Sex-specific Differences in the Dynamics of Cocaine- and Amphetamine-regulated Transcript and Nesfatin-1 Expressions in the Midbrain of Depressed Suicide Victims Vs. Controls

An intriguing novel pathophysiological insight into mood disorders is the notion that one's metabolic status influences mood. In rodents, cocaine- and amphetamine-regulated transcript (CART) and nesfatin-1/NUCB2 have not only been implicated in metabolism, but in the pathobiology of anxiety and depressive-like behaviour, however they have not previously been investigated in depressed subjects. Both peptides are highly expressed in centrally projecting neurons in the Edinger-Westphal nucleus (EWcp) in the midbrain. The EWcp has been implicated in stress adaptation and stress-related mood disorders like major depressive disorder in a sex-specific manner. This is intriguing, given the fact that females have higher prevalence of mood disorders. Here, we hypothesized that the expression of CART and nesfatin-1 in EWcp would exhibit a sex-specific difference between depressed suicide victims vs. controls. We found that CART and nesfatin/NUCB2 colocalized in the human EWcp, and that CART mRNA content was much higher in both male (×3.8) and female (×5.9) drug-free suicide victims than in controls (persons who died without any diagnosed neurodegenerative or psychiatric disorder). Similarly, NUCB2 mRNA content was also higher (×1.8) in male suicides, whereas in female suicide victims, these contents were ×2.7 lower compared to controls. These observations are the first to show changes in the dynamics of CART and nesfatin/NUCB2 expressions in the midbrain of drug-free depressed suicide victims vs. controls. This article is part of a Special Issue entitled 'Anxiety and Depression'.