Further thoughts on inflammation and depression

A search of the literature in Pub Med (3/29/2011), using the search terms depression and inflammation, reveals over 1700 documents published in the medical literature since 1922.  A tentative link between depression as a mental health issue and inflammation was first made in 1981 when Horrobin and Lieb suggested that inflammation and immune disorders could be thought of as “manic depression of the immune system.”[1]   It took another twenty years before it was noticed that elevated levels of inflammatory markers associated with heart disease were also seen in depressed patients who had no history of heart disease. [2]  But by the middle of the first decade of the new millennium, a burst of studies appear that note the link between inflammatory biomarkers and clinical depression [3-8] and dementia [9-11]. 

The role of the immune system was starting to be explored as a co-factor as well.  By 2010 links were reported between depression, inflammation and the immune system and a variety of disease states including depression[12-18], dementia [9-11], multiple sclerosis[19], heart disease [20-27], arthritis [28], and even dental diseases [29].  Also by 2010, the evidence base seemed clear that there was some link between inflammation, the immune system and depression, but it was not at all clear what the causal link was.  The evidence base exploded in the first quarter of 2011 with 24 articles compared to 34 articles in the entire year for 2010.  It could be concluded that the research community has found a new thread with a growing popularity.  But has any of this science been practically applied in the clinical trenches?

As we might expect, the pharmaceutical industry may be intrigued by the possibility of developing new psychiatric drugs based upon the underlying mechanisms of either inflammation or immunomodulation.[30]  There is even speculation that the actual benefit of current antidepressant medications may be due to their anti-inflammatory effects rather than their effects on catecholamines. [5, 31]  This opens up an area of speculation.  Since there are many foods with anti-inflammatory effects [32-43], could we eat our way out of depression?

Obviously whole natural food has limited amounts of anti-inflammatory flavonoids per kilo of food mass.  This limits the amount a person could be expected to consume.   If the effective flavonoids could be isolated and a nutraceutical could be prepared, we might have a way to test the hypothesis that depression can be reduced by ingestion of ant-inflammatory foods.  One nutraceutical preparation combines curcumin with scutellaria (a Chinese medicinal herb) and acacia derived from the bark of the boxwood tree. This combination was shown to reduce both COX and LOX enzymes to safe natural levels producing a corresponding reduction in systemic inflammation. [44]  This preparation was also found to be both safe and effective in double blind, placebo controlled trials, comparing the preparation to standard anti-inflammatory medications for arthritis.  [45-47]

To date I know of no research examining the effect of such natural anti-inflammatory foods on neurodegenerative conditions such as depression, anxiety and dementia.  In fact, despite the ample evidence of the negative effects of inflammation and oxidative stress on neurodegeneration, I have been unable to find any research on the therapeutic effects of anti-inflammatory or antioxidant diet or supplementation.   I have noticed anecdotally that a product containing anti-inflammatory flavonoids, anti-oxidants and a combination of other herbs and plant fractions has resulted in improved mood, mental energy, clarity and focus as well as stress resilience for many of my depressed patients.  This product, manufactured by the Univera company, has caused me to question whether it is time to try to obtain a formal research grant for a double blind human trial with clinically depressed individuals.

Please add your comments if you have personal or professional experience with this or other plant based natural anti-inflammatory products affecting the course of depression.

1.            Horrobin, D.F. and J. Lieb, A biochemical basis for the actions of lithium on behaviour and on immunity: relapsing and remitting disorders of inflammation and immunity such as multiple sclerosis or recurrent herpes as manic-depression of the immune system. Medical hypotheses, 1981. 7(7): p. 891-905.

2.            Kop, W.J., et al., Inflammation and coagulation factors in persons > 65 years of age with symptoms of depression but without evidence of myocardial ischemia. The American journal of cardiology, 2002. 89(4): p. 419-24.

3.            Toker, S., et al., The association between burnout, depression, anxiety, and inflammation biomarkers: C-reactive protein and fibrinogen in men and women. Journal of occupational health psychology, 2005. 10(4): p. 344-62.

4.            Shimbo, D., et al., Role of depression and inflammation in incident coronary heart disease events. The American journal of cardiology, 2005. 96(7): p. 1016-21.

5.            Ozcakar, L., et al., Selective serotonin reuptake inhibitors in familial Mediterranean fever: are we treating depression or inflammation? Rheumatology international, 2005. 25(4): p. 319-20.

6.            Janszky, I., et al., Self-rated health and vital exhaustion, but not depression, is related to inflammation in women with coronary heart disease. Brain, behavior, and immunity, 2005. 19(6): p. 555-63.

7.            Huang, T.L. and J.F. Chen, Cholesterol and lipids in depression: stress, hypothalamo-pituitary-adrenocortical axis, and inflammation/immunity. Advances in clinical chemistry, 2005. 39: p. 81-105.

8.            Hestad, K.A., et al., Inflammation and depression: further studies are needed. The journal of ECT, 2005. 21(1): p. 52.

9.            Sundelof, J., et al., Systemic inflammation and the risk of Alzheimer’s disease and dementia: a prospective population-based study. J Alzheimers Dis, 2009. 18(1): p. 79-87.

10.          Leonard, B.E., Inflammation, depression and dementia: are they connected? Neurochemical research, 2007. 32(10): p. 1749-56.

11.          Leonard, B.E. and A. Myint, Inflammation and depression: is there a causal connection with dementia? Neurotoxicity research, 2006. 10(2): p. 149-60.

12.          Song, C. and H. Wang, Cytokines mediated inflammation and decreased neurogenesis in animal models of depression. Progress in neuro-psychopharmacology & biological psychiatry, 2010.

13.          Shelton, R.C. and A.H. Miller, Eating ourselves to death (and despair): the contribution of adiposity and inflammation to depression. Progress in neurobiology, 2010. 91(4): p. 275-99.

14.          Shelton, R.C., et al., Altered expression of genes involved in inflammation and apoptosis in frontal cortex in major depression. Molecular psychiatry, 2010.

15.          Lucchina, L., et al., Evaluating the interaction between early postnatal inflammation and maternal care in the programming of adult anxiety and depression-related behaviors. Behavioural brain research, 2010. 213(1): p. 56-65.

16.          Lucassen, P.J., et al., Regulation of adult neurogenesis by stress, sleep disruption, exercise and inflammation: Implications for depression and antidepressant action. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2010. 20(1): p. 1-17.

17.          Glover, A.T., et al., Can inflammation be an independent predictor of depression? Brain, behavior, and immunity, 2010. 24(2): p. 173; author reply 174-5.

18.          Gardner, A. and R.G. Boles, Beyond the serotonin hypothesis: Mitochondria, inflammation and neurodegeneration in major depression and affective spectrum disorders. Progress in neuro-psychopharmacology & biological psychiatry, 2010.

19.          Gold, S.M. and M.R. Irwin, Depression and immunity: inflammation and depressive symptoms in multiple sclerosis. Immunology and allergy clinics of North America, 2009. 29(2): p. 309-20.

20.          Davidson, K.W., et al., Relation of inflammation to depression and incident coronary heart disease (from the Canadian Nova Scotia Health Survey [NSHS95] Prospective Population Study). Am J Cardiol, 2009. 103(6): p. 755-61.

21.          Pizzi, C., et al., Analysis of potential predictors of depression among coronary heart disease risk factors including heart rate variability, markers of inflammation, and endothelial function. Eur Heart J, 2008. 29(9): p. 1110-7.

22.          Hannestad, J., Regarding “depression and inflammation in patients with coronary heart disease: findings from the heart and soul study”. Biol Psychiatry, 2008. 63(3): p. e27.

23.          Whooley, M.A., et al., Depression and inflammation in patients with coronary heart disease: findings from the Heart and Soul Study. Biol Psychiatry, 2007. 62(4): p. 314-20.

24.          Vaccarino, V., et al., Depression, inflammation, and incident cardiovascular disease in women with suspected coronary ischemia: the National Heart, Lung, and Blood Institute-sponsored WISE study. J Am Coll Cardiol, 2007. 50(21): p. 2044-50.

25.          Buriachkovskaia, L.I., et al., [Platelet activation and inflammation markers in patients with coronary heart disease and depression]. Ter Arkh, 2006. 78(10): p. 9-14.

26.          Shimbo, D., et al., Role of depression and inflammation in incident coronary heart disease events. Am J Cardiol, 2005. 96(7): p. 1016-21.

27.          Janszky, I., et al., Self-rated health and vital exhaustion, but not depression, is related to inflammation in women with coronary heart disease. Brain Behav Immun, 2005. 19(6): p. 555-63.

28.          Kojima, M., et al., Depression, inflammation, and pain in patients with rheumatoid arthritis. Arthritis and rheumatism, 2009. 61(8): p. 1018-24.

29.          Johannsen, A., et al., Dental plaque, gingival inflammation, and elevated levels of interleukin-6 and cortisol in gingival crevicular fluid from women with stress-related depression and exhaustion. Journal of periodontology, 2006. 77(8): p. 1403-9.

30.          Maes, M., et al., Editorial: (Neuro)inflammation and neuroprogression as new pathways and drug targets in depression: From antioxidants to kinase inhibitors. Progress in neuro-psychopharmacology & biological psychiatry, 2011.

31.          Brustolim, D., et al., A new chapter opens in anti-inflammatory treatments: the antidepressant bupropion lowers production of tumor necrosis factor-alpha and interferon-gamma in mice. International immunopharmacology, 2006. 6(6): p. 903-7.

32.          Bhandare, A.M., et al., Potential analgesic, anti-inflammatory and antioxidant activities of hydroalcoholic extract of Areca catechu L. nut. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 2010. 48(12): p. 3412-7.

33.          Zhou, H., C.S. Beevers, and S. Huang, The targets of curcumin. Current drug targets, 2011. 12(3): p. 332-47.

34.          Shukla, S., et al., Studies on anti-inflammatory, antipyretic and analgesic properties of Caesalpinia bonducella F. seed oil in experimental animal models. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 2010. 48(1): p. 61-4.

35.          Palozza, P., et al., Tomato lycopene and inflammatory cascade: basic interactions and clinical implications. Current medicinal chemistry, 2010. 17(23): p. 2547-63.

36.          Choi, S.P., et al., Protective effects of black rice bran against chemically-induced inflammation of mouse skin. Journal of agricultural and food chemistry, 2010. 58(18): p. 10007-15.

37.          Thakur, G.S., et al., Momordica balsamina: a medicinal and neutraceutical plant for health care management. Current pharmaceutical biotechnology, 2009. 10(7): p. 667-82.

38.          Li, X., et al., Anti-inflammatory and analgesic activities of Chaenomeles speciosa fractions in laboratory animals. Journal of medicinal food, 2009. 12(5): p. 1016-22.

39.          Butt, M.S. and M.T. Sultan, Green tea: nature’s defense against malignancies. Critical reviews in food science and nutrition, 2009. 49(5): p. 463-73.

40.          Ban, J.O., et al., Anti-inflammatory and arthritic effects of thiacremonone, a novel sulfur compound isolated from garlic via inhibition of NF-kappaB. Arthritis research & therapy, 2009. 11(5): p. R145.

41.          Yoshioka, Y., et al., Orally administered apple procyanidins protect against experimental inflammatory bowel disease in mice. International immunopharmacology, 2008. 8(13-14): p. 1802-7.

42.          Takaki, I., et al., Anti-inflammatory and antinociceptive effects of Rosmarinus officinalis L. essential oil in experimental animal models. Journal of medicinal food, 2008. 11(4): p. 741-6.

43.          Kurtz, E.S. and W. Wallo, Colloidal oatmeal: history, chemistry and clinical properties. Journal of drugs in dermatology : JDD, 2007. 6(2): p. 167-70.

44.          Burnett, B.P., et al., A medicinal extract of Scutellaria baicalensis and Acacia catechu acts as a dual inhibitor of cyclooxygenase and 5-lipoxygenase to reduce inflammation. Journal of medicinal food, 2007. 10(3): p. 442-51.

45.          Pillai, L., B.P. Burnett, and R.M. Levy, GOAL: multicenter, open-label, post-marketing study of flavocoxid, a novel dual pathway inhibitor anti-inflammatory agent of botanical origin. Current medical research and opinion, 2010. 26(5): p. 1055-63.

46.          Levy, R.M., et al., Flavocoxid is as effective as naproxen for managing the signs and symptoms of osteoarthritis of the knee in humans: a short-term randomized, double-blind pilot study. Nutrition research, 2009. 29(5): p. 298-304.

47.          Altavilla, D., et al., Flavocoxid, a dual inhibitor of cyclooxygenase and 5-lipoxygenase, blunts pro-inflammatory phenotype activation in endotoxin-stimulated macrophages. British journal of pharmacology, 2009. 157(8): p. 1410-8.

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