Anxiety, repetitive and restricted behaviors and interests, and social communication in autistic adults: an exploratory analysis of a phase 3, randomized clinical trial

Autistic adults are highly vulnerable to mental health problems and yet, our understanding of co-occurring psychiatric disorders in this population is limited. Anxiety is one of the most pervasive psychiatric disorders that affects autistic adults. Here, we investigated the association between anxiety, restricted and repeated behaviors and interests (RRB), and challenges in social communication and interaction (CSCI) as a post-hoc analysis of a large Phase 3 clinical trial (NCT03504917). The study enrolled 322 adults (64 females, age 27 ± 10) assessed at baseline and weeks 12, 24, 36, and 52, with the Hamilton Anxiety Rating Scale, the Repetitive Behaviors Scale - Revised, and the Vineland-II for CSCI. All analyses were blind to treatment assignment as the primary study analysis had found no treatment effects. Anxiety levels were significantly correlated with RRB and CSCI at baseline (RRB: r = 0.19, P < 10^-3; CSCI=-0.13, P = 0.02) and across the entire study (RRB: r = 0.22, P < 10^-3; CSCI=-0.16, P < 0.01). However, a mediation analysis revealed that the effect of CSCI on anxiety was fully explained by RRB (P = 0.17). While no causal relationship between both symptom domains has been established yet, our findings suggest that anxiety symptoms are associated with increased RRB, warranting further exploration of a potential causal association and implications for treatment.Clinical trial registration: The research presented is registered at ClinicalTrials.gov with the code NCT03504917.