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Cytokine aberrations in autism spectrum disorder: a systematic review and meta-analysis

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Abstract

The role of non-diagnostic features in the pathophysiology of autism spectrum disorders (ASDs) is unclear. Increasing evidence suggests immune system alterations in ASD may be implicated in the severity of behavioral impairment and other developmental outcomes. The primary objective of this meta-analysis was to investigate if there is a characteristic abnormal cytokine profile in ASD compared with healthy controls (HCs). We identified relevant studies following a search of MEDLINE, EMBASE, PsycINFO, Web of Knowledge and Scopus. A meta-analysis was performed on studies comparing plasma and serum concentrations of cytokines in unmedicated participants with ASD and HCs. Results were reported according to PRISMA statement. Seventeen studies with a total sample size of 743 participants with ASD and 592 HC were included in the analysis. Nineteen cytokines were assessed. Concentrations of interleukin (IL)-1beta (P<0.001), IL-6 (P=0.03), IL-8 (P=0.04), interferon-gamma (P=0.02), eotaxin (P=0.01) and monocyte chemotactic protein-1 (P<0.05) were significantly higher in the participants with ASD compared with the HC group, while concentrations of transforming growth factor-β1 were significantly lower (P<0.001). There were no significant differences between ASD participants and controls for the other 12 cytokines analyzed. The findings of our meta-analysis identified significantly altered concentrations of cytokines in ASD compared to HCs, strengthening evidence of an abnormal cytokine profile in ASD where inflammatory signals dominate.

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Acknowledgements

We thank Melanie Reuss for assisting with the independent screening of titles, abstracts and full-text articles and subsequent assessment of eligibility. We acknowledge the support of National Health and Medical Research Council project grant (1043664) and Career Development Fellowship (1061922) to Associate Professor Guastella and an Australia Fellowship (494914) to Professor Hickie.

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Ian B Hickie is a member of the Medical Advisory Panel for BUPA Health Insurance (Australia) and also a Board Member of Psychosis Australia Trust. From 2012, he is a Commissioner in Australia’s new National Mental Health Commission. He was until January 2012 a director of headspace: the national youth mental health foundation. Professor Hickie was previously the chief executive officer (till 2003) and clinical adviser (till 2006) of beyondblue, an Australian National Depression Initiative. He is supported principally for clinical research in depression and health services and population health initiatives related to anxiety and depression by an NHMRC Australian Medical Research Fellowship (2007–2012). He has led projects for health professionals and the community supported by governmental, community agency and pharmaceutical industry partners (Wyeth, Eli Lily, Servier, Pfizer, AstraZeneca) for the identification and management of depression and anxiety. He has received honoraria for presentations of his own work at educational seminars supported by a number of non-government organizations and the pharmaceutical industry (including Pfizer, Servier and AstraZeneca). He has served on advisory boards convened by the pharmaceutical industry in relation to specific antidepressants, including nefazodone, duloxetine and desvenlafaxine. He leads a new investigator-initiated study of the effects of agomelatine on circadian parameters (supported in part by Servier but also by other NHMRC funding) and has participated in a multicentre clinical trial of the effects of agomelatine on sleep architecture in depression and a Servier-supported study of major depression and sleep disturbance in primary care settings. In addition to national and international government-based grant bodies, investigator-initiated mental health research at the BMRI, he has been supported by various pharmaceutical manufacturers (including Servier and Pfizer) and not-for-profit entities (including the Heart Foundation, beyondblue and the BUPA Foundation).

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Masi, A., Quintana, D., Glozier, N. et al. Cytokine aberrations in autism spectrum disorder: a systematic review and meta-analysis. Mol Psychiatry 20, 440–446 (2015). https://doi.org/10.1038/mp.2014.59

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