Abstract # 2571 Event # 197:

Scheduled for Monday, September 21, 2009 09:30 AM-09:40 AM: Session 19 (Del Mar Room) Oral Presentation


EARLY LIFE STRESS AND METHYLATION OF THE SEROTONIN TRANSPORTER CPG ISLAND ARE ASSOCIATED WITH BEHAVIORAL STRESS REACTIVITY IN FEMALE BONNET MACAQUES (MACACA RADIATA)

E. L. Kinnally1, J. D. Coplan2 and J. J. Mann1
1Columbia University, Department of Psychiatry, 1051 Riverside Drive, Room 2917, New York, NY 10032, USA, 2State University of New York Downstate Brooklyn, 11203
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Serotonin pathway gene by environment interactions influence behavioral development, but genomic mechanisms have not been conclusively demonstrated. Methylation of a CpG island upstream of the serotonin transporter (5-HTT) gene has recently been associated with 5-HTT expression in humans and rhesus macaques. Further, methylation of this region is higher in carriers of the “short”, low activity 5-HTT promoter polymorphism in both species. We assessed the relative contributions of early life stress (variable foraging demand, VFD) and 5-HTT CpG methylation to behavioral adaptation to stress in twenty-seven female bonnet macaques (aged 4-14 years). Behavioral response to relocation, human intruder exposure, and a fear-conditioned stimulus was recorded during five trials each, and factor analysis was applied to behavioral reactivity composite scores. Three factors described reactivity to low intensity stress, high intensity stress, and during final exposure of stress. Blood DNA was sampled from each subject. Methylation analysis was conducted using direct sodium bisulfite pyrosequencing. The effects of early life stress, average 5-HTT methylation, and their interaction was tested using backward multiple regression. Individuals that experienced early life stress and which also possessed greater 5-HTT CpG methylation exhibited greater reactivity to both low [F(1,26)=9.19, p=0.006] and high [F(2,24)=3.84, p=0.036] intensity stressors. These results point to a role for 5-HTT CpG methylation in genome-environment interactions that influence behavioral development.