Preliminary evidence that blood extracellular nicotinamide phosphoribosyltransferase increases with antidepressant response to chronotherapeutics and to monoaminergic drugs

Mar 28, 2026International clinical psychopharmacology

Early signs that a blood enzyme rises with antidepressant response to timing-based therapy and common antidepressant drugs

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Abstract

Changes in circulating extracellular nicotinamide phosphoribosyltransferase (eNAMPT) were observed in 46 patients with major depressive disorder and bipolar disorder.

Individual variations in eNAMPT levels were noted before and after treatment among participants.
An increase in eNAMPT concentration was associated with individual treatment benefits, regardless of diagnosis or treatment type.
The highest antidepressant effects correlated with the greatest increases in eNAMPT levels.
While eNAMPT increase is not essential for treatment response, it may enhance treatment efficacy.
Findings support a potential link between NAD+ regulation and mood disorders.

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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.

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Preliminary evidence that blood extracellular nicotinamide phosphoribosyltransferase increases with antidepressant response to chronotherapeutics and to monoaminergic drugs

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