Cited by 664Schizophrenia research and treatmentTryptophan and brain disordersMaternal Mental Health During Pregnancy and Postpartum

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The environment and susceptibility to schizophrenia

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Brown, Alan S.·2011·Progress in Neurobiology

DOI 10.1016/j.pneurobio.2010.09.003PMC PMC3521525

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Abstract

In the present article the putative role of environmental factors in schizophrenia is reviewed and synthesized. Accumulating evidence from recent studies suggests that environmental exposures may play a more significant role in the etiopathogenesis of this disorder than previously thought. This expanding knowledge base is largely a consequence of refinements in the methodology of epidemiologic studies, including birth cohort investigations, and in preclinical research that has been inspired by the evolving literature on animal models of environmental exposures. This paper is divided into four sections. In the first, the descriptive epidemiology of schizophrenia is reviewed. This includes general studies on incidence, prevalence, and differences in these measures by urban-rural, neighborhood, migrant, and season of birth status, as well as time trends. In the second section, we discuss the contribution of environmental risk factors acting during fetal and perinatal life; these include infections [e.g. rubella, influenza, Toxoplasma gondii (T. gondii), herpes simplex virus type 2 (HSV-2)], nutritional deficiencies (e.g., famine, folic acid, iron, vitamin D), paternal age, fetal/neonatal hypoxic and other obstetric insults and complications, maternal stress and other exposures [e.g. lead, rhesus (Rh) incompatibility, maternal stress]. Other putative neurodevelopmental determinants, including cannabis, socioeconomic status, trauma, and infections during childhood and adolescence are also covered. In the third section, these findings are synthesized and their implications for prevention and uncovering biological mechanisms, including oxidative stress, apoptosis, and inflammation, are discussed. Animal models, including maternal immune activation, have yielded evidence suggesting that these exposures cause brain and behavioral phenotypes that are analogous to findings observed in patients with schizophrenia. In the final section, future studies including new, larger, and more rigorous epidemiologic investigations, and research on translational and clinical neuroscience, gene-environment interactions, epigenetics, developmental trajectories and windows of vulnerability, are elaborated upon. These studies are aimed at confirming observed risk factors, identifying new environmental exposures, elucidating developmental mechanisms, and shedding further light on genes and exposures that may not be identified in the absence of these integrated approaches. The study of environmental factors in schizophrenia may have important implications for the identification of causes and prevention of this disorder, and offers the potential to complement, and refine, existing efforts on explanatory neurodevelopmental models.

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See all 664

Authors: Brown, A. S.
Affiliations: New York State Psychiatric Institute (US)
Corresponding author: Brown, Alan S.
ORCID: Brown, Alan S.
Venue: Progress in Neurobiology
Publisher: Elsevier BV
Published: 2011-01
Volume: 93
Issue: 1
Pages: 23-58
ISSN: 0301-0082 (ISSN-L)
DOI: 10.1016/j.pneurobio.2010.09.003
PMC: PMC3521525
OpenAlex: W2042914870
Cited by: 664
References: 395
Citations by year: 2026: 19 · 2025: 27 · 2024: 35 · 2023: 41 · 2022: 29 · 2021: 39 · 2020: 40 · 2019: 37 · 2018: 41 · 2017: 32 · 2016: 55 · 2015: 61 · 2014: 65 · 2013: 55 · 2012: 61
FWCI: 6.37
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Progress in Neurobiology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Mental Health (K02MH065422, R01MH082052)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
Keywords: schizophrenia, environmental risk factors, etiopathogenesis, prenatal exposure, perinatal exposure, maternal infection, Toxoplasma gondii, influenza, rubella, herpes simplex virus type 2, nutritional deficiency, paternal age, fetal hypoxia, pregnancy complications, maternal stress, lead exposure, Rh incompatibility, cannabis, socioeconomic status, childhood trauma, brain development, maternal immune activation, oxidative stress, inflammation, apoptosis, gene-environment interaction, epigenetics, window of vulnerability, incidence and prevalence, season of birth, migration, prevention
MeSH terms: Animals, Environment, Environmental Exposure, Female, Humans, Nutritional Status, Pregnancy, Prenatal Exposure Delayed Effects, Risk Factors, Schizophrenia, Genetic Predisposition to Disease

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