Accumulated reports have indicated that depression may be linked to the lack of hippocampal neurogenesis, which is negatively influenced by neuronal nNOS-derived NO, thus suggesting that the overexpression of nNOS in the hippocampus is necessary for chronic stress-induced depression, and inhibiting nNOS signaling in the brain may mitigate these debilitating effects [79].‎ Moreover, the dysregulation of NO signaling can hinder the regenerative abilities of neural stem cells (NSCs) causing an exacerbation in cognitive impairment associated with depression. The gene discussed is NOS1; the disease is major depressive disorder.