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

• Type of Material: Article
• Authors: Jonathan A. Hollander, National Institute of Environmental Health Sciences; Deborah A. Cory-Slechta, University of Rochester; Felice N. Jacka, Deakin University; Steven T. Szabo, Duke University; Tomas R. Guilarte, Florida International University; Staci D. Bilbo, Duke University; Carolyn J. Mattingly, North Carolina State University; Sheryl S. Moy, University of North Carolina; Ebrahim Haroon, Emory University; Mady Hornig, Columbia University; Edward D. Levin, Duke University; Mikhail V. Pletnikov, Johns Hopkins University; Julia L. Zehr, National Institute of Mental Health; Kimberly A. McAllister, National Institute of Environmental Health Sciences; Anika L. Dzierlenga, National Institute of Environmental Health Sciences; Amanda E. Garton, National Institute of Environmental Health Sciences; Cindy P. Lawler, National Institute of Environmental Health Sciences; Christine Ladd-Acosta, Johns Hopkins University
• Language: English
• Date: 2020-02-28
• Publisher: Springer Nature
• Publication Version: Final Published Version
• Copyright Statement: © 2020 Springer Nature Limited.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41386-020-0648-5
• Title of Journal or Parent Work: Neuropsychopharmacology
• Volume: 45
• Issue: 7
• Start Page: 1086
• End Page: 1096
• Grant/Funding Information: U.S. Department of Veterans Affairs grant IK2CX001397 (to ST Szabo).; NIH grants: R01ES014065 and P30ES025128 (to CJ Mattingly); R01ES06189 (to TR Guilarte); R01HD090051 (to M Hornig); U54HD079124 (to SS Moy);; This work was supported in part by the NIH, National Institute of Environmental Health Sciences (to JA Hollander, KA McAllister, AL Dzierlenga, AE Garton, CP Lawler) and National Institute of Mental Health (to JL Zehr),
• Keywords: Science & Technology; Immune activation; Air pollution; Neurosciences & Neurology; Genome wide association; Gut microbiota; DNA Methylation; Pharmacology & Pharmacy; Life Sciences & Biomedicine; Psychiatric disorders; Bisphenol A; Research domain criteria; Neurosciences; Polychlorinated biphenyls; Lead exposure; Psychiatry
• Research Categories: Environmental Sciences; Health Sciences, Pharmacology; Biology, Genetics; Biology, Neuroscience

Abstract

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.