Thesing CS, et al. - Given the uncertainty of the temporality of the association of low omega-3 polyunsaturated fatty acid (n-3 PUFA) plasma levels with depression, researchers sought to ascertain the underlying nature of these associations via investigating the bidirectional longitudinal associations of n-3 PUFA plasma levels with (presence, onset, and course of) depressive disorders and symptoms. The Netherlands Study of Depression and Anxiety (NESDA) yielded baseline (n = 2,912, 28.6% with current depressive disorder) and 6-year follow-up data (n = 1,966, 13.0% with current depressive disorder) for this work. The analysis revealed that depressed persons vs healthy controls exhibit lower n-3 PUFA levels. Over 6 years, they observed a tendency towards dissipation of the difference in n-3 PUFA levels detected at baseline between depressed and non-depressed participants. Finally, n-3 PUFA levels remained low among individuals depressed both at baseline and at 6-year follow up over the entire follow-up as compared with those who had never been depressed. Across waves, change in depressive disorders was not consistently accompanied by a change in n-3 PUFA levels over time. This 6-year longitudinal study could not confirm a uni- or bidirectional association over time despite indicating significant cross-sectional correlations between n-3 PUFA plasma levels and depressive disorders and severity. According to findings, a causal link between depression and n-3 PUFA plasma levels is unlikely.