ω − 3 Fatty acid deficiency in major depressive disorder is caused by the interaction between diet and a genetically determined abnormality in phospholipid metabolism

Summaryω − 3 Fatty acids are a type of polyunsaturated fatty acid (PUFA). A growing body of evidence suggests that this form PUFA is a useful and well tolerated treatment for major depressive disorder, a common and serious mental illness. The efficacy of ω − 3 PUFA is routinely explained as being due to a deficiency caused by inadequate dietary intake of this class of fatty acid. The hypothesis considered states that low ω − 3 PUFA abundance in patients with major depressive and related disorders is due to an underlying genetically determined abnormality. The hypothesis can explain why although a specific and consistent deficit in ω − 3, but not ω − 6, PUFA occurs in major depressive and related disorders, the literature does not consistently support the notion that this is due to deficient dietary intake. Specifically it is hypothesized that having genetically determined low activity of fatty acid CoA ligase 4 and/or Type IV phospholipase A2 combined with the low dietary availability of ω − 3 PUFA results in reduced cellular uptake of ω − 3 PUFA and constitutes a risk factor for depression. The hypothesis also has important consequences for the pharmacological treatment of depression in that it predicts that administering agents which enhance phospholipid synthesis, particularly those containing ethanolamine such as CDP-ethanolamine, should be effective antidepressants especially when co-administered with ω − 3 PUFA.