According to a study published in Molecular Psychiatry, researchers have identified an important molecular mechanism that could aid the development of potential new omega-3 fatty acid treatments for patients with depression. The omega-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) were first applied in high doses to laboratory-grown neurons and then to patients to understand the mechanism by which they reduce inflammation and depression .
Previous research suggests that people with major depressive disorder have higher levels of inflammation in their bodies than those without the disorder, according to the current study. There are currently no anti-inflammatory treatment strategies for depression, and although EPA and DHA have been shown to have anti-inflammatory and antidepressant effects, the exact mechanism of action for this process is unknown.
Researchers used a validated in vitro human cell model called “Depression in a Dish” that uses cells from the hippocampus, a part of the brain that is fundamental to many areas of cognitive, memory and learning. It is believed that the hippocampus plays an important role in depression, and hippocampal cells play an important role in the production of new neurons.
Human hippocampal cells were treated with EPA or DHA before exposure to cytokines, which are chemical messengers involved in inflammation. According to the study’s authors, this prevented increased cell death and decreased neurogenesis.
This effect was previously seen in cells exposed only to cytokines, and further research confirmed that these effects were mediated by the formation of several important lipid mediators produced by EPA and DHA. This is the first time these specific lipid mediators have been detected in human hippocampal neurons, the researchers said. They added that the study further showed that treatment with an enzyme inhibitor increased the availability of 2 of these metabolites, suggesting a potential method of optimizing future treatments.
“The lipid mediators that our research has identified are broken down relatively quickly in the body, which means they may only be available for a relatively short time,” said Anna Nicolaou, BSc, PhD, CChem, FRSC, in a press release. “By testing the effect of inhibitors of the enzymes involved in the metabolism of omega-3 PUFAs, we have shown that we can greatly improve their duration of action in the body and ultimately increase their effectiveness. This is very important in the development of new treatments and means that patients, along with these enzyme inhibitors, could receive higher doses of EPA and DHA to increase the amount of these important compounds in their blood over time. “
The study then examined 22 patients with severe depression who were given either 3 g EPA or 1.4 g DHA daily for a period of 12 weeks. Researchers measured the lipid metabolites of EPA and DHA present in the participants’ blood before and after omega-3 PUFA treatment, along with an assessment of their depressive symptoms.
In both patient groups, the treatments were associated with an increase in their respective metabolites and a significant improvement in depressive symptoms. It was reported that patients had mean reductions in symptom scores of 64% and 71% in the EPA and DHA groups, respectively. In addition, higher concentrations of the same metabolites identified in the in vitro experiments correlated with lower depressive symptoms.
“Through a combination of laboratory and patient research, our study provided exciting new insights into how omega-3 fatty acids have anti-inflammatory effects that improve depression,” said Alessandra Borsini, PhD, in the press release. “We have known for some time that omega-3 PUFAs can produce antidepressant and anti-inflammatory effects, but without further understanding how this happens in the human brain, treatments have been difficult to develop. Our study helped shed light on the molecular mechanisms involved in this relationship that may influence the development of potential new treatments for depression using omega-3 PUFAs. “
Anti-inflammatory effects of omega-3 fatty acids could help reduce depression [news release]. EurekAlert; June 15, 2021. Accessed June 16, 2021. https://www.eurekalert.org/pub_releases/2021-06/kcl-aeo061421.php