N-3 (Omega-3) Polyunsaturated Fatty Acids in the Pathophysiology and Treatment of Depression: Pre-Clinical Evidence

A growing literature suggests the association of low tissue levels and/or dietary intake of n-polyunsaturated fatty acids (PUFA) with depressive illnesses. Animal studies show that low tissue and/or dietary n-3 PUFAs can lead to behaviors and neurobiological effects associated with depression and can potentiate the consequences of stress, whereas higher levels have the opposite effect. These data support the involvement of n-3 PUFAs levels in the disease processes underlying depression. In addition, these pre-clinical findings indicate neurobiological mechanisms whereby n-3 PUFAs may contribute to the disease including control of serotonergic and dopaminergic function, modulation of brain-derived neurotrophic factor (BDNF) in the hippocampus, regulation of the hypothalamic-pituitary-adrenal axis, and effects on neuroinflammation. This evidence for a role for n-3 PUFA in the pathophysiology and treatment of depressive illness are reviewed. The implications of these finding for future pre-clinical research and clinical application are discussed.