Moore G J, Bebchuk J M, Parrish J K, Faulk M W, Arfken C L, Strahl-Bevacqua J, Manji H K
Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Am J Psychiatry. 1999 Dec;156(12):1902-8. doi: 10.1176/ajp.156.12.1902.
The most widely accepted hypothesis regarding the mechanism underlying lithium's therapeutic efficacy in manic-depressive illness (bipolar affective disorder) is the inositol depletion hypothesis, which posits that lithium produces a lowering of myo-inositol in critical areas of the brain and the effect is therapeutic. Lithium's effects on in vivo brain myo-inositol levels were investigated longitudinally in 12 adult depressed patients with manic-depressive illness.
Medication washout (minimum 2 weeks) and lithium administration were conducted in a blinded manner. Regional brain myo-inositol levels were measured by means of quantitative proton magnetic resonance spectroscopy at three time points: at baseline and after acute (5-7 days) and chronic (3-4 weeks) lithium administration.
Significant decreases (approximately 30%) in myoinositol levels were observed in the right frontal lobe after short-term administration, and these decreases persisted with chronic treatment. The severity of depression measured by the Hamilton Depression Rating Scale also decreased significantly over the study.
This study demonstrates that lithium administration does reduce myo-inositol levels in the right frontal lobe of patients with manic-depressive illness. However, the acute myo-inositol reduction occurs at a time when the patient's clinical state is clearly unchanged. Thus, the short-term reduction of myo-inositol per se is not associated with therapeutic response and does not support the inositol depletion hypothesis as originally posited. The hypothesis that a short-term lowering of myo inositol results in a cascade of secondary signaling and gene expression changes in the CNS that are ultimately associated with lithium's therapeutic efficacy is under investigation.
关于锂盐治疗躁郁症（双相情感障碍）疗效机制最广泛接受的假说是肌醇耗竭假说，该假说认为锂盐可使大脑关键区域的肌醇水平降低，且这种作用具有治疗效果。对12名患有躁郁症的成年抑郁症患者的大脑肌醇水平进行了纵向研究。
以盲法进行药物洗脱（至少2周）和锂盐给药。通过定量质子磁共振波谱在三个时间点测量脑区肌醇水平：基线时、急性（5 - 7天）和慢性（3 - 4周）锂盐给药后。
短期给药后右侧额叶肌醇水平显著降低（约30%），且这些降低在长期治疗后持续存在。在研究过程中，用汉密尔顿抑郁量表测量的抑郁严重程度也显著降低。
本研究表明，锂盐给药确实会降低躁郁症患者右侧额叶的肌醇水平。然而，急性肌醇降低发生在患者临床状态明显未改变的时候。因此，肌醇的短期降低本身与治疗反应无关，也不支持最初提出的肌醇耗竭假说。关于肌醇短期降低会导致中枢神经系统一系列二级信号传导和基因表达变化，最终与锂盐治疗效果相关的假说正在研究中。
