New insights into how the anti-inflammatory effects of omega 3 fatty acids help reduce depression

A study led by King’s College London found that when omega-3 polyunsaturated fatty acids (PUFAs) were given to patients with depression, they were metabolized to molecules called lipid mediators, and these levels in the blood improved symptoms. This study was published today in Molecular Psychiatry.

The omega-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are found in oily fish. Researchers at the Moseley Biomedical Research Center at the National Institutes of Health (NIHR) evaluate the effects of high doses of EPA and DHA on laboratory-grown neurons and patients, and how to reduce inflammation and depression. I made it clear. This new approach has allowed scientists to identify important molecular mechanisms that can help inform the development of potential new therapies, including omega-3 fatty acids, for people with depression.

Dr. Alessandra Borsini, Principal Author, NIHR Moseley BRC Senior Postdoctoral Neuroscientist at King’s College London, said: depression. It has long been known that omega 3 PUFA can induce antidepressant and anti-inflammatory effects, but developing treatments without further understanding how this happens in the human brain. Was difficult. Our research has helped shed light on the molecular mechanisms involved in this relationship, which can inform the development of potential new treatments for depression using omega-3 PUFAs. “

Previous studies have shown that people with major depressive disorder have higher levels of inflammation in their bodies than people without the disorder. Currently, anti-inflammatory treatment strategies for depression have not been proven and two important omega 3 PUFAs, EPA and DHA, have been shown to provide anti-inflammatory and antidepressant effects, but the exact way to do this. The mechanism is unknown.

Depression in the dish

This study aims to test the theory that when omega 3 fatty acids are utilized and processed in the body, some of their metabolites (known as lipid mediators) can protect the brain from the harmful effects of inflammation. It is said. Developed at the NIHR Maudsley Biomedical Research Center, researchers use hippocampal cells, which are a basic part of the brain in many cognitive, memory, and learning disciplines, a validation known as “depression in the dish.” We used a pre-existing in vitro human cell model. Being important in depression. Hippocampal cells play an important role in the generation of new neurons, or neurogenesis.

This study showed that treatment of human hippocampal cells with EPA or DHA before exposure to inflammatory chemical mediators called cytokines prevented increased cell death and decreased neurogenesis. Both of these effects were previously observed in cells exposed only to cytokines. Upon further investigation, these effects show some important lipid mediators produced by EPA and DHA: hydroxyeicosapentaenoic acid (HEPE), hydroxydocosahexaenoic acid (HDHA), epoxyeicosatetraenoic acid (EpETE) and It was confirmed to be mediated by the formation of epoxy docosapentaenoic acid (EpDPA). First in human hippocampal neurons. Further research has shown that treatment with enzyme inhibitors increases the availability of two of these metabolites (EpETE and EpDPA), and methods that may optimize future treatment. It was suggested.

Anna Nicolaou, a professor of biochemistry at the University of Manchester’s School of Medicine and Human Sciences, who led a team that measured lipid mediators using mass spectrometry, said: It may be available relatively quickly, that is, for a relatively short period of time. By testing the effects of inhibitors of enzymes involved in the metabolism of omega 3 PUFA, we have shown that they can significantly improve the duration of their effect in the body and ultimately increase their effectiveness. .. This is very important for the development of new therapies, in which patients are given high doses of EPA and DHA with these enzyme inhibitors and the amount of these important compounds in the blood over time. Means that you can increase. “

Patient’s omega 3 metabolites

This study evaluated 22 patients with major depression who received 3 grams of EPA or 1.4 grams of DHA daily for 12 weeks. Lipid metabolites of EPA and DHA were measured in the blood with a depressive symptom score before and after treatment with omega 3 PUFA. In both patient groups, EPA or DHA treatment was associated with an increase in their respective metabolites and a significant improvement in depressive symptoms. Symptom scores for the EPA and DHA groups decreased by an average of 64% and 71%, respectively. In addition, high levels of the same metabolites identified in in vitro experiments correlated with low levels of depressive symptoms.

The levels of EPA and DHA used in this study are the ones most likely not achievable with the dietary intake of oily fish, a rich source of omega 3 PUFAs, but therapeutic supplements are needed.

Future research

Research results show that bioactive lipid mediators produced by the breakdown of EPA and DHA in the body may be targeted as a mechanism to reduce depression and inflammation, but for this approach. To be successful, you need to ensure that their effects are extended. Previous studies have shown that key enzymes in omega-3 fatty acid metabolism are effective drug diversion options and could be used for other inflammation-related brain disorders, such as depression, where at least a subgroup of patients is often at chronic levels. It has been shown to be of sex.

Professor Carmine Pariante, NIHR Maudsley BRC Affective Disorders Interface with Medicine Theme Lead, the lead author of the paper, said: We need to better understand the mechanisms behind these relationships. Our study provided important insights into how the known anti-inflammatory compound, omega-3 PUFA, helps reduce depression. Clinical trials by identifying and measuring the exact lipid mediators involved, identifying enzymes that prolong their effects, finding the same lipid mediators in depressed patients treated with omega-3 PUFAs, and demonstrating improvement in symptoms. For future therapeutic approaches with omega 3 fatty acids that provided important information to help with the formation of.

“It’s important to emphasize that our study does not show that simply increasing dietary omega 3 fatty acids or taking dietary supplements can reduce inflammation and depression. The mechanisms behind the association between and omega 3 PUFAs are complex and require further research and clinical trials to fully understand how they work and to inform future therapeutic approaches. “

This study was a collaborative study by researchers at King’s College in London, the University of Manchester, and China Medical University.

A paper that omega 3 polyunsaturated fatty acids protect against inflammation through the production of LOX and CYP450 lipid mediators: A link between major depression and human hippocampal neurogenesis was published today (Wednesday, June 16) in Molecular Psychiatry. It was.