ScienceDaily.com — The brains of individuals with major depressive disorder appear to react more strongly when anticipating pain and also display altered functioning of the neural network that modifies pain sensitivity, according to a new report.

“Chronic pain and depression are common and often overlapping syndromes,” the authors write as background information in the article. Recurring or chronic pain occurs in more than 75 percent of patients with depression, and between 30 percent and 60 percent of patients with chronic pain report symptoms of depression “Understanding the neurobiological basis of this relationship is important because the presence of comorbid pain contributes significantly to poorer outcomes and increased cost of treatment in major depressive disorder.”

Irina A. Strigo, Ph.D., of the University of California San Diego, La Jolla, and colleagues studied 15 young adults with major depressive disorder (average age 24.5) who were not taking medication and 15 individuals who were the same age (average 24.3 years) and had the same education level but did not have depression. Patients with depression completed a questionnaire that evaluated their tendencies to magnify, ruminate over or feel helpless in the face of pain. All participants underwent functional magnetic resonance imaging (fMRI) while their arms were exposed to a thermal device heated to painful levels (an average of 46.4 degrees to 46.9 degrees Celsius, or about 115 degrees to 116 degrees Fahrenheit) and also to non-painful temperatures. Visual cues (a green shape for non-painful warmth and a red shape for painful warmth) were presented before the heat was applied.

Compared with the controls, patients with depression showed increased activation in certain areas of their brain—including the right amygdala—during the anticipation of painful stimuli. They also displayed increased activation in the right amygdala and decreased activation in other areas, including those responsible for pain modulation (adjusting sensitivity to pain), during the painful experience.

To examine whether the activation of the amygdala was associated with passive coping styles, the researchers compared the percentage change in the activations of the amygdala with the helplessness, rumination and ramification reported by the participants with depression. “Significant positive correlations were observed in the major depressive disorder group between greater helplessness scores and greater activity in the right amygdala during the anticipation of pain,” the authors write.

“The anticipatory brain response may indicate hypervigilance to impending threat, which may lead to increased helplessness and maladaptative modulation during the experience of heat pain,” the authors write. “This mechanism could in part explain the high comorbidity of pain and depression when these conditions become chronic.”

“Future studies that directly examine whether maladaptive response to pain in major depressive disorder is due to emotional allodynia [a pain response to a non-painful stimulus], maladaptive control responses, lack of resilience and/or ineffectual recruitment of positive energy resources will further our understanding of pain-depression comorbidity,” they conclude.

This study was supported by Barrow Neurological Foundation, grants from the National Institute of Mental Health, the National Association for Research in Schizophrenia and Depression and the University of California San Diego Center of Excellence for Stress and Mental Health.

Journal reference:

1. Irina A. Strigo, PhD; Alan N. Simmons, PhD; Scott C. Matthews, MD; Arthur D. (Bud) Craig, PhD; Martin P. Paulus, MD. Association of Major Depressive Disorder With Altered Functional Brain Response During Anticipation and Processing of Heat Pain. Arch Gen Psychiatry, 2008;65(11):1275-1284

Adapted from materials provided by JAMA and Archives Journals.

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The Conflict Of Reward In Depression

Stanford University Psychology Department — In Love and Death, Woody Allen wrote: “To love is to suffer…To be happy is to love. To be happy, then, is to suffer.” The paradoxical merging of happiness and suffering can be a feature of depression. A new study of regional brain activity using functional magnetic resonance imaging may help further our understanding of how happiness and suffering are related in depression.

Stanford University researchers recruited both depressed and non-depressed volunteers to undergo brain scans, via functional magnetic resonance imaging (fMRI), while they participated in an activity where they won and lost money. Dr. Brian Knutson, first author on this article, explains their findings: “When they anticipated winning money, both depressed and nondepressed individuals showed neural activation in the nucleus accumbens, a region implicated in the anticipation of reward. Only the depressed participants, however, additionally showed increased activation in the anterior cingulate, a region of the brain that has been implicated in conflict.”

John H. Krystal, M.D., Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System, notes that this finding indicates that “this complex mixture of findings suggests that depression is not simply the absence of reward, but rather a contamination of neural processing of rewards with features of neural processing of punishments.” Dr. Knutson agrees, commenting that “these findings are consistent with formulations that depression involves difficulties in the processing of positive information, and suggest more specifically that depressed people actually experience conflict when they are faced with the likelihood of receiving a reward.”

Dr. Krystal concludes that “one intriguing potential implication of this work is that some forms of depression may be experienced, not as the absence of pleasure, but as the ubiquitous presence of emotional pain, disappointment, or frustration.” Dr. Knutson and his colleagues are currently examining whether this increased experience of conflict when anticipating reward hinders recovery from depression.

The article is “Neural Responses to Monetary Incentives in Major Depression” by Brian Knutson, Jamil P. Bhanji, Rebecca E. Cooney, Lauren Y. Atlas and Ian H. Gotlib. The authors are affiliated with the Department of Psychology at Stanford University in Stanford, California. The article appears in Biological Psychiatry, Volume 63, Issue 7 (April 1, 2008), published by Elsevier.

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