Neuroinflammatory Biomarkers in Autism Spectrum Disorder: A Systematic Review and Meta-analysis
Anderson Corin1, Mariana Letícia Maximiano2, Maria Clara Lima3, Vitória Mendonça4, Adil Ahmed5, Hellen Mota1, Beatriz Gerente6, Soraya Bussiki1, Wagner Rios-Garcia7, Diogo Santos8, Wyllians Borelli9
1Federal University of Pelotas, 2Federal University Fluminense, 3Pernambuco School of Health, 4University of Miami, Bascom Palmer Eye Institute, 5Department of Medicine, Northwest School of Medicine, 6University of Southern Santa Catarina, 7Faculty of Medicine, National University of San Luis Gonzaga, 8Santa Casa de São Paulo, 9Department of Morphological Sciences, UFRGS
Objective:
This updated and unprecedented systematic review aims to determine whether neuroinflammatory markers were associated with ASD.
Background:
Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by deficits in social communication and the presence of restricted or repetitive behaviors. The pathological process of ASD is multifaceted, yet the precise neurobiological mechanisms remain elusive.
Design/Methods:
We systematically reviewed articles in PubMed, Scopus, Cochrane, Embase and Web of Science from inception until November, 2024. Keywords included “Autism Spectrum Disorder”; “neuroinflammation” and "pro-inflammatory cytokines.” Abstracts were screened independently by two authors, and any discrepancies were resolved with a senior investigator. The primary endpoint was to evaluate the mean concentration differences of blood, plasma and serum biomarkers between patients with ASD and controls. The study followed the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines.
Results:
Of the 3221 articles imported for screening, 71 studies carried out between 2011 and 2023 were included. Overall, 47 neuroinflammatory biomarkers were identified. Among those, 37 pro-inflammatory biomarkers, and 10 anti-inflammatory biomarkers. Among pro-inflammatory markers, IL-1β levels were consistently elevated in ASD compared with controls (SMD = 0.37, p < 0.01), with increases observed in both plasma (SMD = 0.24, p = 0.01) and serum (SMD = 0.55, p = 0.04). Compared with controls, plasma IFN-γ (SMD = 0.35, p = 0.04) levels and IL-12 (SMD = 2.35, p < 0.01) were also elevated in ASD . Regarding anti-inflammatory cytokines, significant increases in IL-4 levels were found in both plasma (SMD = 0.25, p = 0.03) and plasma and serum samples (SMD = 0.30, p < 0.01).
Conclusions:
A myriad of neuroinflammatory biomarkers were altered in ASD patients, with 11 exhibiting statistical significance for ASD. Our findings indicate that neuroinflammatory biomarkers may be a pivotal neurobiological pathway in ASD. Further studies may elucidate the interplay between neuroinflammatory processes, genetic predispositions, and environmental triggers could pave the way for improved outcomes for individuals with ASD.
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.