Psychiatric Times.
No. 7
Clinical
From Chaos to Consilience: Part II
What the New Mind-Body Science Tells Us About the Pathophysiology of Major Depression
By Charles L. Raison, MD, Vladimir Maletic, MD, Rakesh Jain, MD, MPH, and Jon W. Draud, MD, MS |
July 7, 2009
A pdf of this article will be provided on request. Please contact Dr Vladimir Maletic at vmaletic@bellsouth.net.
Dr Raison is assistant professor and clinical director of the Mind-Body Program in the department of psychiatry and behavioral sciences at Emory University School of Medicine in Atlanta. Dr Maletic is clinical professor in the department of neuropsychiatry and behavioral sciences at the University of South Carolina School of Medicine in Columbia. Dr Jain is director of adult and child psychopharmacology research at R/D Clinical Research, Inc, in Lake Jackson, Tex. Dr Draud is medical director of psychiatry and addiction medicine at Baptist Hospital in Nashville and at Middle Tennessee Medical Center in Murphreesboro.
Disclaimer: Dr Raison is paid by CME LLC to provide/present this information. The opinions expressed are those of Dr Raison/CME LLC and do not necessarily reflect the views of Emory University or Emory Healthcare. Dr Raison’s participation in this activity does not constitute or imply endorsement by Emory University or Emory Healthcare. Dr Raison is on speakers’ bureaus for Lilly and Wyeth and serves on advisory boards for Lilly and Wyeth. He receives research support from Centocor.
Dr Maletic is on speakers’ bureaus for Lilly, Takeda, and Novartis and serves on advisory boards for Lilly and Takeda. Dr Draud is on speakers’ bureaus and serves as a consultant for Lilly, Pfizer, Cephalon, Forest, Takeda, AstraZeneca, and Sanofi-Aventis. Dr Jain is on speakers’ bureaus for Jazz, Lilly, Pfizer, Takeda, and Shire; he serves as a consultant for Addrenex, Impax, Lilly, Shire, Takeda, and Pfizer.
Why is depression a risk factor for other diseases and why is it progressive?
While these seem like separate questions, the new mind-body science suggests that they are actually variations on a theme. Depression, in our view, is linked to most other modern illnesses because it shares an underlying pathophysiology with them.18,28 Millions of years of evolution favored the development and retention of extremely robust stress and inflammatory danger pathways. When death and destruction lurked around every corner, the safest policy was to fire off one’s danger pathways first and ask questions later. What did it matter if body and brain tissues were damaged a little each time these pathways activated if this kept one alive for today (an idea that has been popularized as allostatic load).29 No need to worry about heart disease, cancer, or dementia if you were likely to die of infection by age 30. Consider our plight today, however. The boss no longer rips your arm off when he shouts at you, and many of the jobs once done by inflammation have been farmed out to sanitation and modern medicine. But the old danger pathways just go on firing off every time someone looks at us sideways. The more they fire off, the more damage accumulates. When this occurs in the arteries, it is vascular disease30; when it promotes insulin resistance, it is diabetes30; and when it disrupts glial cell integrity and disorganizes neuronal signaling, it manifests as depression.31,32 Given enough time, the damage usually accumulates everywhere—hence the high comorbidity between depression and most other major modern maladies. Why is remission so important?
The new mind-body science suggests that depressive symptoms are a “shout out” that the brain and body are in a state that is inimical to optimal functioning and health in the modern world. Conversely, an implication of the ideas presented here is that depressive symptoms are not likely to improve unless a person’s underlying danger pathway functioning normalizes, at least to some degree.28,33 So remission is the best indicator we currently have that a person’s underlying physiology has returned to a safer state. Of course, symptoms are not perfect. If they were, remission would heal all ills.34 In fact, we know that even when remission is achieved, patients remain at greatly increased risk for sinking again into depression when compared with those who have never suffered depression.35 Join us next month as we apply the implications of recent scientific advances to the practicalities of diagnosing and treating depression.
Q&A Chronic Pain and Mood Disorders
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18. Miller AH, Maletic V, Raison CL. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry. 2009;65:732-741.
19. Su S, Miller AH, Snieder H, et al. Common genetic contributions to depressive symptoms and inflammatory markers in middle-aged men: the Twins Heart Study. Psychosom Med. 2009;71:152-158.
20. Schule C, Zill P, Baghai TC, et al. Brain-derived neurotrophic factor Val66Met polymorphism and dexamethasone/CRH test results in depressed patients. Psychoneuroendocrinology. 2006;31:1019-1025.
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24. Jamison KR. Touched With Fire: Manic-Depressive Illness and the Artistic Temperament. New York: Free Press; 1993.
25. Bull SJ, Huezo-Diaz P, Binder EB, et al. Functional polymorphisms in the interleukin-6 and serotonin transporter genes, and depression and fatigue induced by interferon-alpha and ribavirin treatment. Mol Psychiatry. 2008 May 6. [Epub ahead of print.]
26. Kraus MR, Al-Taie O, Schafer A, et al. Serotonin-1A receptor gene HTR1A variation predicts interferon-induced depression in chronic hepatitis C. Gastroenterology. 2007;132:1279-1286.
27. Gentile DA, Doyle WJ, Zeevi A, et al. Cytokine gene polymorphisms moderate illness severity in infants with respiratory syncytial virus infection. Hum Immunol. 2003;64:338-344.
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29. McEwen BS. Protection and damage from acute and chronic stress: allostasis and allostatic overload and relevance to the pathophysiology of psychiatric disorders. Ann N Y Acad Sci. 2004;1032:1-7.
30. Ridker PM. Inflammatory biomarkers and risks of myocardial infarction, stroke, diabetes, and total mortality: implications for longevity. Nutr Rev. 2007;65
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