Twin studies have been critical in determining the contributions of genetic and environmental factors to normal brain structure and for understanding abnormalities of brain development that underlie neurodevelopmental and neuropsychiatric disorders. In adults and older children, twin studies indicate that genes play a significant role in the variability of global brain volumes, including total brain, total gray and total white matter volumes. Other than this current study, there have been no studies of twin brain development in early childhood, the period of brain development implicated in the pathogenesis of many psychiatric disorders. In the first funding cycle of this grant, we used prenatal ultrasound and neonatal MRI to study discordance of early brain development, and to determine genetic and environmental contributions to neonatal brain structure. We have and have developed a unique and valuable cohort of twins, having recruited and scanned over 100 twin pairs. We found that discordance of prenatal brain size in MZ twins is similar to that in DZ twins, but that by 1 month after birth, discordance of overall brain volume in MZ twins is already less than in DZ twins. Statistical modeling of neonatal MRI brain volumes in our twin cohort indicates that global tissue volumes are highly heritable, similar to that observed in older children and adults, though gray matter heritability may is somewhat less. Therefore, it appears that genetic programs act very early in postnatal brain development to determine global tissue volumes. Interestingly, preliminary longitudinal mapping of correlations in gray matter density indicate correlations decrease in the first year of life, perhaps as the result of rapid brain growth in the first years of life. We also found that while global white matter volumes are highly heritable, diffusion tensor properties of specific white matter tracts are not. In the next funding cycle, we propose to continue enlarging this unique cohort and to follow them through age 6 years with structural MRI, diffusion tensor imaging (DTI), and developmental assessments to determine how genetic and environmental factors contribute to brain development in the first years of life.

Public Health Relevance

Twins studies play an important role in understanding the contributions of genes and environment to brain development and risk for psychiatric disease. While there have been twin studies of brain structure adults and older children, ours is the only twin study of brain development in the first years of life. We propose to continue our study of early childhood brain development in twins, using structural MRI, diffusion tensor imaging, and cognitive assessments.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Special Emphasis Panel (ZRG1-BDCN-N (02))
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Friedman-Hill, Stacia
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University of North Carolina Chapel Hill
Schools of Medicine
Chapel Hill
United States
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Jha, Shaili C; Meltzer-Brody, Samantha; Steiner, Rachel J et al. (2016) Antenatal depression, treatment with selective serotonin reuptake inhibitors, and neonatal brain structure: A propensity-matched cohort study. Psychiatry Res 253:43-53
Wang, Yan; Zhang, Pei; An, Le et al. (2016) Predicting standard-dose PET image from low-dose PET and multimodal MR images using mapping-based sparse representation. Phys Med Biol 61:791-812
Prieto, Juan C; Yang, Jean Y; Budin, François et al. (2016) Autotract: Automatic cleaning and tracking of fibers. Proc SPIE Int Soc Opt Eng 9784:
Rekik, Islem; Li, Gang; Lin, Weili et al. (2016) Multidirectional and Topography-based Dynamic-scale Varifold Representations with Application to Matching Developing Cortical Surfaces. Neuroimage 135:152-62
Meng, Yu; Li, Gang; Gao, Yaozong et al. (2016) Learning-based subject-specific estimation of dynamic maps of cortical morphology at missing time points in longitudinal infant studies. Hum Brain Mapp 37:4129-4147
Sadeghi, Neda; Gilmore, John H; Gerig, Guido (2016) Twin-singleton developmental study of brain white matter anatomy. Hum Brain Mapp :
Li, Gang; Wang, Li; Shi, Feng et al. (2016) Cortical thickness and surface area in neonates at high risk for schizophrenia. Brain Struct Funct 221:447-61
Rekik, Islem; Li, Gang; Lin, Weili et al. (2016) Predicting infant cortical surface development using a 4D varifold-based learning framework and local topography-based shape morphing. Med Image Anal 28:1-12
Wu, Yao; Wu, Guorong; Wang, Li et al. (2015) Hierarchical and symmetric infant image registration by robust longitudinal-example-guided correspondence detection. Med Phys 42:4174-89
Tu, Liyun; Styner, Martin; Vicory, Jared et al. (2015) Skeletal shape correspondence via entropy minimization. Proc SPIE Int Soc Opt Eng 9413:

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