Abstract The etiology of functional somatic syndromes or disorders (FSDs) is generally considered to be a multifactorial interplay between psychological, biological, and social factors. One of the ...most investigated biological factors is stress responsive system dysfunction. Despite more than twenty years of research of the autonomic nervous system and the hypothalamic-pituitary-adrenal axis, however, it is yet unknown whether dysfunctions in these systems play a causal role in the etiology of FSDs and whether they are generic or FSD-specific. In this review, we will give an overview of available evidence on whether or not alterations in these stress responsive systems can be considered causal risk factors of FSDs. We conclude that although not necessary factors for FSDs in general, lowered cardiac vagal activity and hypocortisolism may be pivotal in the etiology and treatment strategy in subgroups of subjects with a FSD. Such subgroups need to be better identified.
There is a long-standing research history on the presumed psychological origin of functional movement disorders. Most studies do not address the heterogeneity in functional movement disorders and do ...not distinguish between risk factors, causes and consequences. We studied the associations between negative affect and objective as well as subjective symptom levels in patients with functional and organic tremor.
Thirty-three patients with a functional (14) or organic tremor (19) completed a web-based diary on subjective symptom burden and negative affect, five times a day for 30 days (total number of observations = 4759). During the same period, the participants wore an accelerometer to objectively record tremor. Vector autoregressive modelling was used to determine the time-lagged and contemporaneous associations between negative affect and objective/subjective tremor symptoms, both on an individual and a group level.
In contrast to previous literature, patients with a functional or organic tremor showed a weak contemporaneous association between negative affect and objective/subjective tremor symptoms (on average r = 0.038 and 0.174 respectively). Time-lagged associations between negative affect and objective/subjective tremor symptoms were mixed in effect and direction and only present in a subset of patients, with no differences between patients with functional or organic tremor.
Negative affect is only weakly associated with objective/subjective tremor symptoms, both on the contemporaneous and time-lagged associations, and these associations were mainly similar between patients with functional or organic tremor. These results argue against a strong influence of daily stress on tremor symptoms in patients with a functional or organic tremor.
•Psychological factors are thought to play a role in functional movement disorders.•We compared the influence of negative affect in functional (FT) and organic tremor (OT).•Contemporaneous associations between negative affect and tremor symptoms were weak.•Time-lagged associations were mixed and only present in a subset of patients.•These associations were mainly similar between patients with FT or OT.
Women are reported to consult general practitioners (GPs) more frequently than men. However, previous studies on sex differences in help-seeking behavior for somatic symptoms do not distinguish ...between sex and gender, do not account for sex differences in presented symptoms, and are frequently conducted in clinical settings, automatically excluding non-help seekers. Therefore, we aim to assess the independent associations of sex and gender with primary care help-seeking for somatic symptoms in the general population.
Records from the longitudinal population-based Lifelines Cohort Study were linked to routine electronic health records from GPs.
Participants reporting new-onset common somatic symptoms.
Associations between sex and gender, operationalized via a novel gender-index, with primary care help-seeking for somatic symptoms and differences in the strength of the association between gender and help-seeking for somatic symptoms between women and men.
Of 20,187 individuals with linked data, 8325 participants (67.5% female; mean age = 44.5 years SD = 12.9) reported at least one new-onset somatic symptom. Hereof, 255 (3.1%) consulted the GP within 6 weeks of symptom onset. Female sex was positively associated with consulting the GP (OR = 1.78; 95%CI = 1.13-2.80), whereas feminine gender was not (OR = 0.67; 95%CI = 0.39-1.16). The latter association did not differ in strength between men and women. More paid working days are negatively associated with help-seeking (OR = 0.95; 95%CI = 0.91-0.98).
The results suggest that female sex rather than feminine gender is associated with primary care help-seeking behavior for somatic symptoms. Nevertheless, clinicians should be aware that gender-related variables, such as mean paid working days, may be associated with help-seeking behavior.
Multiple predictors have been associated with persistent somatic symptoms. However, previous studies problematically defined the persistence of symptoms, conflated participants' sex and gender, and ...focused on patient populations. Therefore, we studied associations between predictors, especially sex and gender, and longitudinal patterns of somatic symptoms in the general adult population. We also assessed whether predictors for persisting symptoms differ between sexes.
To identify developmental trajectories of somatic symptoms, assessed by the SCL-90 SOM, we used latent class trajectory modeling in the Dutch Lifelines Cohort Study
= 150 494; 58.6% female; median time to follow-up: 46.0 (min-max: 22.0-123.0) months. To identify predictors of trajectories, we applied multiple logistic regression analyses. Predictors were measured by surveys at baseline and a composite gender index was previously developed.
A five-class linear LCGA model fitted the data best: 93.7% of the population had a stable symptom trajectory, whereas 1.5% and 4.8% of the population had a consistently increasing or decreasing symptom trajectory, respectively. Female sex predicted severe, stable symptom severity (OR 1.74, 95% CI 1.36-2.22), but not increasing symptom severity (OR 1.15, 95% CI 0.99-1.40). Femininity was protective hereof (OR 0.60, 95% CI 0.44-0.82 and OR 0.66, 95% CI 0.51-0.85, respectively). Merely a few predictors of symptom severity, for instance hours of paid employment and physical functioning, differed in strength between sexes. Yet, effect sizes were small.
Female sex and femininity predict symptom trajectories. No large sex differences in the strength of additional predictors were found, thus it may not be clinically useful to distinguish between predictors specific to male or female patients of persistent somatic symptoms.
Medically Unexplained Symptoms (MUS) are physical symptoms that last for longer than several weeks and for which no (sufficient) somatic explanation can be found. Interventions for treating MUS in ...primary care are available, but their implementation in daily practice appears difficult. In the current study we aim to explore key barriers and facilitators to the implementation of MUS-interventions in primary care.
A three-round modified Delphi study was performed, using the input of 58 experts that are (in)directly involved in the care for patients with MUS (e.g. general practitioners (GPs), GP mental health workers, policy advisors). In the first online questionnaire, we generated ideas about relevant barriers and facilitators on different implementation levels. These ideas were independently coded by two researchers, and reformulated into unique barriers and facilitators. In round two, participants selected the ten most relevant barriers and facilitators from round one, which were ranked on importance in round three.
We identified 42 unique barriers and 57 unique facilitators to the implementation of MUS-interventions. The three highest ranked barriers were all related to time, i.e. too little time for treating complex MUS-patients. The most important facilitator was a positive attitude towards MUS-patients. Results varied somewhat per profession.
Key barriers and facilitators to the implementation of MUS-interventions seem to exist on the level of the patient, intervention, professional, organization, and external context. All of these levels should be taken into account in order to increase implementation success of MUS-interventions in primary care.
•Multiple interventions for Medically Unexplained Symptoms (MUS) are available.•It appears difficult to implement interventions for MUS in primary care.•Clinicians assess lack of time as the most important barrier.•The most important facilitator is a professional's positive attitude towards MUS.
This umbrella review systematically assesses the variety and relative dominance of current aetiological views within the scientific literature for the three most investigated symptom-defined ...functional somatic syndromes (FSS) and their classificatory analogues within psychiatry and psychology.
An umbrella review of narrative and systematic reviews with and without meta-analyses based on a search of electronic databases (PubMed, Web of Science, Embase, PsychINFO) was conducted. Eligible reviews were published in English, focused on research of any kind of aetiological factors in adults diagnosed with fibromyalgia syndrome (FMS), irritable bowel syndrome (IBS), chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), and somatic symptom disorder (SSD)/somatoform disorder (SFD).
We included 452 reviews (132 systematic reviews including meta-analyses, 133 systematic reviews, 197 narrative reviews), of which 132 (29%) focused on two or more of the investigated health conditions simultaneously. Across diagnoses, biological factors were addressed in 90% (k = 405), psychological in 33% (k = 150), social in 12% (k = 54), and healthcare factors in 5% (k = 23) of the reviews. The methodological quality of the included systematic reviews (k = 255) was low (low/critically low: 41% k = 104; moderate: 49% k = 126; high quality: 10% k = 25). The high-quality systematic reviews suggest that deficient conditioned pain modulation, genetic factors, changes in the immune, endocrinological, gastrointestinal, cardiovascular, and nervous system, and psychosocial factors such as sexual abuse and pain catastrophizing increase the risk for FSS.
Only very few systematic reviews have used comprehensive, biopsychosocial disease models to guide the selection of aetiological factors in FSS research. Future research should strive for higher scientific standards and broaden its perspective on these health conditions.
Low baroreflex sensitivity (BRS) was an established risk factor for cardiovascular disorders. We investigated determinants of BRS in a large sample from general population.
In a population-based ...study (n = 901), data were collected on BRS, arm cuff blood pressure (BP), and obesity indices including body mass index, waist-to-hip ratio, waist circumference, and percentage body fat (%BF). BRS was calculated by spectral analysis software based on continuously recorded spontaneous fluctuations in beat-to-beat finger BP for 10-15 minutes. Correlations and multivariable regression analyses were used to test associations of age, sex, obesity indices, and hypertension with BRS while considering effects of lifestyle factors (smoking, alcohol consumption, and physical activity).
In multivariable analysis, age, sex, %BF, and hypertension were independently associated with BRS. BRS decreased with -0.10 (95% confidence interval: -0.15 to -0.06) ms/mm Hg with each year of increase in age. Women had -1.55 (95% confidence interval: -2.28 to -0.73) ms/mm Hg lower mean BRS than men. The effects of %BF (per 10% increase) and hypertension on BRS were -0.55 (95% confidence interval: -0.97 to -0.13) ms/mm Hg and -1.23 (95% confidence interval: -1.92 to -0.46) ms/mm Hg, respectively. There was no evidence of associations between BRS and lifestyle factors. Age, age2, sex, and their interactions plus %BF and hypertension contributed 16.9% of total variance of BRS.
In this large general population study, we confirmed prior findings that age and sex were important factors associated with BRS and found %BF was more strongly related to less favorable BRS levels than body mass index.
Summary Background Function of the hypothalamus–pituitary–adrenal (HPA) axis has been associated with several somatic and psychiatric health problems. The amount of free cortisol excreted in the ...urine during 24 h (24-h UFC) has often been used as a proxy for HPA-axis function. Reference values for 24-h UFC and their stability in the short and long term, as well as sources of variability, are largely lacking. Methods This study was performed in a general population cohort. Participants collected 24-h UFC on two consecutive days (T1), and repeated this collection approximately 2 years later (T2). Cortisol in urine was measured using LC–MS/MS. Height and weight were measured at the research facilities; glomerular filtration rate was estimated using creatinine clearance. Psychological distress (General Health Questionnaire), smoking, alcohol use and exercise were measured by means of questionnaires. Results 24-h UFC stability on a day-to-day basis was 0.69 (T1, N = 1192) and 0.72 (T2, N = 963) (both p < 0.001). Long-term stability as indicated by correlation between 2-day averages of T1 and T2 was 0.60 ( N = 972, p < 0.001). Multivariable linear regression analysis revealed that 24-h UFC was predicted by urine volume (standardized beta 0.282 (T1, N = 1556) and 0.276 (T2, N = 1244); both p < 0.001) and glomerular filtration rate (standardized beta 0.137 (T1) and 0.179 (T2); both p < 0.001), while also sex explained a small part (standardized beta for female sex −0.057 (T1) and −0.080 (T2); both p < 0.05). Conclusion 24-h UFC is moderately stable both in the short and the long term. The effects of urine volume and glomerular filtration rate on 24-h UFC are much stronger than those of sex.
Objective To examine whether parental overprotection contributes to the development of functional somatic symptoms (FSS) in young adolescents. In addition, we aimed to study whether this potential ...effect of parental overprotection is mediated by parenting distress and/or moderated by the adolescent's sex. Study design FSS were measured in 2230 adolescents (ages 10 to 12 years from the Tracking Adolescents' Individual Lives Survey) by the Somatic Complaints subscale of the Youth Self Report at baseline and at follow-up 2½ years later. Parental overprotection as perceived by the child was assessed by means of the EMBU-C (Swedish acronym for my memories of upbringing–child version). Parents completed the Parenting Stress Index. Linear regression analyses were performed adjusted for FSS at baseline and sex. Results Parental overprotection was a predictor of the development of FSS in young adolescents (β = 0.055, P < .01). Stratified analyses revealed that maternal overprotection was a predictor of the development of FSS in girls (β = 0.085, P < .02), whereas paternal overprotection was a predictor of the development of FSS in boys (β = 0.072, P < .01). A small (5.7%) but significant mediating effect of maternal parenting stress in the relationship between parental overprotection and FSS was found. Conclusions Parental overprotection may play a role in the development of FSS in young adolescents.
Autonomic nervous system (ANS) dysfunction is a potential mechanism connecting psychosocial stress to functional somatic disorders (FSD), such as chronic fatigue syndrome, fibromyalgia and irritable ...bowel syndrome. We present the first meta-analysis and systematic review of methodological study quality on the association between cardiac ANS dysfunction, measured as parasympathetic nervous system (PNS) activity using heart rate variability (HRV), and FSD. Literature search revealed 23 available studies including data on 533 FSD patients. Meta-analysis on a subgroup of 14 studies with suitable outcome measures indicated lower PNS activity in FSD patients compared to controls (weighted standardized mean difference (SMD)
=
−0.32, 95% CI −0.63 to −0.01,
p
=
0.04). The reliability of this summary estimate was, however, significantly limited by unexplained heterogeneity in the effect sizes and potential publication bias (weighted SMD after correction for funnel plot asymmetry
=
0.01, 95% CI −0.34 to 0.36,
p
=
0.95). The systematic review of overall methodological quality of HRV studies in FSD demonstrates that there is substantial room for improvement, especially in selection of healthy control subjects, blinding of researchers performing HRV measurements, report of adequate HRV outcomes, and assessment of and adjustment for potential confounders. Methodological study quality was, however, not a significant predictor of study findings. We conclude that current available evidence is not adequate to firmly reject or accept a role of ANS dysfunction in FSD. Quality criteria and recommendations to improve future research on HRV in FSD are provided.
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