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Is Depression a Systemic Inflammatory Disease?

How can exercise and fish oil often be a more effective treatment for depression than antidepressants? Could it be because they are both potent anti-inflammatories? Could it be that depression is a low-grade inflammatory disease of the brain 1? Let's look at the evidence1.

  1. Proinflammatory cytokines IL-1, IL-6, and TNF α (molecular messengers that set off the inflammatory response) and bacterial toxins (produced in our gut) produce symptoms of depression and anxiety.
  2. Cytokines overactivate the HPA (hypothalamic-pituitary-adrenal) axis (the stress response) just like we find in depressed patients.
  3. Cytokines increase the function of an enzyme (IDO) that breaks down tryptophan, leading to less serotonin in the brain3. Serotonin is the happy mood chemical that fights depression.
  4. The immune system is overactive in severe depression, producing brain inflammation.
  5. Using immune therapy like interferon (a cytokine) for diseases like hepatitis C or multiple sclerosis triggers depression.
  6. Depression is more common in inflammatory diseases like autoimmune and heart disease.

As compelling as these pieces of information are, they are not the only indications that depression is caused by an inflamed brain.

A new technique called vagal nerve stimulation is very helpful in depression 4. The vagus nerve is your calming, relaxation nerve. When you take a deep breath, meditate, or do yoga the vagus nerve is activated, and it releases acetylcholine, which reduces the production of inflammatory cytokines.

There may be many reasons deep breathing and relaxation work, but certainly one of them is the fact that inflammation is reduced.

We also know that omega-3 fats help depression and produce remission 5. They work by lowering inflammation and also through their effects on cell membranes and cell communication.

Similarly, we know that exercise is an anti-inflammatory and works better than Prozac in treating depression6.

Another example comes out of Harvard. A group of researchers there discovered an increased number of "white matter lesions," or little white spots in the brain that are seen in autoimmune diseases like multiple sclerosis in depressed patients. This correlated with low levels of folate, which caused high levels of homocysteine, a molecule that triggers inflammation in the brain7. So being vitamin deficient produces toxic molecules that inflame the brain and cause depression.

Of course, we must ask, "Which came first, the chicken or the egg? Does depression cause inflammation or inflammation cause depression?"

The answer is yes. It is a vicious cycle. Inflammation leads to depression, which leads to more inflammation.

The message is that to adequately treat depression we must look for, find, and eliminate the causes of inflammation and then help the body create balance in the immune system turning off this vicious cycle.

For more information on depression, please see Dr. Hyman's new book, The UltraMind Solution.

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[1]
Das UN. Is depression a low-grade systemic inflammatory condition? Am J Clin Nutr. 2007 Jun;85(6):1665-6.
[2]
Anisman H, Merali Z. Cytokines, stress and depressive illness: brain-immune interactions. Ann Med. 2003;35(1):2-11. Review.
[3]
Müller N, Schwarz MJ. Immunological aspects of depressive disorders. Nervenarzt. 2007 Nov;78(11):1261-1273.
[4]
Groves DA, Brown VJ. Vagal nerve stimulation: a review of its applications and potential mechanisms that mediate its clinical effects. Neurosci Biobehav Rev. 2005 May;29(3):493-500. Review.
[5]
Parker G, Gibson NA, Brotchie H, Heruc G, Rees AM, Hadzi-Pavlovic D.Omega-3 fatty acids and mood disorders. Am J Psychiatry. 2006 Jun;163(6):969-78. Review.
[6]
Blumenthal JA, Babyak MA, Doraiswamy PM, Watkins L, Hoffman BM, Barbour KA, Herman S, Craighead WE, Brosse AL, Waugh R, Hinderliter A, Sherwood A. Exercise and pharmacotherapy in the treatment of major depressive disorder. Psychosom Med. 2007 Sep-Oct;69(7):587-96. Epub 2007 Sep 10.
[7]
Papakostas GI, Iosifescu DV, Renshaw PF, Lyoo IK, Lee HK, Alpert JE, Nierenberg AA, Fava M. Brain MRI white matter hyperintensities and one-carbon cycle metabolism in non-geriatric outpatients with major depressive disorder (Part II). Psychiatry Res. 2005 Dec 30;140(3):301-7. Epub 2005 Nov 16.

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