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Schizophrenia (SZ), a devastating psychiatric disorder, has a 1% morbidity rate worldwide. It has been regarded as a neurotransmitter disease for a long time, but the underlying molecular etiologies of schizophrenia are still poorly understood. Since Horrobin first proposed the membrane phospholipid metabolism hypothesis in schizophrenia, schizophrenia begins to be categorized as a systemic disease as well and this hypothesis could explain the molecular etiologies of some abnormal neuronal systems.
Phospholipids usually consist of highly unsaturated fatty acids and lysophospholipids, make up to 60% dry weight of a brain and are very important in constructing neuronal membranes. Any alternations in membranes due to increased phospholipase A2 activity or lipid peroxidation could affect membrane fluidity, neurotransmitter release and receptor binding density in the dopaminergic and serotonergic systems. Meanwhile, eicosanoids and docosanoids produced by highly unsaturated fatty acids, especially arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid, are involved in inflammation. Thus, it is not surprising that some associations could exist between abnormal membrane phospholipid metabolism and schizophrenia, because schizophrenia is also characterized by aberrant neuronal systems and inflammatory states. Besides, phosphatidylserine and phosphatidylcholine may correlate with memory-associated deficits as well as the process of inflammation and the balance between diacylglycerol and phosphatidic acid, further enriching explanations on the abnormal physiological changes in schizophrenia.
Currently, although only very few lipid-metabolizing genes, such as FABP7, SOD and LPL, have been proven to be related to schizophrenia. More studies in this field are expected to be carried out by genetic association study, DNA microarray, shotgun proteomics and corresponding rodent models, to further associate suspicious lipid-metabolizing genes with schizophrenia and discover their roles in the pathologies of schizophrenia. Based on the membrane phospholipid hypothesis in schizophrenia, adjunctive supplementation with antioxidants, non-steroidal anti-inflammatory drugs and essential highly unsaturated fatty acids could be promising treatment for schizophrenia in the near future.