Association between the recombinant human serotonin transporter linked promoter region polymorphism and behavior in rhesus macaques during a separation paradigm.
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.
Spinelli
Simona
S
National Institute on Alcohol Abuse and Alcoholism, NIH Animal Center, P.O. Box 529, Poolesville, MD 20837, USA.
Schwandt
Melanie L
ML
Lindell
Stephen G
SG
Newman
Timothy K
TK
Heilig
Markus
M
Suomi
Stephen J
SJ
Higley
J Dee
JD
Goldman
David
D
Barr
Christina S
CS
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
D011994:Recombinant Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins