Abstract
This study examined whether depression and anxiety differentially relate to fatigue, sleep disturbance, pain catastrophizing, fear of movement, and pain severity in women with fibromyalgia. Baseline data from the Fibromyalgia Activity Study with Transcutaneous Electrical Nerve Stimulation were analyzed. Of 191 participants, 50 percent reported high anxiety and/or depression (17% high anxiety, 9% high depression, and 24% both). Fatigue and sleep impairment were associated with high depression (p < 0.05). Pain severity, pain catastrophizing, and fear of movement were associated with high anxiety and high depression (p < 0.05). Possible implications for underlying mechanisms and the need for targeted treatments are discussed.
Introduction
Fibromyalgia is a chronic pain condition associated with fatigue, sleep disturbance, and cognitive difficulties (Wolfe et al., 2010). For many, this condition is disabling, interfering with multiple functional domains, including physical, social, and mental health (Birtane et al., 2007). Pain, fatigue, and impaired sleep are reported in nearly all individuals with fibromyalgia (Bigatti et al., 2008; Kleinman et al., 2014; Lukkahatai et al., 2016; Salaffi et al., 2016) and are associated with reduced function and quality of life (Dailey et al., 2016; Theadom et al., 2007). Additionally, pain catastrophizing and fear of movement, two important pain-related psychological constructs, are associated with pain-related disability and pain severity (Nijs et al., 2013; Sullivan, 2009; Sullivan and Bishop, 1995; Sullivan et al., 2006). Thus, people with fibromyalgia have widespread symptoms across multiple domains and associated psychological distress and pain-specific distress, which can directly impact function and quality of life.
People with fibromyalgia can also present with high levels of anxiety and depression with prevalence estimates ranging between 20 and 80 percent (Fietta et al., 2007; Marangell et al., 2011; Thieme et al., 2004). One recent study found that 77 percent of their sample reported a high level of emotional distress, including 58 percent reporting clinically relevant levels of anxiety and 63 percent depression (Di Tella et al., 2017). Anxiety, which can be characterized by anticipatory fear (American Psychiatric Association, 2013), is related to pain catastrophizing and fear of movement in chronic pain (Sullivan, 2009; Vlaeyen et al., 1995a, 1995b), including those with fibromyalgia (Martinez et al., 2011). The effects of anxiety may be amplified by the effects of depression, which are often accompanied by fatigue and sleep disturbance (American Psychiatric Association, 2013; Lukkahatai et al., 2016), and in those with fibromyalgia, depression is associated with fatigue (Lukkahatai et al., 2016; Nicassio et al., 2002). Thus, different psychological constructs, like depression and anxiety, are likely associated with differing symptomology. This study will examine the relationships of depression and anxiety together to somatic symptoms and pain-related psychological variables.
Fibromyalgia is a heterogeneous pain syndrome, with a variety of symptomology and psychological dysfunction. Prior studies have examined this heterogeneity and show multiple subgroups among individuals with fibromyalgia. These studies generally found several subgroups that spanned from low symptoms and psychological dysfunction to those that were high in all categories (Docampo et al., 2013; Lipkovich et al., 2014; Luciano et al., 2016; Lukkahatai et al., 2016; Salaffi et al., 2016; Vincent et al., 2014; Yim et al., 2017). Two common presentations of psychological distress, anxiety, and depression are conceptually distinct entities (American Psychiatric Association, 2013) that can be treated with different cognitive behavioral approaches (Norton and Price, 2007; Veale, 2007). Identifying such subsets of patients with fibromyalgia will provide insights for targeted therapeutic approaches, such as tailored cognitive behavioral therapy (CBT) interventions, which can address both psychological distress and specific somatic symptom management. Current multidisciplinary treatments which include psychological interventions appear to be effective for a sub-set of persons with fibromyalgia (Van Den Houte et al., 2017). Understanding the relationships between symptomatology and psychological distress will assist in tailoring interventions to maximize effectiveness for patients with fibromyalgia.
This study will examine whether somatic symptoms (fatigue, sleep disturbance, and pain severity) and pain-related psychological variables (pain catastrophizing and fear of movement) differentially relate to depression and anxiety in participants with fibromyalgia. It is hypothesized that (1a) fatigue and sleep disturbance will be associated with high levels of depression but not anxiety. (1b) In the presence of high depression and high anxiety, the effect of depression will be magnified. (2a) Pain catastrophizing, fear of movement, and pain severity will be associated with high levels of anxiety but not depression. (2b) The effect of anxiety will be magnified by the presence of depression.
Methods and measures
This study is a supplementary analysis of baseline data from a clinical trial investigating Transcutaneous Electrical Nerve Stimulation (TENS) for women with fibromyalgia: the Fibromyalgia Activity Study with TENS (FAST). Participants completed informed consent procedures then provided baseline demographic and survey data. Data were provided through the Research Electronic Data Capture (REDCap) system. All data were collected during in-person visits: demographic data were collected during the consent visit, and the survey and pain severity data used for this analysis were collected at a second visit. Additional details about the parent study have been reported previously (Noehren et al., 2015).
Participants
Participants were recruited from a Midwestern and a Southern medical center. This study was approved by Institutional Review Boards at both study sites. Participants met the following inclusion criteria: (1) females aged 18–70 years; (2) fibromyalgia diagnosis by American College of Rheumatology (ACR) 1990 criteria with 11 of 18 tender points on examination, (3) pain greater than or equal to 4/10 at initial screening, (4) stable treatment regimen for the last 4 weeks and projected stable treatment regimen for the next 2 months, (5) English speaker, and (6) completed baseline measures of depression and anxiety. Participants were excluded due to (1) current or history of cardiac, pulmonary, neurological, endocrine, or renal disease that would preclude study participation; (2) TENS use in the last 5 years; (3) pacemaker; (4) uncontrolled blood pressure or diabetes; (5) neuropathic pain condition; (6) systemic autoimmune disorder; (7) cervical or lumbar fusion or metal implants; (8) severe skin allergy to adhesive; (9) allergy to nickel; (10) pregnancy; (11) epilepsy; (12) unstable medical or psychiatric condition; (13) chest pain with activity; or (14) use of assistive device for ambulation.
Measures
Depression
Depression was assessed with the National Institutes of Health Patient-Reported Outcome Measurement Information System (PROMIS) Short Form (8b). This scale assesses negative mood, views of self, social cognitions, and decreased positive affect or engagement. This 8-item questionnaire assesses depressive symptoms across the past 7 days. Each item is scored from 1 to 5 with a maximum total of 40 on the measure. Raw scores are then converted into standardized T-scores, based on a normative sample with a mean of 50 and standard deviation (SD) of 10 (Patient-Reported Outcomes Measurement Information System (PROMIS), n.d., Available at: http://www.nihpromis.org/). This measure has demonstrated good internal consistency (Cronbach’s alpha = 0.95) as well as convergent and discriminant validity (Bjorner et al., 2014). For this study, scores more than 1 SD above the mean (≥60) was used to indicate a significant degree of depressive symptoms; scores more than 1 SD above the mean on a PROMIS measure indicate moderate to severe symptoms (Cella, 2017).
Anxiety
Anxiety was assessed with the PROMIS Short Form (8a). This scale assesses self-reported fear, anxious misery, hyperarousal, and somatic symptoms related to arousal across eight items. Each item is rated on a scale of 1–5 on symptoms across the past 5 days. Raw scores are converted into T-scores, based on a normative sample with a mean of 50 and an SD of 10 (PROMIS, n.d., Available at: http://www.nihpromis.org/). PROMIS anxiety measures have demonstrated internal consistency and alternate forms (long and short) of reliability and construct validity (Cella et al., 2010). This measure has also demonstrated clinical validity across diverse medical samples (including back pain, chronic obstructive pulmonary disease, chronic heart failure, and cancer; Schalet et al., 2016). For this study, scores more than 1 SD above the mean (≥60) were used to indicate a significant degree of anxious symptoms; scores more than 1 SD above the mean on a PROMIS measure indicate moderate to severe symptoms (Cella, 2017).
Fatigue (Multidimensional Assessment of Fatigue)
The Multidimensional Assessment of Fatigue (MAF) is a self-report measure of fatigue in chronic illness. This 16-item measure includes four subscales: severity, distress, timing, and impact on activities of daily living (ADLs). It also includes a total composite score (Global Fatigue Index (GFI)) from the subscales; scores range from 1 (no fatigue) to 50 (severe fatigue). The GFI was used for this study to capture a more comprehensive assessment of fatigue. The MAF has good internal consistency (r = 0.93) and convergent validity with a fatigue visual analog scale (VAS: r = 0.80, p < 0.05; Lentz et al., 2009).
Sleep disturbance (Pittsburgh Sleep Quality Index)
The Pittsburgh Sleep Quality Index (PSQI) is a 19-item measure which assesses self-reported sleep quality over the previous month. The measure produces seven clinical component scores which combine to create a global score between 0 and 21; this global score was used in this study. This scale has demonstrated high test–retest reliability (r = 0.87) and convergent validity with sleep log data (r = 0.81, for sleep duration and r = 0.71 for sleep onset latency; Backhaus et al., 2002).
Pain Catastrophizing Scale
The Pain Catastrophizing Scale (PCS) is a 13-item measure of pain catastrophizing; it assesses thoughts and feelings related to pain. The PCS includes three subscales: rumination, magnification, and helplessness. A total score can also be calculated and the total PCS score was used for this study. Scores range from 0 to 52 on this measure and 30 is considered clinically significant (Sullivan and Bishop, 1995). The PCS has good internal consistency (Cronbach’s alpha = 0.95) and criterion validity; in a sample of 60 patients with chronic pain and 85 community participants without chronic pain, the PCS total score correctly classified 77 percent of cases (Osman et al., 2000).
Fear of movement (Tampa Scale of Kinesiophobia)
The Tampa Scale of Kinesiophobia (TSK) measures fear of movement in patients with chronic pain. These 17 items are rated from 1 = strongly disagree to 4 = strongly agree; scores range from 17 to 68; the total score was used in this study. This scale demonstrates good test–retest reliability (r = 0.78) and good internal consistency: Chronbach’s alpha = 0.76 (Burwinkle et al., 2005; Roelofs et al., 2004).
Pain severity
Pain severity was assessed at rest with an 11-point Numeric Rating Scale (NRS). The scale was anchored with 0 = “no pain” and 10 = “worst pain imaginable.” The pain NRS demonstrates good construct validity; it has demonstrated high correlations in patients with chronic pain to the visual analog scale (from 0.86 to 0.95; Hawker et al., 2011).
Data analysis
Descriptive characteristics were calculated for demographics and all variables of interest. Since this study did not include diagnostic assessments of depression and anxiety, in order to increase clinical relevance, anxiety and depression scores were dichotomized into “high” and “low” at 1 SD above the mean (t = 60), using established cut-points (Cella, 2017), with this classification being used in the analyses. Fatigue, sleep disturbance, pain catastrophizing, and fear of movement were treated as continuous variables. Two-way analyses of variance (ANOVAs) were run to examine for main effects of depression (high versus low) and of anxiety (high versus low) on sleep disturbance, fatigue, pain catastrophizing, fear of movement, and pain severity. Interaction effects between depression and anxiety on the somatic symptoms (fatigue, sleep disturbance, and pain severity) and pain-related psychological variables (pain catastrophizing and fear of movement) were also examined within the ANOVAs. The tests for interactions determined whether depression and anxiety modified the effect of the other. The pain severity variable was non-normally distributed, so a two-way ANOVA based on ranks was conducted to determine main and interaction effects of depression and anxiety on pain severity.
Results
A total of 191 women met inclusion and exclusion criteria for this study. Participants’ mean age was 49 years (SD = 12 years); 53 percent were single, divorced, or widowed; mean body mass index (BMI) was 34.6 kg/m2 (SD = 9.0); the majority (63%) held a Bachelor’s degree; 70 percent reported an income of US$60,000 or less; and 65 percent reported having had the diagnosis of fibromyalgia for at least 5 years (see Table 1 for further details). Participants generally reported moderate levels of pain catastrophizing and high levels of fatigue, sleep disturbance, pain severity, and fear of movement (see Table 1). Half of the sample (50%) reported less than moderate to severe depression and anxiety, 17 percent reported high levels of anxiety (moderate to severe) without high levels of depression, 9 percent reported high levels of depression (moderate to severe) without high levels of anxiety, and 24 percent reported high levels (moderate to severe) of both depression and anxiety (see Table 1).
Demographics and clinical characteristics.
SD: standard deviation; IQR: interquartile range; BMI: body mass index; NRS: Numeric Rating Scale; TSK: Tampa Scale of Kinesiophobia; MAF: Multidimensional Assessment of Fatigue; GFI: Global Fatigue Index; PSQI: Pittsburgh Sleep Quality Index; PROMIS: Patient-Reported Outcome Measurement Information System.
All ns are the same as the heading unless otherwise noted.
Fatigue
Participants meeting the cutoff for high depression reported significantly higher levels of fatigue on the MAF: (main effect for depression: F(1, 187) = 4.84, p = 0.03). There was no main effect for anxiety on fatigue (F(1, 187) = 1.71, p = 0.19) and no significant interaction effect between anxiety and depression on fatigue (F(1, 187) = 0.78, p = 0.38). The mean fatigue score was 2.87 points higher on the MAF (95% confidence interval (CI): 0.30, 5.45) for participants in the high depression group compared to those in the low depression group (see Table 2).
ANOVA results: means and standard deviations (or medians and interquartile ranges) by high- and low-depression and anxiety subgroups.
ANOVA: analysis of variance.
p < .05.
p < .01.
Sleep quality
Participants meeting the cutoff for high depression reported significantly worse sleep quality on the PSQI: (main effect for depression: F(1, 187) = 6.18, p = 0.01). There was no main effect for anxiety on sleep quality (F(1, 187) = 1.81, p = 0.18) and no significant interaction effect between anxiety and depression on sleep (F(1, 187) = 1.62, p = 0.20). The mean sleep score was 1.46 points higher on the PSQI (95% CI: 0.30, 2.61) for participants in the high depression group compared to the low depression group (see Table 2).
Pain catastrophizing
Participants meeting the cut-off for high depression reported significantly greater pain catastrophizing on the PCS: (main effect for depression: F(1, 187) = 26.57, p < 0.0001). Those meeting the cut-off for high anxiety also reported significantly higher pain catastrophizing (main effect for anxiety: F(1, 187) = 14.70, p = 0.0002), but there was no significant interaction effect between anxiety and depression on pain catastrophizing (F(1, 187) = 0.04, p = 0.85). Mean pain catastrophizing was 10.02 points higher (95% CI: 6.19, 13.86) for participants in the high-depression group compared to the low-depression group and 7.45 points higher (95% CI: 3.62, 11.29) for participants in the high-anxiety group compared to the low-anxiety group (see Table 2).
Fear of movement
Participants meeting the cutoff for high depression reported significantly greater fear of movement on the TSK: (main effect for depression: F(1, 187) = 4.64, p = 0.04)). Those meeting the cutoff for anxiety also reported significantly higher fear of movement (main effect for anxiety: F(1, 187) = 14.11, p = 0.0002), but there was no significant interaction effect between anxiety and depression on fear of movement (F(1, 187) = 0.91, p = 0.34). Mean fear of movement was 2.79 points higher (95% CI: 0.23, 5.35) for participants in the high-depression group compared to the low-depression group and 4.87 points higher (95% CI: 2.31, 7.43) for participants in the high-anxiety group compared to low-anxiety group (see Table 2).
Pain severity
Participants meeting the cutoff for high depression reported significantly greater pain severity on the NRS (main effect for depression: p = 0.01). Those meeting the cutoff for high anxiety also reported significantly greater pain severity (main effect for anxiety: p = 0.04), but no significant interaction effect was found between anxiety and depression on pain severity (i.e. anxiety and depression did not amplify the effect of the other: p = 0.65, see Table 2).
Discussion
This study uniquely examined the relationships between multiple somatic and pain-related psychological variables to depression and anxiety in women with fibromyalgia. Findings indicate that fatigue and sleep disturbance were associated with high depression but not high anxiety, while pain catastrophizing, fear of movement, and pain severity were associated with both high depression and high anxiety. Contrary to our hypotheses, depression and anxiety did not have an amplifying interaction effect on one another in relation to somatic and psychological variables.
The prevalence of anxious and depressive symptoms in this study was within previously reported ranges (Fietta et al., 2007; Marangell et al., 2011; Thieme et al., 2004). Additionally, our data support the heterogeneity of individuals with fibromyalgia. This is consistent with multiple previous cluster studies indicating diverse clinical presentations (Aktas et al., 2010; De Souza et al., 2009; Docampo et al., 2013; Giesecke et al., 2003; Hurtig et al., 2001; Loevinger et al., 2012; Luciano et al., 2016; Rehm et al., 2010; Rutledge et al., 2009; Wilson et al., 2009). This diversity in clinical presentation has resulted in the suggestion that fibromyalgia presents an overlap of syndromes as opposed to a distinct entity (Bennett et al., 2010). The wide variability in this population indicates a need for better identification of subgroups, to allow for targeted treatments (Turk et al., 1998). The current findings contribute to identification of clinically relevant subgroups of patients with fibromyalgia.
This study identified relationships of fatigue and sleep disturbance uniquely to depression. Previous findings suggest that sleep problems are prevalent in this population and may relate to depression through the impact of poor sleep on pain severity and lower physical functioning (Bigatti et al., 2008). Another possibility is that there may be a common mechanism underlying the symptom triad of depression, fatigue, and sleep disturbance in persons with fibromyalgia. Possible underlying mechanisms could include central nervous system sensitization or systemic inflammation (Sluka and Clauw, 2016). Chronic systemic inflammation, for example, has been implicated in both fibromyalgia (Mendieta et al., 2016; Sturgill et al., 2014) and in depression (Berk et al., 2013; Dantzer et al., 2008; Miller et al., 2009); however, this picture is complicated because markers of inflammation have also been reported in relation to pain severity (Dawes et al., 2013). Better understanding of how underlying mechanisms interact to impact the overlapping symptoms of depression, fatigue, and sleep could inform better differentiation between the wide ranges of clinical presentations among patients with fibromyalgia and inform treatment approaches; greater understanding of this symptom triad may contribute to developing targeted treatments.
In contrast to this symptom triad, pain catastrophizing, fear of movement, and pain severity were associated with both depression and anxiety, which may indicate a relationship between these variables and an underlying construct of general distress. This concept is supported by previous work in samples of patients with chronic pain which demonstrated associations between pain catastrophizing and depression, anxiety, and fear (Borsbo et al., 2008; Drahovzal et al., 2006; Edwards et al., 2006; Leeuw et al., 2007) and between pain severity and a range of measures of psychological distress (Gatchel and Turk, 1996). The relationship between distress to pain catastrophizing, fear of movement, and pain in patients with fibromyalgia may indicate a vicious cycle between these variables (such that, they serve to amplify one another).
These results suggest the possible benefit of tailored targeted treatments for symptom management in persons with fibromyalgia. The differences identified in fatigue and sleep quality in relation to depression versus anxiety provide direction for such targeted clinical interventions. Current multidisciplinary treatments which include psychological intervention may be more effective for those with lower baseline depression and anxiety symptoms (Van Den Houte et al., 2017). CBT interventions (or CBT components of multidisciplinary interventions) may be tailored for different psychological presentations in conjunction with various fibromyalgia symptoms. For example, CBT for individuals with fibromyalgia and significant depressive symptoms may emphasize behavioral activation (Veale, 2007) and behavioral sleep management (Morin et al., 2006). Conversely, pain catastrophizing, fear of movement, and pain severity may need to be targeted more generally across distressed persons with fibromyalgia. Further research is needed to determine whether such targeted treatments result in improved outcomes. One important limitation of this study is that the current sample was all women and findings may not generalize to men with fibromyalgia.
In conclusion, this study is unique in its organization of somatic and pain-related psychological symptoms specifically by depression and anxiety. This study identified that half of participants (50%) presented with moderate to severe levels of depression and/or anxiety, including 24 percent of the sample who presented with both. This study highlights that while pain catastrophizing, fear of pain, and pain severity are associated with both anxiety and depression, fatigue and sleep disturbance are only associated with depression. Overall, this study provides support for differing clinical presentations in depressed compared to anxious persons with fibromyalgia.
Footnotes
Declaration of conflicting interests
The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Kathleen A. Sluka, PT, PhD, FAPTA serves as a consultant for Bayer, Inc. Dr. Sluka has an active research grant from Medtronic, Inc and receives royalties from IASP Press. Dana Dailey, PT, PhD, serves as a consultant for Bayer, Inc. The remaining authors of this manuscript have no conflicts of interest to report.
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was funded by National Institutes of Health (NIH) UM1 AR06338 and NIH UM1 AR06338-S1. Data were collected with REDCap electronic data capture tools hosted at University of Iowa (supported by NIH 54TR001013). Study data collection was completed through the Clinical and Translational Science Awards (CTSA) program at University of Iowa (supported by NIH U54TR001356) and Vanderbilt University (supported by NIH UL1TR000445).