Neurodegeneration Within the Spectrum of Pervasive Developmental Disorders

The historical framework of pervasive developmental disorders (PDD) continues to hold relevance despite its replacement by the Neurodevelopmental Disorders category in DSM-5. Emerging evidence indicates that neurodevelopmental and neurodegenerative mechanisms, traditionally considered distinct, may intersect in individuals formerly classified under PDD. Shared biological pathways, including aberrant synaptic pruning, mitochondrial dysfunction, immune dysregulation, and impaired proteostasis, suggest potential long-term neurological vulnerability, particularly in autism spectrum disorder (ASD), the principal diagnosis within the former PDD group. Clinical overlap is most evident in "bridging conditions" such as Rett syndrome, <i>MECP2</i>-related disorders, and Fragile X-associated tremor/ataxia syndrome, which illustrate the continuum between developmental and degenerative processes. As individuals with ASD increasingly reach older adulthood, gaps in longitudinal data hinder understanding of risks related to cognitive decline, dementia, and atypical aging. Additionally, chronic stress, psychiatric comorbidities, and sensory dysregulation may further influence neuroinflammatory and neurodegenerative pathways. Recognizing these intersections provides opportunities for early neuroprotective interventions and biomarker-driven risk stratification. This editorial argues for a lifespan-oriented, integrative model that bridges developmental and degenerative neuroscience, aiming to better characterize and support the long-term neurological health of individuals previously encompassed by the PDD construct.