Omega-3 fatty acids are found in some green vegetables, vegetable oils, and fatty fish. There is some evidence that omega-3 fatty acid supplements can reduce depression, but researchers are trying to clarify which omega-3s are most helpful, and for whom. A new study in Molecular Psychiatry suggests that depressed people with higher inflammation may respond best to EPA omega-3 fatty acids compared to DHA omega-3 fatty acids or placebo. Researchers led by M.H. Rapaport divided people with major depressive disorder into “high” and “low” inflammation groups based on their levels of the inflammatory markers IL-1ra, IL-6, high-sensitivity C-reactive protein, leptin, and adiponectin. Participants were randomized to receive eight weeks of treatment with EPA omega-3 supplements (1060mg/day), DHA omega-3 supplements (900mg/day), or placebo.
While overall treatment differences among the three groups as a whole were negligible, the high inflammation group improved more on EPA than on placebo or DHA, and more on placebo than on DHA. The authors suggest that EPA supplementation may help relieve symptoms of depression in people whose depression is associated with high inflammation levels, a link common among obese people with depression.
Editor’s Note: These data add to a study by Rudolph Uher et al. in which people with high levels of C-reactive protein responded better to the tricyclic antidepressant nortriptylene, while those with low levels of the inflammatory marker responded better to the selective serotonin reuptake inhibitor antidepressant escitalopram.
A new study finds that omega-3 fatty acid supplementation improves attention in boys both with and without attention deficit hyperactivity disorder (ADHD). The study by Dienke J. Bos and colleagues in the journal Neuropsychopharmacology included 40 boys (aged 8–14) with ADHD and 39 demographically matched controls. Participants were given 10 g per day of margarine supplemented with either omega-3 fatty acids (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) or placebo.
The children who received EPA/DHA supplementation showed improvements in attention (as rated by parents) compared to those who received placebo. Improvement was greater in the children with ADHD. Supplementation did not affect cognitive control or brain activity on functional magnetic resonance imaging (fMRI). Those boys who received omega-3s showed higher DHA levels on followup.
Children who have a parent with bipolar disorder are at risk for bipolar illness, but it may first present as depression. Treating these children with antidepressants has the risk of bringing on manic episodes. Researchers are looking for treatment options for youth at risk for bipolar disorder.
Robert McNamara and colleagues found that 12 weeks of omega-3 fatty acids (2,100 mg/day) significantly improved response rates in medication-free youth ages 9–20 years compared to placebo (64% versus 36%). Omega-3 fatty acids but not placebo also reduced the activation of limbic structures in the brain (the left parahippocampal gyrus) in response to emotional stimuli.
Editor’s Note: These data add to the literature on the positive effects of 1–2 grams of omega-3 fatty acids in depression. Given the safety of omega-3 fatty acids and the ambiguous effects of antidepressants in bipolar depression, omega-3 fatty acids would appear to a good alternative, especially since the FDA-approved atypical antipsychotics (quetiapine and lurasidone) are not approved for bipolar depression in people under age 18.
In a recent randomized, controlled clinical study comparing two types of omega-3 fatty acid supplements (one with EPA and one with DHA) with placebo in 196 adults with major depression, there were no statistically significant differences in outcomes across the three groups. The participants received the treatments for eight weeks, and response and remission rates were 40-50% in those receiving either omega-3 preparation (at doses of 1000mg/day) and 30% for placebo. The research was published by David Mischoulon and colleagues in the Journal of Clinical Psychiatry.
Omega-3 fatty acids (especially the type known as DHA) are essential for brain development and functioning, but most people eating a modern western diet consume low amounts of these compared to omega-6 fatty acids. Omega-3s are anti-inflammatory while omega-6s are pro-inflammatory. A large UK study published in the journal PLOS One in 2013 reported that healthy 7- to 9-year-olds with lower levels of omega-3 long-chain polyunsaturated fatty acids in their blood (including DHA, DPA, and EPA) had lower reading ability and working memory, and also had more behavior problems.
The oils in fish are the best source of omega-3 fatty acids, and most of the children with poor reading ability in the study fell short of the UK nutritional guideline that recommends eating two portions of fish per week.
Girls in the study had more dramatic deficits in omega-3 levels than boys. In adults, women tend to metabolize long chain polyunsaturated fatty acids more easily than men, but this difference is driven by hormones, and because the girls in the study had not yet reached child-bearing age, they did not reflect this benefit.
Omega-3 deficits in children have been connected with attention deficit hyperactivity disorder (ADHD), and supplementation with extra omega-3 fatty acids in the diet has led to improvements in ADHD.
Cultures where more omega-3 fatty acids (which have anti-inflammatory effects) and fewer omega-6 fatty acids (which have pro-inflammatory effects) are consumed have a lower incidence of depression and bipolar disorder. However, the exact role that each kind of fatty acid plays in the brain and whether dietary changes can improve mood disorders is still being investigated. A 2012 study in the Journal of Psychiatric Research examined the complete lipid profiles of participants with bipolar disorder to collect data on these questions.
The most significant results to come from the study were that levels of the long-chain omega-6 fatty acid dihomo-gamma-linolenic acid (DGLA) were positively correlated with neuroticism, depression severity, and decreased functioning. Depression severity was negatively correlated with the omega-6 fatty acid linolenic acid (LA) and the omega-3 fatty acid alpha-linolenic acid (ALA), and positively correlated with fatty acid desaturase 2 (FADS2), an enzyme that converts LA to the omega-6 fatty acid gamma-linolenic acid GLA.
The data suggest that particular omega-6 fatty acids and the enzymes that lead to their production may be used as biomarkers that can indicate depression.
Editor’s Note: Levels of specific omega-6 fatty acids and their related enzymes were found to correlate with depression severity in this study. Since omega-6 fatty acids are pro-inflammatory, diets higher in omega-6 fatty acids are associated with more cardiovascular problems, and a 2012 article by Chang et al. in the Journal of Psychiatric Research reported that completed suicides in bipolar patients with cardiovascular disorders were significantly higher than in those with bipolar disorder without cardiovascular illness, it seems a healthy diet can have multiple benefits, including potentially reducing depressive burden, cardiovascular risk, and suicide risk.
Several studies in adults and children suggest that omega-3 fatty acid supplementation may have antidepressant effects. At the 2013 meeting of the American Academy of Child and Adolescent Psychiatry in October, Melissa DelBello, a professor at the University of Cincinnati, reported on a new study of omega-3 fatty acids in depressed children who had a parent with bipolar disorder. The children taking omega-3 fatty acids were more likely to improve than those taking a placebo, but the findings were only of marginal significance.
Cold-water fish are a good source of omega-3 fatty acids, and DelBello said salmon is by far the best in this regard. People who live in countries where fish is consumed in greater quantities are less likely to suffer from depression. Other sources of omega-3 fatty acids include shellfish, plant and nut oils, English walnuts, flaxseed, algae oils, and fortified foods.
The omega-3 fatty acids from fish are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), while the omega-3 fatty acids from plants are alpha-linolenic acid (ALA), which breaks down into EPA and DHA. All of these are anti-inflammatory, though one must consume much greater quantities of ALA to match the benefits of EPA and DHA. In contrast, omega-6 fatty acids, which are much more common in the typical American diet, are pro-inflammatory.
In DelBello’s study of 56 depressed children of a parent with bipolar disorder, the participants were randomized to either 1.8 g of omega-3 fatty acids (1.2 g of EPA and 0.6 g of DHA) or placebo (olive oil). Those who received the omega-3 fatty acids had a 55.6% rate of remission versus 34.5% for those who received placebo, but while the odds ratio of 2.4 favored the omega-3 fatty acids, the difference in remission rates was not statistically significant, likely because of the small size of the study. However, improvement on the Children’s Depression Rating Scale was significantly different across the two groups, with children taking omega-3s improving more. Omega-3 fatty acids are known to have an anticoagulant effect (preventing the clotting of blood), and four children in the study did have prolonged clotting times (but no clinical problems with bleeding).
Editor’s Note: Given the existing literature on omega-3 fatty acids and the trend in this study, omega-3s are worthy of consideration for the treatment and potentially for the prevention of depression in children. This later possibility is further suggested by findings from Australia that, when compared to placebo, omega-3 fatty acids significantly reduced the rate of conversion from prodromal (preliminary) psychotic symptoms to a full-blown diagnosis of schizophrenia.
An article by Bloch & Qawasmi published in the Journal of the American Academy of Child and Adolescent Psychiatry last year suggested that omega-3 fatty acids could improve ADHD in children. The effects were milder than the standard pharmacological treatments for ADHD, but given that omega-3s have few side effects, there would be little risk to using them to supplement traditional treatments or in cases where traditional treatments cannot be used.
Editors note: It would also be worth seeing if omega-3s helped mood symptoms too. A meta-analysis we wrote about here suggests that the omega-3 fatty acid EPA or the combination of EPA plus DHA has positive effects on depression in adults.
An article in Time Healthland last year reported that preliminary research shows that women who took fish oil during pregnancy experienced fewer symptoms of post-partum depression than women who did not take fish oil supplements.
This data has not yet been replicated, but since there are few side effects to taking fish oil supplements, which are high in omega-3 fatty acids, the risk-to-benefits ratio suggests that there is no reason pregnant women shouldn’t take fish oil supplements to decrease the likelihood of depression after delivery.
We have written before about the possible benefits of omega-3 fatty acids.
Iris Manor reported at the 57th Annual Meeting of the American Academy of Child and Adolescent Psychiatry (AACAP) in October 2010 that phosphatidylserine (a phospholipid component) containing omega-3 fatty acids had significant positive effects in children with ADHD. These findings were notable because Manor and other investigators had previously found that omega-3 fatty acids themselves were not effective in ADHD, raising the possibility that the phosphatidylserine component offers unique therapeutic advantages. This compound is currently available in Israel and may become available in the US in the next year.