Patients with higher depression severity generally have low levels of omega-3 polyunsaturated fatty acids (n-3 PUFAs), including docosahexaenoic acid (DHA), yet the reason for this relationship is not clear, according to a study published in the Journal of Psychiatric Research. Notably, over the course of the longitudinal study, fluctuations in n-3 PUFA did not reflect alterations in depressive symptoms.

The study used baseline (n=2912; mean age, 41.9 years; 66.4% women) and 6-year follow-up data (n=1966) from the Netherlands Study of Depression and Anxiety (NESDA). Approximately 28.6% of participants from the baseline data had current depressive disorder, whereas 13.0% of participants in the 6-year follow-up data had current depressive disorder. The researchers used psychiatric interviews and self-reported questionnaires to determine diagnoses and symptoms of depression, and assessed EDTA plasma samples of n-3 PUFA levels in all participants.

Compared with participants without depressive disorders, patients with depressive disorders at baseline had significantly lower overall n-3 PUFA (Beta, −0.047; SE = 0.011; P <.001) and DHA levels (Beta, −0.062, SE = 0.016; P <.001). However, changes in depression severity during the 6-year study period were not associated with n-3 PUFA or DHA levels at baseline in both depressed and nondepressed subjects (Beta = 0.140; SE = 0.222; P =.53). Differences in n-3 PUFA levels between the 2 groups also attenuated over time.

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There was no difference in the change of n-3 PUFA and DHA levels over time in participants with higher depression severity (Beta = 0.009; SE = 0.006; P =.13) and DHA (Beta = 0.007; SE = 0.008; P =.36). However, the researchers observed an association between higher depression severity with consistently lower n-3 PUFA (Beta = −0.018; SE = 0.005; P <.001) and DHA (Beta = −0.024; SE = 0.007; P <.001).

Limitations of the study included the lack of information on eicosapentaenoic acid levels and dietary intake, as well as the reliance on retrospective self-reports for identifying remission and onset of depressive disorders. Although the study suggests that patients with severe depression have lower levels of n-3 PUFA and DHA, there was no consistent evidence for a unidirectional or bidirectional longitudinal relationship between these biologic factors and depression.


Thesing CS, Bot M, Milaneschi Y, Giltay EJ, Penninx BWJH. Bidirectional longitudinal associations of omega-3 polyunsaturated fatty acid plasma levels with depressive disorders. J Psychiatr Res. 2020;124:1-8.