Possible antidepressant mechanisms of omega-3 polyunsaturated fatty acids acting on the central nervous system

Abstract

Omega-3 polyunsaturated fatty acids (PUFAs) can play important roles in maintaining mental health and resistance to stress, and omega-3 PUFAs supplementation can display beneficial effects on both the prevention and treatment of depressive disorders. Although the underlying mechanisms are still unclear, accumulated evidence indicates that omega-3 PUFAs can exhibit pleiotropic effects on the neural structure and function. Thus, they play fundamental roles in brain activities involved in the mood regulation. Since depressive symptoms have been assumed to be of central origin, this review aims to summarize the recently published studies to identify the potential neurobiological mechanisms underlying the anti-depressant effects of omega-3 PUFAs. These include that of (1) anti-neuroinflammatory; (2) hypothalamus-pituitary-adrenal (HPA) axis; (3) anti-oxidative stress; (4) anti-neurodegeneration; (5) neuroplasticity and synaptic plasticity; and (6) modulation of neurotransmitter systems. Despite many lines of evidence have hinted that these mechanisms may co-exist and work in concert to produce anti-depressive effects, the potentially multiple sites of action of omega-3 PUFAs need to be fully established. We also discussed the limitations of current studies and suggest future directions for preclinical and translational research in this field.

Omega-3 Fatty Acids Supplementation in the Treatment of Depression: An Observational Study

“…This was confirmed by comparing inter-arm HRDS scores, which revealed a significant decline during the second and third follow-ups in the patients treated with the combination, compared to the patients administered with any therapy alone. Researchers hypothesize that the benefits of omega-3 fatty acids in depression could be multi-faceted [ 30 ]. Omega-3 fatty acids may change cell signaling and the structure of cell membrane fluidity and lipid bilayer elasticity, affecting how proteins function and interact within the membrane.…”

“…Omega-3 fatty acids affect mitochondrial function, reactive oxygen species homeostasis, cell proliferation, cell viability, and apoptosis. These positive benefits reflect directly on the neurotransmitter system resulting in better neural and synaptic plasticity leading to decreased neuro-degeneration, inflammation, and oxidative stress [ 30 ].…”

The role of Omega-3 Polyunsaturated Fatty Acids in the treatment of Bipolar Disorder – a narrative review

“…Besides n-3 PUFAs modulatory effect on inflammatory processes taking place in the human body, recent studies suggest that they are also engaged in neurogenesis, synaptic pruning, neuronal differentiation and migration, as well as neuronal cell survival [27,28]. Moreover, n-3 PUFAs may have an impact on:…”

Dietary Nutrient Deficiencies and Risk of Depression (Review Article 2018–2023)

“…The bulk of the dry weight of the mature brain is made up of fatty acids, with PUFAs making up about 20% of the dry weight. Both omega-3 fatty acids, mainly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), and omega-6 fatty acids, mainly arachidonic acid (AA), can be found in the brain [66]. DHA acid plays a key role, as it is quantitatively the most important fatty acid and is essential for the proper functioning of the neuronal membrane [67].…”