title: An interaction between a neuropeptide Y gene polymorphism and early adversity modulates endocrine stress responses.
abstract: Interindividual variability in the regulation of the human stress system accounts for a part of the individual's liability to stress-related diseases. These differences are influenced by environmental and genetic factors. Early childhood adversity is a well-studied environmental factor affecting an individual's stress response which has been shown to be modulated by gene-environment interaction (GxE). Neuropeptide Y (NPY) plays a role in stress regulation and genetic variation in NPY may influence stress responses. In this study, we analyzed the association of a common variant in the NPY gene promoter, rs16147, with cortisol and ACTH responses to acute psychosocial stress in young adults from the Mannheim Study of Children at Risk (MARS), an ongoing epidemiological cohort study following the outcome of early adversity from birth into adulthood. We found evidence of a GxE interaction between rs16147 and early adversity significantly affecting HPA axis responses to acute psychosocial stress. These findings suggest that the neurobiological mechanisms linking early adverse experience and later neuroendocrine stress regulation are modulated by a gene variant whose functional relevance is documented by increasing convergent evidence from in vitro, animal and human studies.
authors.affiliation: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health Mannheim, J5, 68159 Mannheim, Germany.
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Witt
authors.forename: Arlette F
authors.initials: AF
authors.lastname: Buchmann
authors.forename: Dorothea
authors.initials: D
authors.lastname: Blomeyer
authors.forename: Vanessa
authors.initials: V
authors.lastname: Nieratschker
authors.forename: Jens
authors.initials: J
authors.lastname: Treutlein
authors.forename: Günter
authors.initials: G
authors.lastname: Esser
authors.forename: Martin H
authors.initials: MH
authors.lastname: Schmidt
authors.forename: Martin
authors.initials: M
authors.lastname: Bidlingmaier
authors.forename: Klaus
authors.initials: K
authors.lastname: Wiedemann
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Manfred
authors.initials: M
authors.lastname: Laucht
authors.forename: Stefan
authors.initials: S
authors.lastname: Wüst
authors.forename: Ulrich S
authors.initials: US
authors.lastname: Zimmermann
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004703:Endocrine System / Q000378:metabolism / Q000502:physiology*; D059647:Gene-Environment Interaction; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000502:physiology; D007223:Infant; D008016:Life Change Events; D008137:Longitudinal Studies; D009478:Neuropeptide Y / Q000235:genetics* / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000378:metabolism / Q000502:physiology; D011110:Polymorphism, Genetic / Q000502:physiology; D012931:Social Environment; D013315:Stress, Psychological / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology; D055815:Young Adult
chemical_list: D009478:Neuropeptide Y