Fibromyalgia syndrome (FMS) is a medical diagnosis of unknown etiology mainly characterized by chronic and widespread pain (1). Other symptoms include fatigue, gastrointestinal symptoms, and joint stiffness (1–3). Furthermore, a growing body of evidence shows a comorbidity of FMS with psychological symptoms, particularly with depression and anxiety (2–9): lifetime prevalence of depression and anxiety in patients with FMS go up to 70 and 60%, respectively (8). Widespread pain and mental disorders compose a relevant public health problem due to the high economic and societal burden (10–13). A better understanding of risk factors for the onset of depressive and anxious symptomatology in FMS might, therefore, be instrumental in identifying strategies for prevention and early interventions, such as those recommended by the European League Against Rheumatism (EULAR) (14, 15). Risk factors for the onset of depression and anxiety have been studied longitudinally, and include pain, a negative perception of health, dysfunctional coping strategies, personality traits (e.g., neuroticism), female gender, and lower education (10, 16). This study will focus on those factors that have shown to be associated with an increased risk of depression and anxiety in chronic pain patients, and that might be easily modifiable in treatment: severity of pain (10, 17–20), coping strategy (21–23), and illness perceptions (24–26). To date, longitudinal studies exploring the contribution of all these risk factors in subsequent depressive and anxious symptomatology in patients with FMS in one study are lacking.

Widespread pain is characteristic for FMS (1) and thorough research exists exploring the association of widespread pain and severity of pain with depressive and anxiety disorders (10, 17–20). In several cross-sectional studies, among which a review and a large survey among 17 countries, multiple pain locations were more strongly associated with depression and anxiety when compared with one pain location and no pain (10, 17, 18). In two longitudinal studies, every additional pain location increased the risk of a new onset and recurrence of a depressive and/or anxiety disorder with 29 and 7%, respectively (19, 20). Moreover, for every increase in the severity of pain the risk increased with 57% for new onset and 11% for recurrence of depression and/or anxiety (19, 20).

Another risk factor associated with depression and anxiety is coping style. Patients with FMS tend to cope passively, such as catastrophizing (27, 28). In patients with FMS, pain is indirectly associated with depression through its relationship with a passive coping style (21). A passive coping style, in turn, is significantly associated with depression (27). Furthermore, in studies among patients with other rheumatic diseases, passive coping strategies, including withdrawal and worrying or catastrophizing, were also associated with psychological distress (22, 23).

A maladaptive coping style is associated with poor illness perceptions (29), that in turn are associated with depressive and anxiety symptoms (24–26, 29, 30). In patients with chronic widespread pain, negative beliefs about their illness, such as that the illness would affect their emotional well-being, were found to be associated with an increase of depressive and anxious symptomatology (24, 25). Also, patients with rheumatoid arthritis who had negative beliefs about the consequences of their illness were more depressed over time (26).

Patients with FMS are characterized by pain in multiple locations, or widespread pain. This makes them vulnerable for depression and anxiety. However, it is unknown whether other characteristics are associated with the onset of depression and anxiety. Cross-sectional studies suggest that more severe pain, a maladaptive (passive) coping style, and negative illness perceptions are related to depression and anxiety in patients with (chronic) pain and in patients with rheumatic diseases (17, 18, 21–25). FMS is a rheumatic disease, characterized by chronic pain, which makes it likely that these factors would also play a role in the onset and persistence of depressive and anxious symptomatology in this population. However, these factors have not been studied in concert and longitudinally in FMS before. Therefore, a study exploring this association in a longitudinal design in FMS is warranted. The aim of this study is to examine pain, pain-related coping, and illness perception as possible risk factors for depressive and anxious symptomatology in patients with FMS. We hypothesize that more pain, passive pain-related coping and poor illness perceptions at baseline are associated with more depressive and anxiety symptoms in FMS.

Table 1 shows the baseline characteristics of the 280 persons in this cohort. Mean age of the study sample was 42.6 years, and 95.4% were female. Mean pain severity was 6.75 on a 10-point Likert scale. Of the participants, 118 (42.1%) had a possible or probable depressive disorder, and 140 (50%) had a possible or probable anxiety disorder at baseline.

Table 2 shows the univariate associations between all predictor variables and the covariates, with depressive and anxious symptomatology at 18-month follow-up (n = 68 for depressive symptoms; n = 80 for anxiety symptoms). Regarding the depression outcome, a passive coping style (OR = 2.92), and the IPQ subscales “timeline” (OR = 1.09), “consequences” (OR = 1.22), “personal control” (OR = 0.89), and “emotional representations” (OR = 1.19) had a significant univariate association with a possible/probable depressive disorder at 18-month follow-up. The covariates’ initial level of depressive symptoms and initial level of anxiety symptoms also had a significant univariate association with a possible/probable depressive disorder at 18-month follow-up (OR = 1.37 and OR = 1.21, respectively). After logistic regression with backward selection (Table 3), the IPQ subscale “emotional representations” (OR = 1.10) was significantly associated with possible/probable depressive disorder at 18-month follow-up, next to initial level of depressive symptoms (OR = 1.30). Thus, subjects who respond emotionally regarding their illness and have more initial depressive symptoms at baseline are at increased risk for a possible or probable depressive disorder at follow-up. Together, these variables in the regression model accounted for 30% of the variance of the depression score at follow-up. The overall fit of the derived model was good (χ² = 13.85, p = 0.09).

Regarding anxiety outcome, a passive coping style (OR = 2.80), and the IPQ subscales “consequences” (OR = 1.17), “treatment control” (OR = 0.90), and “emotional representations” (OR = 1.19) had a significant univariate association with a possible/probable anxiety disorder at 18-month follow-up (Table 2). The covariates’ initial level of depressive symptoms and initial level of anxiety symptoms also had a significant univariate association with a possible/probable anxiety disorder at 18-month follow-up (OR = 1.21 and OR = 1.44, respectively). After logistic regression with backward selection, treatment control (OR = 0.87) was significantly associated with possible/probable anxiety disorder at 18-month follow-up, next to initial level of anxiety symptoms (OR = 1.45) (Table 3). Thus, subjects who think that their treatment is not effective regarding their illness and have more anxiety symptoms at baseline are at increased risk for a possible or probable anxiety disorder. Together, these variables in the regression model accounted for 40% of the variance of the anxiety score at follow-up. The overall fit of the derived model was good (χ² = 13.05, p = 0.11).

To the authors’ knowledge, this is the first study to document on pain, illness perception, and coping style as risk factors for depressive and anxious symptomatology in patients with FMS. The results here indicate that patients with FMS who believe their illness will have a negative effect on their mental well-being, who also have elevated levels of depressive symptoms, are more likely to be depressed on subsequent occasions. Furthermore, patients with FMS who think that treatment of their illness will not be effective and who also have elevated levels of anxiety symptoms are more likely to be anxious on subsequent occasions. Our hypothesis that poor illness perceptions are a risk factor for depressive and anxious symptomatology is therefore confirmed.

Only illness perceptions and initial level of affective symptoms were found to play a significant role in depressive and anxious symptomatology, suggesting that these factors are possibly more important than other well-known risk factors, such as pain, which is contrary to what we expected. These findings are consistent with previous research in similar populations. For example, patients with chronic (widespread) pain who had a strong belief that their illness would affect their mental well-being were more likely to report depressive and anxiety symptoms (24, 25), whereas pain intensity did not show such an association (24). In patients with rheumatoid arthritis, the patients’ beliefs and emotional responses to their illness were key factors explaining the association between pain and depression (46). Furthermore, in two large longitudinal studies, the association between pain and new onset and recurrence of depression and anxiety were mediated by (subthreshold) depressive symptoms (19, 20). This could explain our finding that not pain severity, but negative cognitions about the illness and the initial level of affective symptoms are more important as risk factors in the development of subsequent depressive and anxious symptomatology. Neurobiological abnormalities might also play a role, which persists in patients who have experienced strong negative emotions, possibly through negative biases in the processing of emotional information (47). On the other hand, pain and emotion share neuronal networks, and pain, one of the main characteristics of FMS, might cause a dysregulation in the neuronal network associated with emotion (48). Thus, patients with FMS who experience negative affective symptoms and negative perceptions regarding their illness might, therefore, have developed neurobiological abnormalities, making them vulnerable for subsequent depressive and anxious symptomatology.

Contrary to what we expected, a passive coping style was not a significant risk factor for depressive and anxiety symptoms, in contrast to a previous study in patients with FMS (21). However, they used another construct of passive coping, emphasizing on emotion-focused strategies, whereas passive coping in this study was mostly characterized by avoidant strategies. In a study in patients with systemic sclerosis, a rheumatic disease, emotion-focused coping had a strong association with depressive symptoms, whereas avoidant focused coping did not (22). Furthermore, in patients with chronic heart failure, an avoidant coping style was indirectly associated with depression and anxiety through poor illness perceptions (29), which might explain our findings. This might suggest that emotional components of coping with an illness are more important than other maladaptive forms of coping. In our study, passive coping consisted of three cognitive-behavioral strategies, one of them being catastrophizing or worrying, which is an emotional component also. Therefore, future studies should explore the subcategories of passive coping to explore whether the emotional components of coping are indeed more important than other components.

Strengths of this study are the longitudinal design and the large sample size. However, several limitations need to be addressed. The sample of this study consisted of patients with FMS, which limits the generalizability to other populations. However, comparable results were found in other rheumatologic populations (22, 24, 25, 46). This might suggest that our results are generalizable to populations characterized by a chronic disease. In this study, the HADS, which was developed specifically for medically ill populations, was used to measure depressive and anxious symptomatology. Although this instrument has good internal consistency and can be used as case finding for depressive and anxiety disorders (37), and is widely used in rheumatologic populations, no inferences could be made whether patients met criteria for a depressive or anxiety disorder. For such purposes, diagnostic (semi)structured interviews need to be used, such as the Mini-International Neuropsychiatric Interview (49) or Composite International Diagnostic Interview (50). In addition, we used a single self-reported questionnaire (FIQ) to measure pain severity, which prevents us to make inferences of other aspects of functioning and well-being, such as quality of life. Besides, it is possible that factors not studied here might play a crucial role in depressive and anxious symptomatology in patients with FMS. Received treatment, whether it is physical (51–54), psychological, or pharmacological (55), can influence both depressive as anxiety symptoms. Patients in this study received advice for treatment, based on the recommendations of the EULAR (14, 15), after the baseline measurement. Treatment advice could be referral (back) to the general practitioner, physiotherapist, psychologist, or a multimodal rehabilitation program. Unfortunately, no information was available whether this advice was followed, or if another treatment was received other than advised. We were, therefore, unable to make any inferences on the effect of treatment on depression and anxiety. Other factors that might influence depressive and anxious symptomatology are medication use, comorbidity with other chronic diseases (56), and perceived social support (57). Unfortunately, due to the limited sample size at follow-up (68 patients for depressive symptoms and 80 for anxiety symptoms), it was not possible to include more factors in the statistical models. Future research with larger sample sizes is needed. A larger sample size is also necessary to examine the incidence of depressive and anxious symptomatology, by excluding those patients with depressive and anxiety symptoms at baseline. The sample size of this study was too small, unfortunately.

Our study highlights the importance of illness perceptions in the development of depressive and anxious symptomatology in patients with FMS. Developing treatment interventions aimed at modification of poor illness perceptions is therefore of interest. It has been shown that interventions focusing on illness perceptions, such as cognitive treatment and illness perception focused intervention, is effective in improving maladaptive perceptions in patients with chronic low back pain (58), and even has a positive effect on depressive and anxious symptomatology (59). In addition, cognitive behavior therapy focusing on catastrophizing has shown to be effective at increasing acceptance of the illness and global functioning in patients with FMS (60). Our findings corroborate the recommendations of the EULAR for psychological treatment, such as cognitive behavior therapy, in case of depressed mood (15). Thus, strengthening illness beliefs and reducing catastrophic thinking seem to be important factors in the treatment of patients with FMS, allowing them to improve their health. Future research should further explore the effects of such interventions.

This study was carried out in accordance with the recommendations of the local medical ethical board with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The Institutional Review Board of the University Medical Centre, Nijmegen, approved the study (protocol number: 2011/271).

EH, CF-C, and JV conceived the initial idea for this study, and all the authors contributed to its planning, including defining the aims, variables of interest, and analysis strategy. Analyses were done by JV, but all the authors had access to the statistical outputs. EH drafted the article, and all the authors contributed to revisions., approved the final manuscript, and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.