CIR patients, compared to those with other rheumatological pathologies, presented significantly more frequent severe emotional repression, whereas those with other pathologies had significantly more frequent severe psychological and somatic complaints, potentially attesting to their strong emotional repression.
Temoshok (13) previously described the personality profile of RA patients as type C, which regroups submission, conciliatory approach, repression of hostility, self-effacement of personal needs and depressive vulnerability. Grossarth-Maticek and al. (14)(15) made similar observations in patients with cancer. Bayle and al.(16), devised a psychological vulnerability score and obtained converging results very close to the type C personality, which was significantly higher for patients with secondary Raynaud’s syndrome than a control group with idiopathic or primary Raynaud’s syndrome.
Nagano and al. (17) showed that, for RA patients, rational/anti-emotional behaviors, characterized by an extreme tendency to squelch emotional behaviors and rationalize negative experiences, was associated with poorer prognoses. Ishii and al. (18) found that RA patients, who were easily brought to tears in response to stress, had better responses to treatment and better overall prognoses.
Our results and those reported in the literature highlight the importance of emotional dysregulation, especially emotional repression, on CIR etiology and prognosis. However, the present study and its findings cannot be generalized with respect to identifying it as a factor favoring CIR or a secondary coping strategy of CIR. The repressive behavior has sometimes been analyzed as a consequence of the disease diagnosis, rather than its cause (19)(20).
The intensity of key early life events was significantly more severe for CIR patients than those with other diseases. Cutolo and Straub (21)(22) showed that stressful events preceded RA onset for 86% of their patients.
Reported findings also underscore the role of trying life events in favoring CIR onset or flares, whereas others accorded greater emphasis to the role of minor life events and daily stress. In contrast, we found no significant difference for the actual stress level presented by CIR and other-pathology patients, probably because of a lack of statistical power. Rimón and Laasko (23) described that higher stress at RA onset predicted a poorer prognosis for the disease. O’Donovan and al. (24) also found that veterans experiencing trauma and developing PTSD could enhance the risk of developing autoimmune diseases, including RA. Based on their study of Vietnam veterans, Boscarino and al. (25) reported that those with RA had more PTSD symptoms, compared to their control counterparts.
The results of those studies are in agreement with a biopsychosocial model linking psychological stress and stressful life events with various immune-function changes in the etiology of autoimmune diseases. It could be thought that the impact of stress, resulting from an intense life event, modulated by adjustment strategies, like emotional repression, would increase vulnerability to autoimmune diseases because of dysregulated immune-system function (26)(27)(28)(29)(30) and enhanced inflammatory activity.
Herein, no significant difference was found between CIR and non-CIR patients regarding frequency of depression disorders, depression severity, history of prior depressive episode(s) or anxiety symptoms (100% of each group).
However, depressive and anxiety disorders are described as the most frequent comorbidities psychiatric of CIR patients. Reynier-Legarçon and al. (31) found that patients with autoimmune diseases (systemic lupus erythematosus, systemic scleroderma or primary Goujerot-Sjögren syndrome) presented more severe depressive and anxiety symptoms controls from general population. Baerwald and al. (32) found that the rates of depressive disorders for RA patients were significantly higher in for the general population. We were not able to replicate those findings, probably because of a lack of statistical power. In contrast, the homogeneity of our patients in terms of depressive and anxiety symptoms attenuates any potential bias linked to their emotional dysregulation associated with these psychological comorbidities.
Also, no significant difference were found between RA and SpA groups for the frequency of depression and depression severity. On the other hand, RA presented significantly more frequent prior depressive episodes that those with SpA, which has never been reported previously. Nonetheless, some findings indicated that anxiety symptoms, depression and perception of the disease impacted the physical quality of life differently for SpA and RA patients. Some authors noted that RA patients had more physical quality-of-life difficulties, while those with psoriatic arthritis and ankylosing spondyloarthritis had more mental quality-of-life issues (33)(34)(35). Hyphantis and al. (36) showed that SpA patients’ quality of life of was associated with anxiety linked to the disease but not because of depressive symptoms, unlike those with RA. Our results, in line with those reported previously, suggest a link between depression and RA patients, compared to those with SpA.
Together, these results suggest that CIR (RA or SpA) patients would probably benefit from aid with emotional management (depression, disease representation and living with it) from psychotherapists and antidepressants for symptomatic depressive episode. Moreover, these symptoms can contribute to a poorer prognosis of their rheumatological disease (37). Bijsterbosch and al. (38) showed that arthrosis patients’ perceptions of their disease were predictive of the functional disability and that cognitive-behavioral therapy could modify the representations of the disease and obtain a better functional result.
A biological inflammatory syndrome was significantly associated with low disorder of emotional regulation (mild/moderate emotional repression). However, examination of the literature find more association between emotional disorders and a biological inflammatory syndrome.
Smoak and al. (39) found increased nuclear factor-κB activity in patients with PTSD resulting from childhood violence, compared to healthy controls. Howren et al. (40) reported that patients with depression had significantly higher interleukin-1 and -6, tumor necrosis factor-α and C-reactive protein levels. Goldsmith and al. (41) also found in a meta-analysis of 68 studies, that patients with schizophrenia, bipolar disorder or major depressive episodes had increased inflammatory cytokines levels. In addition, depressive symptoms were more frequent in patients with autoimmune diseases and respond to anti-inflammatory drugs. Gobin and al. (42) found that antidepressants lowered production of inflammatory cytokines, e.g. interleukins-1β and -6 and tumor necrosis factor-α.
Several monoclonal antibodies targeting relevant inflammatory pathways for the treatment of CIRs were associated with neuropsychiatric adverse events, notably depression, or suicidal ideation or behavior (43). Indeed, development of brodalumab, a molecule targeting interleukin-17, was stopped after suicidal behaviors were observed during clinical trials(44).
Our results, in line with the literature suggest a bidirectional relationship between a depressive syndrome and a biological inflammatory syndrome but need to be confirmed by a longitudinal study to establish conclusions. It remains to be determined whether systemic inflammation itself induces emotional symptoms by acting on certain neuronal cells or whether these emotional disorders are at the origin of a biological inflammatory syndrome that subsequently triggers the onset of CIRs.
One of the main limitations of this preliminary study is its lack of statistical power due to of the small sample. However, this pilot study investigated potential associations between CIRs and biopsychosocial factors, and its findings are merely indicative of what items should be examined in greater depth during future studies. In addition, because this was an observational study, no conclusions can be drawn about any association with causality. Because this was a cross-sectional investigation, it was not possible to know whether the primary emotional regulation disorders, possibly contributing to the rheumatological disease onset, or secondary disorders, should be interpreted as adaptive or coping modalities to handle a functional handicap or at limiting pain caused by the disease. Our study suffers from two selection biases: it was monocentric, recruiting patients consulting at a university hospital, who could represent a particular sociodemographic status; and most patients were followed in a day hospital focusing on more severe pathologies and comorbidities. Furthermore, the clinical psychological parameters chosen for assessment, although not subjected to consensual agreement, do correspond to clinical entities. Nonetheless, participants in this study benefited from combined psychiatric and rheumatological work-up during a day of hospitalization, which is novel, enabling evaluation of a large number of psychological factors and to compare them to concomitant rheumatological findings.