title: Interaction of early life stress and corticotropin-releasing hormone receptor gene: effects on working memory.
abstract: BACKGROUND
  Early life stress (ELS) experience is associated with persisting working memory (WM) deficits; changes to the corticotropin-releasing hormone (CRH) system; and structural, functional, and epigenetic changes in the hippocampus. Single nucleotide polymorphisms in the CRH receptor 1 (CRHR1) gene interact with ELS experience to predict depression as well as neuroendocrine and neuronal reactivity. Although these findings indicate that vulnerable genotypes might also show impaired WM performance after ELS experience, no previous study investigated whether there is an interaction effect of CRHR1 polymorphisms and ELS experience on WM performance.
  
  
  METHODS
  Subjects (N = 451) were genotyped for rs110402 and rs242924 within the CRHR1 gene. We used an n-back task to investigate the hypothesis that WM performance in healthy subjects may be subtly influenced by functional differences in CRHR1 and represents an early marker of increased vulnerability after exposure to ELS.
  
  
  RESULTS
  Exposure to ELS had a particularly strong impact on WM performance in subjects with the common homozygous GG GG genotype, whereas only severe exposure to ELS interfered with WM accuracy in AT carriers.
  
  
  CONCLUSIONS
  Our data indicate that specific CRHR1 polymorphisms moderate the effect of ELS experience on WM performance. Exposure to ELS in combination with a vulnerable genotype results in subtle memory deficits in adulthood, which might develop before psychopathological symptoms.
authors.affiliation: Cluster of Excellence "Languages of Emotion", Freie Universitaet Berlin, Berlin, Germany; Department of Psychiatry, Campus Benjamin Franklin, Charité Berlin, Berlin, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Fuge
authors.affiliation: Cluster of Excellence "Languages of Emotion", Freie Universitaet Berlin, Berlin, Germany; Department of Psychiatry, Campus Benjamin Franklin, Charité Berlin, Berlin, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Aust
authors.affiliation: Cluster of Excellence "Languages of Emotion", Freie Universitaet Berlin, Berlin, Germany; Dahlem Institute for Neuroimaging of Emotion, Freie Universitaet Berlin, Berlin, Germany.
authors.forename: Yan
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Cluster of Excellence "Languages of Emotion", Freie Universitaet Berlin, Berlin, Germany; Department of Psychiatry, Campus Benjamin Franklin, Charité Berlin, Berlin, Germany; Dahlem Institute for Neuroimaging of Emotion, Freie Universitaet Berlin, Berlin, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Weigand
authors.affiliation: Cluster of Excellence "Languages of Emotion", Freie Universitaet Berlin, Berlin, Germany; Dahlem Institute for Neuroimaging of Emotion, Freie Universitaet Berlin, Berlin, Germany.
authors.forename: Matti
authors.initials: M
authors.lastname: Gärtner
authors.affiliation: Cluster of Excellence "Languages of Emotion", Freie Universitaet Berlin, Berlin, Germany; Dahlem Institute for Neuroimaging of Emotion, Freie Universitaet Berlin, Berlin, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Feeser
authors.affiliation: Cluster of Excellence "Languages of Emotion", Freie Universitaet Berlin, Berlin, Germany; Department of Psychiatry, Campus Benjamin Franklin, Charité Berlin, Berlin, Germany; Dahlem Institute for Neuroimaging of Emotion, Freie Universitaet Berlin, Berlin, Germany.
authors.forename: Malek
authors.initials: M
authors.lastname: Bajbouj
authors.affiliation: Cluster of Excellence "Languages of Emotion", Freie Universitaet Berlin, Berlin, Germany; Department of Psychiatry, Campus Benjamin Franklin, Charité Berlin, Berlin, Germany; Dahlem Institute for Neuroimaging of Emotion, Freie Universitaet Berlin, Berlin, Germany; Department of Psychiatry, Psychotherapy and Psychosomatics, Hospital of Psychiatry, University of Zurich, Zurich, Switzerland. Electronic address: simone.grimm@fu-berlin.de.
authors.forename: Simone
authors.initials: S
authors.lastname: Grimm
mesh_terms: D000328:Adult; D000367:Age Factors; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics*; D013315:Stress, Psychological / Q000235:genetics*; D000099052:CRF Receptor, Type 1
chemical_list: D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1
keywords: Corticotropin-releasing hormone receptor 1; early life stress; hippocampus; rs110402; rs242924; working memory