Why do people get seriously, chronically depressed, and what helps them?

We lack clear answers, because – as with cancer – there's no single cause and no uniform cure.

But research over the past 25 years strongly suggests that inflammation promotes depression.

Depression often occurs in acute illnesses, and higher inflammation levels in the body raise the risk of developing depression. 

There's ample evidence that chronic, “silent” inflammation raises the risk of depression, which is linked to high blood levels of C-reactive protein ... a pro-inflammatory immune system agent that also signals higher risk for heart disease.

And when cancer patients are given therapeutic – but pro-inflammatory – proteins called interferons, depression often follows. Likewise, interferon therapy triggers depression in almost one-third of hepatitis C patients.

Importantly, depression patients with high levels of inflammation are less likely to respond to standard antidepressant drugs.

Omega-balance matters to inflammation and mood
Omega-3 fatty acids from seafood exert anti-depressant and anti-inflammatory effects.

In fact, immune-system messengers (resolvins and protectins) the body makes from omega-3 DHA and EPA are essential to ending (resolving) inflammation once the body no longer needs it.

Conversely, the excess intake of omega-6 fats typical of the American diet incites chronic inflammation and raises depression risks … see “Omega-6 Overload Linked to Depression”, “Fat Imbalance Drives Depression and Inflammation”, and “Know Your Omega-3/6 Numbers”.)

These facts led a group of international researchers to see whether omega-3 fatty acids could improve inflammation-induced depression … and they just reported very encouraging results.

Clinical trial sees an omega-3 deterring inflammation-driven depression
The British-Taiwanese team behind the study was led by psychiatrist Carmine Pariante, M.D., Ph.D., head of depression research at King's College London.

Four years ago, the same research team found that people with low blood levels of omega-3 EPA ran a greater risk of developing depression (Su KP et al. 2010).

So the authors speculate that supplemental EPA bolsters the body's natural anti-inflammatory capabilities, and thus protects patients from depression when inflammation occurs.

To test that idea, Dr. Pariante's team recruited 152 hepatitis C patients for a randomized, double-blind, placebo-controlled clinical trial.

Each patient was randomly assigned to one of three groups, and was treated for two weeks with omega-3 EPA, omega-3 DHA, or a placebo.

EPA and DHA are the two main omega-3 fatty acids in seafood, fish oil supplements, and human cells. And most research suggests that supplemental omega-3s – especially EPA – can ease or deter depression significantly … see “Omega-3s Affirmed as Mood Lighteners” and “Fish Oil Rivals Antidepressants in Clinical Trial”, and “Omega-3 Mood Benefits Get More Backing”.

(For more about the distinctions among the several types of omega-3s, see our Omega-3 Facts & Sources page … especially the section titled “Long-chain omega-3s: Truly essential to life and health”.)

Following the two-week treatment, the patients received a 24-week course of interferon-alpha treatment and were evaluated repeatedly for symptoms of depression.

The researchers found that, compared to placebo pills, treatment with omega-3 EPA reduced the risk of depression by two-thirds. Omega-3 DHA produced a much smaller benefit. 

The rate of depression among the three groups was as follows:
  • Omega-3 EPA - 10 percent developed major depression
  • Omega-3 DHA - 28 percent became depressed
  • Placebo - 30 percent became depressed
In addition, both EPA and DHA delayed the onset of depression, and were well tolerated, with no serious side effects.

Dr. John Krystal, Editor of Biological Psychiatry, expressed appropriate optimism:
“These new data provide promising support for omega-3 fatty acids to prevent depression, complementing other studies where omega-3s were found to enhance antidepressant treatment.” (Elsevier 2014)

Although their findings must be replicated to be reliable, they indicate that omega-3s may help prevent depression in patients at high risk because of acute or chronic inflammation.

Want to keep your mood healthy?

Evidence like this suggests that it's wise to get ample amounts of fish or fish oil, to help extinguish any smoldering internal fires.

  • Carvalho LA, Torre JP, Papadopoulos AS, Poon L, Juruena MF, Markopoulou K, et al. (2013): Lack of clinical therapeutic benefit of antidepressants is associated overall activation of the inflammatory system. J Affect Disord 148:136–140.
  • Elsevier. Omega-3 fatty acids may prevent some forms of depression. October 1, 2014. Accessed at http://www.elsevier.com/about/press-releases/research-and-journals/reports-new-study-in-biological-psychiatry 
  • Lotrich FE, Sears B, McNamara RK. Elevated ratio of arachidonic acid to long-chain omega-3 fatty acids predicts depression development following interferon-alpha treatment: relationship with interleukin-6. Brain Behav Immun. 2013 Jul;31:48-53. doi: 10.1016/j.bbi.2012.08.007. Epub 2012 Aug 19.
  • Martins JG. EPA but not DHA appears to be responsible for the efficacy of omega-3 long chain polyunsaturated fatty acid supplementation in depression: evidence from a meta-analysis of randomized controlled trials. J Am Coll Nutr. 2009 Oct;28(5):525-42. Review.
  • Pasco JA, Nicholson GC, Williams LJ, Jacka FN, Henry MJ, Kotowicz MA, Schneider HG, Leonard BE, Berk M. Association of high-sensitivity C-reactive protein with de novo major depression. Br J Psychiatry. 2010 Nov;197(5):372-7. doi: 10.1192/bjp.bp.109.076430.
  • Su KP, Huang SY, Peng CY, Lai HC, Huang CL, Chen YC, Aitchison KJ, Pariante CM. Phospholipase A2 and cyclooxygenase 2 genes influence the risk of interferon-alpha-induced depression by regulating polyunsaturated fatty acids levels. Biol Psychiatry. 2010 Mar 15;67(6):550-7. doi: 10.1016/j.biopsych.2009.11.005. Epub 2009 Dec 24.
  • Su KP, Lai HC, Yang HT, Su WP, Peng CY, Chang JP, Chang HC, Pariante CM. Omega-3 Fatty acids in the prevention of interferon-alpha-induced depression: results from a randomized, controlled trial. Biol Psychiatry. 2014 Oct 1;76(7):559-66. doi: 10.1016/j.biopsych.2014.01.008. Epub 2014 Jan 24. 
  • Zimmer R, Riemer T, Rauch B, Schneider S, Schiele R, Gohlke H, Diller F, Steinbeck G, Katus H, Senges J; OMEGA-Study Group. Effects of 1-year treatment with highly purified omega-3 fatty acids on depression after myocardial infarction: results from the OMEGA trial. J Clin Psychiatry. 2013 Nov;74(11):e1037-45. doi: 10.4088/JCP.13m08453.