Polyunsaturated fatty acids and their metabolites in the pathobiology of schizophrenia.

Schizophrenia can be considered as a low-grade systemic inflammatory disease with its origins in the perinatal period. It is likely that genetic, environmental, and nutritional factors interact to induce excess production of pro-inflammatory cytokines that, in turn, damage fetal neurons leading to the adult onset of schizophrenia. Polyunsaturated fatty acids (PUFAs) and their metabolites such as lipoxins, resolvins, protectins, maresins and nitrolipids not only have potent neuroprotective action but also are capable of inhibiting the production of pro-inflammatory cytokines. Decreased formation of PUFAs as a result of low activity of Δ(6) and Δ(5) desaturases can result in an increase in the production of pro-inflammatory cytokines due to the absence of negative control exerted by PUFAs and their anti-inflammatory metabolites that, in turn, may predispose to neuronal damage and development of schizophrenia in adult life. Furthermore, PUFAs are essential for brain growth and development. If this proposal is correct, this implies that perinatal and adult supplementation of PUFAs not only prevents but also helps in the treatment of schizophrenia. Furthermore, synthetic analogs of lipoxins, resolvins, and protectins may be of significant benefit in schizophrenia.