Food and Behaviour Research

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30 Jan 2011 - Scientific American - Diets Low In Omega-3 Linked to Depressive Behavior In Mice

New research shows why some individuals deficient in beneficial fatty acids might be more prone to mood disorders

FAB RESEARCH COMMENT:

Many previous studies have shown that relative deficiencies of omega-3 fatty acids in maternal diets during pregnancy are associated with increased risks of depression, anxiety and related problems in the offspring.

This study reveals a specific mechanism by which omega-3 deficiency, which corresponds to omega-6 excess, could produce these effects.  Omega-3 deficiency in early life was found to downregulate receptors that are usually sensitive to endocannabinoids - and this reduction in sensitivity appeared to be permanent.

Endocannabinoids are substances involved in the regulation of pain, temperature, appetite and many other functions in the brain and body, and the most abundant forms are produced from the key omega-6 fatty acid arachidonic acid. 

See Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions  for more details of the research article reported on here. 

Although most people in developed countries get plenty of calories each day, their diets are often lacking in key nutrients that their bodies have evolved to expect. Omega-3 polyunsaturated fatty acids, such as those found in fish and walnuts, are one category of crucial ingredients that the body cannot make on its own. Although these beneficial fatty acids are known to be good for heart health, researchers are just beginning to learn how omega-3s impact our brains—and by extension, our moods and behavior.

Lipids are integral to the central nervous system, and as studies of statins and diabetes drugs have shown, dropping levels of some lipids can have deleterious cognitive effects. Omega-3 deficiencies specifically have been linked to mood disorders, such as depression, but the underlying neural mechanism has been subject to debate.

New research in mice, published online January 30 in Nature Neuroscience, offers insights into just how dietary intake of these fatty acids might alter the brain's function. (Scientific American is part of Nature Publishing Group.)

"Our results can now corroborate clinical and epidemiological studies which have revealed associations between an omega-3/omega-6 imbalance and mood disorders," scientists behind the new study commented in a prepared statement.

The group, led by Mathieu Lafourcade, of Unité Inserm's Neurocentre Magendie in France, found that mice reared on an omega-3-deficient diet had lower levels of polyunsaturated fatty acids, such as docosahexaenoic acid (DHA), in their brains as well as higher overall levels of the more harmful omega-6. These mice also went on to exhibit a range of depressive symptoms in behavioral tests. The deficient animals, for example, gave up more easily in a classic forced swimming test, were less inclined to explore and were more inclined to stay near the wall of a cage, "a widely accepted index of anxiety," the researchers noted in their study.

More specifically, the team found that a diet lacking ample omega-3 decreased the function of presynaptic cannabinoid receptors, part of the brain's signaling network that is thought to be involved in pain and appetite regulation.  By getting down to synaptic levels in the brain—even if only in mice—the researchers seem to have taken a step toward explaining why omega-3 trials in humans have shown some success in treating mood disorders.

Others who have been following the links between nutrition and neuroscience are excited about the findings. "I think it's an important paper," says Gregory Asnis, a professor of psychiatry at Albert Einstein College of Medicine in the Bronx and who was not involved in the new study. "This raises concern about the true effect of omega-3 on behavior in human beings."

Omega-3 has already been used to treat depression in adults as well as children, but as Asnis points out, "not every depressed patient has omega-3 deficiencies." And although clinical data has shown it to be effective in some patients, "it's not a knock-you-head-over kind of data," he says.

Researchers can now measure a person's omega-3 levels relatively accurately via a blood test. Now that this test is available, "this research is really going to blossom," Asnis says. He suggests that screening might soon become routine for people with depression as well as other key populations, such as pregnant women.

Although malnutrition during pregnancy is known to lead to poor outcomes for babies, "the functional long-term consequences of maternal malnutrition on the brains and behavior of their progeny are mostly unknown," noted the researchers.

"It makes sense" that a baby born to a mother who was not consuming enough omega-3s might be at higher risk for neural deficiencies, Asnis says. Offspring are wholly dependent on their mothers to supply these fatty acids both while in utero and during breastfeeding. And the researchers found that mice born to mothers who had been fed an omega-3-deficient diet and were then themselves given poor diets also suffered from negative behavioral changes.

Omega-3s are of course not the sole actor in neurological development and health. "Behavior is multi-determined, affected by so many things," Asnis says. And depression and other mood disorders can vary widely among individuals.

Animal models for diseases such as cancer have frequently been found lacking and for neurological disorders they also do not always translate  synapse-by-synapse to humans. But Asnis notes that there have been reassuring precedents in studying depressive behavior in animals, such as work with serotonin and tryptophan. "I think there might be a paradigm" that could translate to humans, he says. "It seems like an important discovery that manipulating omega-3 levels can have behavioral effects."

And even if the findings prove relevant only for a subpopulation of patients with depression and omega-3 deficiencies, the implications are substantial. With omega-3-rich fish and flaxseed oils now common in grocery and drug store supplement sections, maintaining a diet replete in these crucial fatty acids is not as hard as it once was. And the promise of being able to treat some depressed individuals—and perhaps prevent the condition in others—with "something that's so easy to give," Asnis says, is incredibly appealing.