Preliminary Evidence That Blood Extracellular Nicotinamide Phosphoribosyltransferase Increases with Antidepressant Response to Chronotherapeutics and to Monoaminergic Drugs

The purpose of the present study is to provide a preliminary evidence of the possible involvement of extracellular nicotinamide phosphoribosyltransferase (eNAMPT) in antidepressant response. NAMPT is the major regulator of the cellular availability of nicotinamide adenine dinucleotide (NAD+), and, when released from the cells, it influences activity, energy expenditure, and neurotransmitter levels in mammals. We studied changes of blood circulating eNAMPT before and after treatment in 46 patients with major depressive disorder, treated with monoaminergic antidepressant drugs for 1 month, or with Bipolar Disorder, treated with antidepressant chronotherapeutics (repeated total sleep deprivation combined with light therapy) for 1 week. Participants showed high individual variation in eNAMPT before and after treatment. The increase in circulating eNAMPT concentration was associated with individual benefit from treatment independent of diagnosis or type of treatment. eNAMPT increase was not necessary to achieve response, but the best antidepressant effects were observed in patients showing the highest increase. These findings suggest that eNAMPT may facilitate treatment efficacy rather than acting as a direct mechanism of symptom reduction. Results are in agreement with the literature affirming a possible role of NAD+ homeostasis and mitochondrial mechanisms in mood disorders. If confirmed, they may pave the way to identify new targets for the treatment of depression.