Changes in brain-derived neurotrophic factor following treatment with mifepristone in bipolar disorder and schizophrenia.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Differing BDNF responses to increasing cortisol levels between patients with schizophrenia and with bipolar disorder may reflect underlying pathophysiological mechanisms.
Mackin
Paul
P
School of Neurology, Neurobiology and Psychiatry, University of Newcastle upon Tyne, Leazes Wing (Psychiatry), Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4LP, UK. paul.mackin@ncl.ac.uk
Gallagher
Peter
P
Watson
Stuart
S
Young
Allan H
AH
Ferrier
I Nicol
IN
D000328:Adult; D000339:Affect / Q000187:drug effects; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006727:Hormone Antagonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D015735:Mifepristone / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D010913:Pituitary-Adrenal System / Q000187:drug effects; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology
D019208:Brain-Derived Neurotrophic Factor; D006727:Hormone Antagonists; D015735:Mifepristone; D006854:Hydrocortisone