Early-life stress, corticotropin-releasing factor, and serotonin transporter gene: a pilot study.
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.
Coplan
Jeremy D
JD
State University of New York (SUNY), Downstate Medical Center, Department of Psychiatry, Brooklyn, NY 11203, USA. Copstat00@aol.com
Abdallah
Chadi G
CG
Kaufman
Joan
J
Gelernter
Joel
J
Smith
Eric L P
EL
Perera
Tarique D
TD
Dwork
Andrew J
AJ
Kaffman
Arie
A
Gorman
Jack M
JM
Rosenblum
Leonard A
LA
Owens
Michael J
MJ
Nemeroff
Charles B
CB
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology / Q000523:psychology*; D003346:Corticotropin-Releasing Hormone / Q000134:cerebrospinal fluid* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006799:Housing, Animal; D008255:Macaca radiata; D008297:Male; D008425:Maternal Behavior / Q000502:physiology; D009425:Nesting Behavior / Q000502:physiology; D010865:Pilot Projects; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D013315:Stress, Psychological / Q000134:cerebrospinal fluid* / Q000235:genetics* / Q000378:metabolism
D050486:Serotonin Plasma Membrane Transport Proteins; D003346:Corticotropin-Releasing Hormone