The link between stress and hyperactivity in a marmoset model of autism

lab animal Research highlights Autism spectrum disorder https://doi.org/10.1038/s41684-026-01707-8 The link between stress and hyperactivity in a marmoset model of autism Check for updates Hyperactivity frequently co-occurs with autism spectrum disorder (ASD). However, the biological mechanisms underlying ASD and its relationship to hyperactivity remain poorly understood. To explore this association, a study in Translational Psychiatry used valproic acid (VPA)–exposed common marmosets, a nonhuman primate model of ASD that closely models human social behavior and ASD-related transcriptomic profiles. Using noninvasive ultraminiature activity tracker Actiwatch® devices, researchers recorded home-cage activity in adult VPA-exposed and unexposed (UE) marmosets. Rather than relying solely on conventional summary variables of activity, the team applied analytical approaches, including cosinor rhythm analysis, behavioral organization metrics and Sample Entropy to Lab Animal | Volume 55 | March 2026 | 73 quantify temporal structure and irregularity in activity patterns and isolate the hyperactivity component of ASD. VPA-exposed marmosets showed significantly higher Sample Entropy than UE marmosets, indicating more unpredictable and disorganized behavioral dynamics. Average hourly activity of VPA-exposed marmosets positively correlated with salivary cortisol levels measured upon waking. Also, moderate positive associations were observed between cortisol and both Sample Entropy and resting-period distribution parameters. These findings suggest that heightened and irregular activity in the ASD model is linked to stress-related physiological responses. In juvenile marmosets, activity was further examined in a three-chamber social test. VPA-exposed juveniles displayed increased locomotor activity when in the presence of an unfamiliar adult compared with the control group, stressing the context- and age-dependent variability in hyperactivity phenotypes. Together, these findings show alterations in activity organization and stress regulation in VPA-exposed marmosets, positioning this model as a powerful platform for dissecting the relationship between hyperactivity, stress and social dysfunction in ASD. By integrating wearable technology supplemented with advanced behavioral analytics, the study shows an effective replication of the symptoms exhibited with patients with ASD. These results open the avenue for the more precise testing of targeted pharmacological, genetic or behavioral interventions tailored to specific ASD-related activity and stress profiles. Jorge Ferreira Original reference: Nakamura, M. et al. Transl. Psychiatry 16, 64 (2026) 73  (...truncated)