Long-term cortisol in bipolar disorder: Associations with age of onset and psychiatric co-morbidity

Introduction: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is hypothesized to play a role in the pathogenesis of bipolar disorder (BD). Conflicting results have been reported when saliva or serum was used to measure cortisol levels. A recently developed method is to measure cortisol in scalp hair, with 1. cm of scalp hair representing 1 month. We studied whether there are differences in long-term hair cortisol levels between BD patients and healthy individuals and whether there are associations between hair cortisol and disease characteristics. Methods: Hair samples were collected in 100 BD patients and 195 healthy controls. Long-term cortisol levels were determined in 3. cm hair segments. Saliva samples were collected on two consecutive evenings. Documented disease characteristics were disease state, age of onset and psychiatric co-morbidity. Results: Hair cortisol levels were not statistically different in BD patients compared to healthy controls (p= 0.233) and were not associated with the disease state at the moment of sample collection (p= 0.978). In the subgroup of patients with age of onset ≥30 years, hair cortisol levels were significantly elevated compared to the subgroup with age of onset <30 years and to healthy controls (p= 0.004). Psychiatric co-morbidity was associated with elevated cortisol levels (44.87 versus 31.41. pg/mg hair; p= 0.021), with the exclusion of panic disorder, which was associated with decreased cortisol levels (22.13 versus 34.67 pg/mg hair; p= 0.019). Conclusions: Elevated long-term cortisol levels might play a role in a subgroup of patients with BD. There may be differences in pathogenesis of younger and older onset BD suggesting two different disease entities.

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