Autonomic dysregulation has been recently reported as a feature of autism spectrum disorder (ASD). However, the nature of autonomic atypicalities in ASD remain largely unknown. The goal of this study was to characterize the cardiac autonomic profile of children with ASD across four domains affected in ASD (anxiety, attention, response inhibition, and social cognition), and suggested to be affected by autonomic dysregulation.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting more than 1% of children. It is characterized by social communication deficits and repetitive behaviors/restricted interests. In the absence of any medications known to improve core symptom domains, parents often use complementary alternative treatments, including omega-3 fatty acid supplements. We conducted a 6-month, randomized, placebo controlled trial of omega-3 fatty acid supplements (1.5 g) vs placebo in children 2 to 5 years of age with ASD. Primary outcome measures included the autism composite score of the Pervasive Developmental Disorders Behavioral Inventory (PDDBI) and the externalizing problems score of the Behavior Assessment System for Children (BASC-2). Secondary outcome measures included clinical global improvement (Clinical Global Impression-Improvement (CGI-I)), adaptive function (Vineland Adaptive Behavior Scale (VABS-II)), and language gains (Preschool Language Scale (PLS-4)), as well as safety. Exploratory analysis investigated potential correlations between changes in cytokine profiles and treatment response. Thirty-eight participants were randomized in a 1:1 fashion. There was no significant difference between groups on the 0- to 24-week change in PDDBI autism composite scores (p = 0.5). There was a significant group by week interaction on the BASC-2 externalizing problem score, with participants randomized to the treatment group demonstrating worsening scores (p = 0.02). There was no statistically significant week by group effect on either adaptive function (p = 0.09) or language (p = 0.6). Omega-3s were relatively well tolerated. Changes in cytokines during the study did not significantly correlate with treatment response. This study does not support high dose supplementation of omega-3 fatty acids in young children with ASD. Clinicaltrials.gov NCT01248728 . Registered 22 November 2010.
Autism spectrum disorder (ASD) has been associated with autonomic atypicalities, although the nature of these differences remains largely unknown. Moreover, existing literature suggests large variability in autonomic function in ASD, motivating the need to examine the existence of subgroups that exhibit more homogeneous autonomic features. Electrodermal activity (EDA), a non-invasive physiological indicator of autonomic activity, was measured in typically developing children (n = 33) and those with ASD (n = 38) as participants performed tasks that elicit anxiety, attention, response inhibition, and social cognition processes. The ASD group was divided into low- (n = 18) and high-anxiety (n = 20) participants, and the groups were compared to mean EDA level and electrodermal reactions frequency (EDR). The ASD group had a significantly blunted mean EDA response to the anxiety tasks (p < 0.004). The EDR response to all tasks, except response inhibition, was also blunted in the ASD group (p < 0.04). For this group, EDR frequency during the anxiety and social cognition tasks was negatively correlated with behavioral scores in the domains that were probed by each task (p < 0.002). The high-anxiety ASD group showed significantly decreased mean EDA compared to both the low-anxiety ASD group (p = 0.02) and the typically developing control group (p = 0.04). The high-anxiety ASD group also had significantly more severe symptoms than the low-anxiety ASD group on domains related to anxiety, attention, rule breaking, aggression, obsessions and compulsions, and depression. Our results suggest atypical autonomic function in children with ASD, specifically with respect to sympathetic activity. Moreover, anxiety symptomatology defined subgroups with distinct physiological and behavioral profiles. Overall, the results add to the body of literature supporting autonomic dysfunction in ASD and highlight the role of anxiety and autonomic features in explaining the variability in the autism spectrum.