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Psychiatric Times. Vol. 26 No. 7
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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.


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We would suggest that psychiatry has spent so many years taking its diagnostic categories as God-given that it has become inured to the fact that these categories tell us very little about the etiology and fundamental nature of the conditions they purport to encompass.1

Nowhere is this truer than in the case of depression. While the DSM—like all mythopoetic creations—has been forced to grapple with the complexities of reality by creating an ever larger cast of characters related to one another in ever more complicated ways, the types of deep, consilient understandings of depression that would unify rather than splinter, and that would empower rather than enfeeble, our therapeutic efforts have been consigned to the province of future science.

In this—the second installment in our series on mind-body approaches to mood disorders—we suggest that the future is now. Although we are far indeed from a full understanding of all the intricacies of depression, scientific advances during the past decade in fields ranging from immunology to evolutionary biology already provide the outlines for a theory of depression that is consistent, inclusive, and (most important) provides intellectually satisfying and testable answers to many basic questions in front of which the DSM must raise a finger to its lips in silence.

Because of space constraints, we can provide only the barest overview of this theory here. We invite you to log on to www.psychiatrictimes.com for a longer and more rigorous discussion of these ideas.

What is depression?
All over the world, depression is the most common emotional/behavioral breakdown pathway for human beings in response to environmental adversity. It is highly stereotyped but also irreducibly probabilistic.2 It is how humans tend to feel and behave when the internal or external environment seems unmanageably threatening. Tethered to systems necessary for survival, depression is a tendency and a vulnerability, an Achilles heel of hominid evolution.

Recent data increasingly suggest that depression is an emotional/behavioral manifestation of hyperactivity in brain-body systems that evolved to cope with danger and to adapt to changing environmental demands.3-10 Hyperactivity in these systems is linked to—and perhaps causes—reductions in the activity of CNS pleasure/novelty and executive decision-making circuitry.11,12 Across human evolution, these “danger pathways” have been most often activated by psychosocial struggles and by pathogen invasion, which goes far toward explaining why psychosocial stress and sickness are the 2 primary environmental risk factors for depression.

Why does depression have the symptoms it does?
The short answer is that depression looks so much like a combination of terrible stress and physical illnesses because, in our view, it is essentially a disorder of pathways in the brain and body that evolved to cope with stress and infection and that produce depressive symptoms when chronically hyperactive.3,5,6,13 Strong support for this idea comes from studies showing that when bidirectional stress—inflammatory danger pathways are chronically activated—such as occurs during treatment with the cytokine inter­feron-alpha—most people become depressed or, if not depressed, then exhausted, achy, and upset.14,15 Conversely, interrupt hyperactivity in key stress-related brain regions, such as the subgenual anterior cingulate, and many profoundly depressed patients have an immediate surcease of their internal torture.16 Recent data also demonstrate that stimulating activity in cortical areas that suppress stress pathway activity, such as the dorso­lateral prefrontal cortex, also leads to profound and rapid improvements in depression.17

Consider a young mammal separated from its mother. First comes the terror—the wailing and the calling out. And then with time a strange thing happens. The little animal grows silent, dull, and perfectly still. This all makes eminent sense: scream out when there is hope of rescue but conserve energy and hide from predators when the time for hope has passed.

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by Manuel Mota-Castillo | May 13, 2010 11:08 AM EDT

I had the privilege of heard to Dr. Maletic and Dr. Jain discussing this topic during a past Psychiatric Congress. The way in which they present depression as an endocrinologic and a "whole body" disease is a revolutionary concept that deserves more attention from the psychiatric establishment.

   Congratulations to them and Dr. Draud for their contribution to advance of psychiatric treatments and diagnoses.

Manuel Mota-Castillo,

Lake Mary, Florida

Q&A Chronic Pain and Mood Disorders

Chronic Pain and Mood Disorders—Identifying and Understanding Shared Neurophysiological Mechanisms

And the Orchestra Played On: Activation of Distress Pathways—A Common Feature of Mood, Anxiety, Sleep, and Pain Disorders?

From Chaos to Consilience: Part II
What the New Mind-Body Science Tells Us About the Pathophysiology of Major Depression

From Chaos to Consilience: Part III






 
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