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Association between the recombinant human serotonin transporter linked promoter region polymorphism and behavior in rhesus macaques during a separation paradigm

Published online by Cambridge University Press:  11 October 2007

Simona Spinelli
Affiliation:
National Institute on Alcohol Abuse and Alcoholism
Melanie L. Schwandt
Affiliation:
National Institute on Alcohol Abuse and Alcoholism
Stephen G. Lindell
Affiliation:
National Institute on Alcohol Abuse and Alcoholism
Timothy K. Newman
Affiliation:
National Institute on Alcohol Abuse and Alcoholism
Markus Heilig
Affiliation:
National Institute on Alcohol Abuse and Alcoholism
Stephen J. Suomi
Affiliation:
National Institute of Child Health and Human Development
J. Dee Higley
Affiliation:
Brigham Young University
David Goldman
Affiliation:
National Institute on Alcohol Abuse and Alcoholism
Christina S. Barr*
Affiliation:
National Institute on Alcohol Abuse and Alcoholism
*
Address correspondence and reprint request to: Christina S. Barr, Laboratory of Clinical and Translational Studies, Primate Section, National Institute on Alcohol Abuse and Alcoholism, NIH Animal Center, P.O. Box 529, Poolesville, MD 20837; E-mail: cbarr@mail.nih.gov.

Abstract

Human studies have suggested an association between a variable length polymorphism in the serotonin transporter gene promoter region and vulnerability to anxiety and depression. Relative to the long (l) allele, the short (s) allele increases the risk of developing depression in individuals exposed to stressful life events. An orthologue of the human variant is present in rhesus macaques and allows for studies in animals exposed to stress. Here, we used an established model of early life stress exposure, in which rhesus macaques are raised without adults in a group of peers (peer-only reared [PR]), or with their mothers. At 6 months of age, animals were subjected to 4-day long social separations for 4 consecutive weeks, with 3 days of reunion in between. Data were collected during both the acute (Day 1) and chronic phases (Days 2–4) of separation. Behavioral factors were separately extracted for each phase of separation. For acute separation, the behavioral factors generated were despair and behavioral pathology and, for the chronic phase despair, agitation, and behavioral pathology. During both phases of social separation, PR l/s animals were more likely to exhibit pathological behaviors, whereas PR l/l monkeys show higher levels of despair compared to the other three groups. These findings indicate that early stress affects the behavioral response to separation differently as a function of recombinant human serotonin transporter linked polymorphic repeat genotype and suggest that carriers of the s allele are not only more anxious but may also be more vulnerable to developing behavioral pathology in the face of chronic adversity.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2007

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