Inflammation, Polyunsaturated Fatty Acids and Their Significance in the Development and Treatment of Depression

Depression and Metabolic Syndrome

Depression is a very common mental disorder and has a significant impact on the quality of life. Recently, researchers have focused on the connection between the development of affective disorders and the simultaneous occurrence of metabolic syndrome. Patients suffering from depression have a higher risk of developing overweight, obesity, and metabolic syndrome, which also applies vice versa. Metabolic syndrome, also known as syndrome X, includes several pathological conditions. These include obesity, hypertension, insulin resistance, or hyperlipidemia, and is often accompanied by subclinical systemic inflammation. This inflammatory condition is characteristic of both depression and metabolic syndrome, explaining their frequent coexistence, and appears to be a possible risk factor for pharmacoresistance to common antidepressants.

Does Inflammation Influence the Development of Depression?

Classic pharmacotherapy for depression is based on the so-called monoamine theory of depression, which assumes that the disease's onset is related to a reduced amount and imbalance of neurotransmitters, such as serotonin and norepinephrine, in the synaptic cleft. Other theories consider the role of the hypothalamus-pituitary axis and, last but not least, the immune system, specifically the imbalance of pro- and anti-inflammatory cytokines. Numerous studies have shown that there is likely a relationship between the development of depression and subclinical inflammation with the presence of pro-inflammatory cytokines. 

Inflammatory processes affect the metabolism of tryptophan, an essential amino acid important for serotonin synthesis. Pro-inflammatory cytokines reduce the amount of tryptophan and also cause it to be degraded more through the kynurenine synthesis pathway instead of serotonin. Kynurenine is metabolized to neuroactive substances that can cause the formation of oxygen radicals and oxidative stress or affect NMDA receptors. This leads to the development of neuropsychiatric symptoms, which is why experts consider the described pathological process significant in the development of depression.

Polyunsaturated Fatty Acids Play an Important Role

Due to the occurrence of resistance to common antidepressants, other treatment strategies also have a place in the pharmacotherapy of depression. Recently, the positive effects of using polyunsaturated fatty acids (PUFAs) have been discussed. 

PUFAs are very important for the function, structure, and development of the brain, neurotransmission, and metabolism. The most crucial PUFAs include omega-3 and omega-6 fatty acids (ω-3 and ω-6 FAs), represented by essential FAs − alpha-linolenic acid (ω-3) and linoleic acid (ω-6). ω-3 and ω-6 FAs are precursors of eicosanoids, inflammatory mediators that also affect smooth muscle contractions and platelet aggregation. Eicosanoids, whose precursor is ω-6 FAs, have a pro-inflammatory effect, whereas eicosanoids derived from ω-3 FAs have an anti-inflammatory effect. Therefore, the ratio of ω-3 to ω-6 FAs intake, ideally 1:1, is important, but in developed countries, it is significantly higher in favor of ω-6 FAs. 

From the above, it follows that ω-3 FAs are anti-inflammatory, and given the theory of inflammation's influence on depression development, it is appropriate to focus on their potential role in the development of psychiatric disorders. Low levels of ω-3 FAs have been detected in patients with depressive illness, which also reflected in the severity of symptoms. Clinical studies have shown that ω-3 FAs are effective in the treatment of affective disorders compared to placebo. However, these studies have so far been smaller in scope and generally shorter in duration. Current guidelines lean more towards supplementing existing pharmacotherapy with ω-3 FAs.

Conclusion

Depression is a serious mental illness. Alongside classical pharmacotherapy, it is important to consider other treatment modalities. Supplementing with nutraceuticals can be appropriate. Among promising dietary supplements that can positively influence the disease's manifestations are products containing ω-3 fatty acids, whose anti-inflammatory effect is very desirable given the inflammatory theory of depression's onset.

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Source: Kotolová H., Hammer T. Inflammation as a Part of the Pathophysiology of Depression and the Possibility of Its Influence by Polyunsaturated Fatty Acids. Psychiatry for Practice 2019; 20(2): 60–63.