Polyunsaturated fatty acids and recurrent mood disorders: Phenomenology, mechanisms, and clinical application

Prog Lipid Res. 2017 Apr:66:1-13. doi: 10.1016/j.plipres.2017.01.001. Epub 2017 Jan 6.


A body of evidence has implicated dietary deficiency in omega-3 polyunsaturated fatty acids (n-3 PUFA), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in the pathophysiology and etiology of recurrent mood disorders including major depressive disorder (MDD) and bipolar disorder. Cross-national and cross-sectional evidence suggests that greater habitual intake of n-3 PUFA is associated with reduced risk for developing mood symptoms. Meta-analyses provide strong evidence that patients with mood disorders exhibit low blood n-3 PUFA levels which are associated with increased risk for the initial development of mood symptoms in response to inflammation. While the etiology of this n-3 PUFA deficit may be multifactorial, n-3 PUFA supplementation is sufficient to correct this deficit and may also have antidepressant effects. Rodent studies suggest that n-3 PUFA deficiency during perinatal development can recapitulate key neuropathological, neurochemical, and behavioral features associated with mood disorders. Clinical neuroimaging studies suggest that low n-3 PUFA biostatus is associated with abnormalities in cortical structure and function also observed in mood disorders. Collectively, these findings implicate dietary n-3 PUFA insufficiency, particularly during development, in the pathophysiology of mood dysregulation, and support implementation of routine screening for and treatment of n-3 PUFA deficiency in patients with mood disorders.

Keywords: Bipolar disorder; Docosahexaenoic acid (DHA); Eicosapentaenoic acid (EPA); Major depressive disorder; Omega-3 fatty acids.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Dietary Supplements
  • Fatty Acids, Unsaturated / biosynthesis
  • Fatty Acids, Unsaturated / metabolism*
  • Fatty Acids, Unsaturated / pharmacology
  • Fatty Acids, Unsaturated / therapeutic use
  • Humans
  • Mood Disorders / drug therapy
  • Mood Disorders / metabolism*
  • Recurrence


  • Fatty Acids, Unsaturated