- Chronic stressors as well as traumatic loss can provoke depression; in turn, depression can increase sensitization to future events.
- Rheumatoid arthritis (RA) pain and depression tend to be predictive of each other and together lead to a downward spiral of functioning characterized by greater disability, increased sleep disturbance and fatigue, and heightened disease activity.
- Some studies suggest that factors other than pain may cause disordered sleep in patients with RA.
While tremendous therapeutic advancements have been made, patients with rheumatoid arthritis (RA) have a myriad of comorbidities, including fatigue, depression, and sleep disturbances. Data on the comorbidity of psychiatric disorders with arthritis are also striking: according to the NIMH Catchment Area program, the lifetime prevalence of psychiatric disorders among patients with RA is 63%. Indeed, approximately 20% of patients with RA are found to have current major depression with potential impact on RA symptoms. In this review, we discuss the biopsychosocial pathways linking stress to behavioral comorbidities with consideration of potential common underlying inflammatory mechanisms. We also describe behavioral treatment strategies that can improve the clinical management of these patients.
Psychological Stress and RA
A broad range of illnesses has been associated with stress, including a failure in regulation of autoimmune responses, which may give rise to inflammatory conditions such as RA. Psychological stress is also thought to aggravate disease activity in RA. Stress, defined as minor hassles and life events lasting hours or days, has been associated with subsequent increases in disease activity.1
Much social psychiatry research focuses on measuring the harmful effects of social stressors, separate from and in combination with dispositional variables such as psychopathology (eg, depression). Zautra and colleagues2 found that stressful experiences led to increases in inflammatory markers in patients with RA, and the combination of stress and depressive symptoms predicted greater elevations of these markers of inflammation.2 However, it is important to acknowledge the bidirectionality of these relationships as well. Chronic stressors as well as traumatic loss experiences can provoke depression; in turn, depression can increase sensitization to future events.
Influence of Depression on Pain and RA
Several longitudinal, prospective studies show that RA pain and depression tend to be predictive of each other and together lead to a downward spiral of functioning characterized by greater disability, increased sleep disturbance and fatigue, and heightened disease activity.3,4 The combined burden of stress, pain, and depression increase vulnerability to illness and reduce capacity for successful adaptation.
Recent evidence also points to a significant influence of depression history on adaptation to illnesses such as RA. One study found that patients with RA who had had an episode of depression (but who were not currently depressed) had significantly greater pain than controls without a history of depression.4 Moreover, Conner and colleagues5 found that long-past episodes of major depression were associated with greater emotional reactivity to daily pain as well as less perceived control over pain episodes and their consequences.
Patients with RA who have had multiple depressive episodes fare the worst. Zautra and colleagues6 found that recurrently depressed patients with RA reported higher levels of pain than patients who had never been depressed and those who had experienced only a single episode of depression.6 Patients with RA who had a history of recurrent depression were also more stress-reactive; they reported more pain and affective reactivity following an experimentally induced interpersonal stressor than never- or once-depressed patients.
These findings indicate that a history of recurrent depression may serve as a hidden vulnerability, which leaves a “scar” that ultimately influences adaptation even after accounting for current mental health. Individuals who have had 2 or more depressive episodes report more stressful life events than their single-episode or never-depressed counterparts. Patients with recurrent depression also manifest greater sleep disturbance than those who had a single depressive episode.7 Hence, it is possible that recurrent depression is associated with a more severe neurophysiological substrate and more social stressors than a single depressive episode.
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Zautra AJ, Davis MC, Reich JW, et al. Comparison of cognitive behavioral and mindfulness meditation interventions on adaptation to rheumatoid arthritis for patients with and without history of recurrent depression. J Consult Clin Psychol. 2008;76:408-421.
Acknowledgments—This work is supported by NIH grants AG026364, HL079955, T32-MH19925, CA 0014152, M01-RR00865, the General Clinical Research Centers Program; and the Cousins Center for Psychoneuroimmunology (to Dr Irwin).