Schizophrenia: the role of abnormal essential fatty acid and prostaglandin metabolism.

There are two series of essential fatty acids (EFAs), the n6 series starting with linoleic acid and the n3 series starting with alpha-linolenic acid. Members of both series are important in brain structure and can act as precursors for prostaglandin formation. Normally the desaturase enzymes which metabolize EFAs have a higher affinity for the n3 series. It is proposed that in schizophrenia mutant desaturases are present which prefer the n6 series. This change would account for the low levels of linoleic acid, dihomogammalinolenic acid and 1 series prostaglandins which have been reported in schizophrenia. It would also explain the high levels of arachidonic and alpha-linolenic acids and the recently described therapeutic response to alpha-linolenic acid. The abnormal pattern in n6 series EFAs in schizophrenics can almost exactly be imitated in rats by depriving them of n3 EFAs. This is the nearest experimental equivalent to an inability to metabolize EFAs because of an enzyme defect. Heterozygotes carrying such a mutant gene would have an advantage over either form of homozygote since they would be better able to cope with variations in dietary intake of n3 and n6 EFAs.