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Using an interactive gene-environment-time (GET) framework, we survey the independent and interactive roles of genetic variation, environmental context, and developmental timing in light of advances in the biology of adversity and resilience, as well as new discoveries in biomedical research. Drawing on this rich evidence base, we identify 4 core concepts that provide a powerful catalyst for fresh thinking about primary health care for young children: (1) all biological systems are inextricably integrated, continuously \u201creading\u201d and adapting to the environment and \u201ctalking back\u201d to the brain and each other through highly regulated channels of cross-system communication; (2) adverse environmental exposures induce alterations in developmental trajectories that can lead to persistent disruptions of organ function and structure; (3) children vary in their sensitivity to context, and this variation is influenced by interactions among genetic factors, family and community environments, and developmental timing; and (4) critical or sensitive periods provide unmatched windows of opportunity for both positive and negative influences on multiple biological systems. These rapidly moving frontiers of investigation provide a powerful framework for new, science-informed thinking about health promotion and disease prevention in the early childhood period.<\/jats:p>","DOI":"10.1542\/peds.2020-1651","type":"journal-article","created":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T09:28:29Z","timestamp":1611566909000},"source":"Crossref","is-referenced-by-count":182,"title":["Genes, Environments, and Time: The Biology of Adversity and Resilience"],"prefix":"10.1542","volume":"147","author":[{"given":"W. Thomas","family":"Boyce","sequence":"first","affiliation":[{"name":"Departments of Pediatrics and Psychiatry, University of California, San Francisco, San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pat","family":"Levitt","sequence":"additional","affiliation":[{"name":"The Saban Research Institute, Children\u2019s Hospital Los Angeles, Los Angeles, California;"},{"name":"Keck School of Medicine, University of Southern California, Los Angeles, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando D.","family":"Martinez","sequence":"additional","affiliation":[{"name":"Asthma and Airway Disease Research Center, The University of Arizona, Tucson, Arizona;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce S.","family":"McEwen","sequence":"additional","affiliation":[{"name":"The Rockefeller University, New York, New York;"},{"name":"Deceased."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack P.","family":"Shonkoff","sequence":"additional","affiliation":[{"name":"Center on the Developing Child and"},{"name":"Harvard Graduate School of Education, Harvard University, Cambridge, Massachusetts;"},{"name":"Department of Social & Behavioral Sciences, Harvard T.H. 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