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

• Published in: Biological psychiatry (1969) Vol. 55; no. 7; pp. 733 - 738
• Main Authors: Barr, Christina S, Newman, Timothy K, Shannon, Courtney, Parker, Clarissa, Dvoskin, Rachel L, Becker, Michelle L, Schwandt, Melanie, Champoux, Maribeth, Lesch, Klaus Peter, Goldman, David, Suomi, Stephen J, Higley, J.Dee
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.04.2004; Elsevier Science
• Subjects: adrenocorticotropic hormone; Adult and adolescent clinical studies; Affectivity. Emotion; Animals; Animals, Newborn; Anxiety disorders. Neuroses; Arousal - genetics; Base Pairing - genetics; Biological and medical sciences; Carrier Proteins - genetics; Chromosome Deletion; cortisol; DNA Transposable Elements - genetics; Female; Fundamental and applied biological sciences. Psychology; Genetic Variation; Hydrocortisone - blood; hypothalamic–pituitary–adrenal axis; Hypothalamo-Hypophyseal System - physiology; Limbic System - physiology; Macaca mulatta; Male; Maternal Deprivation; Medical sciences; Membrane Glycoproteins - genetics; Membrane Transport Proteins; Nerve Tissue Proteins - genetics; Nonhuman primate; Peer Group; Personality. Affectivity; Pituitary-Adrenal System - physiology; Post-traumatic stress disorder; Promoter Regions, Genetic; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry; Serotonin - physiology; Serotonin Plasma Membrane Transport Proteins; serotonin transporter; Social Environment; stress; Stress, Psychological - complications; stress; cortisol; serotonin transporter; adrenocorticotropic hormone; hypothalamic–pituitary–adrenal axis; Nonhuman primate; Affect affectivity; Animal model; Hypothalamohypophysoadrenal axis; Serotonin; Transcription promoter; Central nervous system; Macaca mulatta; Limbic system; Experimental study; Stress; Encephalon; Vertebrata; Mammalia; Maternal separation; Mother young relation; Newborn animal; Animal; Neurotransmitter; Primates; Simioidea; Developmental stage; Anxiety; Serotonine transporter
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2003.12.008

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. 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 ( l/l and l/s) was determined with polymerase chain reaction followed by gel electrophoresis. Cortisol levels increased during separation, and there was a main effect of rearing condition, with decreased cortisol levels among PR macaques. Animals with l/s rh5-HTTLPR genotypes had higher ACTH levels than did l/l animals. Adrenocorticotropic hormone levels increased during separation, and there was a separation × rearing × rh5-HTTLPR interaction, such that PR- l/s animals had higher ACTH levels during separation than did other animals studied. These data demonstrate that serotonin transporter gene variation affects LHPA axis activity and that the influence of rh5-HTTLPR on hormonal responses during stress is modulated by early experience.