Large-scale studies on the relationships between hair corticosteroids and depression, anxiety and cardiometabolic diseases in humans

Background: In pathological conditions (e.g. Cushing's disease) high cortisol levels cause mental disturbances as anxiety and depression, as well abdominal obesity and adverse cardiometabolic sequelae. It has been unclear how long-term measures of cortisol and cortisone are related to common psychiatric and cardiometabolic disorders. Methods:Weused a well-validated LC-MS/MS based method to measure cortisol and cortisone content in 3 cmhair samples of: (1) 1166 participants of the Netherlands Study of Depression and Anxiety (NESDA), with 266 participants having a recent diagnosis of depressive and/or anxiety disorder, 655 having remitted disorders, and 245 healthy controls, and (2) 3019 children participating in the populationbased GenerationR study. Results: Presence of a comorbid depressive and anxiety disorder was associated with increased hair cortisol levels (p = .031), as was the severity of depressive (p = .029) and anxiety symptoms (p = .069). Remitted disorders were not associated with altered cortisol (study 1). Hair cortisol and cortisone were significantly associated with risk of obesity (odd ratio (OR): 9.4 (3.3-26.9) and OR: 1.9 (1.0-3.5), respectively). Both corticosteroids were significantly positively associated with body mass index, and (abdominal) fat mass (study 2). Conclusions: Persons with current severe symptoms of depression and/or anxiety, but not those with remitted symptoms, show higher levels of hair cortisol, indicating chronic overactivation of the HPA-axis. In addition, hair cortisol and cortisone concentrations are strongly associated with an increased risk of childhood obesity and adverse body-fat distribution. Future research may reveal whether these are causal relations and may be a target for therapy.