functional somatic syndromes – American ME and CFS Society

Functional neurological disorder and functional somatic syndromes among sexual and gender minority people: A scoping review

Abstract

Objective: To describe the current literature on functional neurological disorder and functional somatic syndromes among sexual and gender minority people (SGM).

Methods: A search string with descriptors of SGM identity and functional disorders was entered into PubMed, Embase, Web of Science, PsycInfo, and CINAHL for articles published before May 24, 2022, yielding 3121 items entered into Covidence, where 835 duplicates were removed.

A neurologist and neuropsychiatrist screened titles and abstracts based on predefined criteria, followed by full-text review. A third neurologist adjudicated discrepancies. Eligible publications underwent systematic data extraction and statistical description.

Results: Our search identified 26 articles on functional disorders among SGM people. Most articles were case (13/26, 46%) or cross-sectional (4/26, 15%) studies. Gender minority people were represented in 50% of studies. Reported diagnoses included fibromyalgia (n = 8), functional neurological disorder (n = 8), somatic symptom disorder (n = 5), chronic fatigue syndrome (n = 3), irritable bowel syndrome (n = 2), and other functional conditions (n = 3).

Three cohort studies of fibromyalgia or somatic symptom disorder reported an overrepresentation of gender minority people compared to cisgender cohorts or general population measures.

Approximately half of case studies reported pediatric or adolescent onset (7/13, 54%), functional neurological disorder diagnosis (7/13, 54%), and symptom improvement coinciding with identity-affirming therapeutic interventions (7/13, 58%).

Conclusion: Despite a methodologically rigorous literature search, there are limited data on functional neurological disorder and functional somatic syndromes among SGM people. Several studies reported increased prevalence of select conditions among transgender people. More observational studies are needed regarding the epidemiology and clinical course of functional disorders among SGM people.

Source: Lerario, Fusunyan, Stave, Roldán, Keuroghlian, Turban, Perez, Maschi, Rosendale. Functional neurological disorder and functional somatic syndromes among sexual and gender minority people: A scoping review. Journal of Psychosomatic Research: 111491. [Article in Press, Epub ahead of print] https://www.sciencedirect.com/science/article/abs/pii/S0022399923003483

DNA methylation signatures of functional somatic syndromes: Systematic review

Abstract:

Objective: Functional somatic syndromes (FSS) are highly prevalent across all levels of healthcare. The fact that they are characterised by medically unexplained symptoms, such as fatigue and pain, raises the important question of their underlying pathophysiology. Psychosocial stress represents a significant factor in the development of FSS and can induce long-term modifications at the epigenetic level. The aim of this review was to systematically review, for the first time, whether individuals with FSS are characterised by specific alterations in DNA methylation.

Methods: MEDLINE and PsycINFO were searched from the first available date until September 2022. The inclusion criteria were: 1) adults fulfilling research diagnostic criteria for chronic fatigue syndrome, fibromyalgia syndrome, and/or irritable bowel syndrome, 2) healthy control group, and 3) candidate-gene or genome-wide study of DNA methylation.

Results: Sixteen studies (N = 957) were included. In candidate-gene studies, specific sites within NR3C1 were identified, which were hypomethylated in individuals with chronic fatigue syndrome compared to healthy controls. In genome-wide studies in chronic fatigue syndrome, a hypomethylated site located to LY86 and hypermethylated sites within HLA-DQB1 were found. In genome-wide studies in fibromyalgia syndrome, differential methylation in sites related to HDAC4 , TMEM44 , KCNQ1 , SLC17A9 , PRKG1 , ALPK3 , TFAP2A , and LY6G5C was found.

Conclusions: Individuals with chronic fatigue syndrome and fibromyalgia syndrome appear to be characterised by altered DNA methylation of genes regulating cellular signalling and immune functioning. In chronic fatigue syndrome, there is preliminary evidence for these to be implicated in key pathophysiological alterations, such as hypocortisolism and low-grade inflammation, and to contribute to the debilitating symptoms these individuals experience.

Preregistration PROSPERO identifier: CRD42022364720.

Source: Fischer S, Kleinstäuber M, Fiori LM, Turecki G, Wagner J, von Känel R. DNA methylation signatures of functional somatic syndromes: Systematic review. Psychosom Med. 2023 Aug 21. doi: 10.1097/PSY.0000000000001237. Epub ahead of print. PMID: 37531610. https://pubmed.ncbi.nlm.nih.gov/37531610/

Stigma perceived by patients with functional somatic syndromes and its effect on health outcomes – A systematic review

Abstract:

Background: Patients with functional somatic syndromes (FSS) experience stigma which arguably affects their health.

Aim: To determine the presence of perceived stigma and its effects on physical and mental health in patients with FSS compared to patients with comparable explained conditions.

Methods: A comprehensive search of PubMed, Embase, PsycINFO, CINAHL and Cochrane Library was performed to select studies focusing on stigma perceived by patients with irritable bowel syndrome (IBS), fibromyalgia (FM) or chronic fatigue syndrome (CFS), comparing these patients to patients with comparable but explained conditions.

Results: We identified 1931 studies after duplicate removal. After screening we included eight studies: one study about all three FSS, one about IBS, five about FM and one about CFS. We found that patients with IBS did not consistently experience higher levels of stigma than those with a comparable explained condition. Patients with CFS and FM experienced higher levels of stigma compared to patients with comparable explained conditions. All studies showed a correlation between stigma and negative health outcomes.

Discussion: Patients with FSS experience stigma and negative health outcomes. However, experiencing stigma is not restricted to patients with FSS, as many patients with explained health conditions also experience stigma. Whether stigma has more negative health consequences in patients with FSS compared to patients with explained health conditions remains unclear and should be assessed in future research.

Source: Ko C, Lucassen P, van der Linden B, Ballering A, Olde Hartman T. Stigma perceived by patients with functional somatic syndromes and its effect on health outcomes – A systematic review. J Psychosom Res. 2022 Jan 6;154:110715. doi: 10.1016/j.jpsychores.2021.110715. Epub ahead of print. PMID: 35016138. https://pubmed.ncbi.nlm.nih.gov/35016138/

Questioning Biomedicine’s Privileging of Disease and Measurability

Abstract:

Within biomedicine, the diagnosis of disease is often privileged over a patient’s experience of illness. Yet up to 30% of primary care visits might be attributable to persistent illness without a diagnosed disease, including functional somatic syndromes like fibromyalgia and chronic fatigue syndrome. When clinicians are unable to diagnose disease or correlate symptoms with measurable changes in biomarkers, patients experiencing such an illness are at increased risk for suspicion, misplaced questioning, or having their motives misinterpreted through damaging social and cultural narratives about gender, race, ethnicity, socioeconomic status, or disability. Adhering strictly to a biomedical model of thinking about disease and diagnosis can prevent clinicians from empathically engaging with patients and helping them navigate their illness experiences.

Source: Kroll C. Questioning Biomedicine’s Privileging of Disease and Measurability. AMA J Ethics. 2021 Jul 1;23(7):E537-541. doi: 10.1001/amajethics.2021.537. PMID: 34351263. https://pubmed.ncbi.nlm.nih.gov/34351263/

Functional somatic syndromes and joint hypermobility: A systematic review and meta-analysis

Abstract:

Objective: There have been multiple reports of increased joint hypermobility (JH) in functional somatic syndromes (FSS). We sought to evaluate the evidence for an association.

Methods: A systematic search of the databases Medline and PsycINFO was conducted to identify all controlled studies from inception to February 2020 measuring the association of an FSS and JH. Records were identified and screened, and full-text articles assessed for eligibility by two independent authors. Meta-analysis was performed using random-effects modelling with the DerSimonian and Laird method.

Results: We found 220 studies initially, which yielded 11 studies for inclusion in the qualitative review and 10 in the quantitative analysis – 5 studies on fibromyalgia, 3 on chronic fatigue syndrome and 3 on functional gastrointestinal disorder. Nine of the 11 studies found increased rates of JH in FSS compared to controls, though most studies were fair to poor in quality. Meta-analysis showed a weighted summary effect odds ratio of 3.27 (95% CI: 1.83, 5.84; p < 0.001) of JH in FSS, suggesting greater odds of FSS in individuals with JH than in those without.

Conclusions: There is some evidence for an association between FSS and JH, but this is limited by the generally poor quality of studies and the narrow range of FSS studied. Better research is needed to confirm these findings as well as evaluate causation using prospective cohort studies.

Source: Chen G, Olver JS, Kanaan RA. Functional somatic syndromes and joint hypermobility: A systematic review and meta-analysis. J Psychosom Res. 2021 Jun 24;148:110556. doi: 10.1016/j.jpsychores.2021.110556. Epub ahead of print. PMID: 34237584. https://pubmed.ncbi.nlm.nih.gov/34237584/

Long-term economic evaluation of cognitive-behavioural group treatment versus enhanced usual care for functional somatic syndromes

Abstract:

OBJECTIVE: Patients with functional somatic syndromes (FSS) such as fibromyalgia and chronic fatigue syndrome have a poor outcome and can incur high healthcare and societal costs. We aimed to compare the medium-term (16 months) cost-effectiveness and the long-term (40 months) economic outcomes of a bespoke cognitive-behavioural group treatment (STreSS) with that of enhanced usual care (EUC).

METHODS: We obtained complete data on healthcare and indirect costs (i.e. labour marked-related and health-related benefits) from public registries for 120 participants from a randomised controlled trial. Costs were calculated as per capita public expenses in 2010 €. QALYs gained were estimated from the SF-6D. We conducted a medium-term cost-effectiveness analysis and a long-term cost-minimization analysis from both a healthcare (i.e. direct cost) and a societal (i.e. total cost) perspective.

RESULTS: In the medium term, the probability that STreSS was cost-effective at thresholds of 25,000 to 35,000 € per QALY was 93-95% from a healthcare perspective, but only 50-55% from a societal perspective. In the long term, however, STreSS was associated with increasing savings in indirect costs, mainly due to a greater number of patients self-supporting. When combined with stable long-term reductions in healthcare expenditures, there were total cost savings of 7184 € (95% CI 2271 to 12,096, p=0.004) during the third year after treatment.

CONCLUSION: STreSS treatment costs an average of 1545 €. This cost was more than offset by subsequent savings in direct and indirect costs. Implementation could both improve patient outcomes and reduce costs.

Source: Schröder A, Ørnbøl E, Jensen JS, Sharpe M, Fink P. Long-term economic evaluation of cognitive-behavioural group treatment versus enhanced usual care for functional somatic syndromes. J Psychosom Res. 2017 Mar;94:73-81. doi: 10.1016/j.jpsychores.2017.01.005. Epub 2017 Jan 10. https://www.ncbi.nlm.nih.gov/pubmed/28183406

Mood and Anxiety Disorders in Chronic Fatigue Syndrome, Fibromyalgia, and Irritable Bowel Syndrome: Results From the LifeLines Cohort Study

Abstract:

OBJECTIVE: Functional somatic syndromes (FSSs) have often been linked to psychopathology. The aim of the current study was to compare prevalence rates of psychiatric disorders among individuals with chronic fatigue syndrome (CFS), fibromyalgia (FM), and irritable bowel syndrome (IBS).

METHODS: This study was conducted in 94,516 participants (mean [standard deviation] age = 44.6 [12.5] years, 58.7% women) of the general-population cohort LifeLines. FSSs were assessed by self-reports. Mood disorders (i.e., major depressive disorder and dysthymia) and anxiety disorders (i.e., generalized anxiety disorder, social phobia, panic disorder with/without agoraphobia, and agoraphobia) were assessed by means of the Mini International Neuropsychiatric Interview. Risks on psychiatric disorders were compared for individuals with CFS, FM, and IBS by using logistic regression analyses adjusted for age and sex.

RESULTS: Prevalence rates of CFS, FM, and IBS were 1.3%, 3.0%, and 9.7%, respectively. Individuals with CFS, FM, and IBS had significantly more mood (odds ratios [ORs] = 1.72-5.42) and anxiety disorders (ORs = 1.52-3.96) than did individuals without FSSs, but prevalence rates were low (1.6%-28.6%). Individuals with CFS more often had mood (ORs = 2.00-4.08) and anxiety disorders (ORs = 1.63-2.32) than did individuals with FM and IBS. Major depressive disorder was more common in FM than in IBS (OR = 1.58, 95% confidence interval = 1.24-2.01), whereas these groups did not differ on dysthymia or anxiety disorders.

CONCLUSIONS: Mood and anxiety disorders are more prevalent in individuals with FSSs, and particularly CFS, than in individuals without FSSs. However, most individuals with FSSs do not have mood or anxiety disorders.

Source: Janssens KA, Zijlema WL, Joustra ML, Rosmalen JG. Mood and Anxiety Disorders in Chronic Fatigue Syndrome, Fibromyalgia, and Irritable Bowel Syndrome: Results From the LifeLines Cohort Study. Psychosom Med. 2015 May;77(4):449-57. doi: 10.1097/PSY.0000000000000161. https://www.ncbi.nlm.nih.gov/pubmed/25768845

Functional somatic syndromes: sensitivities and specificities of self-reports of physician diagnosis

Abstract:

OBJECTIVE: Functional somatic syndromes have no laboratory or pathologic abnormalities and so are diagnosed by symptom-based case definitions. However, many studies, including recent ones, have used self-reports of physician diagnosis rather than the case definitions. Our objective was to determine the sensitivities and specificities of self-report of physician diagnosis for chronic fatigue syndrome (CFS), fibromyalgia (FM), irritable bowel syndrome (IBS), panic disorder, and migraine.

METHODS: Each of 312 female patients with incident interstitial cystitis/bladder pain syndrome and matched population-based controls were queried on self-report of physician diagnosis and separately on established case definitions for each of these syndromes.

RESULTS: Using the symptom-based case definitions as standards, we found that self-report of physician diagnosis did not identify 90% of the controls who had CFS, 77% who had FM, 69% who had IBS, 43% who had panic disorder, and 23% who had migraine. In addition, it missed most individuals with multiple syndromes. Findings in one cohort (controls) were confirmed in another (patients with interstitial cystitis/bladder pain syndrome).

CONCLUSIONS: Self-report of physician diagnosis did not identify most of the three most venerable functional somatic syndromes, IBS, FM, and, especially, CFS; nor did it identify substantial minorities of individuals with panic disorder and migraine. Self-report of physician diagnosis was particularly poor in recognizing persons with multiple syndromes. The insensitivity of this diagnostic test has effects on not only prevalence and incidence estimates but also correlates, comorbidities, and case recruitment. To reveal individuals with these syndromes, singly or together, queries of symptoms, not diagnoses, are necessary.

Comment in: Recalling, reporting, and thinking about diagnoses. [Psychosom Med. 2012]

Source: Warren JW, Clauw DJ. Functional somatic syndromes: sensitivities and specificities of self-reports of physician diagnosis. Psychosom Med. 2012 Nov-Dec;74(9):891-5. doi: 10.1097/PSY.0b013e31827264aa. Epub 2012 Oct 15. https://www.ncbi.nlm.nih.gov/pubmed/23071343

Chronic fatigue syndrome: Is it one discrete syndrome or many? Implications for the “one vs. many” functional somatic syndromes debate

Abstract:

There is a current debate as to whether “functional somatic syndromes” (FSSs) are more similar to or different from each other. While at the same time, there is evidence of heterogeneity within single syndromes. So, it could be that these syndromes are all part of one big process/illness, are discrete in their own right, or that they are heterogeneous collections of different illnesses lumped together by common symptoms but separated by uncommon pathophysiologies. The example of chronic fatigue syndrome (CFS) is instructive. There is evidence to support all three models of understanding. Three recent large studies have suggested that FSSs are both similar and dissimilar at the same time. The solution to the debate is that we need to both “lump” and “split.” We need to study both the similarities between syndromes and their dissimilarities to better understand what we currently call the FSSs.

Source: White PD. Chronic fatigue syndrome: Is it one discrete syndrome or many? Implications for the “one vs. many” functional somatic syndromes debate. J Psychosom Res. 2010 May;68(5):455-9. doi: 10.1016/j.jpsychores.2010.01.008. Epub 2010 Mar 17. https://www.ncbi.nlm.nih.gov/pubmed/20403504