Affective disturbance in rheumatoid arthritis: psychological and disease-related pathways

Abstract

In addition to recurrent pain, fatigue, and increased rates of physical disability, individuals with rheumatoid arthritis (RA) have an increased prevalence of some mental health disorders, particularly those involving affective or mood disturbances. This narrative Review provides an overview of mental health comorbidities in RA, and discusses how these comorbidities interact with disease processes, including dysregulation of inflammatory responses, prolonged difficulties with pain and fatigue, and the development of cognitive and behavioural responses that could exacerbate the physical and psychological difficulties associated with RA. This article describes how the social context of individuals with RA affects both their coping strategies and their psychological responses to the disease, and can also impair responses to treatment through disruption of patient-physician relationships and treatment adherence. Evidence from the literature on chronic pain suggests that the resulting alterations in neural pathways of reward processing could yield new insights into the connections between disease processes in RA and psychological distress. Finally, the role of psychological interventions in the effective and comprehensive treatment of RA is discussed.

Figure 1. Mental health and disease activity are interconnected in rheumatoid arthritis

Manifestations of rheumatoid arthritis (RA) disease activity (recurrent pain, fatigue, and prolonged inflammation) act as stressors and influence mental health via changes in cognitive appraisal, affective states, and behavioural coping responses. Cognitive appraisal (the patient’s interpretation of their RA disease status) has major implications for their current mood and subsequent behavioural coping responses. Patients who view RA as a catastrophic personal event (catastrophizing) or have a low degree of belief in their ability to function in the presence of the disease might lack effective behavioural coping strategies such as adherence to medical recommendations or active coping responses such as exercise. By contrast, patients with RA who have strong beliefs in their ability to function and manage their disease are likely to adopt healthy behavioural coping approaches. The extent to which patients adopt healthy and active coping responses to RA affects their subsequent attitudes to medical intervention and their ability to self-manage RA, which can then feed back into the severity of the disease itself. Clustering of physical and psychological factors is also evident, such as coincident depression and fatigue states and inflammatory episodes concurrent with periods of high stress levels and negative emotion, suggesting that these processes interact in complex ways.

Figure 2. Chronic inflammation and altered dopaminergic signalling are connected to coping responses through pain perception and decreased positive affect

Rheumatoid arthritis (RA) contributes to chronic inflammatory states in part through dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, which manifests in altered physiological responses to stress, such as downregulation of normal anti-inflammatory responses after stress, and increased sympathetic tone at rest but decreased sympathetic response during stress. Chronic inflammatory states can alter dopamine transmission in the brain (resulting in lower basal levels of presynaptic dopamine, decreased dopamine release from basal ganglia in response to pain states, and decreased D2 and D3 receptor activation in the nucleus accumbens). In turn, these changes enhance pain processing and dampen positive affective responses. Downregulation of positive emotional states can manifest as both increased depression and decreased motivation, thereby impairing otherwise healthy coping responses and potentially affecting disease-relevant behaviour, such as exercise, treatment adherence, and social withdrawal or conflict. These factors can adversely affect RA disease processes in the future. Additionally, the presumed downstream increases in emotional distress that can occur with declines in physical health and function subsequently contribute to chronic inflammatory states via the aforementioned changes in physiological stress processes.

Figure 3. Social factors interact with psychological reactions to rheumatoid arthritis

Cognitive, affective, and behavioural factors are closely related and show a high degree of mutual influence. These factors can have both positive and negative effects on an individual’s adaptation to having rheumatoid arthritis (RA). Individuals who maintain optimistic perspectives or high levels of self-efficacy are more likely (than individuals with pessimistic perspectives or low self-efficacy) to sustain healthy repertoires for coping with RA and are less likely to show pronounced adverse psychological reactions to the physical symptoms caused by RA. Additionally, the broader social environment can impact a patient’s psychological reactions to RA; patients in supportive environments seem to be more resilient against RA-related declines in physical and psychological function, whereas those in stressful environments show elevated physical symptoms, reduced function, and poor psychological adjustment to RA. Individuals with RA can also adversely influence their immediate social environments via behavioural coping responses such as self-imposed isolation or initiating conflict with others when pain or frustration levels are high, which could then have consequences for future emotional states.