For psychiatrists seeing patients with an inflammatory condition, brief explanations of the known links between depression and inflammation can provide patients—particularly those ambivalent about seeking mental health care—support for engaging in treatment and adhering to medication. Describing the links between inflammation and depression also can help encourage regular exercise and healthy diets rich in fruits, vegetables, and omega-3 fatty acids. In cases of treatment-resistant depression, particularly in those with known high inflammatory factors, it may be worthwhile to consider anti-inflammatory agents, such as infliximab, as an adjuvant treatment.

The relationship between inflammation and depression is rapidly unfolding, but the full intricacies have not yet described. However, this beginning awareness of the interplay among stress, inflammation, and depression can broaden our approach to care and treatment.

Bottom Line

Depression and inflammation are linked in many ways, although neither appears to be wholly necessary or sufficient for the other. Most likely there exists a particular subset of patients for whom inflammation will precipitate and perpetuate depression.

Related Resources

• The Emory University Mind-Body Program. www.
  psychiatry.emory.edu/PROGRAMS/mindbody/index.html.
• Gabriel B. The evolutionary advantage of depression. The Atlantic. October 2, 2012. www.theatlantic.com/health/archive/2012/10/the-evolutionary-advantage-of-depression/263124.

Drug Brand Names

Infliximab • Remicade Ribavirin • Rebetol, Virazole
Interferon-α • Intron

Disclosure
Dr. Almond reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

References

1. Dantzer R, O’Connor JC, Freund GG, et al. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci. 2008;9(1):46-56.

2. Hart BL. Biological basis of the behavior of sick animals. Neurosci Biobehav Rev. 1988;12(2):123-137.

3. Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 2006;27(1):24-31.

4. Lamers F, Vogelzangs N, Merikangas KR, et al. Evidence for a differential role of HPA-axis function, inflammation and metabolic syndrome in melancholic versus atypical depression [published online October 23, 2012]. Mol Psychiatry. doi: 10.1038/mp.2012.144.

5. Hoen P, Kupper N, de Jonge P. Depression and cardiovascular disease progression: epidemiology, mechanisms and treatment. In: Hjemdahl P, Rosengren A, Steptoe A, eds. Stress and cardiovascular disease. London, United Kingdom: Springer; 2012:211-233.

6. Anderson RJ, Freedland KE, Clouse RE, et al. The prevalence of comorbid depression in adults with diabetes: a meta-analysis. Diabetes Care. 2001;24(6):1069-1078.

7. Bachen EA, Chesney MA, Criswell LA. Prevalence of mood and anxiety disorders in women with systemic lupus erythematosus. Arthritis Rheum. 2009;61(6):822-829.

8. Dickens C, McGowan L, Clark-Carter D, et al. Depression in rheumatoid arthritis: a systematic review of the literature with meta-analysis. Psychosom Med. 2002;64(1):52-60.

9. Benros ME, Waltoft BL, Nordentoft M, et al. Autoimmunity and infections as risk factors for depression and other severe mental illnesses. Neurology, Psychiatry and Brain Research. 2012;18(2):40-41.

10. National Cancer Institute. Depression (PDQ). http://www.cancer.gov/cancertopics/pdq/supportivecare/depression/HealthProfessional/page1. Updated January 9, 2013. Accessed April 23, 2013.

11. Centers for Disease Control and Prevention. Current depression among adults—United States, 2006 and 2008. Morb Mortal Wkly Rep. 2010;59(38):1229-1235.

12. Krishnadas R, Cavanagh J. Depression: an inflammatory illness? J Neurol Neurosurg Psychiatry. 2012;83(5):495-502.

13. Miller AH, Maletic V, Raison CL. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry. 2009;65(9):732-741.

14. Dowlati Y, Herrmann N, Swardfager W, et al. A meta-analysis of cytokines in major depression. Biol Psychiatry. 2010;67(5):446-457.

15. Maes M, Bosmans E, De Jongh R, et al. Increased serum IL-6 and IL-1 receptor antagonist concentrations in major depression and treatment resistant depression. Cytokine. 1997;9(11):853-858.

16. Raison CL, Borisov AS, Broadwell SD, et al. Depression during pegylated interferon-alpha plus ribavirin therapy: prevalence and prediction. J Clin Psychiatry. 2005;66(1):41-48.

17. Capuron L, Raison CL, Musselman DL, et al. Association of exaggerated HPA axis response to the initial injection of interferon-alpha with development of depression during interferon-alpha therapy. Am J Psychiatry. 2003;160(7):1342-1345.

18. Eisenberger NI, Berkman ET, Inagaki TK, et al. Inflammation-induced anhedonia: endotoxin reduces ventral striatum responses to reward. Biol Psychiatry. 2010;68(8):748-754.

19. Pasco JA, Nicholson GC, Williams LJ, et al. Association of high-sensitivity C-reactive protein with de novo major depression. Br J Psychiatry. 2010;197(5):372-377.

20. Raison CL, Rutherford RE, Woolwine BJ, et al. A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry. 2013;70(1):31-41.

21. Martinez JM, Garakani A, Yehuda R, et al. Proinflammatory and “resiliency” proteins in the CSF of patients with major depression. Depress Anxiety. 2012;29(1):32-38.

22. Lanquillon S, Krieg JC, Bening-Abu-Shach U, et al. Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacology. 2000;22(4):370-379.

23. Raison CL, Miller AH. Is depression an inflammatory disorder? Curr Psychiatry Rep. 2011;13(6):467-775.