Genetic Influences on the Developing Young Brain and Risk for Neuropsychiatric Disorders

doi:10.1016/j.biopsych.2023.01.013

Review

. 2023 May 15;93(10):905-920.

doi: 10.1016/j.biopsych.2023.01.013. Epub 2023 Jan 28.

Genetic Influences on the Developing Young Brain and Risk for Neuropsychiatric Disorders

Ann M Alex¹, Claudia Buss², Elysia Poggi Davis³, Gustavo de Los Campos⁴, Kirsten A Donald⁵, Damien A Fair⁶, Nadine Gaab⁷, Wei Gao⁸, John H Gilmore⁹, Jessica B Girault¹⁰, Karen Grewen⁹, Nynke A Groenewold¹¹, Benjamin L Hankin¹², Jonathan Ipser¹³, Shreya Kapoor¹⁴, Pilyoung Kim¹⁵, Weili Lin¹⁶, Shan Luo¹⁷, Elizabeth S Norton¹⁸, Thomas G O'Connor¹⁹, Joseph Piven¹⁰, Anqi Qiu²⁰, Jerod M Rasmussen²¹, Michael A Skeide²², Dan J Stein²³, Martin A Styner²⁴, Paul M Thompson²⁵, Laurie Wakschlag²⁶, Rebecca Knickmeyer²⁷; ENIGMA ORIGINs group

Affiliations

¹ Institute for Quantitative Health Sciences and Engineering, Michigan State University, East Lansing, Michigan.
² Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Medical Psychology, Berlin, Germany; Department of Pediatrics, University of California Irvine, Irvine, California; Development, Health and Disease Research Program, University of California Irvine, Irvine, California.
³ Department of Pediatrics, University of California Irvine, Irvine, California; Department of Psychology, University of Denver, Denver, Colorado.
⁴ Institute for Quantitative Health Sciences and Engineering, Michigan State University, East Lansing, Michigan; Departments of Epidemiology & Biostatistics, Michigan State University, East Lansing, Michigan; Department of Statistics & Probability, Michigan State University, East Lansing, Michigan.
⁵ Division of Developmental Paediatrics, Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa; Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
⁶ Masonic Institute for the Developing Brain, University of Minnesota Medical School, Minneapolis, Minnesota; Institute of Child Development, College of Education and Human Development, University of Minnesota, Minneapolis, Minnesota; Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota.
⁷ Harvard Graduate School of Education, Harvard University, Cambridge, Massachusetts.
⁸ Cedars-Sinai Biomedical Imaging Research Institute, Los Angeles, California; Departments of Biomedical Sciences and Imaging, Cedars-Sinai Medical Center, Los Angeles, California.
⁹ Department of Psychiatry, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina.
¹⁰ Department of Psychiatry, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina; Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill, Carrboro, North Carolina.
¹¹ Neuroscience Institute, University of Cape Town, Cape Town, South Africa; South African Medical Research Council Unit on Child and Adolescent Health, University of Cape Town, Cape Town, South Africa; Department of Paediatrics and Child Health, University of Cape Town, Faculty of Health Sciences, Cape Town, South Africa.
¹² Psychology Department, University of Illinois Urbana,-Champaign, Illinois.
¹³ Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
¹⁴ Research Group Learning in Early Childhood, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
¹⁵ Department of Psychology, University of Denver, Denver, Colorado.
¹⁶ Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
¹⁷ Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, California; Department of Psychology, University of Southern California, Los Angeles, California; Center for Endocrinology, Diabetes and Metabolism, Children's Hospital Los Angeles, Los Angeles, California.
¹⁸ Roxelyn and Richard Pepper Department of Communication Sciences and Disorders, Northwestern University, Evanston, Illinois; Department of Medical Social Sciences and Institute for Innovations in Developmental Sciences, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
¹⁹ Departments of Psychiatry, Psychology, Neuroscience, Obstetrics and Gynecology, University of Rochester, Rochester, New York.
²⁰ Department of Biomedical Engineering, National University of Singapore, Singapore; NUS (Suzhou) Research Institute, National University of Singapore, China; the Institute for Health, National University of Singapore, Singapore; School of Computer Engineering and Science, Shanghai University, Shanghai, China; Institute of Data Science, National University of Singapore, Singapore; Department of Biomedical Engineering, the Johns Hopkins University, Baltimore, Maryland.
²¹ Department of Pediatrics, University of California Irvine, Irvine, California; Development, Health and Disease Research Program, University of California Irvine, Irvine, California.
²² Department of Psychiatry, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina; Research Group Learning in Early Childhood, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
²³ South African Medical Research Council Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry, University of Cape Town, Cape Town, South Africa; Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
²⁴ Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
²⁵ Imaging Genetics Center, Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of University of the Sunshine Coast, Marina del Rey, California.
²⁶ Department of Medical Social Sciences and Institute for Innovations in Developmental Sciences, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
²⁷ Institute for Quantitative Health Sciences and Engineering, Michigan State University, East Lansing, Michigan; Department of Pediatrics and Human Development, Michigan State University, East Lansing, Michigan. Electronic address: knickmey@msu.edu.

PMID: 36932005
PMCID: PMC10136952
DOI: 10.1016/j.biopsych.2023.01.013

Review

Genetic Influences on the Developing Young Brain and Risk for Neuropsychiatric Disorders

Ann M Alex et al. Biol Psychiatry. 2023.

. 2023 May 15;93(10):905-920.

doi: 10.1016/j.biopsych.2023.01.013. Epub 2023 Jan 28.

Authors

Affiliations

¹ Institute for Quantitative Health Sciences and Engineering, Michigan State University, East Lansing, Michigan.
² Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Medical Psychology, Berlin, Germany; Department of Pediatrics, University of California Irvine, Irvine, California; Development, Health and Disease Research Program, University of California Irvine, Irvine, California.
³ Department of Pediatrics, University of California Irvine, Irvine, California; Department of Psychology, University of Denver, Denver, Colorado.
⁴ Institute for Quantitative Health Sciences and Engineering, Michigan State University, East Lansing, Michigan; Departments of Epidemiology & Biostatistics, Michigan State University, East Lansing, Michigan; Department of Statistics & Probability, Michigan State University, East Lansing, Michigan.
⁵ Division of Developmental Paediatrics, Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa; Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
⁶ Masonic Institute for the Developing Brain, University of Minnesota Medical School, Minneapolis, Minnesota; Institute of Child Development, College of Education and Human Development, University of Minnesota, Minneapolis, Minnesota; Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota.
⁷ Harvard Graduate School of Education, Harvard University, Cambridge, Massachusetts.
⁸ Cedars-Sinai Biomedical Imaging Research Institute, Los Angeles, California; Departments of Biomedical Sciences and Imaging, Cedars-Sinai Medical Center, Los Angeles, California.
⁹ Department of Psychiatry, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina.
¹⁰ Department of Psychiatry, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina; Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill, Carrboro, North Carolina.
¹¹ Neuroscience Institute, University of Cape Town, Cape Town, South Africa; South African Medical Research Council Unit on Child and Adolescent Health, University of Cape Town, Cape Town, South Africa; Department of Paediatrics and Child Health, University of Cape Town, Faculty of Health Sciences, Cape Town, South Africa.
¹² Psychology Department, University of Illinois Urbana,-Champaign, Illinois.
¹³ Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
¹⁴ Research Group Learning in Early Childhood, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
¹⁵ Department of Psychology, University of Denver, Denver, Colorado.
¹⁶ Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
¹⁷ Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, California; Department of Psychology, University of Southern California, Los Angeles, California; Center for Endocrinology, Diabetes and Metabolism, Children's Hospital Los Angeles, Los Angeles, California.
¹⁸ Roxelyn and Richard Pepper Department of Communication Sciences and Disorders, Northwestern University, Evanston, Illinois; Department of Medical Social Sciences and Institute for Innovations in Developmental Sciences, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
¹⁹ Departments of Psychiatry, Psychology, Neuroscience, Obstetrics and Gynecology, University of Rochester, Rochester, New York.
²⁰ Department of Biomedical Engineering, National University of Singapore, Singapore; NUS (Suzhou) Research Institute, National University of Singapore, China; the Institute for Health, National University of Singapore, Singapore; School of Computer Engineering and Science, Shanghai University, Shanghai, China; Institute of Data Science, National University of Singapore, Singapore; Department of Biomedical Engineering, the Johns Hopkins University, Baltimore, Maryland.
²¹ Department of Pediatrics, University of California Irvine, Irvine, California; Development, Health and Disease Research Program, University of California Irvine, Irvine, California.
²² Department of Psychiatry, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina; Research Group Learning in Early Childhood, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
²³ South African Medical Research Council Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry, University of Cape Town, Cape Town, South Africa; Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
²⁴ Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
²⁵ Imaging Genetics Center, Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of University of the Sunshine Coast, Marina del Rey, California.
²⁶ Department of Medical Social Sciences and Institute for Innovations in Developmental Sciences, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
²⁷ Institute for Quantitative Health Sciences and Engineering, Michigan State University, East Lansing, Michigan; Department of Pediatrics and Human Development, Michigan State University, East Lansing, Michigan. Electronic address: knickmey@msu.edu.

PMID: 36932005
PMCID: PMC10136952
DOI: 10.1016/j.biopsych.2023.01.013

Abstract

Imaging genetics provides an opportunity to discern associations between genetic variants and brain imaging phenotypes. Historically, the field has focused on adults and adolescents; very few imaging genetics studies have focused on brain development in infancy and early childhood (from birth to age 6 years). This is an important knowledge gap because developmental changes in the brain during the prenatal and early postnatal period are regulated by dynamic gene expression patterns that likely play an important role in establishing an individual's risk for later psychiatric illness and neurodevelopmental disabilities. In this review, we summarize findings from imaging genetics studies spanning from early infancy to early childhood, with a focus on studies examining genetic risk for neuropsychiatric disorders. We also introduce the Organization for Imaging Genomics in Infancy (ORIGINs), a working group of the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium, which was established to facilitate large-scale imaging genetics studies in infancy and early childhood.

Keywords: Childhood; Genetics; Imaging; Infant; Magnetic resonance imaging; Pediatric.

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Figures

**Figure 1**
Early neurodevelopment is a sensitive period for accumulating transdiagnostic risk for psychiatric disorders. Neurodevelopment in the human brain begins from approximately 2 weeks after conception. Neurogenesis and neural migration are primarily prenatal processes, and neurite outgrowth is minimal after 4 years of age. Myelination and synaptic pruning continue beyond 6 years of age (indicated by the small arrows). Genetic influences on these various processes contribute to psychiatric risk, which accumulates across development and may not manifest until later in life (large orange arrow).

**Figure 2**
PhenoGram of genes associated with brain imaging phenotypes in infants and young children from candidate gene studies and genome-wide association studies. CT, cortical thickness; FA, fractional anisotropy; GMV, gray matter volume; ICV, intracranial volume; MWF, myelin water fraction; PFC, prefrontal cortex; SA, surface area; TBV, total brain volume; WM, white matter; WMV, white matter volume.

**Figure 3**
Data analysis plan for the ORIGINs (Organization for Imaging Genomics in Infancy). DIP, developmental imaging phenotype; DTI, diffusion tensor imaging; fMRI, functional magnetic resonance imaging; PGC, Psychiatric Genomics Consortium.

See this image and copyright information in PMC

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References

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[1] Strike L.T., Couvy-Duchesne B., Hansell N.K., Cuellar-Partida G., Medland S.E., Wright M.J. Genetics and brain morphology. Neuropsychol Rev. 2015;25:63–96. - PubMed

[2] Strike L.T., Couvy-Duchesne B., Hansell N.K., Cuellar-Partida G., Medland S.E., Wright M.J. Genetics and brain morphology. Neuropsychol Rev. 2015;25:63–96. - PubMed

[3] Gao W., Grewen K., Knickmeyer R.C., Qiu A., Salzwedel A., Lin W., Gilmore J.H. A review on neuroimaging studies of genetic and environmental influences on early brain development. Neuroimage. 2019;185:802–812. - PMC - PubMed

[4] Gao W., Grewen K., Knickmeyer R.C., Qiu A., Salzwedel A., Lin W., Gilmore J.H. A review on neuroimaging studies of genetic and environmental influences on early brain development. Neuroimage. 2019;185:802–812. - PMC - PubMed

[5] Thompson P.M., Jahanshad N., Ching C.R.K., Salminen L.E., Thomopoulos S.I., Bright J., et al. ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries. Transl Psychiatry. 2020;10:100. - PMC - PubMed

[6] Thompson P.M., Jahanshad N., Ching C.R.K., Salminen L.E., Thomopoulos S.I., Bright J., et al. ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries. Transl Psychiatry. 2020;10:100. - PMC - PubMed

[7] Fatemi S.H., Folsom T.D. The neurodevelopmental hypothesis of schizophrenia, revisited. Schizophr Bull. 2009;35:528–548. - PMC - PubMed

[8] Fatemi S.H., Folsom T.D. The neurodevelopmental hypothesis of schizophrenia, revisited. Schizophr Bull. 2009;35:528–548. - PMC - PubMed

[9] Chen J.A., Peñagarikano O., Belgard T.G., Swarup V., Geschwind D.H. The emerging picture of autism spectrum disorder: Genetics and pathology. Annu Rev Pathol. 2015;10:111–144. - PubMed

[10] Chen J.A., Peñagarikano O., Belgard T.G., Swarup V., Geschwind D.H. The emerging picture of autism spectrum disorder: Genetics and pathology. Annu Rev Pathol. 2015;10:111–144. - PubMed

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Genetic Influences on the Developing Young Brain and Risk for Neuropsychiatric Disorders

Affiliations

Genetic Influences on the Developing Young Brain and Risk for Neuropsychiatric Disorders

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