Membrane phospholipids and cytokine interaction in schizophrenia.
Although the potential key role that lipids may have in schizophrenia is not fully understood, multiple lines of evidence to date implicate the lipid environment in the behavior of neurotransmitter systems. Decreased phospholipid polyunsaturated fatty acids (PUFAs) have been demonstrated in both brain and peripheral membranes in schizophrenia, which is consistent with the hypothesis of myelin-related dysfunction in schizophrenia. Membrane defects, such as those induced by decreased PUFAs in phospholipids, can significantly alter a broad range of membrane functions and ipso facto behavior through multiple "downstream" effects. A number of putative mechanisms have been identified to explain the decreased PUFAs in schizophrenia, notably the increased turnover of phospholipids and decreased incorporation of arachidonic acid (AA) in membranes. In addition to increased oxidative stress, altered immune function may also be responsible for increased phospholipase activities. This association is particularly relevant in relation to phospholipids/PUFA, as AA can be converted to a variety of biologically active compounds, such as eicosanoids, which serve as potent messengers in regulating the inflammatory response, as well as endocannabinoids, which may affect schizophrenic psychopathology. Direct evidence of immune changes in some patients with schizophrenia have come to light, particularly in the activities of several cytokines known to be altered in autoimmune dysfunction. Given the diverse physiological function of AA, the specific behavioral symptomatology of schizophrenia is related mostly to the effect of AA changes that regulates neurodevelopment, neurotransmitter homeostasis, phosphatidylinositol signaling, and neuromodulatory actions of endocannabinoids in schizophrenia. Hence, in the current conceptualization, AA may be at a nexus point in the cascade leading to the syndrome of schizophrenia and represents a common biochemical pathway leading to the varied symptomatology of this disorder.
VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania 15206, USA.
Jeffrey K
JK
Yao
Daniel P
DP
van Kammen
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000503:physiopathology; D010743:Phospholipids / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism* / Q000503:physiopathology; D013312:Stress, Physiological / Q000276:immunology
D016207:Cytokines; D005231:Fatty Acids, Unsaturated; D010743:Phospholipids