In a rat model of depression–insomnia co-morbidity with CUMS combined with sleep deprivation, dysfunction in the PINK1/Parkin signaling pathway led to impaired mitophagy in the pineal gland, which in turn triggered a significant reduction in 5-HT levels and an increase in the release of markers of oxidative stress (ROS, Malondialdehyde). Here, PRKN is linked to major depressive disorder.