Background
Deficits in neuropsychological performance are found in patients with bipolar disorder
and represent a potential treatment target for novel therapeutic strategies. We have
previously demonstrated a beneficial effect on spatial working memory (SWM) of treatment
for 1 week with the progesterone and glucocorticoid receptor antagonist mifepristone,
evident 2 weeks after the cessation of treatment.
Methods
We examined the longer-term efficacy of 600 mg/day of mifepristone as an adjunctive
treatment, for 1 week, in a placebo-controlled, randomized, double-blind trial in
60 patients with bipolar depression, with SWM as the primary outcome measure. A comparator
group of healthy control subjects was also recruited.
Results
At baseline, neuropsychological performance of patients was impaired, but hypothalamic-pituitary-adrenal
axis function did not differ from that of control subjects. Mifepristone treatment
was associated with a time-limited increase in cortisol awakening response and with
a sustained improvement in SWM performance, which was evident 7 weeks after the cessation
of treatment. The magnitude of this neuropsychological response was predicted by the
magnitude of the cortisol response to mifepristone. The response occurred in the absence
of a significant improvement in depressed mood.
Conclusions
These data accord with the findings of animal studies and demonstrate that brief treatment
with mifepristone is associated with a sustained improvement in SWM, an effect that
might be mediated by a persistent enhancement in hippocampal mineralocorticoid receptor
function.
Key Words
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Article info
Publication history
Published online: July 09, 2012
Accepted:
May 15,
2012
Received in revised form:
April 24,
2012
Received:
February 17,
2012
Identification
Copyright
© 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
