Neurocognitive deficits in schizophrenia are associated with alterations in blood levels of neurosteroids: a multiple regression analysis of findings from a double-blind, randomized, placebo-controlled, crossover trial with DHEA.
BACKGROUND
While neurosteroids exert multiple effects in the central nervous system, their associations with neurocognitive deficits in schizophrenia are not yet fully understood. The purpose of this study was to identify the contribution of circulating levels of dehydroepiandrosterone (DHEA), its sulfate (DHEAS), androstenedione, and cortisol to neurocognitive deficits through DHEA administration in schizophrenia.


METHODS
Data regarding cognitive function, symptom severity, daily doses, side effects of antipsychotic agents and blood levels of DHEA, DHEAS, androstenedione and cortisol were collected among 55 schizophrenia patients in a double-blind, randomized, placebo-controlled, crossover trial with DHEA at three intervals: upon study entry, after 6weeks of DHEA administration (200mg/d), and after 6weeks of a placebo period. Multiple regression analysis was applied for predicting sustained attention, memory, and executive function scores across three examinations controlling for clinical, treatment and background covariates.


RESULTS
Findings indicated that circulating DHEAS and androstenedione levels are shown as positive predictors of cognitive functioning, while DHEA level as negative predictor. Overall, blood neurosteroid levels and their molar ratios accounted for 16.5% of the total variance in sustained attention, 8-13% in visual memory tasks, and about 12% in executive functions. In addition, effects of symptoms, illness duration, daily doses of antipsychotic agents, side effects, education, and age of onset accounted for variability in cognitive functioning in schizophrenia.


CONCLUSIONS
The present study suggests that alterations in circulating levels of neurosteroids and their molar ratios may reflect pathophysiological processes, which, at least partially, underlie cognitive dysfunction in schizophrenia.
Ritsner
Michael S
MS
The Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Sha'ar Menashe Mental Health Center, Hadera, Israel.
Strous
Rael D
RD
D000328:Adult; D000735:Androstenedione / Q000097:blood*; D003072:Cognition Disorders / Q000097:blood* / Q000188:drug therapy* / Q000209:etiology; D018592:Cross-Over Studies; D003687:Dehydroepiandrosterone / Q000097:blood*; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011863:Radioimmunoassay / Q000379:methods; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy; D012565:Schizophrenic Psychology; D015599:Trauma Severity Indices; D055815:Young Adult
D000735:Androstenedione; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D006854:Hydrocortisone