LEP and major depressive disorder: In addition, following diabetes, dysfunction of the intestinal-cerebral axis is associated with disorders of hormones such as leptin, ghrelin, adiponectin, and melatonin, which leads to an increase in inflammatory factors in brain tissue, and ultimately, damage to the serotonergic, dopaminergic, and orexinergic systems can lead to anxiety and depression (Subba et al., 2021 ▶).