Implications of lipid biology for the pathogenesis of schizophrenia

被引:52
作者
Berger, GE
Wood, SJ
Pantelis, C
Velakoulis, D
Wellard, RM
McGorry, PD
机构
[1] Early Psychosis Prevent & Intervent Ctr, MH SKY, Parkville, Vic 3052, Australia
[2] Univ Melbourne, Cognit Neuropsychiat Res & Acad Unit, Parkville, Vic 3052, Australia
[3] Sunshine Hosp, Melbourne, Vic, Australia
[4] Austin & Repatriat Med Ctr, Brain Res Inst, Heidelberg, Vic, Australia
基金
英国医学研究理事会;
关键词
essential fatty acids; magnetic resonance spectroscopy; niacin; phospholipases; phospholipids;
D O I
10.1046/j.1440-1614.2001.01021.x
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
Objective: Preclinical and clinical data suggest that lipid biology is integral to brain development and neurodegeneration. Both aspects are proposed as being important in the pathogenesis of schizophrenia. The purpose of this paper is to examine the implications of lipid biology, in particular the role of essential fatty acids (EFA), for schizophrenia. Methods: Medline databases were searched from 1966 to 2001 followed by the cross-checking of references. Results: Most studies investigating lipids in schizophrenia described reduced EFA, altered glycerophospholipids and an increased activity of a calcium-independent phospholipase A(2) in blood cells and in post-mortem brain tissue. Additionally, in vivo brain phosphorus-31 Magnetic Resonance Spectroscopy ((31) P-MRS) demonstrated lower phosphomonoesters (implying reduced membrane precursors) in first- and multi-episode patients. In contrast, phosphodiesters were elevated mainly in first-episode patients (implying increased membrane breakdown products), whereas inconclusive results were found in chronic patients. EFA supplementation trials in chronic patient populations with residual symptoms have demonstrated conflicting results. More consistent results were observed in the early and symptomatic stages of illness, especially if EFA with a high proportion of eicosapentaenoic acid was used. Conclusion: Peripheral blood cell, brain necropsy and (31) P-MRS analysis reveal a disturbed lipid biology, suggesting generalized membrane alterations in schizophrenia. (31) P-MRS data suggest increased membrane turnover at illness onset and persisting membrane abnormalities in established schizophrenia. Cellular processes regulating membrane lipid metabolism are potential new targets for antipsychotic drugs and might explain the mechanism of action of treatments such as eicosapentaenoic acid.
引用
收藏
页码:355 / 366
页数:12
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