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Neonatal Cytokine Profiles Associated With Autism Spectrum Disorder
Open accessAbstract
Background Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that can be reliably diagnosed at age 24 months. Immunological phenomena, including skewed cytokine production, have been observed among children with ASD. Little is known about whether immune dysregulation is present before diagnosis of ASD.Methods We examined neonatal blood spots from 214 children with ASD (141 severe, 73 mild/moderate), 62 children with typical development, and 27 children with developmental delay as control subjects who participated in the Childhood Autism Risks from Genetics and the Environment study, a population-based case-control study. Levels of 17 cytokines and chemokines were compared across groups and in relation to developmental and behavioral domains.Results Interleukin (IL)-1β and IL-4 were independently associated with ASD compared with typical development, although these relationships varied by ASD symptom intensity. Elevated IL-4 was associated with increased odds of severe ASD (odds ratio [OR] = 1.40, 95% confidence interval [CI], 1.03, 1.91), whereas IL-1β was associated with increased odds of mild/moderate ASD (OR = 3.02, 95% CI, 1.43, 6.38). Additionally, IL-4 was associated with a higher likelihood of severe ASD versus mild/moderate ASD (OR = 1.35, 95% CI, 1.04, 1.75). In male subjects with ASD, IL-4 was negatively associated with nonverbal cognitive ability (β = -3.63, SE = 1.33, p = .04).Conclusions This study is part of a growing effort to identify early biological markers for ASD. We demonstrate that peripheral cytokine profiles at birth are associated with ASD later in childhood and that cytokine profiles vary depending on ASD severity. Cytokines have complex roles in neurodevelopment, and dysregulated levels may be indicative of genetic differences and environmental exposures or their interactions that relate to ASD.
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“Several pre-clinical and clinical studies found increased levels of inflammatory markers in the systemic circulation of ASD individuals when compared to neurotypical controls, such as increased IL-1B [107, 108] and heightened systemic TNF-alpha [108–110].”
From Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders (2022) · cites this paper as [107]
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“The inclusion criteria were the following: (1) original articles; (2) case-control studies; (3) sample type: peripheral blood, plasma, or serum; (4) analysis of immune cell percentages; (5) analysis of cytokine levels in plasma, serum, or bloodspot; (6) analysis of cytokine levels in immune cells at baseline or after…”
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“Indeed, in neonatal blood spots collected from ASD patients and normally developing control children, the presence of elevated concentrations of IL1β and IL4 were independently associated with ASD [48].”
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Metadata
- Authors
- Krakowiak, P., Goines, P. E., Tancredi, D. J., Ashwood, P., Hansen, R. L., Hertz-Picciotto, I., & Van de Water, J.
- Affiliations
- University of California, Davis (US)
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2017-03
- Volume
- 81
- Issue
- 5
- Pages
- 442-451
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC4753133
- OpenAlex
- W1409858176
- Cited by
- 249
- References
- 65
- Citations by year
- 2026: 15 · 2025: 14 · 2024: 34 · 2023: 32 · 2022: 35 · 2021: 16 · 2020: 27 · 2019: 26 · 2018: 28 · 2017: 12
- FWCI
- 10.02
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (P01 ES11269 and R01 ES015359)
- U.S. Environmental Protection Agency through the Science to Achieve Results (STAR) (R829388, R833292)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- autism spectrum disorder, IL-1β, IL-4, immune dysregulation, ASD severity, biomarkers, nonverbal cognitive ability, developmental delay, chemokines, brain development
- MeSH terms
- Autism Spectrum Disorder, Child, Preschool, Female, Humans, Male, Severity of Illness Index, Biomarkers, Interleukin-4, Case-Control Studies, Cytokines, Interleukin-1beta
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