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 concentrafions, and neuroelectric funcfioning 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.
|Malm, Heli; Brown, Alan S; Gissler, Mika et al. (2016) Gestational Exposure to Selective Serotonin Reuptake Inhibitors and Offspring Psychiatric Disorders: A National Register-Based Study. J Am Acad Child Adolesc Psychiatry 55:359-66|
|Bansal, Ravi; Peterson, Bradley S; Gingrich, Jay et al. (2016) Serotonin signaling modulates the effects of familial risk for depression on cortical thickness. Psychiatry Res 248:83-93|
|Wang, Zhishun; Jacobs, Rachel H; Marsh, Rachel et al. (2016) Sex-specific neural activity when resolving cognitive interference in individuals with or without prior internalizing disorders. Psychiatry Res 249:76-83|
|Subaran, Ryan L; Odgerel, Zagaa; Swaminathan, Rajeswari et al. (2016) Novel variants in ZNF34 and other brain-expressed transcription factors are shared among early-onset MDD relatives. Am J Med Genet B Neuropsychiatr Genet 171B:333-41|
|Talati, Ardesheer; Odgerel, Zagaa; Wickramaratne, Priya J et al. (2016) Brain derived neurotrophic factor moderates associations between maternal smoking during pregnancy and offspring behavioral disorders. Psychiatry Res 245:387-391|
|Malm, Heli; Sourander, Andre; Gissler, Mika et al. (2015) Pregnancy Complications Following Prenatal Exposure to SSRIs or Maternal Psychiatric Disorders: Results From Population-Based National Register Data. Am J Psychiatry 172:1224-32|
|Jacobs, Rachel H; Orr, Jonathan L; Gowins, Jennifer R et al. (2015) Biomarkers of intergenerational risk for depression: a review of mechanisms in longitudinal high-risk (LHR) studies. J Affect Disord 175:494-506|
|Spann, Marisa N; Serino, Dana; Bansal, Ravi et al. (2015) Morphological features of the neonatal brain following exposure to regional anesthesia during labor and delivery. Magn Reson Imaging 33:213-21|
|Talati, Ardesheer; Guffanti, Guia; Odgerel, Zagaa et al. (2015) Genetic variants within the serotonin transporter associated with familial risk for major depression. Psychiatry Res 228:170-3|
|Suri, Deepika; Teixeira, CÃ¡tia M; Cagliostro, Martha K Caffrey et al. (2015) Monoamine-sensitive developmental periods impacting adult emotional and cognitive behaviors. Neuropsychopharmacology 40:88-112|
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