Biomarkers of Change in Social Impairment and Aberrant Behaviors Among Children with Autism

Background: Inflammation, as evidenced by abnormal cytokine levels, may interfere with neuronal development and activity resulting in social and behavioral impairments. Studies show that both the core deficits and associated aberrant behaviors in autism may be associated with altered cytokine levels, and fatty acid supplementation may alter cytokine production and release. The extent to which changes in cytokine levels are associated with changes in core symptoms and behaviors of autism is not known.

Objectives: To examine associations between fatty acid supplementation, cytokine level changes, and changes in behavior among children aged 5 to 12 years with ADOS-confirmed autism.

Methods: Plasma fatty acid and cytokine measures (TNF alpha, IL-1 beta, IFN gamma, IL-10) were analyzed pre- and post-intervention of 12 weeks of unsaturated fatty acid supplementation (n=58). These measures were correlated with changes on several behavioral scales: the Aberrant Behavior Checklist (ABC) for parents, the Pervasive Developmental Disorder Behavior Inventory (PDD-BI), and the Clinical Global Impressions (CGI) Scale. Pearson’s correlation coefficients were calculated for changes in fatty acid and cytokine levels, and changes in behaviors based on the ABC, PDD-BI, and CGI scores.

Results: Significant correlations between behavior change scores and cytokine change scores were found. Changes in IFN Gamma levels were associated with a broad range of changes in scores on both the PDD-BI and ABC, including changes in aggressiveness, arousal regulation problems, approach/withdrawal problems, expressive language, expressive social communications abilities, specific fears, learning, memory, and receptive language, receptive/expressive social communications abilities, ritualisms/resistance to change, semantic pragmatic, social approach behaviors problems, social pragmatic problems, hyperactivity/noncompliance, stereotypic behavior, and inappropriate speech. Changes in sensory/perceptual approach scores were also associated with changes in IL-1 beta levels. TNF alpha and IL-10 changes were not correlated with behavioral changes in any domain. Changes in EPA levels also significantly correlated with changes in autism composite scores.

Conclusions: The correlated changes in cytokine levels as biomarkers of inflammation with changes in behavioral scores extends previous findings that autism is associated with various immune system abnormalities. Results may provide a clue as to the mechanism of how these behavioral changes occur, and suggest that more direct methods of reducing inflammation in autism may be appropriate for further study.