Diminished Motivation for Voluntary Exercise and Metabolic Dysfunction in Psychiatric Disorders: A Behavioral Perspective on Autism Spectrum Disorder and Depression.

Abstract

Purpose: This study investigated spontaneous locomotor activity and metabolic phenotype in animal models of autism spectrum disorder (ASD) and major depressive disorder (MDD), with a focus on motivation to engage in voluntary exercise.

Methods: Spontaneous locomotion, voluntary wheel running, and metabolic phenotypes were assessed in Shank3B-knockout mice (ASD model) and stress-susceptible mice exposed to chronic restraint stress (CRSTSUS, MDD model) using indirect calorimetry and behavioral tests.

Results: Shank3B-knockout mice exhibited self-injurious repetitive behaviors resulting in skin lesions, while CRSTSUS mice showed behavioral despair indicative of stress vulnerability, along with a marked reduction in spontaneous locomotor activity and decreased motivation for voluntary exercise. Metabolic dysregulation was evident, including alterations in oxygen consumption, carbon dioxide production, respiratory exchange ratio, and energy expenditure.

Conclusion: Behavioral and metabolic alterations in psychiatric disorders are closely linked, with reduced motivation for exercise emerging as a salient phenotypic signature. These findings highlight the need for targeted interventions that restore intrinsic motivation and energy balance. Future research should focus on elucidating the underlying mechanisms and developing therapies to enhance physical activity engagement in psychiatric conditions.