Article Text

Original research
Suggestibility in functional neurological disorder: a meta-analysis
  1. Lillian Wieder1,
  2. Richard Brown2,
  3. Trevor Thompson3,
  4. Devin B. Terhune1
  1. 1 Department of Psychology, Goldsmiths, University of London, London, UK
  2. 2 School of Health Sciences, The University of Manchester, Manchester, UK
  3. 3 School of Human Sciences, University of Greenwich, London, UK
  1. Correspondence to Dr Devin B. Terhune, Psychology, Goldsmiths' College, London SE14 6NW, UK; d.terhune{at}gold.ac.uk

Abstract

Objective Responsiveness to direct verbal suggestions (suggestibility) has long been hypothesised to represent a predisposing factor for functional neurological disorder (FND) but previous research has yielded conflicting results. The aim of this study was to quantitatively evaluate whether patients with FND display elevated suggestibility relative to controls via meta-analysis.

Methods Four electronic databases were searched in November 2019, with the search updated in April 2020, for original studies assessing suggestibility using standardised behavioural scales or suggestive symptom induction protocols in patients with FND (including somatisation disorder) and controls. The meta-analysis followed Cochrane, Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guidelines. Data extraction and study quality coding were performed by two independent reviewers. Standardised suggestibility scores and responsiveness to symptom induction protocols were used to calculate standardised mean differences (SMDs) between groups.

Results Of 26 643 search results, 19 articles presenting 11 standardised suggestibility data sets (FND: n=316; control: n=360) and 11 symptom suggestibility data sets (FND: n=1285; control: n=1409) were included in random-effect meta-analyses. Meta-analyses revealed that patients with FND displayed greater suggestibility than controls on standardised behavioural scales (SMD, 0.48 (95% C, 0.15 to 0.81)) and greater responsiveness to suggestive symptom induction (SMD, 1.39 (95% CI 0.92 to 1.86)). Moderation analyses presented mixed evidence regarding the extent to which effect sizes covaried with methodological differences across studies. No evidence of publication bias was found.

Conclusions These results corroborate the hypothesis that FND is characterised by heightened responsiveness to verbal suggestion. Atypical suggestibility may confer risk for FND and be a cognitive marker that can inform diagnosis and treatment of this condition.

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Introduction

Functional neurological disorder (FND) is characterised by impaired motor, cognitive and/or sensory functioning that resembles neurological pathology but is not adequately explained by, and is clinically distinguishable from, it.1 2 FND encompasses a diverse array of symptom subtypes including non-epileptic seizures (NES) and functional movement disorder and is often conceptualised as a dissociative disorder.3 It is also related to somatization disorder, where a broader variety of functional symptoms can occur. Previously referred to as hysteria, and also known as conversion disorder, functional neurological symptom disorder and dissociative neurological symptom disorder, FND has a prevalence of 4–12 per 100 0004 5 and is found in 16% of neurology outpatients.6 It is associated with considerable diagnostic delays and frequent misdiagnosis,7 which add to the already significant psychological, social and economic impact of the condition.8

FND has long been hypothesised to be characterised by elevated responsiveness to direct verbal suggestions (suggestibility),9 and suggestion and the expression of functional symptoms have been hypothesised to recruit overlapping mechanisms.10 Suggestibility is theorised to confer vulnerability for FND11 through aberrant meta-awareness of intentions,12–15 the capacity for suggestions to trigger automatised behavioural routines or mental representations11 and/or a tendency to form precise (symptom) priors that override motor and perceptual systems.16 17 The use of suggestion to provoke FND symptoms is widely used to aid diagnosis18 19 and functional symptoms are responsive to suggestion-based treatments such as hypnosis and placebo.20 Conditions with germane symptom profiles, such as dissociative disorders, are also characterised by elevated hypnotic suggestibility.21

Despite these various strands of evidence, the empirical association between suggestibility and FND seems to be highly variable.10 22 In order to quantify the evidence for atypical suggestibility in this population, we conducted a random-effects meta-analysis of controlled studies of suggestibility on standardised behavioural scales and in response to suggestive symptom induction protocols in all FND subtypes including somatisation disorder/Briquet’s syndrome. Secondary analyses investigated moderating influences on patient–control differences, including FND subtype, experimenter blindness,23 methodological quality, the inclusion of a hypnotic induction24 and symptom provocation method.18

Method

Eligibility criteria

Inclusion criteria included (1) English language, (2) full paper in a peer-reviewed journal, (3) patient sample characterised by FND symptoms, encompassing conversion disorder Diagnostic and Statistical Manual (DSM), dissociative neurological disorder (ICD), specific functional neurological syndromes (eg, NES) and conditions where functional neurological symptoms are a diagnostic feature (ie, DSM-IV somatisation disorder; Briquet’s syndrome), (4) inclusion of a control group, and either (5) use of a standardised behavioural measure of direct verbal suggestibility24 or (6) assessment of symptom induction through suggestion (eg, suggestive seizure induction).18

Exclusion criteria included (1) studies in which suggestion was used to aid diagnosis, (2) case studies/series or non-empirical papers, (3) overlapping/insufficient data, (4) use of interrogative suggestibility scales, which capture a different form of suggestibility characterised by high compliance25 and (5) studies of patients with functional somatic syndromes not specifically characterised by functional neurological symptoms (eg, fibromyalgia).

Search strategy

PubMed, PsycINFO, Web of Science and Academic Search Complete databases were searched in November 2019 for eligible studies using terms relating to suggestibility and FND (see online supplemental content 1) and then integrated into a single database. The search was repeated in April 2020 but yielded no new studies. The reference lists of all eligible studies (and relevant review papers) were manually searched to identify additional studies. Authors were contacted when data were unavailable or to clarify ambiguities in methodology.

Supplemental material

Study selection

Two raters (LW and a second rater) independently screened and assessed all studies for their eligibility using a two-stage procedure. First, all titles and abstracts were screened and articles not meeting eligibility criteria were rejected. Second, all remaining papers were reviewed to establish a final list of articles. Discrepancies at either stage were resolved in consultation with a third reviewer (DBT) and sometimes a fourth reviewer (RB). Authors of eligible studies were contacted to address any questions regarding insufficient data. Of five author groups contacted, four (80%) provided data sufficient to permit study inclusion or answered queries that justified exclusion.

Data extraction

The two outcome types (standardised suggestibility and symptom suggestibility) were measured using continuous and categorical measures, respectively. After exclusion of two studies with overlapping data, data from eligible studies were extracted and coded independently by LW and the second rater using a data extraction form including: (1) study details (title, year, geographical location), (2) diagnosis, (3), diagnosis method, (4) demographics (sample size and gender and age distributions), (5) study design details (suggestibility type (standardised or symptom), inclusion of a hypnotic induction, scale, administration method (live or recorded presentation) and scoring method (self or experimenter), provocation method (see table 1), symptom subtype, experimenter blindness (blind, unblind or unreported)) and (6) descriptive statistics (Ms and SDs (standardised suggestibility) or response counts (symptom suggestibility)). Symptom suggestibility response counts include only responses identified as typical for the respective patient (typicality reported: k=8; unreported: k=3). When studies reported results for more than one provocation method (k=2), the rounded mean was used. Two studies included data for both standardised and symptom suggestibility. There was 91% agreement between the two raters and discrepancies were resolved with a third reviewer (DBT).

Table 1

Characteristics of included studies measuring symptom suggestibility in FND

Table 2

Characteristics of included studies measuring standardised suggestibility in FND

Study quality

A 13-item scale was developed to assess study quality (see online supplemental content 1). Items were adapted from an earlier meta-analysis that included items based on Cochrane criteria and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations26 and a range of other methodological criteria such as experimenter blindness. LW and the second rater independently rated each item categorically (0=criterion not met, 1=criterion met) and a summed total was computed for each study. Agreement between raters was 90% (kappa=0.73) and discrepancies were resolved with DBT.

Meta-analysis and meta-regression

Individual study effect sizes included between-group differences in suggestibility that were computed with standardised mean differences (SMDs; Hedges’s gs) using Review Manager (RevMan V.5.3, 2014; The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen). Symptom suggestibility data consisted of binary outcomes that were used to compute ORs, which were subsequently transformed to SMDs27 in MATLAB (V.2017b, MathWorks, Natick, Massachusetts, USA). SMDs were coded such that positive values reflected greater suggestibility in patients with FND than controls. SMDs around 0.2, 0.5 and 0.8 are typically interpreted as reflecting small, moderate and large effects, respectively.

Publication bias was assessed by examining funnel plots of effect sizes against SEs for asymmetry, as might occur due to a small number of studies with small or non-significant effect sizes. We also tested for asymmetry using Egger’s bias test28 where p<0.05 is indicative of asymmetry and we report revised effect sizes correcting for asymmetry using the trim-and-fill method29 and funnel plots.

Random-effects meta-analyses were performed in JASP (V.0.8.6, 2019; JASP Team, the Netherlands). Outlier detection was made on the basis of studentized residuals (>|3.3|).30 There were no outliers in the standardised suggestibility data (range: −1.63 to 1.33) or the symptom suggestibility data (range: −2.01 to 1.26). Moderating effects were assessed using meta-regression analyses whenever data were available for at least 2 studies at each level of a categorical moderator and at least 10 studies for continuous moderators.31 Moderators included five categorical measures (symptom subtype, experimenter blindness, hypnotic induction, symptom provocation method (suggestion vs nocebo; symptom studies), symptom typicality (not reported vs report; symptom studies) and control type (non-clinical vs clinical; standardised studies)) and one continuous measure (methodological quality).

Results

Study inclusion

A PRISMA diagram showing study selection is presented in figure 1. Principal features of these studies, including diagnosis criteria and procedures, are presented in tables 1 and 2.

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart of study selection process.

Study and participant characteristics

The 19 papers included 11 standardised suggestibility studies (FND: n=316, control: n=360) and 11 symptom suggestibility studies (FND: n=1285, control: n=1409) (see online supplemental content 1 for references). Patients with FND primarily comprised those with NES (k=6 (standardised); k=9 (symptom)), with small numbers of studies of patients with mixed conversion disorder (k=3 (standardised) and k=1 (symptom)), somatisation disorder/Briquet’s syndrome (k=2 (standardised)) and psychogenic tremor (k=1 (symptom)). The standardised studies were published between 1984 and 2009 and were conducted in the USA (k=5), the Netherlands (k=4) and the UK (k=2). The symptom studies were published between 1994 and 2018 and were conducted in the USA (k=7), Puerto Rico (k=1), France (k=1), India (k=1) and the UK (k=1). The mean percentage of women for standardised studies was 86.13 for FND (k=8) and 45.71 for controls (k=7), whereas for symptom studies (k=6), it was 77.17 for FND and 61.33 for controls. In the standardised studies, the mean age for FND was 31.22 (SD=8.01) (k=6), and for controls, it was 36.96 (SD=5.09) (k=7), whereas for the symptom studies (k=6), mean age for FND was 33.41 (SD=8.79) and 37.20 (SD=14.38) for controls.

Details of the types of standardised scales and provocation methods as well as the use of a hypnotic induction are provided in tables 1 and 2, respectively. A hypnotic induction was used in nine standardised studies and three symptom studies. All symptom studies included verbal suggestion but varied in their use of various nocebo procedures.

Methodological quality criteria

Ratings for each study on each of the methodological quality criteria items are shown in online supplemental tables 1 and 2. Although some of the criteria were met by the majority of studies, multiple criteria were not reliably met. Only 5 of 22 studies (23%) reported that the experimenter was blind to group, 18 (82%) described the inclusion/exclusion criteria, 16 (73%) described the diagnosis procedure and criteria in adequate detail, 10 (45%) described participant characteristics and 3 (14%) exhibited demographic comparability between patients and controls. In the standardised studies, 7 of 11 (64%) described the scale and procedure in adequate detail and only 1 (9%) included a measure to correct for compliance. In the symptom studies, 8 of 11 (73%) clearly described the provocation method.

Meta-analysis of standardised suggestibility

Meta-analysis of 11 standardised behavioural suggestibility studies found that patients with an FND exhibited greater suggestibility than controls, SMD=0.48 (0.15, 0.81), Z=2.84, p=0.004 (see figure 2). Positive results were observed in eight studies with a high inconsistency of effect sizes across studies, I2=73%. Jackknife analysis in which each study effect was sequentially omitted and the analysis reperformed indicated that the group difference was reliably significant (SMD range: 0.40–0.56).

Figure 2

Forest plots of SMDs (with 95% CIs) from (left) 11 standardised suggestibility studies and (right) 11 symptom suggestibility studies. Marker sizes reflect the study weights with smaller markers denoting smaller weights. FND, functional neurological disorder; SMD, standardised mean difference.

Meta-analysis of symptom suggestibility

Meta-analysis of 11 symptom suggestibility studies found that patients with FND displayed greater responsiveness than controls, SMD=1.39 (0.92, 1.86), z=5.77, p<0.001 (see figure 2). Overall positive responses were observed in 49% of patients with FND and 6% of controls (sensitivity=49%, specificity=94%). Ten of the 11 studies exhibited positive SMDs although there was substantial heterogeneity in effect sizes across studies, I2=99%. Jackknife analysis revealed that the group difference remained significant after omitting each study in a sequential manner (SMD range: 1.25–1.54).

Meta-analysis of standardised versus symptom suggestibility

The weighted effect size for symptom studies was significantly greater than that for standardised studies, z=2.60, p=0.009. This difference remained stable, z=2.29, p=0.022, after removing the two studies included in both data sets. When the two data sets were aggregated, the cumulative standardised effect size was slightly less than 1, SMD=0.96 (0.62, 1.29).

Publication bias

Egger’s test did not suggest asymmetry in the distribution of effect sizes in the standardised studies, z=0.69, p=0.49, or in the symptom studies, z=1.50, p=0.13. A trim and fill estimate produced only a slight reduction in effect sizes for standardised studies, ΔSMD=−0.05, and symptom studies, ΔSMD=−0.10 (see figure 3).

Figure 3

Funnel plots of standardised mean differences (SMDs) from (left) 11 standardised suggestibility studies and (right) 11 symptom suggestibility studies. Filled circles denote individual study effect sizes and empty circles denote estimated missing individual effect sizes due to publication bias imputed using the trim and fill method. Summary SMDs (95% CI) using the trim and fill method were SMD=0.43 (0.10, 0.76) (standardised suggestibility studies) and SMD=1.29 (0.84, 1.75) (symptom suggestibility studies).

Meta-regression of standardised and symptom suggestibility

Given the observed inconsistency in the magnitude of effects, a set of meta-regression analyses considered whether group differences were moderated by binary and continuous predictors pertaining to symptom subgroups and study methodologies (see table 3). Patients with NES exhibited marginally significantly larger effect sizes than patients with mixed FND in the symptom studies although this difference was driven by a single non-significant mixed-FND study. These symptom subgroups did not significantly differ in the standardised studies. Effect sizes were significantly larger when a hypnotic induction was included in standardised studies, but not in symptom studies. Effect sizes were also larger in studies that reported whether suggested symptoms were typical for the patient relative to those that did not report this information; this implies that effect sizes are not inflated by the inclusion of atypical symptoms in response rates for suggestive symptom induction. By contrast, effect sizes were not significantly related to the type of control (clinical vs non-clinical; standardised studies) or suggestive induction protocol (suggestion vs nocebo (suggestion and sham); symptom studies). Experimenter blindness did not significantly moderate group differences with numerical differences in opposing directions for standardised and symptom studies. Similarly, methodological quality related to effect sizes in opposing directions: greater quality was significantly associated with lower effect sizes in standardised studies, but with larger, although non-significantly, effect sizes in symptom studies. These effects were primarily driven by procedure description. Standardised effect sizes were smaller in studies that met criteria for clarity of inclusion/exclusion criteria: z=−2.54, p=0.011; diagnostic procedure: z=−2.82, p=0.005 and scale administration procedure: z=−2.28, p=0.022 (all other ps >0.09). In contrast, symptom effect sizes were larger in studies that met criteria for clarity of diagnostic procedure, z=3.23, p=0.001 (all other ps >0.09).

Table 3

Meta-regression analyses for standardised and symptom suggestibility studies (SMD (95% CIs) (k))

Discussion

The results of this meta-analysis suggest that patients with FND display elevated suggestibility on standardised behavioural scales and in response to suggestive symptom induction protocols, consistent with theoretical predictions to this effect.9 10 22 There was no evidence for publication bias although there was considerable heterogeneity in both data sets, which was partly explained by methodological variability.

These findings are consistent with models proposing responsiveness to suggestion as a vulnerability factor for FND and those attributing functional symptoms to precise symptom priors.11 16 Recent theoretical work conceptualises functional symptoms as arising from the automatic activation of ‘rogue’ mental representations or symptom priors akin to Janet’s fixed ideas. Numerous factors have been proposed to moderate this process including autonomic arousal, inhibitory deficits and problems with body perception.11 Suggestibility may confer heightened sensitivity to symptom-specific cues or dissociative responses to stressors.32 Moreover, suggestibility has been proposed to reflect a generalised tendency to form precise priors that override motor and perceptual systems,33 which is thought to be a key process in FND16 and symptom reporting more generally.17 This aligns with research showing that hypnotic suggestibility predicts symptom severity in patients with FND.34 Observed links between hypnotic suggestibility and emotional responsiveness to social cues24 highlight the potential role of suggestibility in symptom modelling or triggering through social observation.11 The perception that functional symptoms are extravolitional may be further augmented by aberrant meta-awareness of intentions, as observed in both FND14 15 and high hypnotic suggestibility.12 13

Although the two forms of suggestibility moderately covary,35 patients with FND were more responsive to symptom specific (SMD=1.39 (0.92, 1.86)) than to standardised suggestions (SMD=0.48 (0.15, 0.81)), implying selectively greater suggestibility for functional symptoms. Indeed, the sole non-significant provocation study36 administered suggestions for generic symptoms that did not necessarily mirror patients’ symptom profiles. Previous research similarly found that highly dissociative individuals and dissociative and acute stress disorder patients are more responsive to suggestions for dissociative experiences (eg, amnesia).21 Symptom suggestibility in FND may thus partly reflect a kindling process, whereby symptoms become more responsive to verbal suggestion over time.11 37

Atypical suggestibility in patients with FND complements research showing greater suggestibility in germane conditions such as dissociative and stress disorders10 21 and somatoform disorders.38 The overlapping symptom profiles of these conditions imply an association between suggestibility and dissociative psychopathology, the specificity of which is corroborated by research indicating that suggestibility does not seem to be a characteristic of general psychopathology.39 40 Variability in detachment and compartmentalisation symptoms41 and exposure to stressful life events may account for heterogeneity in the suggestibility profiles of patients with FND, with heightened responsiveness to suggestions being specific to, or more pronounced among, patients with marked dissociative symptomatology.34 42 Further research is required to assess whether this heterogeneity is attributable to the presence of a highly suggestible subtype among patients with FND who may be particularly likely to benefit from suggestion-based interventions. An additional outstanding question is whether atypical suggestibility is a feature shared across different FND symptom subtypes. The available evidence suggests this is the case: patients with NES were not reliably more suggestible than other patients with FND and independent research has documented or implied elevated responsiveness to suggestion in psychogenic parkinsonism,43 functional movement disorders44–47 and functional vision loss.48 Moderation analyses indicated that the administration of a hypnotic induction was associated with greater standardised suggestibility among patients with FND. This is consistent with the proposal that individuals with compartmentalisation symptoms benefit more from a hypnotic induction21 although the mechanistic basis of this effect remains unclear.24

These effects attest to the efficacy of suggestion in the diagnosis of FND.18 Suggestive symptom induction displayed high specificity (94%) although sensitivity is poor (49%), indicating that this technique is insufficient as a standalone diagnostic procedure. The inclusion of sham methods or a hypnotic induction was not associated with greater discrimination of patients with FND and controls relative to verbal suggestion alone but warrant further attention. Suggestive symptom induction is likely to be especially valuable in suggestible populations such as adolescent and elderly samples24 or patients with comorbid dissociative or stress disorder diagnoses.10 21 It may also inform diagnosis of comorbid NES in epilepsy patients49 and medication prescription50 and prognosis51 in patients with FND. Insofar as suggestibility is a positive predictor of outcome with suggestion-based treatments,52 these results also support greater incorporation of suggestion techniques in treatment protocols, which show promising results in randomised controlled trials.20 However, they also highlight the need to control for suggestion, or consider its role, in diagnostic and treatment procedures, particularly those that evoke strong response expectancies.46

Limitations

The principal limitations of these data concern methodological variability across studies. Methodological quality was significantly or descriptively related to effect sizes in both data sets although in opposite directions. Among standardised studies, older studies that did not precisely specify inclusion/exclusion criteria and/or diagnostic and scale administration procedures tended to exhibit larger effect sizes; in contrast, precise specification of diagnostic procedures was associated with larger effect sizes in symptom studies. In most studies, the operator administering the assessment was not blind to patient group, which may inflate effect sizes,23 although there was no evidence for an experimenter effect in the standardised studies. The sole blind symptom study had a lower effect size than the remainder of the studies but was still large in magnitude (SMD=0.93 (0.61, 1.26)). Most studies included clinical controls (eg, patients with epilepsy), which raises issues regarding generalisability although effect sizes did not significantly related to control type. Similarly, the majority of FND samples comprised patients presenting with NES and thus further controlled research is required to assess responsiveness to suggestion across a range of FND symptom subtypes, particularly those presenting with cognitive symptoms. Symptom suggestibility estimates are also confounded by baseline symptom frequency, which is not incorporated into these assessments.18 This potentially renders patients with high symptom frequency at an increased risk of false-positive responses, although there is evidence that this is not the case.53 The studies also varied in whether successful responses to symptom induction protocols were contingent on the typicality of the response, which accounted for variability in effect sizes. Standardised studies were limited insofar as only one controlled for compliance. In addition, standardised suggestibility scales include a disproportionate number of suggestions for dissociative and functional symptoms (eg, paralysis),10 24 34 raising the question of whether elevated suggestibility in FND generalises beyond these symptoms. Collectively, these findings underscore the need for optimisation and standardisation of suggestive symptom induction protocols,18 compliance-correction24 and more diverse suggestion batteries.

Conclusions

This meta-analysis corroborates the long-held view that FND is characterised by elevated suggestibility. Increased suggestibility has direct implications for the risk factors underlying this condition, the use of suggestion to aid diagnosis, the utility of suggestion-based treatments for functional symptoms and heterogeneity within this population.

Acknowledgments

The authors thank Che Ofuasia, Goldsmiths, University of London, for contributing to the data coding and evaluation.

References

Supplementary materials

  • Supplementary Data

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Footnotes

  • Contributors All authors conceived the project. LW carried out the database searches and data coding with assistance from RB, TT and DBT. LW and DBT performed the meta-analysis with assistance from RB and TT. LW and DBT drafted the initial manuscript. All authors reviewed and approved the final version of the manuscript.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information. Data are freely available from previous research studies.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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