Horrobin D F, Huang Y S
Med Hypotheses. 1983 Mar;10(3):329-36. doi: 10.1016/0306-9877(83)90119-6.
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.
必需脂肪酸（EFA）有两个系列，n6系列以亚油酸为起始，n3系列以α-亚麻酸为起始。这两个系列的成员在大脑结构中都很重要，并且可以作为前列腺素形成的前体。正常情况下，代谢必需脂肪酸的去饱和酶对n3系列具有更高的亲和力。有人提出，精神分裂症患者体内存在突变的去饱和酶，这些酶更倾向于n6系列。这种变化可以解释精神分裂症患者中亚油酸、二高γ-亚麻酸和1系列前列腺素水平较低的现象。这也可以解释花生四烯酸和α-亚麻酸的高水平以及最近报道的对α-亚麻酸的治疗反应。通过剥夺大鼠的n3必需脂肪酸，几乎可以在大鼠身上精确模拟精神分裂症患者n6系列必需脂肪酸的异常模式。这是由于酶缺陷导致无法代谢必需脂肪酸的最接近的实验等效情况。携带这种突变基因的杂合子将比任何一种纯合子具有优势，因为它们能够更好地应对n3和n6必需脂肪酸饮食摄入量的变化。
