A study on mice found that adding omega-3 polyunsaturated fatty acids to their diets effectively counteracts depressive and anxiety-like behaviors induced by stress. Not only did the supplementation reduce these stress-induced symptoms, but it also lowered anxiety levels in mice that were not exposed to stress. These findings, published in Neurobiology of Stress, suggest that omega-3 fatty acids may have protective mental health benefits.

Omega-3 polyunsaturated fatty acids are essential fats that the body cannot produce, meaning they must be obtained through food. There are three main types of omega-3s: alpha-linolenic acid (ALA), found in plant oils, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), primarily found in fish and seafood. These fats play a key role in maintaining brain function, preserving the integrity of cell membranes, and reducing inflammation throughout the body.

Omega-3s are widely recognized for their cardiovascular benefits, such as lowering blood pressure and reducing the risk of heart disease. They are equally important for mental health. Research indicates that omega-3s may alleviate symptoms of depression and anxiety, likely due to their anti-inflammatory properties and their role in maintaining brain health.

Several recent rodent studies have shown that incorporating these fatty acids into the diet can help counteract some of the negative effects of chronic stress, particularly during critical developmental periods. Omega-3s are most abundant in fatty fish like salmon and tuna, as well as in plant sources such as flaxseeds, walnuts, and chia seeds.

Study author Tatyana Strekalova and her colleagues wanted to explore whether exposing young mice to prolonged stress would induce behaviors similar to anxiety and depression in humans, and if supplementing the diet with omega-3 fatty acids would help prevent the development of these symptoms. Chronic stress was induced through exposure to ultrasound frequencies, simulating emotional stress that could lead to depressive-like symptoms. This method is an established way to model stress-induced depression in animals, which is used to better understand how these conditions develop in humans.

The experiments were conducted using 40 C57BL/6 male mice, each one month old. This strain of mice is commonly used in research because of their genetic uniformity and their susceptibility to diet-related conditions, such as obesity and diabetes. They are frequently used in studies on neurobiology, immunology, and cancer, making them ideal for this experiment. The mice were housed individually, with unlimited access to food and water.

The researchers divided the mice into four groups of ten. One group served as a control and received a regular diet without exposure to stress. The second group was subjected to chronic stress in the form of unpredictable ultrasound frequencies for 21 days, without any dietary supplementation. The third group received omega-3 fatty acids in their diet but was not exposed to stress. The fourth group was both exposed to stress and given the omega-3 supplement. The supplement included 0.55 mg/kg/day each of EPA and DHA, matching the recommended dosage of omega-3s for humans, scaled appropriately for mice.

After the 21-day period of stress exposure, the mice underwent several behavioral tests designed to measure symptoms analogous to human depression and anxiety. These tests included the sucrose preference test, which assesses anhedonia (the loss of interest in pleasurable activities), the novel cage test, the dark-light box test, and the open field test, which measure anxiety and exploratory behaviors. Once the behavioral tests were completed, the mice were killed, and their blood and tissues were analyzed to assess the biological effects of stress and omega-3 supplementation.

Mice that were exposed to ultrasound stress but received no dietary supplements showed significant anxiety- and depression-like behaviors. They displayed reduced sucrose consumption, indicating anhedonia, and exhibited less exploratory behavior in the tests. Furthermore, their blood samples revealed elevated levels of corticosterone, a hormone linked to stress responses.

The researchers also detected increased expression of TNF and interleukin-1 beta (IL-1β) genes in the brain, both of which are markers of inflammation. Inflammation in the brain is associated with various neurological disorders and can exacerbate conditions like depression and anxiety. The enhanced gene expression suggests that chronic stress had triggered an inflammatory response in these mice, leading to changes in their brain function and behavior.

In contrast, the mice that were exposed to stress but received omega-3 supplementation did not show the same degree of behavioral and physiological changes. They continued to drink sucrose, indicating they were less affected by stress-induced anhedonia, and they explored their environment more freely during the tests. Their levels of corticosterone and inflammatory markers, including TNF and IL-1β, were also lower than those in the stressed mice without supplementation.

These findings suggest that omega-3 fatty acids may protect against the harmful effects of chronic stress by reducing inflammation in the brain. Interestingly, even the mice that were not exposed to stress but received omega-3 supplements showed fewer anxiety-like behaviors compared to the control group, highlighting the broad mental health benefits of these fatty acids.

“Chronic omega-3 intake counteracted depressive- and anxiety-like behaviors in a US model of juvenile depression in mice [mice exposed to chronic stress as juveniles using ultrasound]. These effects likely stem from the anti-inflammatory properties of the supplement, suggesting potential therapeutic applications in juvenile depression,” the study authors concluded.

The study demonstrates the protective effects of omega-3 fatty acid supplements in mice exposed to chronic stress. However, it should be emphasized that this study was done on mice, not on humans. While mice and humans share many physiological similarities, there are significant differences between the two species. The effects observed in this study may not necessarily translate directly to human patients, and further research is needed to confirm whether omega-3 supplements would have the same benefits in people.

The paper, “Omega-3 alleviates behavioral and molecular changes in a mouse model of stress-induced juvenile depression,” was authored by Tatyana Strekalova, Daniel Radford-Smith, Isobel K. Dunstan, Anna Gorlova, Evgeniy Svirin, Elisaveta Sheveleva, Alisa Burova, Sergey Morozov, Aleksey Lyundup, Gregor Berger, Daniel C. Anthony, and Susanne Walitza.