When anticipating pain, the brains of subjects with major depressive disorder appear to react more strongly, and appear to display altered functioning of the neural network that moderates pain sensitivity, according to an article released on November 3, 2008 in Archives of General Psychiatry, one of the JAMA/Archives journals.

“Chronic pain and depression are common and often overlapping syndromes,” write the authors. More than 75% of patients with depression also manifest with recurring or chronic pain, while between 30 and 60% of patients with chronic pain report symptoms of depression. According to the authors, this association could have important implications if there is a biological mechanism that can be attributed. “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,” they say.

To investigate the association between major depressive disorder and brain function in response to pain, Irina A. Strigo, Ph.D., of the University of California San Diego, La Jolla, and colleagues examined 15 young adults diagnosed with major depressive disorder who were not taking medication and 15 controls with the same level of education but without depression. The depressed patients were given a survey, examining any tendencies to magnify, ruminate over, or feel helpless when faced with pain. The study subjects all were studied using functional magnetic resonance imagine (fMRI) as their arms were exposed to a device heated to painfully high temperatures, which averaged 115 to 116ºF (46.4 to 46.9ºC). Visual images were also applied before any heat was applied: either a green shape, indicating non-painful warmth, and a red shape, indicating painful warmth.

Patients with depression tended to have increased activation in specific areas of the brain, including the right amygdala, when they anticipated painful stimuli, in comparison to the reactions of the controls. Depressed patients also showed decreased activation in other areas, such as those responsible for modifying pain by adjusting sensitivity, over the course of the painful experience.

The percentage change in activation in the amygdala was then examined in the context of the survey descriptions of helplessness, rumination and victimization, to see if this action was associated with passive coping styles. The authors write that the correlation existed: “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 indicate that this association could help elucidate the basis behind the common comorbidity of chronic pain and depression. “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,” they write. “This mechanism could in part explain the high comorbidity of pain and depression when these conditions become chronic.”

They conclude: “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.”

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