Beyond the looking glass: recent advances in understanding the impact of environmental exposures on neuropsychiatric disease

Hollander, Jonathan A., Cory-Slechta, Deborah A., Jacka, Felice N., Szabo, Steven T., Guilarte, Tomás R., Bilbo, Staci D., Mattingly, Carolyn J., Moy, Sheryl S., Haroon, Ebrahim, Hornig, Mady, Levin, Edward D., Pletnikov, Mikhail V., Zehr, Julia L., McAllister, Kimberly A., Dzierlenga, Anika L., Garton, Amanda E., Lawler, Cindy P., and Ladd-Acosta, Christine (2020) Beyond the looking glass: recent advances in understanding the impact of environmental exposures on neuropsychiatric disease. Neuropsychopharmacology, 45 (7). pp. 1086-1096.

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The etiologic pathways leading to neuropsychiatric diseases remain poorly defined. As genomic technologies have advanced over the past several decades, considerable progress has been made linking neuropsychiatric disorders to genetic underpinnings. Interest and consideration of nongenetic risk factors (e.g., lead exposure and schizophrenia) have, in contrast, lagged behind heritable frameworks of explanation. Thus, the association of neuropsychiatric illness to environmental chemical exposure, and their potential interactions with genetic susceptibility, are largely unexplored. In this review, we describe emerging approaches for considering the impact of chemical risk factors acting alone and in concert with genetic risk, and point to the potential role of epigenetics in mediating exposure effects on transcription of genes implicated in mental disorders. We highlight recent examples of research in nongenetic risk factors in psychiatric disorders that point to potential shared biological mechanisms—synaptic dysfunction, immune alterations, and gut–brain interactions. We outline new tools and resources that can be harnessed for the study of environmental factors in psychiatric disorders. These tools, combined with emerging experimental evidence, suggest that there is a need to broadly incorporate environmental exposures in psychiatric research, with the ultimate goal of identifying modifiable risk factors and informing new treatment strategies for neuropsychiatric disease.

Item ID: 67195
Item Type: Article (Research - C1)
ISSN: 1470-634X
Copyright Information: © 2020, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply. This article is published with open access. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
Funders: National Institute of Health (NIH), National Institute of Environmental Health Sciences (NIEHS), National Institute of Mental Health (NIMH), U.S. Department of Veterans Affairs (US DVA)
Projects and Grants: NIH grant R01ES014065, NIH grant P30ES025128, NIH grant R01ES06189, NIH grant R01HD090051, NIH grant U54HD079124, US DVA grant IK2CX001397
Date Deposited: 12 May 2021 01:50
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320221 Psychiatry (incl. psychotherapy) @ 100%
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