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

Autism Spectrum Disorder (ASD) represents a highly heteroge-
neous group of neurodevelopmental conditions defined by core symp-
toms of impaired social communication and restricted, repetitive be-
haviors. Severe autism cases, which often include intellectual dis-
ability, epilepsy, and profound functional impairments, remain par-
ticularly resistant to existing therapeutic interventions. Recent ge-
nomic discoveries—many spearheaded by Silvia De Rubeis and col-
leagues—have highlighted the critical role of synaptic, transcriptional,
and chromatin regulatory pathways in ASD. These insights have shifted
focus toward a mechanistic understanding of ASD at the molecular
level.
At the same time, circadian biology has emerged as a central reg-
ulator of neurodevelopment, synaptic plasticity, and behavior. Circa-
dian rhythms, orchestrated by transcriptional–translational feedback
loops (TTFLs) in the suprachiasmatic nucleus (SCN), regulate thou-
sands of genes involved in metabolism, neurotransmission, and DNA
repair. Disruption of these rhythms exacerbates excitatory–inhibitory
imbalance, a hallmark of ASD pathophysiology.
The convergence of circadian regulation, time cell dynamics, and
ASD genetics creates a promising landscape for therapeutic innova-
tion. A precision medicine framework that incorporates circadian bi-
ology could enable the rational design of novel drugs targeting oscil-
latory mechanisms at the molecular level.