GHRL and depressive disorder: The highest expression of ghrelin receptors is found within the brain.544,548 The central ghrelin signaling plays a pivotal role in diverse physiological functions, including the regulation of food intake, hippocampal synaptic plasticity and neurogenesis, anxiety, depression, and cognitive function.544,549–551 Notably, age-related reductions in ghrelin signaling have been associated with a decline in cognitive function.551 The gut microbiome, along with its metabolites, has been reported to modulate ghrelin secretion and CNS functions.552,553