Research Article

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

Simona Spinelli^a1, Melanie L. Schwandt^a1, Stephen G. Lindell^a1, Timothy K. Newman^a1, Markus Heilig^a1, Stephen J. Suomi^a2, J. Dee Higley^a3, David Goldman^a1 and Christina S. Barr^a1 c1

^a1 National Institute on Alcohol Abuse and Alcoholism

^a2 National Institute of Child Health and Human Development

^a3 Brigham Young University

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.

Correspondence:

^c1 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.

Footnotes

Stephen J. Suomi, J. Dee Higley, David Goldman, and Christina S. Barr contributed equally to this work. We thank Courtney Lindell, the research staff, and the animal care staff at the National Institutes of Health Animal Center for their assistance in data collection. Subjects were treated in accordance with the Guide for the Care and Use of Laboratory Animals, as adopted and promulgated by the National Institutes of Health. The procedures performed in this study were approved by the Institutional Animal Care and Use Committee. This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Alcohol Abuse and Alcoholism, and National Institute of Child Health and Development.