Oxytocin (OXT) and dopamine (DA) can mediate social behavior in multiple species. Despite social behavior shows a strong genetic component, the genes underlying this heritability remain unknown. The central hypothesis of this proposal, based on preliminary data is that genetic variation in dopamine D2 receptor (DRD2) modulates social behavior. The goal of this study is to tease out direct effects genetic variants of DRD2 and its interaction with OXT pathway on brain structure, function and social behavior. The applicant plans to test this hyphotesis at the Italian Institute of Technology in collaboration with two departments of the National Institutes of Health (USA), from where he returns by pursuing the following aims:
1) To characterize the effects of DRD2 polymorphisms on brain structure and function underlying social behavior;
2) To evaluate the impact of an interaction between DRD2 and OXTR polymorphism on brain structure and function underlying social behavior;
3) To determine modulatory effects of genetic variation in DRD2 on exogenous Oxytocin administration.
We will use an association approach to identify the gene effects on neuroimaging phenotypes (structural and functional) underlying social behavior. Furthermore, we will perform a double-blind placebo –controlled multimodal pharmaco-genomics imaging trial of oxytocin to test the effects of DRD2 on the response to this drug.
This collaborative project is expected to provide greater knowledge of the molecular mechanism underlying social behavior and to identify predictors of response to oxytocin treatment. The accomplishment of this proposal is important for elucidating pathophysiology and treatment of neuropsychiatric disorders as well as to contribute to the improvement of the quality of European research and to the transfer of knowledge acquired by the fellow at the NIH.
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