Pao-Yen Lin, Shih-Yi Huang, Kuan-Pin SuBackground: On the basis of evidence from studies showing the antidepressant effects of omega-3 polyunsaturated fatty acids and the inverse relation between fish consumption and the prevalence of depression, the phospholipid hypothesis seems promising in ascertaining the etiology and treatment of depression. Although several studies have shown lower levels of omega-3 (n-3) polyunsaturated fatty acids in depressive patients, the results of individual polyunsaturated fatty acids, including docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and the omega-6 (n-6) polyunsaturated fatty acid arachidonic acid (AA), were inconsistent.Methods: We conducted the meta-analyses of 14 studies comparing the levels of polyunsaturated fatty acids between depressive patients and control subjects. The effect size of each study was synthesized by using a random effects model.Results: Compared with control subjects, the levels of EPA, DHA, and total n-3 polyunsaturated fatty acids were significantly lower in depressive patients. There was no significant change in AA or total n-6 polyunsaturated fatty acids.Conclusions: The results showed lower levels of EPA, DHA, and total n-3 polyunsaturated fatty acids in patients with depression, thus implying that n-3 polyunsaturated fatty acids play a role in the pathogenesis of depression. Our findings provide further support to the phospholipid hypothesis of depression and a rationale for using n-3 polyunsaturated fatty acids as an alternative treatment for depression. With these results, future studies examining specific roles of DHA and EPA in different clusters of depressive symptoms are warranted.