Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis.

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling long-term condition of unknown cause. The National Institute for Health and Care Excellence (NICE) published a guideline in 2021 that highlighted the seriousness of the condition, but also recommended that graded exercise therapy (GET) should not be used and cognitive-behavioural therapy should only be used to manage symptoms and reduce distress, not to aid recovery. This U-turn in recommendations from the previous 2007 guideline is controversial.We suggest that the controversy stems from anomalies in both processing and interpretation of the evidence by the NICE committee. The committee: (1) created a new definition of CFS/ME, which 'downgraded' the certainty of trial evidence; (2) omitted data from standard trial end points used to assess efficacy; (3) discounted trial data when assessing treatment harm in favour of lower quality surveys and qualitative studies; (4) minimised the importance of fatigue as an outcome; (5) did not use accepted practices to synthesise trial evidence adequately using GRADE (Grading of Recommendations, Assessment, Development and Evaluations trial evidence); (6) interpreted GET as mandating fixed increments of change when trials defined it as collaborative, negotiated and symptom dependent; (7) deviated from NICE recommendations of rehabilitation for related conditions, such as chronic primary pain and (8) recommended an energy management approach in the absence of supportive research evidence.We conclude that the dissonance between this and the previous guideline was the result of deviating from usual scientific standards of the NICE process. The consequences of this are that patients may be denied helpful treatments and therefore risk persistent ill health and disability.

Migraine in the context of chronic primary pain, chronic overlapping pain disorders, and functional somatic disorders: A narrative review.

OBJECTIVE: To contextualize migraine as the most common primary headache disorder in relation to other chronic primary pain and non-pain functional somatic and mental conditions. BACKGROUND: Migraine is increasingly understood as a sensory processing disorder within a broader spectrum of symptom disorders. This has implications for diagnosis and treatment. METHOD: Narrative review based on a search of the literature of the last 15 years on the overlap of migraine with other symptom disorders. RESULTS: Migraine as the prototypical primary headache disorder not only comprises many non-headache symptoms in itself, it also shows high comorbidity with other chronic pain and non-pain conditions (e.g., fibromyalgia syndrome, irritable bowel syndrome, functional non-epileptic seizures, depression, anxiety, and posttraumatic stress disorder). Such "symptom disorders" share several etiological factors (e.g., female preponderance, psychological vulnerability) and psychophysiological mechanisms (e.g., altered sensory processing, pain expectancy). These facts are acknowledged by several recent integrative conceptualizations such as chronic primary pain, chronic overlapping pain conditions, or functional somatic disorders. Accordingly, migraine management increasingly addresses the total symptom burden and individual contributors to symptom experience, and thus incorporates centrally acting pharmacological and non-pharmacological, that is, psychological and behavioral, treatment approaches. CONCLUSIONS: Migraine and also other primary headache disorders should be seen as particular phenotypes within a broader spectrum of symptom perception and processing disorders that require integrative diagnostics and treatment. A harmonization of classifications and better interdisciplinary collaboration are desirable.

Fibromyalgia revisited: do latent class analyses of symptom profiles in the general population confirm 2016 fibromyalgia diagnostic criteria?

OBJECTIVES: The definition of the 2016 diagnostic criteria of fibromyalgia (FM) syndrome and of FM severities was based on studies with clinical samples. We tested if somatic symptom profiles consistent with the symptom pattern of the FM 2016 diagnostic criteria and of severities of FM can be found in the general population. METHODS: Somatic symptom burden was measured by the Somatic Symptom Scale - 8 in 2,531 persons aged ≥14 years representative for the general German population. We used latent class analysis of SSS-8 items to identify somatic symptom profiles. The profiles were described by their association with age, gender, self-reported disabling somatic disease, psychological symptom burden, illness worries and self-perceived health. RESULTS: We identified five somatic symptom profiles. The majority of the population (40.9%) had a profile characterised by the absence of bothering symptoms. 5.9% had a profile defined by "considerable bothering" back and extremities pains, fatigue and sleep problems. This symptom profile was associated with older age, self-reported somatic diseases, psychological symptom burden and fair to poor general health. 63.2% of persons meeting FM 2016 criteria belonged to this profile. 17.8% of the sample were characterized by little perturbation by multiple somatic symptoms and good to fair general health. 36.8% of persons meeting FM 2016 criteria belonged to this profile. CONCLUSIONS: Two somatic symptom profiles consistent with the 2016 FM diagnostic criteria were identified in the general German population. These symptom profiles differed in somatic and psychological symptom burden and general health supporting the distinction of FM severities.

Prevalence and overlap of somatic symptom disorder, bodily distress syndrome and fibromyalgia syndrome in the German general population: A cross sectional study.

OBJECTIVE: To study the prevalence and clinical characteristics of Somatic Symptom Disorder (SSD), Bodily Distress Syndrome (BDS) and fibromyalgia syndrome (FMS) and their overlap in the general German population. METHODS: A cross-sectional nationally representative population survey was performed. 2531 participants (mean age 48.8 ±â€¯17.85 years, 53.3% women) completed the Somatic Symptom Scale SSS-8, the Bodily Distress Syndrome (BDS) 25 checklist, the Whiteley Index 7 (WI-7), the self-administered comorbidity questionnaire and the Michigan Body Map. Case definitions of SSD, BDS and FMS were assigned using established criteria. RESULTS: 4.5% of participants met the criteria of SSD (SSS - 8 at least one item "bothered very much" and WI- 7 total score ≥ 1). 9.6% met the criteria of single-organ BDS and 1.3% of multi-organ BDS. Prevalence of FMS according to 2016 criteria was 3.4%. 82.3% of FMS cases met any BDS criteria.28.1% of FMS cases satisfied SSD criteria. 28.8% of any BDS cases met the criteria of SSD. 75.1% of SSD cases met the criteria of any BDS. FMS cases reported the highest amount of somatic and psychological symptom burden and health anxieties. There were no differences in age and gender between any BDS and SSD cases. SSD cases reported worse general health and more fibromyalgia-related variables than any BDS cases. CONCLUSIONS: In the general population, there is a substantial overlap between FMS and BDS, but not of FMS and SSD, and not of SSD and any BDS. Case definitions of the three disorders partially captured different groups in the general population.

Validation of the German version of the Bodily Distress Syndrome 25 checklist in a representative German population sample.

OBJECTIVE: The Bodily Distress Syndrome 25 (BDS 25) checklist is a self-report instrument that can be used for case finding of a BDS in both clinical practice and research. We assessed the reliability and the internal and external validity of the German version of the BDS 25 in a sample of the general German population. METHODS: The psychometric properties of the BDS 25 German were examined in a representative cross-sectional German population survey which included 2386 persons aged ≥14 years. Validation instruments included the Somatic Symptom Scale 8, the Giessen Subjective Complaints List 8 and the Patient Health Questionnaire 4. Participants were asked if they had been diagnosed with fibromyalgia or irritable bowel syndrome by a physician in the past. RESULTS: The acceptance was high. Only 81 (2.3%) single items were not answered. Internal consistency was sufficiently high for all four subscales and the total score (α > 0.800). Exploratory and confirmatory factor analysis revealed clear evidence for a four-factorial structure with cardiopulmonary, gastrointestinal, musculoskeletal and general symptoms. Moderate to high correlations with other measures of somatic and psychological symptom burden were found. In latent class analysis, the model featuring three classes with no, moderate and severe BDS symptoms evinced the best model fit. Participants with self-reported fibromyalgia and irritable bowel syndrome were mainly found in the moderate and severe BDS group. CONCLUSIONS: The BDS 25 German has excellent psychometric properties to screen for BDS in the general population.

Management of Functional Somatic Syndromes and Bodily Distress.

Functional somatic syndromes (FSS), like irritable bowel syndrome or fibromyalgia and other symptoms reflecting bodily distress, are common in practically all areas of medicine worldwide. Diagnostic and therapeutic approaches to these symptoms and syndromes vary substantially across and within medical specialties from biomedicine to psychiatry. Patients may become frustrated with the lack of effective treatment, doctors may experience these disorders as difficult to treat, and this type of health problem forms an important component of the global burden of disease. This review intends to develop a unifying perspective on the understanding and management of FSS and bodily distress. Firstly, we present the clinical problem and review current concepts for classification. Secondly, we propose an integrated etiological model which encompasses a wide range of biopsychosocial vulnerability and triggering factors and considers consecutive aggravating and maintaining factors. Thirdly, we systematically scrutinize the current evidence base in terms of an umbrella review of systematic reviews from 2007 to 2017 and give recommendations for treatment for all levels of care, concentrating on developments over the last 10 years. We conclude that activating, patient-involving, and centrally acting therapies appear to be more effective than passive ones that primarily act on peripheral physiology, and we recommend stepped care approaches that translate a truly biopsychosocial approach into actual management of the patient.

[Competence-based catalogue of learning objectives for conducting medical consultations]. / Kompetenzbasierter Lernzielkatalog ¼Ärztliche Gesprächsführung« .

ISSUE: In 2012 the German medical licensure regulations (Approbationsordnung) made teaching and assessing the conduction of medical consultations a mandatory part of medical education. A catalogue of learning objectives (LO) based on existing references was developed to assist medical schools in meeting this requirement. METHODS: A body of relevant material was compiled using literature research and surveying experts. Then, in a multiphase Delphi process, this was evaluated and condensed by an interdisciplinary working group in dialogue with external (clinical) experts. Competence levels and examples of clinical application were assigned to enhance implementation. The catalogue was revised by the medical faculties, professional associations and the BVMD. RESULTS: This learning catalogue comprised 116 learning objectives for the specific skills necessary to conducting medical consultations as well as exemplary application contexts. The catalogue proved to be practical in terms of developing curricula and networking at medical schools. DISCUSSION: This catalogue of learning objectives can serve as the basis for developing a sample communication curriculum for use by medical faculties.

Irritable bowel syndrome: relations with functional, mental, and somatoform disorders.

This review describes the conceptual and clinical relations between irritable bowel syndrome (IBS), other functional, somatoform, and mental disorders, and points to appropriate future conceptualizations. IBS is considered to be a functional somatic syndrome (FSS) with a considerable symptom overlap with other FSSs like chronic fatigue syndrome or fibromyalgia syndrome. IBS patients show an increased prevalence of psychiatric symptoms and disorders, especially depression and anxiety. IBS is largely congruent with the concepts of somatoform and somatic symptom disorders. Roughly 50% of IBS patients complain of gastrointestinal symptoms only and have no psychiatric comorbidity. IBS concepts, treatment approaches, as well as health care structures should acknowledge its variability and multidimensionality by: (1) awareness of additional extraintestinal and psychobehavioral symptoms in patients with IBS; (2) general and collaborative care rather than specialist and separated care; and (3) implementation of "interface disorders" to abandon the dualistic classification of purely organic or purely mental disorders.

Untying chronic pain: prevalence and societal burden of chronic pain stages in the general population - a cross-sectional survey.

BACKGROUND: Chronic pain is a major public health problem. The impact of stages of chronic pain adjusted for disease load on societal burden has not been assessed in population surveys. METHODS: A cross-sectional survey with 4360 people aged ≥ 14 years representative of the German population was conducted. Measures obtained included demographic variables, presence of chronic pain (based on the definition of the International Association for the Study of Pain), chronic pain stages (by chronic pain grade questionnaire), disease load (by self-reported comorbidity questionnaire) and societal burden (by self-reported number of doctor visits, nights spent in hospital and days of sick leave/disability in the previous 12 months, and by current unemployment). Associations between chronic pain stages with societal burden, adjusted for demographic variables and disease load, were tested by Poisson and logistic regression analyses. RESULTS: 2508 responses were received. 19.4% (95% CI 16.8% to 22.0%) of participants met the criteria of chronic non-disabling non-malignant pain. 7.4% (95% CI 5.0% to 9.9%) met criteria for chronic disabling non-malignant pain. Compared with no chronic pain, the rate ratio (RR) of days with sick leave/disability was 1.6 for non-disabling pain and 6.4 for disabling pain. After adjusting for age and disease load, the RRs increased to 1.8 and 6.8. The RR of doctor visits was 2.5 for non-disabling pain and 4.5 for disabling pain if compared with no chronic pain. After adjusting for age and disease load, the RR fell to 1.7 and 2.6. The RR of days in hospital was 2.7 for non-disabling pain and 11.7 for disabling pain if compared with no chronic pain. After adjusting for age and disease load, the RR fell to 1.5 and 4.0. Unemployment was predicted by lower educational level (Odds Ratio OR 3.27 [95% CI 1.70-6.29]), disabling pain (OR 3.30 [95% CI 1.76-6.21]) and disease load (OR 1.70 [95% CI 1.41-2.05]). CONCLUSION: Chronic pain stages, but also disease load and societal inequalities contributed to societal burden. Pain measurements in epidemiology research of chronic pain should include chronic pain grades and disease load.

Patient Health Questionnaire 15 as a generic measure of severity in fibromyalgia syndrome: surveys with patients of three different settings.

OBJECTIVE: Graduated treatment of patients with functional somatic syndromes (FSS) and fibromyalgia syndrome (FMS) depending on their severity has been recommended by recent guidelines. The Patient Health Questionnaire 15 (PHQ 15) is a validated measure of somatic symptom severity in FSS. We tested the discriminant and transcultural validity of the PHQ 15 as a generic measure of severity in persons with FMS. METHODS: Persons meeting recognized FMS-criteria of the general German population (N=98), of the US National Data Bank of Rheumatic Diseases (N=440), and of a single German pain medicine center (N=167) completed validated self-report questionnaires on somatic and psychological distress (Polysymptomatic Distress Scale, Patient Health Questionnaire 4), health-related quality of life (HRQOL) (Short Form Health Survey 12 or 36) and disability (Pain Disability Index). In addition, self-reports of working status were assessed in the clinical setting. Overall severity of FMS was defined by PHQ 15 scores: mild (0-9), moderate (10-14) and severe (15-30). RESULTS: Persons with mild, moderate and severe FMS did not differ in age and gender. Irrespective of the setting, persons with severe FMS reported more pain sites, fatigue, depressed mood, impaired HRQOL and disability than persons with moderate or mild FMS. Patients with severe FMS in the NDB and in the German clinical center reported more work-related disability than patients with mild FMS. CONCLUSION: The PHQ 15 is a valid generic measure of overall severity in FMS.

[Fibromyalgia syndrome as a psychosomatic disorder - diagnosis and therapy according to current evidence-based guidelines]. / Das Fibromyalgiesyndrom als psychosomatische Erkrankung - empfehlungen Aktueller Evidenzbasierter Leitlinien zu Diagnostik und Therapie.

OBJECTIVES: The classification and therapy of patients with chronic widespread pain without evidence of somatic factors as an explanation is currently a matter of debate. The diagnostic label "fibromyalgia syndrome"(FMS) has been rejected by some representatives of general and psychosomatic medicine. METHODS: A summary is given of the main recommendations from current evidence-based guidelines on FMS and nonspecific/functional/somatoform bodily complaints. RESULTS: The criteria of FMS and of persistent somatoform pain disorder or chronic pain disorder with somatic and psychological factors partly overlap. They include differential clinical characteristics of persons with chronic widespread pain but without sufficiently explaining somatic factors. Not all patients diagnosed with FMS meet the criteria of a persistent somatoform pain disorder. FMS is a functional disorder, in which in most patients psychosocial factors play an important role in both the etiology and course of illness. FMS can be diagnosed by looking at the history of a typical symptom cluster and excluding somatic differential diagnoses (without a tender point examination) using the modified 2010 diagnostic criteria of the American College of Rheumatology. Various levels of severity of FMS can be distinguished from a psychosomatic point of view, ranging from slight (single functional syndrome) to severe (meeting the criteria of multiple functional syndromes) forms of chronic pain disorder with somatic and psychological factors, of persistent somatoform pain disorder or of a somatization disorder. The diagnosis of FMS as a functional syndrome/stress-associated disorder should be explicitly communicated to the patient. A therapy within collaborative care adapted to the severity should be provided. For long-term management, nonpharmacological therapies such as aerobic exercise are recommended. In more severe cases, psychotherapy of comorbid mental disorders should be conducted. CONCLUSIONS: The coordinated recommendations of both guidelines can synthesize general medical, somatic, and psychosocial perspectives, and can promote graduated care of patients diagnosed with FMS.

Classification and clinical diagnosis of fibromyalgia syndrome: recommendations of recent evidence-based interdisciplinary guidelines.

Objectives. Fibromyalgia syndrome (FMS), characterized by subjective complaints without physical or biomarker abnormality, courts controversy. Recommendations in recent guidelines addressing classification and diagnosis were examined for consistencies or differences. Methods. Systematic searches from January 2008 to February 2013 of the US-American National Guideline Clearing House, the Scottish Intercollegiate Guidelines Network, Guidelines International Network, and Medline for evidence-based guidelines for the management of FMS were conducted. Results. Three evidence-based interdisciplinary guidelines, independently developed in Canada, Germany, and Israel, recommended that FMS can be clinically diagnosed by a typical cluster of symptoms following a defined evaluation including history, physical examination, and selected laboratory tests, to exclude another somatic disease. Specialist referral is only recommended when some other physical or mental illness is reasonably suspected. The diagnosis can be based on the (modified) preliminary American College of Rheumatology (ACR) 2010 diagnostic criteria. Discussion. Guidelines from three continents showed remarkable consistency regarding the clinical concept of FMS, acknowledging that FMS is neither a distinct rheumatic nor mental disorder, but rather a cluster of symptoms, not explained by another somatic disease. While FMS remains an integral part of rheumatology, it is not an exclusive rheumatic condition and spans a broad range of medical disciplines.

Functional network connectivity of pain-related resting state networks in somatoform pain disorder: an exploratory fMRI study.

BACKGROUND: Without stimulation, the human brain spontaneously produces highly organized, low-frequency fluctuations of neural activity in intrinsic connectivity networks (ICNs). Furthermore, without adequate explanatory nociceptive input, patients with somatoform pain disorder experience pain symptoms, thus implicating a central dysregulation of pain homeostasis. The present study aimed to test whether interactions among pain-related ICNs, such as the default mode network (DMN), cingular-insular network (CIN) and sensorimotor network (SMN), are altered in somatoform pain during resting conditions. METHODS: Patients with somatoform pain disorder and healthy controls underwent resting functional magnetic resonance imaging that lasted 370 seconds. Using a data-driven approach, the ICNs were isolated, and the functional network connectivity (FNC) was computed. RESULTS: Twenty-one patients and 19 controls enrolled in the study. Significant FNC (p < 0.05, corrected for false discovery rate) was detected between the CIN and SMN/anterior DMN, the anterior DMN and posterior DMN/SMN, and the posterior DMN and SMN. Interestingly, no group differences in FNC were detected. LIMITATIONS: The most important limitation of this study was the relatively short resting state paradigm. CONCLUSION: To our knowledge, our results demonstrated for the first time the resting FNC among pain-related ICNs. However, our results suggest that FNC signatures alone are not able to characterize the putative central dysfunction underpinning somatoform pain disorder.

Behavioral and neuronal investigations of hypervigilance in patients with fibromyalgia syndrome.

Painful stimuli are of utmost behavioral relevance and thereby affect attentional resources. In health, variable effects of pain on attention have been observed, indicating alerting as well as distracting effects of pain. In the human brain, these effects are closely related to modulations of neuronal gamma oscillations. As hypervigilance as an abnormal increase of attention to external stimuli has been implicated in chronic pain states, we assumed both attentional performance and pain-induced gamma oscillations to be altered in patients with fibromyalgia syndrome (FMS). We recorded electroencephalography from healthy subjects (n = 22) and patients with FMS (n = 19) during an attention demanding visual reaction time task. In 50% of the trials we applied painful laser stimuli. The results of self-assessment questionnaires confirm that patients with FMS consider themselves hypervigilant towards pain as compared to healthy controls. However, the experimental findings indicate that the effects of painful stimuli on attentional performance and neuronal gamma oscillations do not differ between patients and healthy subjects. We further found a significant correlation between the pain-induced modulation of visual gamma oscillations and the pain-induced modulation of reaction times. This relationship did not differ between groups either. These findings confirm a close relationship between gamma oscillations and the variable attentional effects of pain, which appear to be comparable in health and disease. Thus, our results do not provide evidence for a behavioral or neuronal manifestation of hypervigilance in patients with FMS.

Functional bowel disorders in adults.

BACKGROUND: Chronic abdominal pain, bloating, constipation, diarrhea, and stool irregularity are common symptoms in primary care and gastroenterology. A routine diagnostic evaluation fails to reveal any underlying somatic condition in about half of the affected patients, who are therefore said to have a functional bowel disorder. Physicians are often unsure how extensive the work-up must be to exclude a somatic cause. METHODS: This review is based on a selective review of the literature, including published guidelines from Germany and abroad. RESULTS: Functional bowel disorders are diagnosed on the basis of a typical constellation of symptoms and the absence of pathological findings that would adequately explain them (exclusive criteria). The basic diagnostic assessment, consisting of a physical examination, basic laboratory tests, abdominal ultrasonography, and (in women) a gynecological examination, is supplemented by further testing that depends on the patient's symptoms. Colonoscopy is obligatory to rule out underlying pathological abnormalities. By communicating the diagnosis of irritable bowel syndrome to the patient, the physician shows that the patient's symptoms and concerns have been taken seriously. The mainstays of treatment are patient education on the benign course of the disease and the encouragement of a salubrious lifestyle. Further treatment options include dietary measures, time-limited symptomatic treatment with drugs, and psychotherapy. CONCLUSION: The diagnosis of a functional bowel disorder is based on a thorough history (positive criteria) and a small battery of diagnostic tests to exclude somatic disease. Both the diagnostic assessment and the treatment should be carried out in accordance with published guidelines.

[Development of a novel device for adaptive testing according to ICD-10: PsyPAM--psychosomatic physician-patient module]. / Entwicklung eines neuen Instruments zur adaptierten Diagnostik psychischer Störungen nach ICD-10: PsyPAM - Psychosomatisches Patienten-Arzt-Modul.

OBJECTIVES: There is a high demand for efficient and time-saving diagnostic procedures. The paper deals with the development and first clinical testing of a computerized diagnostic system, facilitating adaptive testing. METHODS: For diagnostic of the most common disorders, in accordance with Chapter F of the ICD-10, a psychosomatic physician-patient module (PsyPAM) was developed, which is a partially standardized, computerized interview procedure. In a pilot study the diagnostic results achieved with the PsyPAM-system were compared with clinical diagnoses, according with ICD-10 in n=115 patients. RESULTS: About 88% of clinical diagnoses used as a reference base were also established by the PsyPAM-system. The average total processing time for PsyPAM-diagnostics was 22.3 min. CONCLUSIONS: The PsyPAM-system is a promising and user-friendly screening tool with a short processing time, and is well worth further development and testing in daily clinical practice.

Fibromyalgia syndrome: classification, diagnosis, and treatment.

BACKGROUND: This S3 guideline takes positions on currently contentious issues in the classification and treatment of fibromyalgia syndrome (FMS). METHODS: A panel of experts from 10 specialist societies and patients belonging to 2 patient self-help organizations reviewed a total of approximately 8000 publications. Recommendations were developed according to the suggested procedure for S3 guidelines and were then reviewed and approved by the boards of the participating specialist societies. The steering committee ensured that the literature review and the recommendations were kept up to date. RESULTS: Because this disorder is defined by its symptoms and signs, rather than by any consistently identifiable bodily lesion, the term "fibromyalgia syndrome" is a more appropriate designation for it than "fibromyalgia." FMS is defined by the criteria of the American College of Rheumatology and is classified as a functional somatic syndrome. FMS is diagnosed from the typical constellation of symptoms and by the exclusion of inflammatory and metabolic diseases that could cause the same symptoms. A stepwise treatment approach in which the patient and the physician decide jointly on the treatment options is recommended. The most strongly recommended forms of treatment are aerobic exercise, amitriptyline, cognitive behavioral therapy, and spa therapy. CONCLUSIONS: The guideline recommendations are intended to promote more effective treatment of this disorder.

Patients with pain disorder show gray-matter loss in pain-processing structures: a voxel-based morphometric study.

OBJECTIVE: To investigate whether the functional changes in pain disorder might be reflected by structural brain changes. Pain disorder assessed with the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria is characterized by persistent and distressing chronic pain at one or more body sites which cannot be fully explained by a physiological process or somatic disorder. Psychological factors are thought to play a major role. Recent neuroimaging studies evidenced altered pain processing in patients suffering from this disorder. METHODS: Fourteen right-handed women fulfilling the DSM-IV criteria for pain disorder and 25 healthy age-matched women were investigated with magnetic resonance imaging. In the voxel-based morphometry analysis, we compared both groups for changes of gray-matter density. We included age and Beck Depression Inventory scores as nuisance variables to minimize possible confounding effects of age or depressive comorbidity. RESULTS: In the patient group, we found significant gray-matter decreases in the prefrontal, cingulate, and insular cortex. These regions are known to be critically involved in the modulation of subjective pain experiences. CONCLUSIONS: In the context of similar results in patients with other functional pain syndromes, such as fibromyalgia and chronic back pain, we suggest that structural changes in fronto-limbic brain circuits represent not only an objective marker of these pain syndromes but also constitute a critical pathophysiological element. These findings represent a further proof of the important role of central changes in pain disorder.

Functional incapacity and physical and psychological symptoms: how they interconnect in chronic fatigue syndrome.

BACKGROUND: It has been argued that perceived functional incapacity might be a primary characteristic of chronic fatigue syndrome (CFS) and could be explained by physical symptoms. If so, it could be expected to be closely associated with physical, but not psychological symptoms. The study tests this hypothesis. SAMPLING AND METHODS: The sample consisted of 73 patients, with a diagnosis of CFS according to the Oxford criteria, randomly selected from clinics in the Departments of Immunology and Psychiatry at St. Bartholomew's Hospital, London. The degree of fatigue experienced by patients was assessed using the Chalder Fatigue Questionnaire and a visual analogue scale. Self-rated instruments were used to measure physical and social functioning, quality of life, and physical and psychological symptoms. RESULTS: Principal-component analysis of all scale scores revealed 2 distinct components, explaining 53% of the total variance. One component was characterized by psychological symptoms and generic quality of life indicators, whilst the other component was made up of physical symptoms, social and physical functioning and indicators of fatigue. CONCLUSIONS: The findings suggest that perceived functional incapacity is a primary characteristic of CFS, which is manifested and/or explained by physical symptoms.