Beyond Muscle: New Review Illuminates the Cognitive and Emotional Landscape of Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) has long been characterized by its devastating physical toll, but a new narrative review underscores a broader clinical reality: the disease also significantly affects cognition, mental health, and psychosocial well-being. Published in Brain Sciences, the review integrates findings from neuroscience, psychology, and clinical care to reframe DMD as a condition with profound implications for the brain and mind—not just the muscles.

Mutations in the dystrophin gene, while directly responsible for muscle deterioration, also disrupt various dystrophin isoforms expressed in the brain—particularly Dp427, Dp140, and Dp71. These disruptions are now understood to influence cognitive development, neuropsychiatric vulnerability, and even social adaptability. Dystrophin deficiency in the hippocampus, cerebellum, and frontal cortex has been linked to impaired executive functions, language processing, and emotional regulation.

Cognitive impairment in DMD is non-progressive but prevalent. Full-scale IQ scores average one standard deviation below the population norm, with verbal IQ more severely affected than performance IQ. Language-based deficits—including challenges with verbal memory, comprehension, and processing speed—are especially common, and may significantly interfere with academic achievement. Mutations affecting Dp140 and Dp71 are associated with more severe intellectual disability and learning difficulties.

Psychiatric comorbidities also appear at elevated rates. Autism spectrum disorder occurs in up to 20% of individuals with DMD, and attention-deficit/hyperactivity disorder in as many as 32%, both well above general population estimates. Obsessive-compulsive disorder, anxiety, and depressive symptoms are also disproportionately observed. Notably, the authors caution that physical limitations—such as reduced mobility—may obscure or complicate standard assessments of hyperactivity or emotional expression.

Emerging evidence also suggests genotype–phenotype correlations. Individuals with mutations affecting multiple brain dystrophin isoforms, particularly downstream of exon 30, face higher risks of cognitive and psychiatric disorders. However, the relationship between genetic alterations and emotional symptoms appears more complex and likely influenced by environmental stressors, family coping strategies, and disease awareness.

Yet the review doesn’t dwell solely on deficits. It highlights a growing body of research exploring resilience, psychological flexibility, and positive adaptation in individuals with DMD. Despite increasing physical limitations, many report stable or even improving quality of life (QoL), especially when bolstered by strong family support and psychosocial resources. In some studies, QoL levels were more closely associated with environmental and emotional factors than with disease severity or mobility status.

Importantly, the self-reported well-being of youth with DMD often exceeds parental perceptions, pointing to a potential gap in how quality of life is externally judged versus internally experienced. Adolescents with DMD generally report average levels of emotional functioning, even when acknowledging social challenges such as reduced peer interaction.

The authors advocate for a shift from a strictly biomedical model to a more holistic, biopsychosocial approach in DMD care. They call for the integration of psychological assessment into routine clinical management, early identification of cognitive and emotional challenges, and greater access to interventions such as cognitive-behavioral therapy, psychoeducation, and family counseling.

As gene therapies and disease-modifying treatments continue to evolve, understanding the full neuropsychiatric and psychosocial profile of DMD becomes essential. This review offers a compelling argument that improving life with DMD means addressing the brain and the body—together.