Rearing condition and rh5-HTTLPR interact to influence limbic-hypothalamic-pituitary-adrenal axis response to stress in infant macaques

Background. In humans and macaques, a promoter polymorphism that decreases transcription of the serotonin transporter gene is associated with anxiety. Serotonin transporter gene disruption in rodents produces anxious animals with exaggerated limbic-hypothalamic-pituitary-adrenal (LHPA) responses to stress. We wanted to determine whether serotonin transporter gene promoter variation (rh-5HTTLPR) and rearing condition would interact to influence endocrine responses to stress in infant rhesus macaques. Methods: Animals were reared with their mothers (MR, n = 141) or in peer-only groups (PR, n = 67). At 6 months of age, adrenocorticotropic hormone (ACTH) and cortisol levels were determined at baseline and during separation stress. Serotonin transporter genotype (1/1 and 1/s) was determined with polymerase chain reaction followed by gel electrophoresis. Results: Cortisol levels increased during separation, and there was a mar. n effect of rearing condition, with decreased cortisol levels among PR macaques. Animals with 1/s rh5-HTTLPR genotypes bad higher ACTH levels than did 1/1 animals. Adrenocorticotropic hormone levels increased during separation, and there was a separation X rearing X rh5-HTTLPR interaction, such that PR4/s animals bad higher ACTH levels during separation than did other animals studied affects LHPA axis activity and that the influence Conclusions: These data demonstrate that serotonin transporter gene variation of rh5-HTTLPR on hormonal responses during stress is modulated by early experience.