Introduction: Elevated levels of the hypothalamic-pituitary-adrenal axis hormone cortisol are a frequently replicated finding in major depressive disorder (MDD). However, the current state of research is inconclusive as to whether hypercortisolism represents a trait- or state-like biological signal of MDD. The aim of the present study was to investigate, for the first time, whether cortisol in fingernails, a highly accessible tissue, could distinguish currently remitted individuals with MDD from healthy controls. A further aim was to identify potential confounders of nail cortisol. Methods: A total of N = 100 individuals from the general population were recruited. A structured clinical interview was administered, which resulted in two groups: n = 48 with lifetime MDD and n = 52 healthy controls. All participants answered questions on sociodemographic, lifestyle, and psychosocial characteristics. They also grew their nails for 14 days and cut them for the subsequent determination of cortisol. Results: The groups differed in their nail cortisol concentrations, such that the individuals with lifetime MDD had significantly higher concentrations than the healthy controls (p = 0.041). Within the group of individuals with lifetime MDD, the number of experienced episodes was significantly correlated with cortisol (p = 0.011). Income emerged as the only significant confounder of cortisol (p = 0.008). Conclusion: Elevated fingernail cortisol appears to be a biological signal of MDD, even in the absence of a current major depressive episode. Its high accessibility and robustness render it a promising methodology for remote research as well as for the integration of biomarkers into clinical research and practice.
