Neurotransmitter Regulation of Circadian Rhythms and Its Role in Sleep Disorders

ABSTRACT This review examines the neurobiological mechanisms governing circadian rhythm regulation and their disruption in sleep–wake disorders. Endogenous circadian clocks, coordinated by the suprachiasmatic nucleus, synchronize physiological and behavioral functions across a 24‐h cycle. Modern lifestyle factors such as artificial lighting, shift work, and irregular sleep schedules increasingly disrupt this synchronization, leading to chronic circadian misalignment. Such disruption is strongly associated with metabolic disorders, cardiovascular disease, and neuropsychiatric conditions. The review focuses on the role of key neurotransmitters, including serotonin, dopamine, GABA, glutamate, and melatonin, in maintaining circadian stability and sleep–wake regulation. Serotonin and dopamine contribute to photic and non‐photic entrainment, while GABA and glutamate regulate inhibitory‐excitatory balance and phase resetting within the suprachiasmatic nucleus. Melatonin functions as the primary hormonal signal of darkness, reinforcing circadian phase and modulating clock gene expression. Dysregulation of these neurochemical systems contributes to disorders such as insomnia, delayed sleep phase disorder, shift work disorder, and jet lag, often influenced by genetic predisposition and environmental stressors. Therapeutic approaches now target orexin signaling, melatonin pathways, and circadian timing through pharmacological, behavioral, and neuromodulatory strategies. Advances in wearable technologies and digital phenotyping enable individualized assessment and chronotherapy‐based interventions. These developments highlight the importance of integrating neurotransmitter dynamics with circadian biology to improve diagnosis and treatment strategies in sleep medicine. Precision‐based circadian interventions offer a promising direction for restoring sleep health and biological synchrony in modern populations.