In an editorial published in Arthritis Research & Therapy, Afton Hassett and Daniel Clauw, of University of Michigan Medical School, discuss some aspects of the complex interactions between psychological stress and the onset, expression and progression of rheumatic diseases.
According to the authors some studies in this research area are limited by the use of cross-sectional designs and the pitfalls associated with self-report retrospective data, but they nevertheless highlight some interesting findings found therein. A relatively large study of Vietnam combat veterans with current post-traumatic stress disorder (n = 2,490) suggested an increased risk for autoimmune diseases compared to veterans without post-traumatic stress disorder.
This is further substantiated by studies proposing that early life stressors increase vulnerability to autoimmune disease, and studies describing relationships between psychological stress and poor outcomes, and disease flares in both rheumatoid arthritis and systemic lupus erythematosus.
The mechanisms presumed to underlie these associations include stress-related changes in functioning of the autonomic, neuroendocrine and/or immune systems. One recent study found that individuals reporting two or more traumatic childhood events were at a 100% increased risk for rheumatic diseases compared with those reporting no childhood trauma. The authors propone that the mechanisms presumed to underlie these associations include stress-related changes in autonomic, neuroendocrine and/or immune system functioning.
Furthermore, work performed to examine how stress modulates symptoms, especially pain, in nonautoimmune rheumatic conditions such as ﬁbromyalgia may also help elucidate the role of stress in symptom expression.
For example, in ﬁbromyalgia, observable changes in the autonomic nervous system or the hypothalamic–pituitary–adrenal axis tone in some individuals may represent a baseline diathesis or risk factor for the subsequent development of chronic pain; alternatively, such changes may manifest due to pain itself or to the indirect effects of pain such as deconditioning secondary to decreased exercise.
From a vast array of experimental studies, it is reasonable to conclude that a variety of stressors may cause pain, that pain may cause stress, and, more importantly, that a simple unidirectional relationship between changes in stress-response function and pain and other symptoms probably does not exist. Imaging studies of pain processing in fibromyalgia indicate that psychological stress (that is, depression, anxiety) and pain are processed somewhat independently in the central nervous system.
Supporting this conclusion are the clinical data indicating that drugs acting as both antidepressants and analgesics (for example, tricyclics or serotonin-norepinephrine reuptake inhibitors) are equally effective analgesics in chronic pain conditions in patients with and without depression. The lack of direct overlap in the central processing of stress and pain suggests that the degree to which stress influences pain, and vice versa, may be moderated by individual factors such as cognitions, coping/appraisal and social support.
The authors conclude stating that ‘when our patients say that stress worsens their disease, they may be correct’, and that there are ‘clearly both immune mechanisms and nonimmune mechanisms that may be responsible for increased disease activity and/or symptom expression during periods of stress’.
In the Annals of Rheumatic Diseases study, mentioned above, Andrea Evers and colleagues evaluated for a link between real-life stressors and subjective and objective assessments of disease activity, while integrating measurements of cortisol and pro-inflammatory cytokine levels. Worrying specifically was predictive of more swollen joints and more pain 4 weeks later, while daily stressors, IL-1β and IFN-γ predicted fatigue 4 weeks later.