Cited by 357Tryptophan and brain disordersAutism Spectrum Disorder ResearchSchizophrenia research and treatment

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Schizophrenia and Autism: Both Shared and Disorder-Specific Pathogenesis Via Perinatal Inflammation?

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MEYER, URS, FELDON, JORAM, DAMMANN, OLAF·2011·Pediatric Research

DOI 10.1203/pdr.0b013e318212c196PMC PMC3086802

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Abstract

Prenatal exposure to infection and subsequent inflammatory responses have been implicated in the etiology of schizophrenia and autism. In this review, we summarize current evidence from human and animal studies supporting the hypothesis that the pathogenesis of these two disorders is linked via exposure to inflammation at early stages of development. Moreover, we propose a hypothetical model in which inflammatory mechanisms may account for multiple shared and disorder-specific pathological characteristics of both entities. In essence, our model suggests that acute neuroinflammation during early fetal development may be relevant for the induction of psychopathological and neuropathological features shared by schizophrenia and autism, whereas postacute latent and persistent inflammation may contribute to schizophrenia- and autism-specific phenotypes, respectively.

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“This idea of multiple hits with either sensitizing or preconditioning effects is also central to several theories of prenatal immune priming, which have been put forward by others in the context of peripheral immunity, CNS inflammation, perinatal brain damage, retinopathy, and various forms of learning and memory (68–…”
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Behaviour and hippocampus-specific changes in spiny mouse neonates after treatment of the mother with the viral-mimetic poly I:C at mid-pregnancy
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Meyer, U. (2011) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2011.05.014 · Cited by 72
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“…Bergen et al., in press; Hamshere et al., in press; Jia et al., 2012), consistent with the increasingly large number of genetic and environmental associations shared specifically by these two disorders (Patterson, 2009; Gejman et al., 2011; Meyer et al., 2011; Brown, 2012; Reichelt et al., 2012).”
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Early adversity, neural development, and inflammation
Chiang, J. J., Taylor, S. E., & Bower, J. E. (2015) · Developmental Psychobiology · doi:10.1002/dev.21329 · Cited by 72
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Is a Subtype of Autism an Allergy of the Brain?
Theoharides, T. C. (2013) · Clinical Therapeutics · doi:10.1016/j.clinthera.2013.04.009 · Cited by 65
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Lipopolysaccharide Exposure Induces Maternal Hypozincemia, and Prenatal Zinc Treatment Prevents Autistic-Like Behaviors and Disturbances in the Striatal Dopaminergic and mTOR Systems of Offspring
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“Prenatal/perinatal exposure to numerous pathogens, including rubella, measles, and cytomegalovirus, has been implicated in the etiology of autism, suggesting that the infectionassociated risk of autism might not be pathogen specific [5].”
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Translational opportunities in the prenatal immune environment: Promises and limitations of the maternal immune activation model
Bauman, M. D., & de Water, J. V. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104864 · Cited by 65
“While we focus on the two neurodevelopmental disorders more strongly associated with maternal infection, SZ and ASD (Meyer et al., 2011), emerging evidence has also established links with other offspring CNS disorders, including depression, ADHD and bipolar depression (Knuesel et al.”
Background
Systematic meta-analysis of childhood social withdrawal in schizophrenia, and comparison with data from at-risk children aged 9–14 years
Matheson, S. L., Vijayan, H., Dickson, H., Shepherd, A. M., Carr, V. J., & Laurens, K. R. (2013) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2013.03.013 · Cited by 69
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“Finally, SCZ and autism share several genetic factors such as mutations in ProSAP2/Shank3 and environmental risk factors, such as zinc deficiency and pre- and perinatal inflammation (Meyer et al., 2011).”
Background
Microglial Function during Glucose Deprivation: Inflammatory and Neuropsychiatric Implications
Churchward, M. A., Tchir, D. R., & Todd, K. G. (2018) · Molecular Neurobiology · doi:10.1007/s12035-017-0422-9 · Cited by 63
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“prefrontal serotonin 5-HT(2) receptors in a rat model of psychiatric vulnerability.”
BackgroundInfluential
Interplay Between Peripheral and Central Inflammation in Autism Spectrum Disorders: Possible Nutritional and Therapeutic Strategies
Cristiano, C., Lama, A., Lembo, F., Mollica, M. P., Calignano, A., & Raso, G. M. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00184 · Cited by 60
“This relationship has been observed in pregnant obese women, leading to endothelial (Stewart et al., 2007), placental dysfunction (Leung and Bryant, 2000; Nordahl et al., 2008), and impaired fetal development contributing to the risk of ASD in children (Meyer et al., 2011).”
Background
Neurodevelopmental and neurological effects of chemicals associated with unconventional oil and natural gas operations and their potential effects on infants and children
Webb, E., Moon, J., Dyrszka, L., Rodriguez, B., Cox, C. S., Patisaul, H. B., Bushkin, S. C., & London, E. (2017) · Reviews on Environmental Health · doi:10.1515/reveh-2017-0008 · Cited by 57
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“Neuroinflammation during early fetal development caused by exposure to cytokine-releasing agents may be pathophysiologically relevant to the progression of schizophrenia (Meyer et al. 2011).”
Background
Maternal Bisphenol A Diet Induces Anxiety-Like Behavior in Female Juvenile with Neuroimmune Activation
Luo, G., Wang, S., Li, Z., Wei, R., Zhang, L., Liu, H., Wang, C., Niu, R., & Wang, J. (2014) · Toxicological Sciences · doi:10.1093/toxsci/kfu085 · Cited by 55
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Background
Impaired Interneuron Development in a Novel Model of Neonatal Brain Injury
Lacaille, H., Vacher, C., Bakalar, D., O’Reilly, J. J., Salzbank, J., & Penn, A. A. (2019) · eNeuro · doi:10.1523/eneuro.0300-18.2019 · Cited by 55
“In this model, the potentiation of inflammation by postnatal CSH may increase the risk of psychiatric-related neurobehavioral deficits by producing latent inflammation with microglial activation across a critical developmental time (Meyer et al., 2011).”
Background
Prophylactic (R,S)-ketamine selectively protects against inflammatory stressors
Mastrodonato, A., Cohensedgh, O., LaGamma, C. T., McGowan, J. C., Hunsberger, H. C., & Denny, C. A. (2020) · Behavioural Brain Research · doi:10.1016/j.bbr.2019.112238 · Cited by 48
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“A growing body of evidence suggests the involvement of inflammatory processes in the pathophysiology of psychiatric disorders, and a leading role of astrocytes in mediating neuroinflammation (Meyer, 2011; Meyer et al., 2011; Muller et al., 2013; Shastri et al., 2013).”
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“Maternal infections can, and do result in inflammatory responses (Gotsch et al., 2007; Agrawal and Hirsch, 2012; Burd et al., 2012), and these are intimately related to the onset of spontaneous labor and preterm birth (Burd et al., 2009; Brown, 2011; Meyer et al., 2011).”
Background
Prenatal immune activation alters the adult neural epigenome but can be partly stabilised by a n-3 polyunsaturated fatty acid diet
Basil, P., Li, Q., Gui, H., Hui, T. C. K., Ling, V. H. M., Wong, C. C. Y., Mill, J. S., McAlonan, G. M., & Sham, P. C. (2018) · Translational Psychiatry · doi:10.1038/s41398-018-0167-x · Cited by 47
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“In the last few decades, a strong consensus has developed around the immune aetiology of autism spectrum disorder (ASD), particularly after the description of a chronic microglial activation in brains of individuals with ASD.1 From then on, an increasing amount of studies have described the association and causative l…”
BackgroundInfluential
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Authors: MEYER, U., FELDON, J., & DAMMANN, O.
Affiliations: ETH Zurich (CH)
Tufts Medical Center (US)
Corresponding author: MEYER, URS
ORCID: MEYER, URS
DAMMANN, OLAF
Venue: Pediatric Research
Publisher: Springer Science and Business Media LLC
Published: 2011-05
Volume: 69
Issue: 5 Part 2
Pages: 26R-33R
ISSN: 0031-3998 (ISSN-L)
DOI: 10.1203/pdr.0b013e318212c196
PMC: PMC3086802
OpenAlex: W2011183628
Cited by: 357
References: 86
Citations by year: 2026: 7 · 2025: 7 · 2024: 14 · 2023: 20 · 2022: 13 · 2021: 18 · 2020: 19 · 2019: 22 · 2018: 30 · 2017: 31 · 2016: 30 · 2015: 36 · 2014: 32 · 2013: 32 · 2012: 30
FWCI: 1.83
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Pediatric Research (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Science Foundation
National Alliance for Research on Schizophrenia and Depression
European Commission (LSHM‐CT‐2006‐036534, 241778)
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (116719, 100309)
Eidgenössische Technische Hochschule Zürich (11 07/03)
National Institutes of Health
National Eye Institute (R21EY019253)
Topics: Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Keywords: schizophrenia, autism spectrum disorder, perinatal inflammation, prenatal infection, neuroinflammation, fetal development, shared pathogenesis, chronic inflammation, psychopathology, neuropathology
MeSH terms: Autistic Disorder, Female, Humans, Inflammation, Models, Theoretical, Pregnancy, Pregnancy Complications, Schizophrenia

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Schizophrenia and Autism: Both Shared and Disorder-Specific Pathogenesis Via Perinatal Inflammation?

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