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

doi:10.1016/j.psyneuen.2010.07.011

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

Psychiatry & Behavioral Sciences

Research output: Contribution to journal › Article › peer-review

32 Scopus citations

Abstract

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 language	English (US)
Pages (from-to)	289-293
Number of pages	5
Journal	Psychoneuroendocrinology
Volume	36
Issue number	2
DOIs	https://doi.org/10.1016/j.psyneuen.2010.07.011
State	Published - Feb 2011

Keywords

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

ASJC Scopus subject areas

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

UN SDGs

This output contributes to the following Sustainable Development Goal(s)

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Coplan, J. D., Abdallah, C. G., Kaufman, J., Gelernter, J., Smith, E. L. P., Perera, T. D., Dwork, A. J., Kaffman, A., Gorman, J. M., Rosenblum, L. A., Owens, M. J., & Nemeroff, C. B. (2011). Early-life stress, corticotropin-releasing factor, and serotonin transporter gene: A pilot study. Psychoneuroendocrinology, 36(2), 289-293. https://doi.org/10.1016/j.psyneuen.2010.07.011

Early-life stress, corticotropin-releasing factor, and serotonin transporter gene : A pilot study. / Coplan, Jeremy D.; Abdallah, Chadi G.; Kaufman, Joan; Gelernter, Joel; Smith, Eric L.P.; Perera, Tarique D.; Dwork, Andrew J.; Kaffman, Arie; Gorman, Jack M.; Rosenblum, Leonard A.; Owens, Michael J.; Nemeroff, Charles B.

In: Psychoneuroendocrinology, Vol. 36, No. 2, 02.2011, p. 289-293.

Research output: Contribution to journal › Article › peer-review

Coplan, Jeremy D. ; Abdallah, Chadi G. ; Kaufman, Joan ; Gelernter, Joel ; Smith, Eric L.P. ; Perera, Tarique D. ; Dwork, Andrew J. ; Kaffman, Arie ; Gorman, Jack M. ; Rosenblum, Leonard A. ; Owens, Michael J. ; Nemeroff, Charles B. / Early-life stress, corticotropin-releasing factor, and serotonin transporter gene : A pilot study. In: Psychoneuroendocrinology. 2011 ; Vol. 36, No. 2. pp. 289-293.

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abstract = "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.",

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

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

note = "Funding Information: Supported in part by NIMH grants R21MH066748, MH-42088, MH-52899. Funding Information: Dr. Coplan receives grant support from GlaxoSmithKline, Pfizer, and Alexza Pharmaceuticals. He is on the Pfizer advisory board and gives talks for BMS, AstraZeneca, GSK, and Pfizer. No biomedical financial interests or potential conflicts of interest are reported for Drs Abdallah, Kaufman, Gelernter, Smith, Perera, Dwork, or Kaffman. Dr. Gorman is an employee of Comprehensive NeuroScience, Inc., a corporation that receives funding from the pharmaceutical industry for some of its projects. Dr. Owens receives research grants from Eli Lilly, Pfizer, GlaxoSmithKline, Merck, Lundbeck, Cyberonics, Ortho-McNeil Janssen and served as consultant for Pfizer, Lundbeck, Sepracor, Johnson & Johnson, Sanofi-Aventis, Forest Labs and as speaker's honoraria for GlaxoSmithKline. He is an inventor on the patent “A method to estimate transporter occupancy”. Currently, Dr. Nemeroff serves on the Scientific Advisory Board for the American Foundation for Suicide Prevention (AFSP); NARSAD, PharmaNeuroboost and CeNeRx. He serves on the Board of Directors of AFSP; NovaDel Pharma, and Mt Cook Pharma, Inc. He owns equity or is stock holder in Revaax; NovaDel Pharma; CeNeRx, and PharmaNeuroboost. He is an inventor on the following patents: method and devices for transdermal delivery of lithium (US 6,375,990 B1) and method to estimate serotonin and norepinephrine transporter occupancy after drug treatment using patient or animal serum (US 7,148,027 B2). ",

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AU - Smith, Eric L.P.

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N2 - 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.

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KW - Corticotropin-releasing hormone

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KW - Gene-by-environment interaction

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KW - Nonhuman primates

KW - Serotonin transporter gene

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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