Neuropeptide Y (NPY) has been implicated in stress resilience and depression, yet findings on circulating levels in major depressive disorder (MDD) remain inconsistent, possibly due to confounders such as age, sex, and body mass index (BMI). This study aimed to assess NPY concentrations in individuals with MDD and in matched controls from the Danish PRISME cohort of public-sector employees.

We investigated plasma NPY (p-NPY) concentrations in 77 adults with a current ICD-10 diagnosis of MDD and 77 age- and sex-matched controls. The plasma samples were analysed using a commercial ELISA kit. A general linear model examined the effects of group, age, sex, and BMI, including a sex-by-group interaction. Plasma NPY values were log10-transformed prior to analysis.

p-NPY concentrations did not differ significantly between MDD and controls (p = .785). No main effect of sex or sex-by-group interaction was observed (all p > .17), and BMI was unrelated to p-NPY (p = .917). By contrast, age was a strong predictor (β = .38, p < .001), explaining 13% of the variance in p-NPY levels.

In this community-based sample of high-functioning individuals with MDD, we found no evidence of altered p-NPY concentrations compared with matched controls. Instead, age emerged as a robust determinant of circulating NPY levels, independent of depression status and BMI, after adjustment for sex. These findings suggest that peripheral NPY variation may be more strongly related to demographic factors than to depression per se in this type of cohort and may not generalise to more severe or chronic forms of the disorder.