Khan Mohammad M, Evans Denise R, Gunna Vijayasudha, Scheffer Russell E, Parikh Vinay V, Mahadik Sahebarao P
Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta, GA 30912, USA.
Schizophr Res. 2002 Nov 1;58(1):1-10. doi: 10.1016/s0920-9964(01)00334-6.
Abnormal membrane phospholipid essential polyunsaturated fatty acid (EPUFA) metabolism (i.e., reduced incorporation into phospholipids and increased breakdown) has been suggested to contribute to the etiopathophysiology of schizophrenia. However, most of the published studies have reported changes in the levels of membrane EPUFA in chronic medicated patients or in drug-naive patients long after onset of illness (1-2 years). Since the EPUFA metabolism can be altered by years of untreated illness or differentially altered by various antipsychotics, the significance of EPUFA membrane status to schizophrenia psychopathophysiology is unclear. We report the erythrocyte membrane EPUFA levels in drug-naive patients within +/- 4.5 days of onset of psychosis from an Army Medical Center, and in patients treated years with antipsychotics from a Veterans Affairs Medical Center. The levels of plasma lipid peroxides (TBARS, thiobarbituric acid reactive substances), products of damaged EPUFAs, were also determined. The levels of EPUFAs, particularly arachidonic acid (AA) and docosahexaenoic acid (DHA) were significantly lower (P < 0.001) in drug-naive patients at the onset of psychosis compared to matched normal controls. These lower EPUFA levels were associated with significantly higher levels of TBARS in patients (P < 0.001). The levels of AA and DHA were also lower (P < 0.001) and TBARS higher in chronic medicated patients than normal controls. However, the EPUFA levels were higher in chronic medicated patients than drug-naive first-episode patients. These data indicate that lower membrane AA and DHA most likely predate the illness and probably contribute to the onset of illness, and furthermore treatment with some antipsychotics may increase the levels of EPUFAs. The lipid peroxidation data suggest that possible increased oxidative stress, either as a part of the illness and/or its treatment with antipsychotics, may be one of the mechanisms of reduced membrane EPUFAs. These findings may have a significant impact on improving strategies for supplementation of EPUFAs and antioxidants to improve the outcome of schizophrenia.
异常的膜磷脂必需多不饱和脂肪酸（EPUFA）代谢（即掺入磷脂减少和分解增加）被认为与精神分裂症的病因病理生理学有关。然而，大多数已发表的研究报告了慢性用药患者或发病后很长时间（1 - 2年）未用药患者的膜EPUFA水平变化。由于多年未治疗的疾病可能会改变EPUFA代谢，或者各种抗精神病药物会使其发生不同的改变，因此EPUFA膜状态对精神分裂症心理病理生理学的意义尚不清楚。我们报告了来自陆军医疗中心的初发精神病患者在发病后±4.5天内未用药患者的红细胞膜EPUFA水平，以及来自退伍军人事务医疗中心接受多年抗精神病药物治疗患者的该水平。还测定了血浆脂质过氧化物（TBARS，硫代巴比妥酸反应性物质）的水平，这是受损EPUFA的产物。与匹配的正常对照组相比，初发精神病未用药患者在发病时EPUFAs的水平，尤其是花生四烯酸（AA）和二十二碳六烯酸（DHA）显著降低（P < 0.001）。这些较低的EPUFA水平与患者中显著更高的TBARS水平相关（P < 0.001）。慢性用药患者的AA和DHA水平也低于正常对照组（P < 0.001），TBARS水平更高。然而，慢性用药患者的EPUFA水平高于初发未用药患者。这些数据表明，较低的膜AA和DHA水平很可能在疾病发生之前就已存在，并可能促成疾病的发作，此外，一些抗精神病药物治疗可能会增加EPUFAs的水平。脂质过氧化数据表明，可能增加的氧化应激，要么是疾病的一部分，和/或其抗精神病药物治疗，可能是膜EPUFAs减少的机制之一。这些发现可能对改善补充EPUFAs和抗氧化剂以改善精神分裂症结局的策略产生重大影响。
