Integrating Circadian Rhythm and Neurobiology in Precision Medicine: A Novel Approach for Treating Severe Autism Through the Exploration of Time Cells and Genetic Mechanisms

Rodent SHANK3 model: Circadian disruption worsens repetitive grooming behaviors. Restoring circadian alignment with light entrainment improves social exploration.

SYNGAP1 haploinsufficient mice: Exhibit disrupted circadian gene expression and impaired time cell coding. NMDA receptor modulators partially restore cognitive performance.

Clinical melatonin trials: Demonstrate modest improvement in sleep and social responsiveness, though effect sizes are small. These trials underscore the importance of developing more potent and selective circadian-targeted drugs.

Future directions include circadian-phase–specific drug screening, high-throughput identification of small molecules targeting TTFL regulators, and use of time cell activity as a biomarker for therapeutic efficacy. Ultimately, integrating circadian neurobiology with genetic diagnostics may provide a path to novel, mechanism-based therapies for severe autism.

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Peter De Ceuster. (2026). Integrating Circadian Rhythm and Neurobiology in Precision Medicine: A Novel Approach for Treating Severe Autism Through the Exploration of Time Cells and Genetic Mechanisms

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