The Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Sha'ar Menashe Mental Health Center, Hadera, Israel.
J Psychiatr Res. 2010 Jan;44(2):75-80. doi: 10.1016/j.jpsychires.2009.07.002. Epub 2009 Aug 7.
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.
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.
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.
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.
神经甾体在中枢神经系统中发挥多种作用，但它们与精神分裂症患者的神经认知缺陷的关系尚未完全阐明。本研究的目的是通过在精神分裂症患者中给予脱氢表雄酮（DHEA），鉴定循环水平的 DHEA、硫酸脱氢表雄酮（DHEAS）、雄烯二酮和皮质醇对神经认知缺陷的贡献。
在一项双盲、随机、安慰剂对照、交叉试验中，收集了 55 名精神分裂症患者的认知功能、症状严重程度、抗精神病药物的日剂量、副作用以及 DHEA、DHEAS、雄烯二酮和皮质醇的血液水平数据。在三个时间点进行 DHEA 治疗：研究开始时、DHEA 治疗 6 周后（200mg/d）和安慰剂治疗 6 周后。应用多元回归分析，在控制临床、治疗和背景协变量的情况下，预测三次检查中的持续注意力、记忆和执行功能评分。
研究结果表明，循环 DHEAS 和雄烯二酮水平是认知功能的正预测因子，而 DHEA 水平则是负预测因子。总的来说，血液神经甾体水平及其摩尔比解释了持续注意力总方差的 16.5%、视觉记忆任务的 8-13%和执行功能的 12%左右。此外，症状、疾病持续时间、抗精神病药物的日剂量、副作用、教育程度和发病年龄等因素也会影响精神分裂症患者的认知功能。
本研究表明，循环神经甾体水平及其摩尔比的改变可能反映了病理生理过程，这些过程至少部分地导致了精神分裂症患者的认知功能障碍。
