Twin studies have provided very important insights into the contributions of genetic and environmental factors to neuropsychiatric disorders. Structural imaging studies in MZ twins with neuropsychiatric disorders find a significant discordance of brain structure associated with illness in the affected co-twin. Discordant brain development in MZ twins appears to be associated with risk for neuropsychiatric disorders. Recently, sophisticated statistical modeling has been combined with high-resolution magnetic resonance imaging (MRI) to determine the contributions of genetic and environmental factors to brain structure. The available studies indicate that prenatal and neonatal brain structure in MZ twins are much more discordant than in adults, indicating that neonatal brain structure is under less genetic control than adult brain structure. The cumulative effect of genetic programs over childhood brain development appears to lead to greater correlations and higher heritability estimates in adult brain structures compared to prenatal and neonatal brain structure. This also appears true for cognitive functioning. This study will provide critical, unavailable information about early brain development and the contributions of genetic and environmental factors to discordant brain structure in twins. There are several published twin studies of brain structure in adults and a study of brain structure in older children is now being conducted at NIMH. We propose to take advantage of a unique and rare opportunity to extend the body of work on brain structure in twins to the earliest and most important period of brain development. We have assembled highly qualified multidisciplinary research team to conduct the proposed research, combining expertise in state-of-the-art image MRI acquisition and image analysis in neonates, prenatal ultrasound, infant cognitive development, and twin statistical modeling. This novel approach will fill in an important gap in our knowledge of brain development in twins and will ultimately improve our understanding of the meaning of twin studies of neurodevelopmental and neuropsychiatric disorders. We propose to study prenatal and neonatal brain structure in MZ and DZ twins with ultrasound and high resolution MRI. We will prospectively study prenatal brain structure during the second and third trimester in 250 twin pairs using ultrasound. After birth, we will use 3D ultrasound and high resolution MRI (including diffusion tensor imaging) to study neonatal brain structure in 74 MZ and 88 DZ same-gender twin pairs. Cognitive development in these twins will be followed prospectively at ages one and two years with the Mullen Scales of Early Learning. With this approach, we will determine the degree and timing of discordant brain structure in twins, the contribution of genetic and environmental factors to early brain structure using statistical modeling, and the relationship of discordant brain structure at birth to cognitive development at two years of age.
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