland .
authors.forename: Andrea Hans
authors.initials: AH
authors.lastname: Meyer
authors.affiliation: b National Center of Competence in Research (NCCR), Swiss Etiological Study of Adjustment and Mental Health (sesam), University of Basel , Switzerland .|d Department of Research & Development , University of Applied Sciences in Special Needs Education , Zürich , Switzerland .
authors.forename: Susan C A
authors.initials: SC
authors.lastname: Burkhardt
authors.affiliation: e University of Exeter Medical School, Exeter University , Exeter , UK .
authors.forename: Emma
authors.initials: E
authors.lastname: Dempster
authors.affiliation: a Department of Psychology, Division of Clinical Psychology and Epidemiology , University of Basel , Basel , Switzerland .|f Institute of Psychobiology, University of Trier , Trier , Germany .
authors.forename: Simon
authors.initials: S
authors.lastname: Staehli
authors.affiliation: g Division of Psychiatry Research , University of Zurich , Zurich , Switzerland , and.
authors.forename: Nathan
authors.initials: N
authors.lastname: Theill
authors.affiliation: a Department of Psychology, Division of Clinical Psychology and Epidemiology , University of Basel , Basel , Switzerland .|b National Center of Competence in Research (NCCR), Swiss Etiological Study of Adjustment and Mental Health (sesam), University of Basel , Switzerland .
authors.forename: Roselind
authors.initials: R
authors.lastname: Lieb
authors.affiliation: a Department of Psychology, Division of Clinical Psychology and Epidemiology , University of Basel , Basel , Switzerland .|b National Center of Competence in Research (NCCR), Swiss Etiological Study of Adjustment and Mental Health (sesam), University of Basel , Switzerland .|h Faculty of Medicine , Ruhr-University Bochum , Germany.
authors.forename: Gunther
authors.initials: G
authors.lastname: Meinlschmidt
mesh_terms: D000328:Adult; D000368:Aged; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003430:Cross-Sectional Studies; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D008297:Male; D008425:Maternal Behavior; D008875:Middle Aged; D018045:Receptors, Oxytocin / Q000235:genetics*; D013315:Stress, Psychological / Q000235:genetics*; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C569600:OXTR protein, human; D018045:Receptors, Oxytocin; C579455:BDNF protein, human
keywords: BDNF; OXTR; brain-derived neurotrophic factor; early life adversities; epigenetics; oxytocin receptor; parental care; white blood cells