title: Association between the recombinant human serotonin transporter linked promoter region polymorphism and behavior in rhesus macaques during a separation paradigm.
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.
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, NIH Animal Center, P.O. Box 529, Poolesville, MD 20837, USA.
authors.forename: Simona
authors.initials: S
authors.lastname: Spinelli
authors.forename: Melanie L
authors.initials: ML
authors.lastname: Schwandt
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Lindell
authors.forename: Timothy K
authors.initials: TK
authors.lastname: Newman
authors.forename: Markus
authors.initials: M
authors.lastname: Heilig
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Suomi
authors.forename: J Dee
authors.initials: JD
authors.lastname: Higley
authors.forename: David
authors.initials: D
authors.lastname: Goldman
authors.forename: Christina S
authors.initials: CS
authors.lastname: Barr
mesh_terms: D000483:Alleles; D000818:Animals; D001007:Anxiety / Q000235:genetics*; D001522:Behavior, Animal; D003863:Depression / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics*; D008253:Macaca mulatta; D008297:Male; D008426:Maternal Deprivation; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012931:Social Environment; D012934:Social Isolation
chemical_list: D011994:Recombinant Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins