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Nutrition, psychoneuroimmunology and depression: the therapeutic implications of omega-3 fatty acids in interferon-α-induced depression.

Su KP (2015) Biomedicine (Taipei)  2015 Dec 5(4) 21 doi: 10.7603/s40681-015-0021-x. Epub 2015 Nov 28.

Web URL: View this and related abstract via PubMed here. Free full text is available online.


The unmet need of current pharmacotherapy and the high occurrence of somatic symptoms and physical illness in depression imply that the 'monoamine hypothesis' is insufficient in approaching the aetiology of depression.

Clinically, depressed patients manifest higher levels of inflammatory biomarkers, while proinflammatory cytokines induce neuropsychiatric symptoms (sickness behaviour) as well as major depressive episodes. Indeed, accumulating evidence suggests that inflammation dysregulation plays an important role in the pathophysiology of depression. Biological mechanisms that link inflammation to neuropsychiatric symptoms are vital in the understanding of the "mind-body" interface. IFN-α-induced depression is the most powerful support for the inflammation theory of depression.

This clinical observation provides an excellent model for depression research. By comparing subjects with and without major depression induced by the cytokine treatment, statistical powers could be largely increased by reducing phenotypic variation (homogeneity in aetiological factors). In addition, the anti-inflammatory pathway has recently become an important topic in looking for new antidepressant therapies. For example, anti-inflammatory compounds, omega-3 polyunsaturated fatty acids (omega-3 PUFAs or n-3 PUFAs), have been found to be associated with the development and treatment for depression in human and animal models.

Here I review recent epidemiological studies, cross-sectional and longitudinal case-controlled studies, interventional clinical trials, as well as basic animal and cellular studies to prove the linkage among omega-3 PUFAs, inflammation, and depression.


Depression is a highly heterogenous condition, but increasing evidence points to inflammation as a contributory factor.  

This review by one of the world's leading researchers into omega-3 and depression summarises the latest research on vulnerability factors and treatments for 'inflammatory depression', including existing evidence showing that

(1) Treatment with the pro-inflammatory cytokine interferon-alpha (IFN-α) causes depression in up to 50% of patients. Importantly, low omega-3 status has been shown to be a risk factor for this interferon-induced depression. Furthermore:

(2) supplementation with long-chain omega-3 fatty acids can prevent interferon-induced depression in at least some individuals, as shown by clinical trials.

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