Ghrelin's role in sleep and sleep deprivation: a narrative review

Deprivation of sleep (DS) is widespread in modern societies and is associated with cardiometabolic, cognitive, and psychiatric disturbances. Acute DS has also been reported to produce short-lived improvements in mood in some individuals with depression, suggesting the involvement of specific biological mediators. Ghrelin, a stomach-derived peptide with central actions in hypothalamic and limbic circuits, has emerged as a candidate linking DS with alterations in sleep, circadian regulation, mood, and cognition. Both acylated and unacylated isoforms exhibit distinct biological activities, and accumulating evidence points to roles in sleep architecture, stress responsivity, and neuroplasticity, as well as in disorders such as insomnia, obstructive sleep apnea, and narcolepsy. Experimental studies indicate that DS frequently coincides with changes in circulating ghrelin, although findings remain heterogeneous and influenced by methodological and contextual factors. Overall, ghrelin may contribute to the pathways through which DS influences emotional regulation and cognitive functioning. A more detailed understanding of its isoform-specific, sex-dependent, and circadian-stage effects could help guide future research and support the development of therapeutic approaches that complement existing strategies for mood and sleep disorders.