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 1cm 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.