NEUROBIOLOGY OF INCREASED VULNERABILITY TO SOCIAL STRESSORS DURING ADOLESCENCE

Emory University, Atlanta GA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Using a rhesus monkey model, this project is designed to provide a better understanding of how psychosocial stress, imposed by social subordination, affects brain maturation and emotional development in females and whether this is influenced by polymorphisms in the gene that encodes the serotonin re-uptake transporter (5HTT), a protein essential for normal serotonin neurotransmission and emotionality. Significant progress was made during the current year on the first cohort of adolescents (n = 37) that are housed in large social groups at the Field Station. Data show that adolescent females are less sensitivity to glucocorticoid negative, suggesting the may be particularly vulnerable to the stress of social subordination. Furthermore, subordinate adolescent females with the s-variant polymorphism in the gene encoding the 5HTT are more reactive to novel objects, reflecting greater emotional reactivity. Structural MR, DTI, and PET imaging of 5HTT and 5HT 1A receptor binding density were completed on this cohort and data show significant differences in 5HT1A binding and white matter integrity in components of limbic [unreadable]cortical circuits in subordinate versus dominant females. As expected, the more socially dominant females of this cohort have entered puberty whereas the subordinate females have not. The experimental delay in puberty with Lupron administration for the second cohort (n = 39) was continued this year.. Behavioral testing, glucocorticoid assessments, and neuroimaging have begun on this cohort. These studies will show the importance of estradiol for behavioral and brain maturation during adolescence in females.