Project 3: A Multimodal Imaging Study of the Effects of Altered Serotonin

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The central concept underlying all of the projects in this center is that during early development serotonin is a vitally important neural growth factor and regulator of brain maturation. Thus, environmental, genetic, and pathological factors that influence serotonin availability will profoundly influence brain structure, function and ultimately, behavior. Results from animal and human studies suggest that differences in serotonin function, either associated with polymorphisms in regulatory regions of the serotonin transporter gene or prenatal exposure to SSRIs, may underlie individual differences in fundamental neurobehavioral traits. No studies thus far have characterized early life phenotypes of polymorphisms in the serotonin system, and investigations of how pharmacologic perturbations of this system influence neurobehavioral traits in infants have been very limited. To date, no human studies have identified variation in the anatomical and functional characteristics of the newborn brain that are associated with altered serotonin signaling. In Project 3, we propose assessing the effects of both genetic variation and prenatal exposure to SSRIs on brain structure and function as a convergent strategy to identify the influences of altered serotonin signaling on early brain development. Because both SSRIs and the SS genotype of the serotonin transporter should promote increased levels of extracelluar serotonin, the overall hypothesis of this project is that the effects of prenatal exposure to SSRIs on brain development will be similar to those of the SS polymorphism. The primary goals of the project are to define the effects that prenatal exposure to SSRIs and genetic variation in regulation of the serotonin transporter have on brain structure, blood flow, neurometabolite concentrations, and neuroelectric functioning using MRI data and high-density (128 lead) EEG recordings acquired within the month of life. In Aim 1, these studies will focus on groups of infants with or without exposure to SSRIs during gestation. In Aim 2, a similar series of measurements will be made on groups of infants that vary with regard to polymorphisms in the serotonin transporter.