The suggested mechanisms that mediate insulin signaling and dopaminergic neurotransmission, including mitochondrial dysfunction [95,96,97], oxidative stress [98,99,100], impaired leptin [101,102] and purinergic signaling [103], and disrupted dopaminergic neurotransmission [104], are known to play important roles in the pathophysiology of depression. Here, INS is linked to major depressive disorder.