Healing Words: Title and subTitle BreakEmotional Expression and Disease Outcome

We have been closet Cartesians in modern medicine, treating the mind as though it were reactive to but otherwise disconnected from disease in the body. Although medical science has productively focused on the pathophysiology of disease, such as tumor biology, coronary artery disease, and immunology, it has done so at the expense of studying the body's psychophysiological reactions to these disease processes. These reactions are mediated by brain and body mechanisms, including the endocrine, neuroimmune, and autonomic nervous systems. While a large portion of the variance in any disease outcome is accounted for by the specific local pathophysiology of that disease, some variability must also be explained by host resistance factors, which include the manner of response to the stress of the illness. For example, in a series of classic experiments in animals, Riley^{1 - 2} showed that crowding accelerated the rate of tumor growth and mortality. In a recent authoritative review of human stress literature, McEwen³ documented the adverse health effects of cumulative stressors and the body's failure to adapt the stress response to them. Activation of the hypothalamic-pituitary-adrenal axis (HPA) is an adaptive response to acute stress, but over time, in response to cumulative stress, the system's signal-to-noise ratio can be degraded, so that it is partially "on" all the time, leading to adverse physiological consequences, including abnormalities of glucose metabolism,⁴ hippocampal damage,⁵ and depression.^{6 - 7}

Abnormalities of hypothalamic function, including glucocorticoid receptor hypersensitivity, have also been found to be associated with posttraumatic stress disorder.^{8 - 9} Thus, adverse emotional events, ranging from traumatic stressors to cumulative minor ones, are associated with HPA dysregulation. Glucocorticoids are potently immunosuppressive, so the effects of acute and chronic stress and hypercortisolemia may include functional immunosuppression as well, as has been shown extensively in animals,^{10 - 13} and for which there is a growing body of evidence in humans.^{14 - 15}

On the other hand, the social environment can have a buffering effect on stress. The same stressor that when given to an animal who is alone increases plasma cortisol levels by 50% does not increase it at all when the animal is surrounded by familiar companions.¹⁶ Being socially imbedded is associated with less autonomic arousal than social isolation.¹⁷ Indeed, social connection has profound consequences for health. Being well integrated socially reduces all-cause age-adjusted mortality by a factor of 2-fold, about as much as having low vs high serum cholesterol levels or being a nonsmoker.¹⁸ Furthermore, the nature of one's position in the social hierarchy has health consequences, including relatively higher status within the same social class.¹⁹ People are statistically more likely to die after rather than before their birthdays and important holidays.²⁰

Thus, the presence of adverse emotional events such as traumatic stressors seems to have negative potential health consequences, while good social relations seem to be associated with positive health outcomes. Results from a recent randomized trial of patients who after experiencing myocardial infarction had participated in a program that included group support, stress management, and a vegetarian diet showed a long-term reversal of coronary artery occlusion.^{21 - 22} Similarly, 3^{23 - 25} of 6^{26 - 28} published randomized trials have provided evidence that psychosocial support is associated with longer survival for patients with breast cancer, malignant melanoma, and lymphoma. Patients with psoriasis exposed to mindfulness-meditation training tapes during treatment showed more rapid healing of lesions than those who were not exposed.²⁹ One component of the effective interventions is dealing directly with emotional distress associated with fears regarding disease progression.³⁰

There is evidence that resilience to stress, including disease-related distress, is associated with how people handle their emotions.³¹ Indeed, finding meaning in the midst of a distressing situation has been linked with a positive psychological state.³² Adaptating to a situation well does not require that a person maintain an upbeat or a rigidly positive attitude. Rather, it involves dealing directly with negative affect. Positive and negative emotions are not merely opposite sides of 1 dimension.³³ Rather, the suppression of negative emotion tends to reduce a person's ability to experience any emotion, positive or negative. There is evidence that patients with breast cancer who express negative emotion, including anger and uncooperativeness,³⁴ or patients who express realistic optimism, often termed having the fighting spirit,³⁵ actually live longer than those who don't.

In this issue of THE JOURNAL, Smyth and colleagues³⁶ demonstrate that merely writing about past stressful life experiences results in symptom reduction among patients with asthma or rheumatoid arthritis. Patients wrote about the "most stressful experience in their entire life" for just 20 minutes over 3 consecutive days, while controls wrote about their daily schedule, following a method developed by Pennebaker et al,³⁷ who showed that such an experience improves immune function.³⁸ Patients with asthma randomized to spend this limited amount of time writing about distressing experiences showed increased forced expiratory volume at 4-month follow-up, and similarly, patients with rheumatoid arthritis had significant reduction in disease-related symptoms, moving from a moderate to a mild range. This study adds important data to the growing evidence that even limited interventions designed to improve management of stress may have lasting somatic effects. It is quite plausible that the interaction between disease and the stress it causes can set up an interaction that reinforces the illness, through autonomic hyperactivity, increased HPA activity or dysregulation, and effects on immune function.

Were the authors to have provided similar outcome evidence about a new drug, it likely would be in widespread use within a short time. Why? We would think we understood the "mechanism" (whether we did or not) and there would be a mediating industry to promote its use. Manufacturers of paper and pencils are not likely to push journaling as a treatment addition for the management of asthma and rheumatoid arthritis. But the authors have provided evidence that medical treatment is more effective when standard pharmacological intervention is combined with the management of emotional distress. Ventilation of negative emotion, even just to an unknown reader, seems to have helped these patients acknowledge, bear, and put into perspective their distress. As has been noted before,³⁹ it is not so much the nature of the "treatment on offer that determines whether the medicine is orthodox or alternative but the quality of evidence adduced in its favour."³⁹ In this and a growing number of studies, it is not simply mind over matter, but it is clear that mind matters.