Enhanced corticotropin response to corticotropin-releasing hormone as a predictor of mania in euthymic bipolar patients

Background. Dysregulation of corticotropin (ACTH) and cortisol response aft er corticotropin-releasing hormone (CRH) stimulation has been reported in b ipolar patients. Most findings involve the pathophysiology of the depressiv e phase of the illness and its prediction. However, the possible predictive value of the CRH challenge test with respect to manic episodes remains unk nown. Methods. The ACTH and free cortisol response to the injection of 100 mu g o f synthetic human CRH and plasma cortisol-binding globulin levels were meas ured in 42 lithium-treated patients suffering from Research Diagnostic Crit eria bipolar I disorder in remission, and 21 age- and sex-matched normal co ntrols. A 1-year follow-up was conducted to assess any possible relationshi p between outcome and the hormonal response. Results. Bipolar patients showed higher baseline and peak ACTH concentratio ns than control subjects. A higher area under ACTH concentration curve afte r CRH stimulation predicted manic/hypomanic relapse within 6 months by mult iple regression analysis. Conclusion. Bipolar patients in remission show mild abnormalities in ACTH l evels before and after CRH stimulation. CRH challenge may be a potentially good predictor of manic or hypomanic relapse in remitted bipolar patients.