From Chaos to Consilience: Part III
What the New Mind-Body Science Tells Us About the Pathophysiology of Major Depression—Focus on Treatment
By Charles L. Raison, MD, Rakesh Jain, MD, MPH, Vladimir Maletic, MD, and Jon W. Draud, MD, MS |
August 7, 2009
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.
Editor’s note: The concept of a mind-body neurobiological approach to depression will be explored in detail at this year’s US Psychiatric and Mental Health Congress, to be held in Las Vegas on November 2-5, 2009. For details please visit www.psychcongress.com. You can also call 800-447-4474
Hypothesis 3b points to a delicious paradox inherent in the mind-body view of depression we espouse. Despite its vulnerability to criticism for being overly general (ie, explains all psychiatric phenomena on the basis of several simple postulates), a major implication of this theory is that psychiatric generalities (ie, diagnoses) don’t really exist. They are categorical descriptions for nondiscrete and shifting patterns of symptoms—nothing more. Because of this, nothing is more real than the actual symptoms experienced by individual patients sitting in our offices at any given moment. It is the idiosyncratic mélange of symptoms and situations suffered by each patient that must be put right if the well-documented benefits of remission are to be achieved. It is not the diagnoses that go into remission; in the end it is not even the symptoms. It is the individual in all of his or her unique complexity.
We leave you with a startling implication of this line of thinking. Although symptoms are not perfect guides to the underlying biological abnormalities from which they arise, they are our best guides to the intricate workings of brain and body, given the current limitations of our knowledge. Therefore, anything that leads to the remission of symptoms (and that is not illegal, immoral, or fattening as one of our fathers used to say) should be in our treatment armamentarium. The surest way to help our patients is to set remission up as the guiding star toward which our efforts strive. If our patients approach this goal, we are moving in the right direction, no matter what intervention we are employing. If they move away from this goal, we need to analyze why and take steps to correct the arc of the patient’s emotional/physical life. In a world in which antipsychotics have been shown to work as well as antidepressants for panic disorder50 and in which placebo appears to affect the brain in ways similar to active treatments,51 many of our old certainties are crumbling.
Who are we to say what combination of interventions will heal any given patient? What we can say—on the basis of the new mind-body science—is that whichever therapeutic pathway we tread with any given individual under our care is right if it leads to symptomatic remission and a full human life. And it is wrong, or incomplete, if it fails in this regard. When we find the right interventions, we can feel fairly sure that we have brought a patient’s underlying danger pathway activity into line with the actual needs of the real world he faces, and that we all share—at least for now.
Q&A Chronic Pain and Mood Disorders
1. Westendorp RG. Are we becoming less disposable? EMBO Rep. 2004;5:2-6.
2. 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.
3. Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of major depression. Trends Immunol. 2006;27:24-31.
4. Fitzgerald PB, Laird AR, Maller J, Daskalakis ZJ. A meta-analytic study of changes in brain activation in depression [published correction appears in Hum Brain Mapp. 2008;29:736]. Hum Brain Mapp. 2008;29:683-695.
5. Raison CL, Miller AH. When not enough is too much: the role of insufficient glucocorticoid signaling in the pathophysiology of stress-related disorders. Am J Psychiatry. 2003;160:1554-1565.
6. Maletic V, Raison CL. Neurobiology of depression, fibromyalgia and neuropathic pain. Front Biosci. 2009;14:5291-5338.
7. Tzoulaki I, Murray GD, Lee AJ, et al. C-reactive protein, interleukin-6, and soluble adhesion molecules as predictors of progressive peripheral atherosclerosis in the general population: Edinburgh Artery Study. Circulation. 2005;112:976-983.
8. Pradhan AD, Manson JE, Rifai N, et al. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA. 2001;286:327-334.
9. Ridker PM. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000;342:836-843.
10. Pyter LM, Pineros V, Galang JA, et al. Peripheral tumors induce depressive-like behaviors and cytokine production and alter hypothalamic-pituitary-adrenal axis regulation. Proc Natl Acad Sci U S A. 2009;106:9069-9074.
11. Abercrombie HC, Giese-Davis J, Sephton S, et al. Flattened cortisol rhythms in metastatic breast cancer patients. Psychoneuroendocrinology. 2004;29:1082-1092.
12. Kuo HK, Yen CJ, Chang CH, et al. Relation of C-reactive protein to stroke, cognitive disorders, and depression in the general population: systematic review and meta-analysis. Lancet Neurol. 2005;4:371-380.
13. Cole SW, Hawkley LC, Arevalo JM, et al. Social regulation of gene expression in human leukocytes. Genome Biol. 2007;8:R189.
14. Kiecolt-Glaser JK, Preacher KJ, MacCallum RC, et al. Chronic stress and age-related increases in the proinflammatory cytokine IL-6. Proc Natl Acad Sci U S A. 2003;100:9090-9095.
15. Mendlewicz J, Kriwin P, Oswald P, et al. Shortened onset of action of antidepressants in major depression using acetylsalicylic acid augmentation: a pilot open-label study. Int Clin Psychopharmacol. 2006;21:227-231.
16. Müller N, Schwarz MJ, Dehning S, et al. The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine. Mol Psychiatry. 2006;11:680-684.
17. Akhondzadeh S, Jafari S, Raisi F, et al. Clinical trial of adjunctive celecoxib treatment in patients with major depression: a double blind and placebo controlled trial. Depress Anxiety. 2009;26:607-611.
18. Tyring S, Gottlieb A, Papp K, et al. Etanercept and clinical outcomes, fatigue, and depression in psoriasis: double-blind placebo-controlled randomised phase III trial. Lancet. 2006;367:29-35.
19. Persoons P, Vermeire S, Demyttenaere K, et al. The impact of major depressive disorder on the short- and long-term outcome of Crohn’s disease treatment with infliximab. Aliment Pharmacol Ther. 2005;22:101-110.
20. 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.
21. Zautra AJ, Davis MC, Reich JW, et al. Comparison of cognitive behavioral and mindfulness meditation interventions on adaptation to rheumatoid arthritis for patients with and without a history of recurrent depression. J Consult Clin Psychol. 2008;76:408-421.
22. Pace TW, Negi LT, Adame DD, et al. Effect of compassion meditation on neuroendocrine, innate immune and behavioral responses to psychosocial stress. Psychoneuroendocrinology. 2009;34:87-98.
23. Kohut ML, McCann DA, Russell DW, et al. Aerobic exercise, but not flexibility/resistance exercise, reduces serum IL-18, CRP, and IL-6 independent of beta-blockers, BMI, and psychosocial factors in older adults. Brain Behav Immun. 2006;20:201-209.
24. Dai J, Miller AH, Bremner JD, et al. Adherence to the Mediterranean diet is inversely associated with circulating interleukin-6 among middle-aged men: a twin study. Circulation. 2008;117:169-175.
25. Irwin MR, Wang M, Ribeiro D, et al. Sleep loss activates cellular inflammatory signaling. Biol Psychiatry. 2008;64:538-540.
26. Schatzberg AF, Lindley S. Glucocorticoid antagonists in neuropsychiatric [corrected] disorders [published correction appears in Eur J Pharmacol. 2008;592:168]. Eur J Pharmacol. 2008;583:358-364.
27. Lewis-Tuffin LJ, Jewell CM, Bienstock RJ, et al. Human glucocorticoid receptor beta binds RU-486 and is transcriptionally active. Mol Cell Biol. 2007;27:2266-2282.
28. DeBattista C, Belanoff J, Glass S, et al. Mifepristone versus placebo in the treatment of psychosis in patients with psychotic major depression. Biol Psychiatry. 2006;60:1343-1349.
29. Blasey CM, Debattista C, Roe R, et al. A multisite trial of mifepristone for the treatment of psychotic depression: a site-by-treatment interaction. Contemp Clin Trials. 2009;30:284-248.
30. Karavidas MK, Lehrer PM, Vaschillo E, et al. Preliminary results of an open label study of heart rate variability biofeedback for the treatment of major depression. Appl Psychophysiol Biofeedback. 2007;32:19-30.
31. Hassett AL, Radvanski DC, Vaschillo EG, et al. A pilot study of the efficacy of heart rate variability (HRV) biofeedback in patients with fibromyalgia. Appl Psychophysiol Biofeedback. 2007;32:1-10.
32. Zucker TL, Samuelson KW, Muench F, et al. The effects of respiratory sinus arrhythmia biofeedback on heart rate variability and posttraumatic stress disorder symptoms: a pilot study. Appl Psychophysiol Biofeedback. 2009;34:135-143.
33. Siepmann M, Aykac V, Unterdorfer J, et al. A pilot study on the effects of heart rate variability biofeedback in patients with depression and in healthy subjects. Appl Psychophysiol Biofeedback. 2008;33:195-201.
34. Mead GE, Morley W, Campbell P, et al. Exercise for depression. Cochrane Database Syst Rev. 2008;(4):CD004366.
35. Arias AJ, Steinberg K, Banga A, Trestman RL. Systematic review of the efficacy of meditation techniques as treatments for medical illness. J Altern Complement Med. 2006;12:817-832.
36. Tanskanen A, Hibbeln JR, Tuomilehto J, et al. Fish consumption and depressive symptoms in the general population in Finland. Psychiatr Serv. 2001;52:529-531.
37. Westover AN, Marangell LB. A cross-national relationship between sugar consumption and major depression? Depress Anxiety. 2002;16:118-120.
38. Roberts RE, Deleger S, Strawbridge WJ, Kaplan GA. Prospective association between obesity and depression: evidence from the Alameda County Study. Int J Obes Relat Metab Disord. 2003;27:514-521.
39. Kloiber S, Ising M, Reppermund S, et al. Overweight and obesity affect treatment response in major depression. Biol Psychiatry. 2007;62:321-326.
40. Soreca I, Rosano C, Jennings JR, et al. Gain in adiposity across 15 years is associated with reduced gray matter volume in healthy women. Psychosom Med. 2009;71:485-490.
41. Glassman AH, O’Connor CM, Califf RM, et al. Sertraline treatment of major depression in patients with acute MI or unstable angina. JAMA. 2002;288:701-709.
42. Robinson RG. Treatment issues in poststroke depression. Depress Anxiety. 1998;8(suppl 1):85-90.
43. Abrahamian H, Hofmann P, Prager R, Toplak H. Diabetes mellitus and co-morbid depression: treatment with milnacipran results in significant improvement of both diseases (results from the Austrian MDDM study group). Neuropsychiatr Dis Treat. 2009;5:261-266.
44. Yeh HL, Tsai SJ. Lithium may be useful in the prevention of Alzheimer’s disease in individuals at risk of presenile familial Alzheimer’s disease. Med Hypotheses. 2008;71:948-951.
45. Spiegel D, Giese-Davis J. Depression and cancer: mechanisms and disease progression. Biol Psychiatry. 2003;54:269-282.
46. Linden W, Phillips MJ, Leclerc J. Psychological treatment of cardiac patients: a meta-analysis. Eur Heart J. 2007;28:2972-2984.
47. Ridker PM, Cannon CP, Morrow D, et al. C-reactive protein levels and outcomes after statin therapy. N Engl J Med. 2005;352:20-28.
48. Young-Xu Y, Chan KA, Liao JK, et al. Long-term statin use and psychological well-being. J Am Coll Cardiol. 2003;42:690-697.
49. Goldstein BI, Kemp DE, Soczynska JK, McIntyre RS. Inflammation and the phenomenology, pathophysiology, comorbidity, and treatment of bipolar disorder: a systematic review of the literature. J Clin Psychiatry. 2009 Jun 2; [Epub ahead of print].
50. Prosser JM, Yard S, Steele A, et al. A comparison of low-dose risperidone to paroxetine in the treatment of panic attacks: a randomized, single-blind study. BMC Psychiatry. 2009;9:25.
51. Benedetti F, Mayberg HS, Wager TD, et al. Neurobiological mechanisms of the placebo effect. J Neurosci. 2005;25:10390-10402.
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