The GC-MS metabolomics signature in patients with fibromyalgia syndrome directs to dysbiosis as an aspect contributing factor of FMS pathophysiology.

INTRODUCTION: Fibromyalgia syndrome (FMS) is a chronic pain syndrome. Previous analyses of untargeted metabolomics data indicated altered metabolic profile in FMS patients. OBJECTIVES: We report a semi-targeted explorative metabolomics study on the urinary metabolite profile of FMS patients; exploring the potential of urinary metabolite information to augment existing medical diagnosis. METHODS: All cases were females. Patients had a medical history of persistent FMS (n = 18). Control groups were first-generation family members of the patients (n = 11), age-related individuals without indications of FMS (n = 10), and healthy, young (18-22 years) individuals (n = 41). The biofluid investigated was early morning urine samples. Data generation was done through gas chromatography-mass spectrometry (GC-MS) analysis and data processing and analyses were performed using Matlab, R, SPSS and SAS software. RESULTS: Quantitative analysis revealed the presence of 196 metabolites. Unsupervised and supervised multivariate analyses distinguished all three control groups and the FMS patients, which could be related to 14 significantly increased metabolites. These metabolites are associated with energy metabolism, digestion and metabolism of carbohydrates and other host and gut metabolites. CONCLUSIONS: Overall, urinary metabolite profiles in the FMS patients suggest: (1) energy utilization is a central aspect of this pain disorder, (2) dysbiosis seems to prevail in FMS patients, indicated by disrupted microbiota metabolites, supporting the model that microbiota may alter brain function through the gut-brain axis, with the gut being a gateway to generalized pain, and (3) screening of urine from FMS is an avenue to explore for adding non-invasive clinical information for diagnosis and treatment of FMS.

The involvement of melatonin in the clinical status of patients with fibromyalgia syndrome.

OBJECTIVES: The aim of this study was to evaluate the levels of 6-sulphatoxymelatonin (6-SMT) in the urine of patients with fibromyalgia (FM) and correlate them with the score obtained by these patients in four clinical assessment instruments. METHODS: Fifty-eight women with primary FM and 39 healthy women matched for age and body mass index were included in the study sample. The levels of 6-SMT were evaluated in urine collected from 8 pm until 8 am the next day by the immunosorbent assay. For the clinical evaluation we used the Fibromyalgia Impact Questionnaire (FIQ); Pittsburg Sleep Quality Index (PSQI); Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) and Satisfaction with Life Scale (SWLS). Data normality was assessed using the Kolmogorov-Smirnov test, the differences between groups by means of the Mann-Whitney test and correlation analysis by Spearman's correlation test. RESULTS: The levels of 6-SMT in the urine of patients with FM were significantly lower than those found in the urine of healthy controls. The score obtained by patients with FM was significantly different from the score achieved by the healthy controls in the four assessment tools. However, no significant correlation between urinary levels of 6-SMT and scores on assessment instruments was observed. CONCLUSIONS: The results of this study do not discard the involvement of melatonin in the pathophysiology of FM, but may suggest that changes in melatonin levels when associated with other neuroimmunoendocrine changes may impact directly and negatively on the manifestation of symptoms that make up the clinical picture of FM.

Urinary 6-sulphatoxymelatonin levels are depressed in chronic migraine and several comorbidities.

OBJECTIVE: To assess urinary 6-sulphatoxymelatonin levels in a large consecutive series of patients with migraine and several comorbidities (chronic fatigue, fibromyalgia, insomnia, anxiety, and depression) as compared with controls. BACKGROUND: Urine analysis is widely used as a measure of melatonin secretion, as it is correlated with the nocturnal profile of plasma melatonin secretion. Melatonin has critical functions in human physiology and substantial evidence points to its importance in the regulation of circadian rhythms, sleep, and headache disorders. METHODS: Urine samples were collected into a single plastic container over a 12-hour period from 8:00 pm to 8:00 am of the next day, and 6-sulphatoxymelatonin was measured by quantitative ELISA. All of the patients were given a detailed questionnaire about headaches and additionally answered the following questionnaires: Chalder fatigue questionnaire, Epworth somnolence questionnaire, State-Trait Anxiety Inventory, and the Beck Depression Inventory. RESULTS: A total of 220 subjects were evaluated - 73 (33%) had episodic migraine, 73 (33%) had chronic migraine, and 74 (34%) were enrolled as control subjects. There was a strong correlation between the concentration of 6-sulphatoxymelatonin detected and chronic migraine. Regarding the comorbidities, this study objectively demonstrates an inverse relationship between 6-sulphatoxymelatonin levels and depression, anxiety, and fatigue. CONCLUSIONS: To our knowledge, this is the first study to evaluate the relationship between the urinary concentration of melatonin and migraine comorbidities. These results support hypothalamic involvement in migraine pathophysiology.

[Evaluation of urinary cortisol levels in women with fibromyalgia]. / Evaluación de la cortisoluria en mujeres diagnosticadas de fibromialgia.

OBJECTIVE: We propose a comparative study of urinary cortisol in a controlled simple group of patients diagnosed with fibromyalgia (FM) during a minimum time frame (3 years) vs. a normal group with the same characteristics of age and gender. Our objective is to demonstrate if urinary cortisol at lower levels than those found in the normal population, as long as FM is regarded, could help to evaluate the fatigue. METHODS: We determined the urinary cortisol in a group of 47 women with a clinical diagnosis of FM using the criteria from the American College of Rheumatology (ACR) 1990, with ages between 29 and 64 years, in whom an accurate sample was collected and cortisol was determined using an FPIA method. The results were compared with the urinary cortisol obtained in a group of 88 healthy women within the same age range as those with FM. RESULTS: Urinary cortisol in FM was 65.0 microg/l (median), which was significantly lower than that of the healthy group (80.0 microg/l), p<0.001. CONCLUSION: 33.4% of patients with FM displayed urinary cortisol concentrations significantly lower than the group of women without FM.

Development and validation of a chemical hydrolysis method for dextromethorphan and dextrophan determination in urine samples: application to the assessment of CYP2D6 activity in fibromyalgia patients.

Dextromethorphan (DEM) is a widely used probe drug for human cytochrome P450 2D6 isozyme activity assessment by measuring the ratio between DEM and its N-demethylated metabolite dextrorphan (DOR). DOR is excreted in urine mainly conjugated to glucuronic acid. Prior to quantification, DOR must be deconjugated to avoid variability caused by the polymorphic glucuronosyltransferase enzyme. A chemical hydrolysis method was optimized using a chemometric approach. Three factors (acid concentration, hydrolysis time and temperature) were selected and simultaneously varied to study their effect on conjugated DOR hydrolysis. Hydrolysis conditions that maximize DOR release without significant degradation of both DEM and DOR were chosen and results were compared to those obtained by enzymatic method using beta-glucuronidase. An HPLC method with fluorescence detection was developed for the simultaneous quantitation of DEM, DOR and levallorphan, used as an internal standard. Separation was performed on a phenyl analytical column (150 mmx4.6 mm i.d., 5 microm) with a mobile phase consisting of 18% acetonitrile and 50 mM phosphoric acid (pH 3). The overall analytical procedure was validated and showed good performances in terms of selectivity, linearity, sensitivity, precision and accuracy. Finally, this assay was used to determine DEM/DOR molar ratios in fibromyalgia patients for the purpose of determining phenotype status for the CYP2D6.

Metabolic syndrome in women with chronic pain.

Fibromyalgia is a prevalent syndrome characterized by chronic pain, fatigue, and insomnia. Patients with fibromyalgia commonly have an elevated body mass index and are physically inactive, 2 major risk factors for metabolic syndrome. Yet little is known about the relationship between chronic pain conditions and metabolic disturbances. Our study evaluated the risk for, and neuroendocrine correlates of, metabolic syndrome in this patient population. Women with fibromyalgia (n = 109) were compared with control healthy women (n = 46), all recruited from the community. Metabolic syndrome was identified by using criteria from the Adult Treatment Panel III with glycosylated hemoglobin concentrations substituted for serum glucose. Catecholamine and cortisol levels were determined from 12-hour overnight urine collections. Women with fibromyalgia were 5.56 times more likely than healthy controls to have metabolic syndrome (95% confidence interval, 1.25-24.74). Fibromyalgia was associated with larger waist circumference (P = .04), higher glycosylated hemoglobin (P = .01) and serum triglyceride (P < .001) levels, and higher systolic (P = .003) and diastolic (P = .002) blood pressure. Total and low-density lipoprotein cholesterol were also significantly higher in women with fibromyalgia (P = .001 and .02, respectively), although high-density lipoprotein cholesterol was in the reference range. These associations were not accounted for by age or body mass index. Meeting criteria for more metabolic syndrome components was related to higher urinary norepinephrine (NE)/epinephrine and NE/cortisol ratios (P < .001 and P = .009, respectively). Women with chronic pain from fibromyalgia are at an increased risk for metabolic syndrome, which may be associated with relatively elevated NE levels in conjunction with relatively reduced epinephrine and cortisol secretion.

Trace element pattern in patients with fibromyalgia.

An imbalance of the trace element status in human tissues and body fluids has been suggested as a contributing factor for the development of fibromyalgia (FM). The study comprised 38 females with defined fibromyalgia (FM) according to generally accepted criteria from the American College of Rheumatology (ACR). They were compared with 41 females matched for age and geographic location. The concentrations of about 30 trace element and ions were determined in whole blood, urine and drinking water of all participants by inductively coupled plasma mass spectrometry (ICP-MS) and inductively coupled plasma optical emission spectroscopy (ICP-OES). Significantly higher concentrations in whole blood of Cd, Co, Cu, Fe, Se, Sn and Zn (p< or =0.046) were observed in the FM-cases in comparison with the referents. A different pattern was noted in urine with increased urinary excretion of Ag (p=0.003) among the FM-patients. The urinary excretion of the other elements were of the same magnitude or slightly lower in FM-cases as compared to referents. As nearly all of the concentrations of the studied elements in blood and urine were within reported reference intervals in non-occupationally exposed populations, the clinical significance of the differences observed seems to be limited. The element concentrations of the studied elements in drinking water were within present national and international guideline values (EU, WHO) and the concentrations of potentially toxic metals such as e.g. Cd, Hg and Pb were low. In conclusion, the present investigation could not demonstrate abnormal levels of trace elements in blood or urine of FM-patients and, thus, does not support the hypothesis that trace element abnormalities play a significant role in the development of FM.

Urinary electrophoretic profiles from chronic fatigue syndrome and chronic fatigue syndrome/fibromyalgia patients: a pilot study for achieving their normalization.

Aim of our study was to determine if there were distinct, disease-related patterns of urinary analytes in chronic fatigue syndrome (CFS) and chronic fatigue syndrome/fibromyalgia (CFS/FM) compared to normal controls (NC). Urine was collected from these subjects for two consecutive 24 h periods and aliquots were submitted to micellar electrokinetic chromatography (MEKC). To compensate for the differences in peak migration times, these were normalized from the 35 min duration of run to a 100-point scale, and each peak was assigned its normalized time measure. Peak heights were also normalized by dividing the mAU by that of the internal standard (creatinine) and multiplying by 100. MEKC with normalization for peak height and migration time generated comparable results within each of the patient groups. CFS/FM and CFS had significant differences in peaks compared to NC that may be of significance as biomarkers of illnesses.

Reduced hypothalamic-pituitary and sympathoadrenal responses to hypoglycemia in women with fibromyalgia syndrome.

PURPOSE: To perform a detailed comparison of the hypothalamic-pituitary-adrenal axis and the sympathoadrenal system in women with and without fibromyalgia. SUBJECTS AND METHODS: Fifteen premenopausal women who met the 1990 American College of Rheumatology criteria for the diagnosis of fibromyalgia and 13 healthy, premenopausal women were enrolled. We measured baseline 24-hour urinary free cortisol levels and evening and morning adrenocorticotropic hormone (ACTH) and cortisol levels, performed stepped hypoglycemic hyperinsulinemic clamp studies in which serum glucose levels were decreased from 5.0 to 2.2 mmol/L, and compared the effects of infusions of placebo and ACTH. RESULTS: Women with fibromyalgia had normal 24-hour urinary free cortisol levels and normal diurnal patterns of ACTH and cortisol. There was a significant, approximately 30%, reduction in the ACTH and epinephrine responses to hypoglycemia in women with fibromyalgia compared with controls. Prolactin, norepinephrine, cortisol, and dehydroepiandrosterone responses to hypoglycemia were similar in the two study groups. In subjects with fibromyalgia, the epinephrine response to hypoglycemia correlated (P = 0.01) inversely with overall health status as measured by the fibromyalgia impact questionnaire. Graded ACTH infusion revealed similar increases in cortisol in women with fibromyalgia and healthy controls. CONCLUSIONS: Patients with fibromyalgia have an impaired ability to activate the hypothalamic-pituitary portion of the hypothalamic-pituitary-adrenal axis as well as the sympathoadrenal system, leading to reduced ACTH and epinephrine responses to hypoglycemia.

Immune markers in fibromyalgia: comparison with major depressed patients and normal volunteers.

BACKGROUND: There is a high degree of comorbidity between fibromyalgia and major depression. The latter is characterized by signs of immune activation, whereas the immune status in fibromyalgia is not yet elucidated. The aims of the present study were to examine (i) neopterin and biopterin excretion in 24-h urine of patients with fibromyalgia compared with normal volunteers and patients with major depression; and (ii) the effects of subchronic treatment with sertraline (11 weeks) on the urinary excretion of neopterin and biopterin. METHODS: Measurements of neopterin, biopterin, pseudouridine, creatinine and uric acid in 24-h urine were performed by means of HPLC in 14 fibromyalgia and ten major depressed patients and 17 normal volunteers. RESULTS: There were no significant differences in urine excretion of the above five analytes between patients with fibromyalgia and normal volunteers. Patients with major depression showed significantly higher urinary neopterin excretion than normal volunteers and fibromyalgia patients. Patients with fibromyalgia and major depression had a significantly increased neopterin/creatinine ratio. Fibromyalgia patients had significantly lower urinary excretion of creatinine than patients with major depression. In fibromyalgia patients, there were no significant effects of sertraline treatment on any of the urine analytes. CONCLUSIONS: The findings suggest that fibromyalgia, in contrast to major depression, may not be accompanied by activation of cell-mediated immunity. LIMITATION: Other immune markers should be measured in fibromyalgia before drawing definite conclusions. CLINICAL RELEVANCE: Increased urinary excretion of neopterin can be used as a marker for major depression, but not fibromyalgia.

Catecholamines and heart rate in female fibromyalgia patients.

BACKGROUND: Fibromyalgia syndrome is a disease of unknown pathogenesis characterised by widespread chronic musculoskeletal pain. Fibromyalgia has been associated with dysregulation of the stress systems, but results are inconsistent. PURPOSE: To investigate autonomic nervous system activity (urinary noradrenaline, adrenaline, dopamine, and heart rate) of fibromyalgia patients and healthy controls. METHODS: Urinary catecholamines and heart rate were assessed for a 24-hour period in a controlled hospital setting (including relaxation, a test with prolonged mental stress, and sleep), and during daily activity in 29 female fibromyalgia patients and 29 age-matched female healthy controls. RESULTS: With repeated measures ANOVAs, catecholamine levels were lower in patients than controls (P=.035 for noradrenaline; P=.005 for adrenaline; P=.001 for dopamine). One-way ANOVAs for the single periods showed that patients compared to controls had significantly lower adrenaline levels during the night (P=.010) and the second day (P=.010), significantly lower dopamine levels during the first day (P=.008), the night (P=.001), and the second day (P=.004). However, single time point noradrenaline levels were not significantly different between the groups. Overall, heart rate was significantly higher in patients than controls (P=.014). Specifically, significant differences emerged during relaxation (P=.016) and sleep (P=.011), but not during stress provocation or daily activities. CONCLUSIONS: The results indicate an altered regulation of the autonomic nervous system in fibromyalgia patients, with attenuated activity of both the sympathetic (adrenal medulla component) and the parasympathetic branch.

Objective measures of disordered sleep in fibromyalgia.

OBJECTIVE: Patients with fibromyalgia syndrome (FM) complain of inadequate sleep, which could contribute to common symptoms including sleepiness, fatigue, or pain. However, measures that consistently and objectively distinguish FM patients remain elusive. METHODS: Fifteen women with FM and 15 age- and gender-matched controls underwent 3 nights of polysomnography; Multiple Sleep Latency Tests to assess sleepiness; testing of auditory arousal thresholds during non-REM stage 2 and stage 4 sleep; overnight assessment of urinary free cortisol; and analysis of 24-hour heart rate variability. RESULTS: On the second night of polysomnography, women with FM in comparison to controls showed more stage shifts (p = 0.04) but did not differ significantly on any other standard polysomnographic measure or on the Multiple Sleep Latency Tests. Alpha EEG power during deep non-REM sleep, alone or as a proportion of alpha power during remaining sleep stages, also failed to distinguish the groups, as did auditory arousal thresholds. Urinary free cortisol did not differ between FM and control subjects in a consistent manner. However, decreased short-term heart rate variability (HRV) and especially ratio-based HRV among FM subjects suggested diminished parasympathetic and increased sympathetic activity, respectively. Other HRV measures suggested decreased complexity of HRV among the FM subjects. CONCLUSION: Standard measures of sleep, a gold-standard measure of sleepiness, quantified alpha-delta EEG power, auditory arousal thresholds, and urinary free cortisol largely failed to distinguish FM and control subjects. However, HRV analyses showed more promise, as they suggested both increased sympathetic activity and decreased complexity of autonomic nervous system function in FM.

Urinary markers of altered collagen metabolism in fibromyalgia patients.

OBJECTIVE: To assess the metabolism of collagen in fibromyalgia (FM) patients, and to compare the occurrence of collagen metabolism markers to the severity of FM symptoms. METHODS: Morning urine was collected from 27 FM women fulfilling the American College of Rheumatology (ACR) criteria for FM, and from seven controls. FM patients completed the Fibromyalgia Impact Questionnaire (FIQ). Bone mineral density (BMD), isokinetic muscle strength in knee and elbow, and hand-grip strength were measured. Urinary concentrations of collagen type I cross-linked C-telopeptide (CTX-I) and collagen type II cross-linked C-telopeptide (CTX-II) were determined by enzyme-linked immunosorbent assay (ELISA). Pyridinoline (Pyd) and deoxypyridinoline (Dpd) were determined by liquid chromatography, and hydroxyproline (Hyp) by spectrophotometry. All concentration data were normalized to creatinine. RESULTS: Mean values in the FM group and the control group, respectively, were: urinary CTX-I 246.8 and 337.5 microg/mmol (p = 0.060); CTX-II 110.4 and 185.1 ng/mmol (p = 0.035); Pyd 56.1 and 52.3 nmol/mmol (NS); Dpd 15.1 and 14.0 nmol/mmol (NS); Pyd : Dpd ratio 4.05 and 3.96 (NS); Hyp 26.1 and 21.1 micromol/mmol (NS). Significant inverse correlations were seen between CTX-I and the intensity of fatigue, and between CTX-II and anxiety. An inverse correlation between CTX-I and muscle strength was apparent, but relied on extreme values from one patient, and no significant correlation was found between CTX-I or CTX-II and tender points or BMD in the FM group. CONCLUSIONS: Low urinary concentrations of CTX-II and CTX-I and normal levels of Pyd and Dpd were found in FM, but their relationship to the intensity of FM symptoms was unclear.

Normal melatonin levels in patients with fibromyalgia syndrome.

OBJECTIVE: To assess urine levels of melatonin measured by 6-sulphatoxymelatonin (aMT6s) in patients with fibromyalgia (FM). METHODS: Nocturnal aMT6s urine levels were measured by ELISA, in a sample of urine collected from 10 PM to 7 AM from 39 female patients with FM and 39 age matched healthy female controls. All subjects were interviewed and assessed for nonarticular tenderness, FM symptoms, quality of life, and physical functioning. RESULTS: Nocturnal aMT6s levels of patients with FM were not statistically different from those of controls: 16.7+/-9.2 vs 16.0+/-11.3 microg, respectively. No association was observed between aMT6s levels of patients with FM and disease duration, reproductive status, sleep and mood disturbances. CONCLUSION: Nocturnal urine aMT6s levels were similar in patients with FM and controls. Studies are needed to elucidate the possible role of melatonin in FM and should include larger samples of newly diagnosed untreated patients with FM.

A controlled study on serum insulin-like growth factor-I and urinary excretion of growth hormone in fibromyalgia.

OBJECTIVE: It has been hypothesized that secretory deficiencies of growth hormone may play a pathophysiological role in fibromyalgia (FM). Our objective was thus to evaluate the secretion of growth hormone in FM. METHODS: The 24-h urinary growth hormone excretion and serum levels of insulin-like growth factor-I (IGF-I) was measured in 17 middle aged women with FM and 19 healthy women. The degree of subjective sleep disturbance was also determined. RESULTS: Sleep was significantly more disturbed in the patients than the controls. We found no significant differences in the urinary excretion of growth hormone and serum levels of IGF-I between patients with FM and healthy controls. CONCLUSION: Major secretory deficiencies were not documented. However, the power of our study does not allow us to discard the role of minor secretory deficiencies of human growth hormone in FM.

Fibromyalgia--a syndrome associated with decreased nocturnal melatonin secretion.

OBJECTIVE: Most patients with fibromyalgic syndrome (FMS) complain of sleep disturbances, fatigue, and pain. These symptoms might be a consequence of changed melatonin (MT) secretion, since MT is known to have sleep promoting properties. Moreover, serum concentrations of two MT precursors (tryptophan and serotonin)--affecting both sleep and pain perception--appear to be low in patients with FMS. Therefore, the objective of this investigation was to study whether serum MT (s-MT) level is also low in these patients. DESIGN: Eight patients with FMS and 8 healthy sex-, BMI-, and age-matched controls were included in the study. s-MT concentrations were determined every second hour between 1800 and 0800 h. Urine was collected between 2200 and 0700 h for determination of urinary MT excretion. To evaluate total MT secretion between 1800 and 0800 h and MT secretion during the hours of darkness (between 23 and 07 h) individual MT areas under the curve (AUC) were calculated and expressed as group means. RESULTS: The FMS patients had a 31% lower MT secretion than healthy subjects during the hours of darkness (MT AUC 2300-0700 h (mean +/- SEM): 1.70 +/- 0.17 vs 2.48 +/- 0.38 nmol/l; P < 0.05). Also the s-MT peak value was significantly lower in the patient group: 0.28 +/- 0.03 vs 0.44 +/- 0.06 nmol/l; P < 0.05). CONCLUSION: Patients with fibromyalgic syndrome have a lower melatonin secretion during the hours of darkness than healthy subjects. This may contribute to impaired sleep at night, fatigue during the day, and changed pain perception.

Increased 24-hour urinary cortisol excretion in patients with post-traumatic stress disorder and patients with major depression, but not in patients with fibromyalgia.

There is now firm evidence that major depression is accompanied by increased baseline activity of the hypothalamic-pituitary-adrenal (HPA) axis, as assessed by means of 24-h urinary cortisol (UC) excretion. Recently, there were some reports that fibromyalgia and post-traumatic stress disorder (PTSD), two disorders which show a significant amplitude of depressive symptoms, are associated with changes in the baseline activity of the HPA axis, such as low 24-h UC excretion. The aim of the present study was to examine 24-h UC excretion in fibromyalgia and PTSD patients compared to normal controls and patients with major depression. In the three patient groups, severity of depressive symptoms was measured by means of the Hamilton Depression Rating Scale (HDRS) score. Severity of fibromyalgia was measured using a dolorimetrically obtained myalgic score, and severity of PTSD was assessed by means of factor analytical scores computed on the items of the Composite International Diagnostic Interview (CIDI), PTSD Module. Patients with PTSD and major depression had significantly higher 24-h UC excretion than normal controls and fibromyalgia patients. At a threshold value of > or = 240 micrograms/24 h, 80% of PTSD patients and 80% of depressed patients had increased 24 h UC excretion with a specificity of 100%. There were no significant differences in 24-h UC excretion either between fibromyalgia patients and normal controls, or between patients with major depression and PTSD patients. In the three patient groups, no significant correlations were found between 24-h UC excretion and the HDRS score. In fibromyalgia, no significant correlations were found between 24-h UC excretion and the myalgic score. In PTSD, no significant correlations were found between 24-h UC excretion and severity of either depression-avoidance or anxiety-arousal symptoms. In conclusion, this study found increased 24-h UC excretion in patients with PTSD comparable to that in patients with major depression, whereas in fibromyalgia no significant changes in 24-h UC were found.

Plasma and urinary catecholamines in primary fibromyalgia: a controlled study.

Plasma and urinary catecholamines were measured in a blinded manner among 30 patients with primary fibromyalgia (PF) and 30 healthy controls without significant pain to determine possible elevations of catecholamines in PF, as well as their correlations with psychological and clinical variables in this syndrome. Results showed no significant differences between fibromyalgia and control groups in any of the catecholamines measured, nor was there a correlation between catecholamine levels and any of the clinical features or psychologic measures.