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The environment and susceptibility to schizophrenia
Open accessAbstract
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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“Epidemiological evidence points to maternal infection being a risk factor in schizophrenia 1 and maternal infection in mice is sufficient to induce long-term PPI and social behavioural changes in the offspring, changes that are attributable to inflammation 89 .”
From Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis (2016) · cites this paper as [1]
In the citing paper
“In this context, the neuropathology of schizophrenia has been reported to be closely associated with cytokines and microglial activation (Bayer et al., 1999; Brown, 2011; Juckel et al., 2011; Meyer et al., 2009; Monji et al., 2009; Najjar et al., 2013; Radewicz et al., 2000; Vuillermot et al., 2010).”
From Perineuronal nets and schizophrenia: The importance of neuronal coatings (2014) · cites this paper as Brown, 2011
In the citing paper
“Recent studies have revealed anomalies in hippocampal and/or prefrontal PVI in many preclinical animal models aiming to reproduce genetic vulnerabilities (Carlson et al., 2011; Fazzari et al., 2010; Hikida et al., 2007; Wen et al., 2010) or environmental risk factors (Brown, 2011) such as prenatal maternal stress (Stevens et al., 2013), maternal and perinatal immune challenge (Jenkins et al., 2009”
From Redox dysregulation, neuroinflammation, and NMDA receptor hypofunction: A “central hub” in schizophrenia pathophysiology? (2016) · cites this paper as Brown, 2011
In the citing paper
“Both human epidemiological and animal model studies point to genetic and environmental factors that affect critical periods in early and adolescent brain development and that take place in advance of symptoms 1 .”
From Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis (2016) · cites this paper as [1]
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“The existence of prenatal risk factors for schizophrenia, such as maternal infections, nutritional deficiency, obstetrical complications and stress, suggests that there is a developmental window of sensitivity in which a transient early insult leads to long-lasting developmental perturbations 1 .”
From Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis (2016) · cites this paper as [1]
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Metadata
- 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)
- 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
- 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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