Abstract
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Peet, M.; Glen, I.; Horrobin, D.F. (eds.)
Phospholipid spectrum disorder in psychiatry
Marius Press, Carnforth. 339pp 1999.


Abstract

Psychiatric disorders, because they cause so much distress to sufferers, their relatives and friends, and because they may persist for many years, cause more damage than any other group of illnesses. The World Health Organisation now estimates that depression is the illness causing the greatest total disease burden. Schizophrenia is not far behind. Yet, as Robert Kendell recently emphasised in his plenary welcoming lecture to 3000 psychiatrists and psychopharmacologists at the 1998 Glasgow CINP conference, there has been no improvement in the effi- cacy of drugs for schizophrenia and depression for 40 years. Adverse effects of newer drugs maybe less, but their effects on symptoms are no better than they were in the late 1950s. Our modern concepts of psychiatric diseases have almost all been derived from exploring the mechanisms of drugs which were found to work on the basis of acci- dental clinical observation. Thus antidepressants enhance the function of catecholamine systems, so depression must be caused by inadequate catecholamine activity. Or antipsychotic drugs block dopamine recep- tors, and so schizophrenia must be caused by dopamin- ergic excess. Evidence for these hypotheses, which is truly independent of drug actions, is scanty and rarely convincing. We have thus become locked into a cycle where drug actions provide the best evidence of mech- anisms, and where all we can do is discover variants of existing drugs. This is because the drug discovery models are all ultimately based on the actions of drugs which empirically have been found to work, and not on a truly independent model of disease mechanism, which is derived from evidence other than that supplied by drugs. The lecture by Kendell indicates that dissatisfaction with current biochemical models of psychiatric disor- ders is growing. New concepts are required which will allow new questions to be asked and new treatments developed. One such concept is the idea that psychiatric disor- ders may be related to abnormalities in phospholipid metabolism. Phospholipids make up the bulk of all internal and external neuronal membranes. Most neuronal proteins are embedded in, or attached to phos- pholipid membranes. Protein quaternary structure, and therefore function, depends on the precise composition of the immediate phospholipid environment. Neuronal signal transduction processes depend on diacylglycerols, inositols, and fatty acids and their derivatives, which are released from membrane phospholipids during neuronal activation. Phospholipid biochemistry is therefore central in brain function. There is now evidence, from many different labo- ratories, that phospholipid abnormalities are involved in several psychiatric disorders. If this is the case, then new avenues of investigation and new approaches to treatment can be opened up. This book summarises much of the evidence available. We believe that it may prove to be an important stage in redirecting psychiatric research into more productive channels. [Editor's introduction]


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