Early-life stress, corticotropin-releasing factor, and serotonin transporter gene: A pilot study

Jeremy D. Coplan, Chadi G. Abdallah, Joan Kaufman, Joel Gelernter, Eric L.P. Smith, Tarique D. Perera, Andrew J. Dwork, Arie Kaffman, Jack M. Gorman, Leonard A. Rosenblum, Michael J. Owens, Charles B. Nemeroff

Research output: Contribution to journalArticlepeer-review


Recent studies have indicated a gene-by-environment interaction between serotonin transporter gene (5-HTTLPR) polymorphism and childhood abuse on depressive symptoms. In addition, persistent elevation of cerebrospinal fluid (CSF) corticotropin-releasing factor (CRF) concentrations following early-life adversity has been posited to underlie the subsequent development of major depression. This pilot study tested the hypothesis that elevations of juvenile CSF CRF concentrations are, in part, determined by an interaction between polymorphisms of the 5-HTTLPR and early-life stress. Nine juvenile male bonnet macaques (Macaca radiata) had been raised under variable foraging demand (VFD) conditions, a nonhuman primate model of early-life stress, whereas nine subjects were normatively raised under LFD (low foraging demand) conditions. Genotyping revealed that four (44.4%) of the VFD-reared monkeys possessed at least one " s" allele whereas five VFD monkeys were of the l/l genotype. Of the nine LFD subjects, two (22%) had the s/l genotype and seven had the l/l genotype. A " juvenile" CSF sample was obtained at approximately 3 years of age. CSF CRF concentrations were elevated specifically in the VFD " s/s" and " s/l" allele group in comparison to each of the remaining three groups, indicating a gene-by-environment (G. × E) interaction.

Original languageEnglish (US)
Pages (from-to)289-293
Number of pages5
Issue number2
StatePublished - Feb 2011
Externally publishedYes


  • Anxiety disorders
  • Corticotropin-releasing hormone
  • Early-life stress
  • Gene-by-environment interaction
  • Major depression
  • Nonhuman primates
  • Serotonin transporter gene

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Psychiatry and Mental health
  • Biological Psychiatry


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