Changes in Brain-Derived Neurotrophic Factor Following Treatment with Mifepristone in Bipolar Disorder and Schizophrenia

Abstract

Brain-derived neurotrophic factor (BDNF) is stress-responsive and has been implicated in a number of disparate neuropsychiatric disorders. Glucocorticoid antagonists have been shown to have beneficial effects on mood and cognitive function in bipolar disorder but not in schizophrenia. The aim of the present study was to investigate BDNF levels in patients with bipolar disorder and schizophrenia before and after treatment with the glucocorticoid receptor antagonist mifepristone. Peripheral BDNF levels were measured in patients with bipolar disorder (n=20), schizophrenia (n=20) and 14 matched healthy controls following 7 days of adjunctive mifepristone (600 mg day(-1)) treatment in a double-blind, placebo-controlled crossover design study. Baseline BDNF values were similar in both patient groups and in healthy controls. Following treatment with mifepristone, cortisol levels were significantly increased and BDNF levels decreased in both schizophrenia and bipolar disorder. A significant correlation existed between change in cortisol level and change in BDNF levels following mifepristone treatment in schizophrenia, but not in bipolar disorder. Differing BDNF responses to increasing cortisol levels between patients with schizophrenia and with bipolar disorder may reflect underlying pathophysiological mechanisms.