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 report in the November issue of Archives of General Psychiatry, one of the JAMA/Archives journals.

"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% of patients with depression, and between 30% and 60% 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, PhD, 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° to 46.9° Celsius, or about 115° to 116° Fahrenheit), and also to nonpainful temperatures. Visual cues (a green shape for nonpainful 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.

(Arch Gen Psychiatry. 2008;65[11]:1275-1284.)

Editor’s Note: 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.

[Source: JAMA]