The Role of Inflammation in Depression

Background

Inflammation is your body’s response to when something is wrong. It is how your body signals to the immune system to find and repair damaged cells. Inflammation is also important in signaling the immune system to find bacteria and viruses. Short term inflammation is important for the body to protect itself but problems can arise when the body thinks it is under minor attack for a long period of time. This is called chronic, low-grade inflammation and one-third of depressed individuals have increased inflammatory markers. Commonly measured markers of inflammation include tumor necrosis factor (TNF) interleukin 1β, IL-6 and C-reactive protein (CRP).

The mean value of inflammatory markers tends to be modestly higher in depressed patients (2-3 times the levels of healthy patients). Not all patients with depression have increased inflammation markers. Chronic, low-grade inflammation can still contribute to large changes over time. Cardiovascular disease, stroke, cancer, diabetes and dementia also have moderately increased inflammatory signaling.

One of my questions was if depression causes inflammation or if inflammation causes depression. Or maybe they can contribute to each other. It seems to be that inflammation leads to depression and not the other way around. Mildly elevated levels of CRP and IL-6 predict the subsequent development of depression over a decade. Patients with depression did not predict an increase in inflammation biomarkers at follow up.¹

What causes the inflammation?

1. Stress and trauma

Stress can be taxing on the body. A stress response by the body releases hormones, neurotransmitters, can increase heart rate and blood pressure. Over time this can contribute to inflammatory processes.

A longitudinal study in New Zealand followed 1,000 patients from birth to 32 years old and found that individuals experiencing stress in childhood from maltreatment, abuse, social isolation, or economic hardship were twice as likely to suffer chronic inflammation.²

2. Diet:

The gut and gastrointestinal tract are common places where inflammation can occur. Current dietary practices can contribute to inflammation. Certain foods are anti-inflammatory and may help with the problem. Tomatoes, strawberries, blueberries, nuts, olive oil, and leafy greens are all anti-inflammatory. Evidence supports this as well. A 2004 study concluded that a dietary pattern of high intakes of fruits and vegetables, whole grains, fish and legumes was associated with reduced plasma concentrations of inflammatory markers while a “Western” diet, high in red and processed meats, refined carbohydrates and processed foods was associated with an increase in inflammatory markers.³

Exercise:

Exercise increasing inflammation in the short term. Muscle fatigue, pain, and soreness are all associated with inflammation. After the body releases inflammatory substances during exercise, it follows this up by increasing anti-inflammatory substances. Regular exercise dampens the inflammatory response.

Common areas of inflammation include the gut, skin, and mouth. Inflammation in the gut can be addressed through dietary changes seen above. Inflammation of the skin can be addressed by treating Eczema and other rashes. The mouth is another area of inflammation. Gingivitis is inflammation of the gums and can be caused by poor oral care. Periodontal disease is a predictor of inflammatory illnesses like cardiovascular disease, and outcomes like mortality in diabetes and heart disease.4

Supplements:

It is not surprising that a lot of supplements that are helpful in treating depression have anti-inflammatory properties. Some that I have taken include Saffron, Curcumin, Vitamin D and Omega-3 fatty acids. Additional supplements that may decrease inflammation include Alpha-Lipoic Acid and Ginger.

Evidence:

The current evidence supports that antidepressant selection can be improved by measuring inflammation levels.

A study from Europe in 2014 assessed if the amount of inflammation would predict which medication would be helpful. The study analyzed the level of C-reactive protein in 241 patients with depression. The patients were then treated with SSRI, Escitalopram or the Tri-cyclic antidepressant, Nortriptyline. Patients with low levels of CRP responded better to Escitalopram, while patient with high levels responded better to Nortriptyline.5

Another study assessed C-reactive protein and antidepressant selection. 106 patients either received escitalopram plus placebo or bupropion plus escitalopram. Higher baseline CRP patients responded better to bupropion plus escitalopram while low baseline CRP patients responded better to escitalopram plus placebo.6

References:

  1. Raison C, Miller A. Is Depression an Inflammatory Disorder? Curr Psychiatry Rep. 2011 Dec; 13(6): 467–475.
  2. Danese A, Pariante C, Caspi A, et al. Childhood maltreatment predicts adult inflammation in a life-course study. Proc Natl Acad Sci U S A. 2007 Jan 23;104(4):1319-24.
  3. Lopez-Garcia E, Schulze M, Fung T, et al. Major dietary patterns are related to plasma concentrations of markers of inflammation and endothelial dysfunction. Am J Clin Nutr. 2004 Oct;80(4):1029-35.
  4. Berk M, Williams L, Jacka F, et al. So depression is an inflammatory disease, but where does the inflammation come from? BMC Med. 2013 Sep 12;11:200. doi: 10.1186/1741-7015-11-200.
  5. Uher R, Tansey K, Dew T, et al. An inflammatory biomarker as a differential predictor of outcome of depression treatment with escitalopram and nortriptyline. Am J Psychiatry. 2014 Dec 1;171(12):1278-86.
  6. Jha M, Minhajuddin A, Gadad B, et al. Can C-reactive protein inform antidepressant medication selection in depressed outpatients? Findings from the CO-MED trial. Psychoneuroendocrinology. 2017 Apr;78:105-113.

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