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Dissociation and its biological and clinical associations in functional neurological disorder: systematic review and meta-analysis

Published online by Cambridge University Press:  01 December 2022

Malcolm C. Campbell
Affiliation:
Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK; and Central and North West London NHS Foundation Trust, London, UK
Abigail Smakowski
Affiliation:
Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK; and University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Maya Rojas-Aguiluz
Affiliation:
Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK
Laura H. Goldstein
Affiliation:
Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK
Etzel Cardeña
Affiliation:
Center for Research on Consciousness and Anomalous Psychology (CERCAP), Department of Psychology, Lund University, Lund, Sweden
Timothy R. Nicholson
Affiliation:
Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK
Antje A. T. S. Reinders
Affiliation:
Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK
Susannah Pick*
Affiliation:
Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK
*
Correspondence: Susannah Pick. Email: susannah.pick@kcl.ac.uk
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Abstract

Background

Studies have reported elevated rates of dissociative symptoms and comorbid dissociative disorders in functional neurological disorder (FND); however, a comprehensive review is lacking.

Aims

To systematically review the severity of dissociative symptoms and prevalence of comorbid dissociative disorders in FND and summarise their biological and clinical associations.

Method

We searched Embase, PsycInfo and MEDLINE up to June 2021, combining terms for FND and dissociation. Studies were eligible if reporting dissociative symptom scores or rates of comorbid dissociative disorder in FND samples. Risk of bias was appraised using modified Newcastle–Ottawa criteria. The findings were synthesised qualitatively and dissociative symptom scores were included in a meta-analysis (PROSPERO CRD42020173263).

Results

Seventy-five studies were eligible (FND n = 3940; control n = 3073), most commonly prospective case–control studies (k = 54). Dissociative disorders were frequently comorbid in FND. Psychoform dissociation was elevated in FND compared with healthy (g = 0.90, 95% CI 0.66–1.14, I2 = 70%) and neurological controls (g = 0.56, 95% CI 0.19–0.92, I2 = 67%). Greater psychoform dissociation was observed in FND samples with seizure symptoms versus healthy controls (g = 0.94, 95% CI 0.65–1.22, I2 = 42%) and FND samples with motor symptoms (g = 0.40, 95% CI −0.18 to 1.00, I2 = 54%). Somatoform dissociation was elevated in FND versus healthy controls (g = 1.80, 95% CI 1.25–2.34, I2 = 75%). Dissociation in FND was associated with more severe functional symptoms, worse quality of life and brain alterations.

Conclusions

Our findings highlight the potential clinical utility of assessing patients with FND for dissociative symptomatology. However, fewer studies investigated FND samples with motor symptoms and heterogeneity between studies and risk of bias were high. Rigorous investigation of the prevalence, features and mechanistic relevance of dissociation in FND is needed.

Type
Review
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.
Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press on behalf of the Royal College of Psychiatrists

Functional neurological disorder (FND) is characterised by alterations in motor and/or sensory function that are not explained by or not compatible with identifiable neuropathology, according to DSM-5.1 FND symptoms vary; traditionally they have been characterised by motor symptoms (denoted here as FND-motor; e.g. muscle weakness, paralysis, disordered movements), seizures (FND-seizures) and sensory symptoms (FND-sensory; e.g. numbness). Increasingly, subjective cognitive difficulties, dizziness and auditory problems are being recognised and classified as FND.2

Dissociative symptoms are frequently reported in FND. A recent meta-analysis demonstrated this, but was limited by inclusion of one singular measure of dissociation – thus a broader inclusion of dissociation measures is needed.Reference Lyssenko, Schmahl, Bockhacker, Vonderlin, Bohus and Kleindienst3 Dissociation as a neurocognitive process has been theorised to underlie FND, reflecting its categorisation in ICD-11, where the official term is dissociative neurological symptom disorder;2,Reference Brown, Cardeña, Nijenhuis, Sar and van der Hart4,Reference Brown and Reuber5 here, it is classified as a dissociative disorder, alongside several other dissociative disorders, including dissociative identity disorder (DID) and depersonalisation/derealisation disorder (DPDR).2 Nevertheless, the conceptualisation of FND as a dissociative disorder, with dissociation as a core underlying mechanism, is not universally accepted. There is a paucity of high-quality empirical evidence supporting the conclusion that dissociation is a causal process in the generation of FND symptoms. Furthermore, there is no reference to dissociation as a mechanism in the DSM-5 classification of FND and so there is currently a notable and unhelpful discrepancy between the two major classification systems. The critical need to resolve this discrepancy necessitates more rigorous examination of the prevalence and potential mechanistic role of dissociation in FND in future studies.

Dissociation can broadly be viewed as the loss of control or awareness of cognitive or physical processes that are normally readily controlled or engaged in conscious awareness. As a symptom it can manifest as memory disturbance, subjective disconnectedness from the self (depersonalisation) or external stimuli (derealisation), loss of bodily sensation and voluntary control, or altered sense of identity.Reference Cardeña and Carlson6Reference Romero-López9 Although dissociation is considered a natural response to certain triggers, such as sleep deprivation or extreme fear (especially threat to life), we focus here specifically on pathological dissociation.Reference Medford, Baker, Hunter, Sierra, Lawrence and Phillips8,Reference Hunter, Phillips, Chalder, Sierra and David10,Reference Ross, Joshi and Currie11 Dissociative symptoms are seen in a variety of psychiatric disorders;Reference Lyssenko, Schmahl, Bockhacker, Vonderlin, Bohus and Kleindienst3,Reference Brown, Cardeña, Nijenhuis, Sar and van der Hart4,Reference Hendrickson, Popescu, Ghearing and Bagic12Reference Roydeva and Reinders15 symptoms can be chronic and severely disabling.Reference Lyssenko, Schmahl, Bockhacker, Vonderlin, Bohus and Kleindienst3,Reference Medford, Baker, Hunter, Sierra, Lawrence and Phillips8

Dissociation has previously been partitioned into compartmentalisation and experiential detachment;Reference Brown, Cardeña, Nijenhuis, Sar and van der Hart4,Reference Treise and Perez16 however, recent evidence from network analyses of dissociative experiences has extended this to include absorption (becoming absorbed in an external stimulus or one's own imagination to the point of reduced awareness of self and surroundings) and depersonalisation/derealisation.Reference Cardeña, Gušić and Cervin17,Reference Schimmenti and Sar18 In compartmentalisation, individuals lose the ability to govern processes or actions over which they would normally have control; it is theorised to underpin FND-seizures and dissociative amnesia, for example.Reference Holmes, Brown, Mansell, Fearon, Hunter and Frasquilho19 In detachment, individuals ‘detach’ from the ordinary sense of integration of self, body or external environment.Reference Holmes, Brown, Mansell, Fearon, Hunter and Frasquilho19

Dissociative symptoms can also be categorised as somatoform symptoms, which are sensory (e.g. pain, loss or alteration in sensory modalities) or motor (e.g. weakness, involuntary movements), or psychoform, which relate to mental experiences such as memory impairment or depersonalisation.Reference Nijenhuis, Spinhoven, Van Dyck, Van der Hart and Vanderlinden20,Reference van der Boom, van den Hout and Huntjens21 Various symptom rating scales screen for these clusters of symptoms. Table 1 describes some of the most commonly administered scales. The Somatoform Dissociation Questionnaire (SDQ-20), for example, primarily assesses somatoform dissociative symptoms,Reference Nijenhuis, Spinhoven, Van Dyck, Van der Hart and Vanderlinden20 whereas the Dissociative Experiences Scale (DES) predominantly assesses psychoform dissociation.Reference Bernstein22 Little is currently known about the biological processes underpinning dissociation, and although several areas for further exploration have been highlighted recently,Reference Roydeva and Reinders15 this is a crucial direction for future research to improve recognition, understanding and treatment of dissociative disorders.

Table 1 Example dissociation symptom rating scales

DID, dissociative identity disorder.

Dissociative symptoms contribute to morbidity in psychiatric populations, especially in those who have experienced trauma. The dissociative subtype of post-traumatic stress disorder (PTSD), for example, has been associated with more severe illness.Reference Hansen, Ross and Armour23Reference Huijstee and Vermetten25 Individuals with a dissociative disorder are more likely to report self-harm and attempted suicide relative to other psychiatric populations, and psychiatric in-patients with a history of attempted suicide reported more severe dissociative symptoms than those without.Reference Calati, Bensassi and Courtet26 Pathological dissociation contributes heavily to healthcare spending; however, timely diagnosis and treatment can mitigate this cost.Reference Langeland, Jepsen, Brand, Kleven, Loewenstein and Putnam27 Therefore, conditions involving significant dissociative symptom burden merit careful review with regard to risk assessment and management.

It is possible that dissociation is a negative mediator or prognostic marker in the overall clinical presentation and morbidity of FND. If true, a case can be made for broadening the treatment lens through which FND is managed by incorporating assessment and management of dissociative symptomatology. However, not enough is known about the extent of the role that dissociation plays in FND.

Aims

The purpose of this systematic review and meta-analysis was to summarise the available evidence pertaining to dissociation in FND, as a symptom, comorbid disorder and potential prognostic marker. The primary aim was to critically appraise and report on rates of dissociative symptoms and disorders among people with FND. The secondary aim was to examine whether dissociation varies in severity in different FND symptom subgroups. The third was to report on the available data pertaining to biological and clinical associations of elevated dissociation in FND.

Method

Protocol registration

A protocol for this review was registered on PROSPERO on 24 April 2020 (ref CRD42020173263).

Search strategy and study selection

The following databases were searched using the Ovid platform on 29 March 2020: Embase, PsycInfo and MEDLINE. The searches were updated on 1 June 2021. Studies were eligible for inclusion if they reported on comorbid dissociative disorder diagnoses and/or severity of dissociative symptoms in FND populations. The search terms for dissociation and FND are shown in the Appendix. Further articles were identified by reviewing the references of relevant systematic reviews, in addition to studies published during the selection process. The search strategy, including Boolean operators, is shown in supplementary Box 1, available at https://doi.org/10.1192/bjo.2022.597.

Inclusion and exclusion criteria

The inclusion criteria were as follows:

  1. (a) studies that reported on dissociative symptoms, as measured by validated rating scales (e.g. DES, SDQ-20)

  2. (b) studies reporting on comorbid dissociative disorder diagnoses based on ICD or DSM criteria (e.g. using the Structured Clinical Interview for DSM Dissociative Disorders; SCID-DReference Steinberg, Rounsaville and Cicchetti31)

  3. (c) participants aged 18 years or older

  4. (d) participants with specific FND diagnostic codes reflecting ICD or DSM criteria (supplementary Table 1)

  5. (e) studies written in English, French, Spanish or Swedish

  6. (f) studies published from 1 January 1980 or later, reflecting when DSM-III was released and the term ‘conversion disorder’ was adopted, replacing the outdated ‘hysteria’.

The exclusion criteria were:

  1. (a) studies that explicitly stated that participants with FND had a comorbid major neurological diagnosis, e.g. FND-seizures with comorbid epilepsy

  2. (b) studies in which participants with FND were included in mixed samples with additional psychiatric or physical health diagnoses, without presentation of disorder-specific dissociation data

  3. (c) reviews and meta-analyses

  4. (d) newspaper articles, editorials, non-peer reviewed sources, conference abstracts and other grey literature.

Study screening

After removing duplicates, all titles and abstracts were screened by pairs of authors (M.C.C. and S.P. or A.S. and S.P.) and any that clearly did not meet the eligibility criteria were removed. The full texts of the remaining articles were then screened for eligibility by one author (M.C.C. or A.S.); reasons for study exclusion were documented.

Data extraction

For each study, the following information was extracted and tabulated by one investigator (M.C.C. or A.S.), where available: FND sample (e.g. seizures, motor symptoms, mixed symptoms, unspecified), control group type (e.g. non-clinical, neurological, psychiatric), sample size, average age, gender ratio, dissociative symptom scales used and dissociative disorders diagnosed. Mean/median values for dissociation scales were recorded where available, in addition to measures of dispersion. Data from eligible studies that additionally used objective biological measures were also extracted, as were data on any clinical associations of dissociation in these studies.

Quality appraisal

Studies were evaluated for quality and potential risk of bias by two independent raters (A.S. and M.R.-A.) using modified Newcastle–Ottawa criteria for case–control, cohort and cross-sectional studies.Reference Moskalewicz and Oremus32 Discrepancies were discussed and resolved, with input from a third rater (S.P. or M.C.C.) where necessary. The criteria used are shown in supplementary Table 2.

Synthesis method

The available data on rates of comorbid dissociative disorders, dissociative symptom scores and the clinical and biological associations of dissociation were first tabulated and synthesised qualitatively. We then conducted a meta-analysis of dissociative symptom scale scores. In the first meta-analysis, studies were included if they provided ‘adequate data’ (mean, standard deviation) for at least one validated measure of dissociative symptoms and control comparison. Studies with missing data were not included in the meta-analysis. A combined ‘psychoform dissociation measure’ was created by pooling data from the DES, Dissociation Questionnaire (DIS-Q) and Clinician Administered Dissociative States Scale (CADSS). The DES data were used for studies that reported more than one of these scales. The Somatoform Dissociation Questionnaire (SDQ) was calculated separately because it measures a different construct of somatoform dissociation.Reference Nijenhuis, Spinhoven, Van Dyck, Van der Hart and Vanderlinden20 Studies that gave measures of central tendency as medians were excluded unless the authors also gave means and standard deviations. Studies that reported data from more than one dissociation measure or symptom subgroup were included in each measure group. Standard errors were converted to standard deviations according to Cochrane recommendations.Reference Higgins, Li, Deeks, Higgins, Thomas, Chandler, Cumpston, Li, Page and Welch33

Meta-analyses calculating dissociation scores used a random-effects model, with restricted maximum likelihood estimationReference Viechtbauer34 to calculate heterogeneity variance τ2, Hartung–Knapp adjustmentsReference Hartung, Knapp, Schulze, Holling and Böhning35 and Hedges’ g effect size metric, and were run on Windows 10 using the meta-R packageReference Balduzzi, Rücker and Schwarzer36 with guidance.Reference Harrer, Cuijpers, Furukawa and Ebert37 Funnel plots were generated to assess the risk of bias due to missing results. Meta regressions incorporating risk of bias categories were used to assess confidence in the body of evidence for each outcome.

We were able to explore the heterogeneity of our data by subgroup analyses because our meta-analyses contained more than ten studies. Subgroup analyses were conducted on studies that provided data for at least one FND group and a least one comparison group. The first subgroup analysis investigated dissociation scores by control group (healthy control, psychiatric and neurological). The second investigated the effect of FND symptom (seizures versus motor). Subgroup analyses applied a mixed-effects model using the subgroup function of the meta-R package.Reference Balduzzi, Rücker and Schwarzer36 All meta-analyses are displayed in forest plots. Subgroup analyses were interpreted using Cochran's Q.Reference Cochran38 I2 heterogeneity statistics were interpreted using recommended levels.Reference Higgins and Thompson39

Results

Study selection

The results of the study selection process are shown in the PRISMA flow diagram (Fig. 1). Seventy-five studies were included for qualitative review.

Fig. 1 PRISMA flowchart. FND, functional neurological disorder.

Study characteristics

Details for each study – participant characteristics, design, principal findings, key strengths and weaknesses – are shown in supplementary Table 3. The majority of the included studies were case–control prospective studies (k = 54). FND samples were predominantly recruited in out-patient settings (k = 52). Of the FND participants, the most prevalent symptom profile reported was FND-seizures (n = 2160). FND-unspecified and FND-motor were the next most reported symptom types, with 956 and 523 participants respectively. Fifty-four studies included control groups. The most common control groups were healthy samples (k = 28), followed by epilepsy samples (k = 13). The mean age of FND participants ranged from 20.5 to 50.4 years. The female:male gender ratio ranged from 1.1:1 to 19.5:1; all studies that had male and female participants reported a greater female: male gender ratio. There were five studies with an all-female FND group and one with an all-male FND group.

Quality appraisal and risk of bias

We used modified Newcastle–Ottawa Scale (NOS) criteria to rate the quality of all cohort and case–control studies.Reference Wells, Shea, O'Connell, Peterson, Welch and Losos40 For cross-sectional studies, we applied an adapted version of the NOS.Reference Moskalewicz and Oremus32 Overall, two of the case–control studies were rated as having a very high risk of bias, 32 a high risk of bias and 20 a low risk. Five cohort studies were rated as having high risk of bias; the sixth was at very high risk of bias. Ten cross-sectional studies were rated as high risk and the remaining five were at very high risk.

There were possible risks of bias identified across the studies; details of the key strengths and weaknesses of each study are shown in supplementary Tables 4–6. Examples of possible sources of bias observed in some studies include (but are not limited to) the following: small sample size; inadequate control for confounding variables (e.g. medication, age, severe psychiatric comorbidity); lack of control group(s); not explicitly stating that gold-standard diagnostic measures were used or not stipulating that diagnosis was made by a psychiatrist or neurologist; non-consecutive recruitment of FND participants.

Comorbid dissociative disorders in FND samples

Table 2 presents the results of studies that reported on comorbid dissociative disorders in FND samples. The prevalence of comorbid dissociative disorders varied considerably across studies, with rates ranging from 8% to 80%. The highest proportion of individuals with a comorbid dissociative disorder was 80% in a sample of 10 participants with FND-seizures;Reference Litwin and Cardeña41 the lowest was 8% in a group of 13 participants with FND-seizures.Reference Marchetti, Kurcgant, Neto, Von Bismark and Fiore42 The most common comorbid dissociative disorder identified was dissociative disorder not otherwise specified (DDNOS); the least common was dissociative fugue. Diagnoses of dissociative amnesia, DPDR and DID were also reported in a proportion of participants in several studies.

Table 2 Subset of studies reporting on rates of comorbid dissociative disorders in samples with functional neurological disorder (FND)

DDIS, Dissociative Disorders Interview Schedule; DDNOS, dissociative disorder not otherwise specified; DID, dissociative identity disorder; DPDR, depersonalisation/derealisation disorder; SCID-D, Structured Clinical Interview for DSM Dissociative Disorders.

Dissociative symptom scale scores in FND

Table 3 details the reported scores for the subset of studies that used validated dissociative symptom scales and presented measures of central tendency. A small subset of studies (k = 5) did not present measures of central tendency and are detailed only in supplementary Table 3.

Table 3 Dissociative symptom scale scores in samples with functional neurological disorder (FND)

CADSS, Clinician-Administered Dissociative States Scale; CADSS-DA, CADSS Dissociative Amnesia; CADSS-DP, CADSS Depersonalisation; CADSS-DR, CADSS Derealisation; CPP, chronic pelvic pain; CADSS-DSS, CADSS Dissociative State Subscale; CDS, Cambridge Depersonalisation Scale; CRPS, Complex Regional Pain Syndrome; DES, Dissociative Experiences Scale; DIS-Q, Dissociation Questionnaire; DIS-Q-1, Identity confusion and depersonalisation; DIS-Q-2, DIS-Q Self-control; DIS-Q-3, DIS-Q Amnesia and dissociation; DIS-Q-4, DIS-Q absorption; FDS, Fragebogen zu Dissoziativen Symptomen; MDD, major depressive disorder; MDI, Multiscale Dissociation Index; MDI-DIS, MDI Disengagement; MDI-DP, MDI Depersonalisation; MDI-DR, MDI Derealisation; MDI-EN, MDI Emotional numbing; MDI-ID, MDI Identity dissociation; MDI-ME, MDI Memory disturbance; MixP, mixed psychiatric disorders; PAS, Perceptual Alteration Scale; PMD, psychogenic movement disorder; PTSD, post-traumatic stress disorder; SomD, somatisation disorder; SDQ-20, Somatoform Dissociation Questionnaire; TSI, Trauma Scale Index; WDS, Wessex Dissociation Scale;

a. Scores in bold show the median and interquartile range. All data are rounded to one decimal point where possible.

b. Data obtained directly from the author.

Dissociative Experiences ScaleReference Bernstein22

Thirty-nine studies presented DES scores; the mean DES score ranged from 4.71, in a sample of 17 individuals expressing multiple unspecified FND symptoms, to 86.6, in a sample of 17 with FND-seizures.Reference Tezcan, Atmaca, Kuloglu, Gecici, Buyukbayram and Tutkun48,Reference Mousa, Latchford, Weighall, Nash, Murray-Leslie and Reuber82 FND-motor and FND-sensory samples endorsed lower DES scores in several studies.Reference Tezcan, Atmaca, Kuloglu, Gecici, Buyukbayram and Tutkun48,Reference Demartini, Goeta, Romito, Anselmetti, Bertelli and D'Agostino57,Reference Ekanayake, Kranick, LaFaver, Naz, Frank Webb and LaFrance58,Reference Guz, Doganay, Ozkan, Colak, Tomac and Sarisoy66,Reference Kranick, Ekanayake, Martinez, Ameli, Hallett and Voon77,Reference Spitzer, Spelsberg, Grabe, Mundt and Freyberger97 Participants without a comorbid dissociative disorder also reported lower DES scores.Reference Yayla, Bakım, Tankaya, Ozer, Karamustafalioglu and Ertekin14,Reference Tezcan, Atmaca, Kuloglu, Gecici, Buyukbayram and Tutkun48 Conversely, participants with FND-seizures, mixed symptoms or comorbid dissociative disorders appeared to present with higher DES scores relative to the other FND subtypes.Reference Yayla, Bakım, Tankaya, Ozer, Karamustafalioglu and Ertekin14,Reference Tezcan, Atmaca, Kuloglu, Gecici, Buyukbayram and Tutkun48,Reference Akyuz, Kugu, Akyuz and Dogan49,Reference Goldstein and Mellers64,Reference Guz, Doganay, Ozkan, Colak, Tomac and Sarisoy66,Reference Martino, Bruni, Labate, Vasta, Cerasa and Borzì80,Reference Mousa, Latchford, Weighall, Nash, Murray-Leslie and Reuber82,Reference Proença, Castro, Jorge and Marchetti91,Reference Spinhoven, Roelofs, Moene, Kuyk, Nijenhuis and Hoogduin96 Although some of the highest scores on the DES were seen in FND-seizures samples (e.g.Reference Mousa, Latchford, Weighall, Nash, Murray-Leslie and Reuber82), this was not a wholly consistent pattern as DES scores were low for this symptom type in some studies.Reference Alper, Devinsky, Perrine, Luciano, Vazquez and Pacia50,Reference Jungilligens, Ospina, Williams, Mello, MacLean and Ranford74,Reference Spitzer, Spelsberg, Grabe, Mundt and Freyberger97

Scores of 30 or more suggest severe pathological psychoform dissociation; this score is typically seen in dissociative disorders.Reference Carlson, Putnam, Ross, Torem, Coons and Dill107 Mean or median scores exceeded 30 in six separate samples: four with the FND-seizures subtype; two with a comorbid dissociative disorder; one with recorded prior suicide attempts; one with a history of sexual abuse; and one with multiple symptom types.Reference Tezcan, Atmaca, Kuloglu, Gecici, Buyukbayram and Tutkun48,Reference Espirito-Santo and Pio-Abreu60,Reference Güleç, Ýnanç, Yanartaþ, Üzer and Güleç68,Reference Martino, Bruni, Labate, Vasta, Cerasa and Borzì80,Reference Mousa, Latchford, Weighall, Nash, Murray-Leslie and Reuber82,Reference Proença, Castro, Jorge and Marchetti91 A statistically significant elevation in DES scores was reported in FND samples relative to controls in 18 comparisons, with control groups including both clinical and non-clinical participants.Reference Akyuz, Kugu, Akyuz and Dogan49,Reference Del Río-Casanova, González-Vázquez, Justo, Andrade, Páramo and Brenlla55Reference Demartini, Goeta, Romito, Anselmetti, Bertelli and D'Agostino57,Reference Goldstein, Drew, Mellers, Mitchell-O'Malley and Oakley63,Reference Goldstein and Mellers64,Reference Güleç, Ýnanç, Yanartaþ, Üzer and Güleç68Reference Herrero, Tarrada, Haffen, Mignot, Sense and Schwan70,Reference O'Brien, Fortune, Dicker, O'Hanlon, Cassidy and Delanty87,Reference Proença, Castro, Jorge and Marchetti91,Reference Reuber, House, Pukrop, Bauer and Elger93,Reference Reuber, Pukrop, Mitchell, Bauer and Elger94

Dissociation QuestionnaireReference Vanderlinden, Van Dyck, Vandereycken, Vertommen and Verkes30

Eight studies measured dissociation using the Dissociation Questionnaire (DIS-Q).Reference Moene, Spinhoven, Hoogduin, Sandyck and Roelofs45,Reference Bodde, Janssen, Theuns, Vanhoutvin, Boon and Aldenkamp51,Reference Kuyk, Siffels, Bakvis and Swinkels78,Reference Ozcetin, Belli, Ertem, Bahcebasi, Ataoglu and Canan85,Reference Roelofs, Keijsers, Hoogduin, Näring and Moene95,Reference Spinhoven, Roelofs, Moene, Kuyk, Nijenhuis and Hoogduin96,Reference van der Hoeven, Broersma, Pijnenborg, Koops, van Laar and Stone101,Reference van der Kruijs, Jagannathan, Bodde, Besseling, Lazeron and Vonck102 Five articles reported one or more control group scores, with seven control groups in total; the majority (four) were healthy control groups.Reference Moene, Spinhoven, Hoogduin, Sandyck and Roelofs45,Reference Ozcetin, Belli, Ertem, Bahcebasi, Ataoglu and Canan85,Reference van der Hoeven, Broersma, Pijnenborg, Koops, van Laar and Stone101,Reference van der Kruijs, Jagannathan, Bodde, Besseling, Lazeron and Vonck102 DIS-Q scores were significantly greater in FND samples versus controls in four comparisons.Reference Ozcetin, Belli, Ertem, Bahcebasi, Ataoglu and Canan85,Reference van der Hoeven, Broersma, Pijnenborg, Koops, van Laar and Stone101,Reference van der Kruijs, Jagannathan, Bodde, Besseling, Lazeron and Vonck102 However, DIS-Q scores varied without any clear trends across FND subtypes; in some cases, FND group DIS-Q scores were equal to or lower than control group scores.Reference Moene, Spinhoven, Hoogduin, Sandyck and Roelofs45,Reference Roelofs, Keijsers, Hoogduin, Näring and Moene95

Trauma Symptom InventoryReference Briere108

Two studies, both with participants with FND-seizures, used the Trauma Symptom Inventory (TSI); this includes a dissociation subscale.Reference Boesten, Myers and Wijnen52,Reference Myers, Trobliger, Bortnik, Zeng, Saal and Lancman83 Boesten and colleaguesReference Boesten, Myers and Wijnen52 observed significantly higher TSI dissociation scores in their cohort of patients with previous trauma compared with the non-traumatised cohort (P = 0.03), whereas Myers et alReference Myers, Trobliger, Bortnik, Zeng, Saal and Lancman83 did not observe an appreciable difference in TSI dissociation scores when comparing people with epilepsy with people with FND-seizures (P = 0.97).

Cambridge Depersonalisation ScaleReference Sierra and Berrios109

Demartini and colleagues presented data for the Cambridge Depersonalisation Scale (CDS) in 20 individuals with FND-motor symptoms and 20 with FND-seizures.Reference Demartini, Goeta, Barbieri, Ricciardi, Canevini and Turner56 Depersonalisation as measured by this scale was significantly higher in the FND-seizures than the FND-motor group.

Clinician-Administered Dissociative States ScaleReference Bremner, Krystal, Putnam, Southwick, Marmar and Charney29

Four studies presented state dissociation scores using the Clinician-Administered Dissociative States Scale (CADSS).Reference Akyuz, Kugu, Akyuz and Dogan49,Reference Nisticò, Caputo, Tedesco, Marzorati, Ferrucci and Priori84,Reference Pick, Rojas-Aguiluz, Butler, Mulrenan, Nicholson and Goldstein89,Reference Stins, Kempe, Hagenaars, Beek and Roelofs100 Most scoring systems measure trait dissociation, whereas the CADSS measures state dissociation.Reference Bremner, Krystal, Putnam, Southwick, Marmar and Charney29 Total CADSS scores were significantly higher in the FND group relative to controls in three studies.Reference Nisticò, Caputo, Tedesco, Marzorati, Ferrucci and Priori84,Reference Pick, Rojas-Aguiluz, Butler, Mulrenan, Nicholson and Goldstein89,Reference Stins, Kempe, Hagenaars, Beek and Roelofs100 In one study the FND group CADSS score increased following a laboratory-based dissociation induction procedure.Reference Pick, Rojas-Aguiluz, Butler, Mulrenan, Nicholson and Goldstein89 In one study, total CADSS score was higher in the epilepsy than in the FND-seizures group.Reference Akyuz, Kugu, Akyuz and Dogan49

Multiscale Dissociation InventoryReference Brière28

Two studies used the Multiscale Dissociation Inventory (MDI).Reference Koreki, Garfkinel, Mula, Agrawal, Cope and Eilon76,Reference Pick, Mellers and Goldstein90 The MDI has six subscales measuring dissociation (depersonalisation, derealisation, amnesia, identity alterations, disengagement and emotional constriction).Reference Brière28 Pick et alReference Pick, Mellers and Goldstein90 included all subscales whereas Koreki and colleaguesReference Koreki, Garfkinel, Mula, Agrawal, Cope and Eilon76 reported data for the depersonalisation subscale. Both studies investigated FND-seizures samples compared with healthy control groups; MDI scores for FND-seizures participants were significantly higher than for control groups in both studies. Pick et al reported statistically significant elevations in dissociation scores for all subscales. After controlling statistically for anxiety and depression, elevations remained significant for four subscales (disengagement, depersonalisation, derealisation and memory disturbance).Reference Pick, Mellers and Goldstein90

Perceptual Alteration ScaleReference Sanders110

Some studies did not report significantly elevated dissociation in FND samples. Goldstein et al measured dissociative tendencies using the Perceptual Alteration Scale (PAS) in 20 FND-seizures participants.Reference Goldstein, Drew, Mellers, Mitchell-O'Malley and Oakley63 Although the FND-seizures group had higher PAS scores than healthy controls, this difference was not statistically significant.

Wessex Dissociation ScaleReference Kennedy, Clarke, Stopa, Bell, Rouse and Ainsworth111

One study used the Wessex Dissociation Scale (WDS) in samples with pure FND-seizures, pure epilepsy, comorbid FND-seizures and epilepsy, ‘other non-epileptic events’ and unclear diagnoses.Reference Holper, Foster, Lloyd, Rayner, Rychkova and Ali71 The pure FND-seizures group endorsed lower WDS scores than the other groups.

Fragebogen zu Dissoziativen SymptomenReference Freyberger, Spitzer, Stieglitz, Kuhn, Magdeburg and Bernstein-Carlson112

Two studies used the German-version of the DES, the Fragebogen zu Dissoziativen Symptomen (FDS).Reference Irorutola, Gerhardt, Hamouda, Rose, Hinkelmann and Senf-Beckenbach72,Reference Walther, Volbers, Erdmann, Dogan Onugoren, Gollwitzer and Kasper103 The FDS has included 16 new domains that are mainly FND symptoms and is thus not a pure psychoform measure. Walther and colleagues reported a significantly higher FDS score in FND-seizures participants with ongoing symptoms relative to those whose symptoms had abated.Reference Walther, Volbers, Erdmann, Dogan Onugoren, Gollwitzer and Kasper103 Irorutola et al observed a statistically significant elevation in FDS scores in FND-seizures participants relative to healthy controls.Reference Irorutola, Gerhardt, Hamouda, Rose, Hinkelmann and Senf-Beckenbach72

Somatoform Dissociation QuestionnaireReference Nijenhuis, Spinhoven, Van Dyck, Van der Hart and Vanderlinden20

Twenty-four studies presented SDQ-20 scores (Table 3). A score of 35 or higher on the SDQ-20 is associated with dissociative disorders and suggests severe somatoform dissociation.Reference Nijenhuis113 Thirteen samples of FND participants had SDQ-20 scores ≥35.Reference Brown, Bouska, Frow, Kirkby, Baker and Kemp53,Reference Del Río-Casanova, González-Vázquez, Justo, Andrade, Páramo and Brenlla55,Reference Espirito-Santo and Pio-Abreu59,Reference Espirito-Santo and Pio-Abreu60,Reference González-Vázquez, Del Río-Casanova, Seijo-Ameneiros, Cabaleiro-Fernández, Seoane-Pillado and Justo-Alonso65,Reference Kienle, Rockstroh, Bohus, Fiess, Huffziger and Steffen-Klatt75,Reference Koreki, Garfkinel, Mula, Agrawal, Cope and Eilon76,Reference Martino, Bruni, Labate, Vasta, Cerasa and Borzì80,Reference Ozdemir, Gur, Cokluk, Isik and Tapan86 The highest scores were seen in an FND-motor sample, an FND-mixed sample, an FND-seizures sample (in which individuals who also reported previous sexual abuse scored far higher) and a sample of individuals with unspecified FND symptoms.Reference Espirito-Santo and Pio-Abreu59,Reference Martino, Bruni, Labate, Vasta, Cerasa and Borzì80,Reference Ozdemir, Gur, Cokluk, Isik and Tapan86 Relative to other FND samples, several FND-seizures samples endorsed lower SDQ-20 scores; nevertheless, they still scored higher than the control groups in these studies.Reference Demartini, Goeta, Barbieri, Ricciardi, Canevini and Turner56,Reference Martino79,Reference van der Kruijs, Jagannathan, Bodde, Besseling, Lazeron and Vonck102,Reference Xue, Wang, Xiong, Tian, Wang and Xu106 However, this was not consistent, as four FND-seizures groups had scores above 35.Reference Brown, Bouska, Frow, Kirkby, Baker and Kemp53,Reference Gerhardt, Hamouda, Irorutola, Rose, Hinkelmann and Buchheim62,Reference Koreki, Garfkinel, Mula, Agrawal, Cope and Eilon76,Reference Martino, Bruni, Labate, Vasta, Cerasa and Borzì80

Twenty-two studies included control groups; some studies had multiple control groups, amounting to a total of thirty different control groups.Reference Brown, Bouska, Frow, Kirkby, Baker and Kemp53,Reference Del Río-Casanova, González-Vázquez, Justo, Andrade, Páramo and Brenlla55,Reference Demartini, Goeta, Barbieri, Ricciardi, Canevini and Turner56,Reference Espirito-Santo and Pio-Abreu59,Reference Espirito-Santo and Pio-Abreu60,Reference Gerhardt, Hamouda, Irorutola, Rose, Hinkelmann and Buchheim62,Reference González-Vázquez, Del Río-Casanova, Seijo-Ameneiros, Cabaleiro-Fernández, Seoane-Pillado and Justo-Alonso65,Reference Jungilligens, Ospina, Williams, Mello, MacLean and Ranford74Reference Koreki, Garfkinel, Mula, Agrawal, Cope and Eilon76,Reference Martino79,Reference Ozdemir, Gur, Cokluk, Isik and Tapan86,Reference Perez, Matin, Williams, Tanev, Makris and LaFrance88,Reference Pick, Mellers and Goldstein90,Reference Reedijk, van Rijn, Roelofs, Tuijl, Marinus and van Hilten92,Reference Roelofs, Keijsers, Hoogduin, Näring and Moene95,Reference Spinhoven, Roelofs, Moene, Kuyk, Nijenhuis and Hoogduin96,Reference Steffen, Fiess, Schmidt and Rockstroh98,Reference Steffen-Klatt, Fiess, Beckha, Schmidt and Rockstroh99,Reference van der Hoeven, Broersma, Pijnenborg, Koops, van Laar and Stone101,Reference van der Kruijs, Jagannathan, Bodde, Besseling, Lazeron and Vonck102,Reference Xue, Wang, Xiong, Tian, Wang and Xu106 Of these, five studies controlled for anxiety, depression or other psychopathology.Reference Koreki, Garfkinel, Mula, Agrawal, Cope and Eilon76,Reference Perez, Matin, Williams, Tanev, Makris and LaFrance88,Reference Pick, Mellers and Goldstein90,Reference Spinhoven, Roelofs, Moene, Kuyk, Nijenhuis and Hoogduin96,Reference van der Hoeven, Broersma, Pijnenborg, Koops, van Laar and Stone101 In eighteen studies, SDQ-20 scores were statistically higher for FND participants relative to control groups.Reference Brown, Bouska, Frow, Kirkby, Baker and Kemp53,Reference Del Río-Casanova, González-Vázquez, Justo, Andrade, Páramo and Brenlla55,Reference Espirito-Santo and Pio-Abreu59,Reference Espirito-Santo and Pio-Abreu60,Reference González-Vázquez, Del Río-Casanova, Seijo-Ameneiros, Cabaleiro-Fernández, Seoane-Pillado and Justo-Alonso65,Reference Jungilligens, Ospina, Williams, Mello, MacLean and Ranford74Reference Koreki, Garfkinel, Mula, Agrawal, Cope and Eilon76,Reference Martino79,Reference Ozdemir, Gur, Cokluk, Isik and Tapan86,Reference Perez, Matin, Williams, Tanev, Makris and LaFrance88,Reference Pick, Mellers and Goldstein90,Reference Roelofs, Keijsers, Hoogduin, Näring and Moene95,Reference Steffen, Fiess, Schmidt and Rockstroh98,Reference Steffen-Klatt, Fiess, Beckha, Schmidt and Rockstroh99,Reference van der Hoeven, Broersma, Pijnenborg, Koops, van Laar and Stone101,Reference van der Kruijs, Jagannathan, Bodde, Besseling, Lazeron and Vonck102,Reference Xue, Wang, Xiong, Tian, Wang and Xu106 Conversely, SDQ-20 scores in FND groups were similar to or lower than scores in some control group comparisons, including PTSD, complex regional pain syndrome, dissociative disorders, chronic pelvic pain and one healthy control group.Reference Demartini, Goeta, Barbieri, Ricciardi, Canevini and Turner56,Reference Espirito-Santo and Pio-Abreu59,Reference Espirito-Santo and Pio-Abreu60,Reference Kienle, Rockstroh, Bohus, Fiess, Huffziger and Steffen-Klatt75,Reference Reedijk, van Rijn, Roelofs, Tuijl, Marinus and van Hilten92,Reference Spinhoven, Roelofs, Moene, Kuyk, Nijenhuis and Hoogduin96

Clinical characteristics relative to dissociation

Several studies examined the relationship between dissociation and severity of clinical outcome in FND-seizures samples. Statistically significant positive associations between dissociation scores and frequency of seizures were reported in five studies using various measures of dissociation.Reference Bodde, Janssen, Theuns, Vanhoutvin, Boon and Aldenkamp51,Reference Kuyk, Siffels, Bakvis and Swinkels78,Reference Martino, Bruni, Labate, Vasta, Cerasa and Borzì80,Reference O'Brien, Fortune, Dicker, O'Hanlon, Cassidy and Delanty87,Reference Walther, Volbers, Erdmann, Dogan Onugoren, Gollwitzer and Kasper103 Two studies reported significant associations between dissociation scores and severity of ictal symptoms.Reference Pick, Mellers and Goldstein90,Reference Reuber, House, Pukrop, Bauer and Elger93 Pick and colleagues observed that MDI depersonalisation and derealisation were positively associated with ictal mental state symptoms, whereas MDI identity dissociation was correlated with cognitive ictal symptoms; all of these associations were significant.Reference Pick, Mellers and Goldstein90 Reuber and colleagues observed a weak but significant association between DES score and severity of ictal symptoms; this association was no longer significant after incorporating other psychopathological scores into the analysis.Reference Reuber, House, Pukrop, Bauer and Elger93

Two studies measured emotion dysregulation in FND participants using the Difficulties in Emotion Regulation ScaleReference Gratz and Roemer114 (DERS).Reference Brown, Bouska, Frow, Kirkby, Baker and Kemp53,Reference Del Río-Casanova, González-Vázquez, Justo, Andrade, Páramo and Brenlla55 Emotion dysregulation was positively correlated with psychoform and somatoform dissociation in an unspecified FND sample.Reference Del Río-Casanova, González-Vázquez, Justo, Andrade, Páramo and Brenlla55 More severe alexithymia and emotion dysregulation was reported in a subset of FND-seizures participants who scored higher on the SDQ-20 than the less emotionally dysregulated subgroup.Reference Brown, Bouska, Frow, Kirkby, Baker and Kemp53 Elsewhere, greater alexithymia severity was seen to vary with higher DES and SDQ-20 scores in a mixed FND sample.Reference Kienle, Rockstroh, Bohus, Fiess, Huffziger and Steffen-Klatt75 Quality of life of people with FND-seizures was significantly associated with dissociative symptoms in two studies.Reference Mitchell, Ali and Cavanna81,Reference Gagny, Grenevald, El-Hage, Chrusciel, Sanchez and Schwan115 Both measured quality of life using the 31-item Quality of Life in Epilepsy Inventory (QOLIE-31).Reference Devinsky, Vickrey, Cramer, Perrine, Hermann and Meador116 Individuals with higher degrees of dissociation measured by the DES had worse QOLIE-31 scores than those with lower DES scores. Two studies reported an association between history of sexual abuse, severity of clinical presentation and dissociation scores.Reference Martino, Bruni, Labate, Vasta, Cerasa and Borzì80,Reference Pick, Mellers and Goldstein90

One study found a significant association between psychological dissociation and psychopathology (general psychopathology, personality disorders) in an FND-motor group.Reference van der Hoeven, Broersma, Pijnenborg, Koops, van Laar and Stone101 DES scores were significantly higher in a sample with multiple FND symptoms who had attempted suicide than in a group who had not.Reference Güleç, Ýnanç, Yanartaþ, Üzer and Güleç68 Significant positive associations between severity of dissociation and various psychological features were reported in several samples of FND subtypes, including measures of alexithymia, emotion dysregulation, fearful attachment style and post-traumatic avoidance symptoms.Reference Del Río-Casanova, González-Vázquez, Justo, Andrade, Páramo and Brenlla55,Reference Kienle, Rockstroh, Bohus, Fiess, Huffziger and Steffen-Klatt75,Reference Pick, Mellers and Goldstein90,Reference Williams, Ospina, Jalilianhasanpour, Fricchione and Perez104,Reference Kienle, Rockstroh, Fiess, Schmidt, Popov and Steffen-Klatt117 Other associations included significant positive correlations between dissociation and number of FND symptoms, early onset of FND, in-patient treatment and rates of comorbid psychiatric illnesses.Reference Yayla, Bakım, Tankaya, Ozer, Karamustafalioglu and Ertekin14,Reference Moene, Spinhoven, Hoogduin, Sandyck and Roelofs45,Reference Spinhoven, Roelofs, Moene, Kuyk, Nijenhuis and Hoogduin96

Biological associations of dissociation in FND

The subset of studies that used objective means to study biological associations are described in Table 4.

Table 4 Studies reporting biological correlates of dissociation in functional neurological disorder (FND)

EEG, electroencephalography; fMRI, functional magnetic resonance imaging; MRI, magnetic resonance imaging; SCL, skin conductance levels; SCR, skin conductance response.

Structural neuroimaging

Perez and colleagues investigated cortical thickness in people with FND by use of T1-weighted structural magnetic resonance imaging to compare participants with FND-motor symptoms and healthy controls.Reference Perez, Matin, Williams, Tanev, Makris and LaFrance88 FND participants with higher SDQ-20 scores (score ≥35; n = 10) had significantly reduced cortical thickness in the left caudal (dorsal) anterior cingulate cortex (ACC) relative to controls; this association was not present in the complete FND cohort. Conversely, higher DES depersonalisation/derealisation subscores correlated with increased right lateral occipital cortical thickness in participants with FND.

Functional neuroimaging

Van der Kruijs and colleagues used functional magnetic resonance imaging (fMRI) in two studies to investigate alterations in functional connectivity in people with FND-seizures.Reference van der Kruijs, Jagannathan, Bodde, Besseling, Lazeron and Vonck102,Reference van der Kruijs, Bodde, Vaessen, Lazeron, Vonck and Boon118 In the first study,Reference van der Kruijs, Bodde, Vaessen, Lazeron, Vonck and Boon118 participants with FND-seizures were compared with healthy controls during four separate fMRI phases, comprising pre- and post-resting states and two cognitive tasks. No significant differences were seen between the FND-seizures group and healthy controls during tasks. However, significant correlations were observed between functional connectivity values and DES, DIS-Q and SDQ-20 scores. Of note, in the FND-seizures cohort functional connectivity was significantly higher within the ACC and inferior frontal gyrus, which also correlated significantly with DES scores.

In a subsequent study, participants with FND-seizures and healthy controls underwent resting-state fMRI.Reference van der Kruijs, Jagannathan, Bodde, Besseling, Lazeron and Vonck102 Relative to controls, those with FND-seizures were observed to have increased co-activation of resting-state networks in frontoparietal (e.g. orbitofrontal cortex), executive (cingulate and insular cortex), sensorimotor (e.g. cingulate gyrus; supplemental motor cortex) and default mode (precuneus, para-cingulate gyri) networks. There was a significant positive correlation between increased functional connectivity in these regions of interest in the FND-seizures group and all dissociation scores (DES, DIS-Q and SDQ-20).

Electroencephalography

Two studies employed electroencephalography (EEG) to investigate brain connectivity in FND participants.Reference Xue, Wang, Xiong, Tian, Wang and Xu106,Reference Kienle, Rockstroh, Fiess, Schmidt, Popov and Steffen-Klatt117 Xue and colleagues performed EEG with 15 participants with FND-seizures and 15 matched controls; all participants additionally completed the SDQ-20.Reference Xue, Wang, Xiong, Tian, Wang and Xu106 The FND-seizures group had less linkage between frontal and posterior brain areas relative to controls; no significant associations between clustering coefficients and SDQ-20 scores were found.

Kienle et al investigated possible cortical indices of emotion regulation in a mixed FND sample and matched controls during an emotion regulation task.Reference Kienle, Rockstroh, Fiess, Schmidt, Popov and Steffen-Klatt117 Participants performed one of three emotionally arousing tasks during EEG recording and completed the SDQ-20. This protocol was repeated after a 4 week treatment period of physiotherapy and psychological therapy. Both groups had similar cortical regions of interest in response to unpleasant or neutral stimuli, as well as similar EEG representation during the emotion regulation task (referred to as the ‘regulation effect’). No significant change in these findings was observed after the treatment period; however, a significant association between the regulation effect and SDQ-20 score was seen in the FND group.

Skin conductance

Skin conductance is used as a metric of autonomic response to stimuli, employed by two of our included studies.Reference Herrero, Tarrada, Haffen, Mignot, Sense and Schwan70,Reference Pick, Rojas-Aguiluz, Butler, Mulrenan, Nicholson and Goldstein89 Skin conductance levels (SCL) represent baseline or tonic level of conductance of skin, whereas skin conductance response (SCR) represents a phasic change of skin conductance in response to a stimulus.Reference Boucsein119 Pick and colleagues measured SCL in 17 participants with mixed FND symptoms and matched controls throughout a mirror-gazing dissociation induction protocol.Reference Pick, Rojas-Aguiluz, Butler, Mulrenan, Nicholson and Goldstein89 The FND group had greater average SCL than the controls at all measured points of the protocol; however, this group effect was not significant. No significant associations between dissociation (CADSS score) and SCL were noted.

Herrero et al studied physiological, cognitive and behavioural emotional response to image stimuli in 34 female FND-seizures participants and 34 matched controls.Reference Herrero, Tarrada, Haffen, Mignot, Sense and Schwan70 The DES was used to measure dissociative tendencies. SCR amplitude was significantly lower in the FND-seizures group than in controls in response to all images (P = 0.04); however, in response to negative images only there was no significant group difference. A significant negative correlation between DES score and SCR amplitude was observed in the FND-seizures group. A non-significant trend of increased SCR amplitude in response to strong-arousal negative images compared with low-arousal negative images was observed in the FND-seizures group but not in the control group.

Sleep actigraphy

Mousa and colleagues investigated objective and subjective sleep complaints in a sample of 17 participants with FND-seizures and 20 age- and gender-matched healthy controls; the DES measured dissociative tendencies.Reference Mousa, Latchford, Weighall, Nash, Murray-Leslie and Reuber82 Participants followed a daily protocol of actigraphy and recording of state dissociative symptoms (using the State Scale of DissociationReference Krüger and Mace120), mood, number of FND-seizures and subjective sleep quality. The FND-seizures group reported more disturbed sleep overall than the control group; however, the only significantly worse parameter was sleep quality. Objectively, participants with FND-seizures had significantly worse sleep with respect to efficiency, awakenings and wakefulness after sleep. DES scores were significantly higher in the FND-seizures group relative to the control group. A multivariate linear mixed model did not find any association between sleep parameters (sleep time and number of awakenings) and state dissociation the following day.

Postural control

Stins and colleagues investigated postural control in a sample of participants with FND and matched controls.Reference Stins, Kempe, Hagenaars, Beek and Roelofs100 Participants were asked to stand on a stabilometric platform under various conditions (eyes open, eyes closed and while performing a mental arithmetic task with their eyes open). Physicians administered the CADSS to assess state dissociation. The degree to which participants swayed on the platform under the different conditions was recorded. A greater radius of swaying was noted in the FND group relative to controls; this was more pronounced during the eyes-closed procedure. Distraction using the arithmetic task improved postural stability in the FND group. A significant correlation between dissociative symptoms and postural instability was observed, with higher dissociative scores associated with postural instability during the eyes-closed procedure. However, this was a total sample observation (participants with FND and controls), and this correlation became insignificant when examined in the two groups separately.

Meta-analysis of dissociative symptom scale scores

Somatoform dissociation: FND versus healthy controls

Figure 2 displays results obtained from a meta-analysis comparing SDQ-20 scores of samples with FND and healthy controls (k = 9, n = 659). A higher score indicates a greater level of somatoform dissociation. The variance between groups was substantial (I 2 = 85.5%), indicating a substantial degree of heterogeneity between the studies. A funnel plot of data available for this meta-analysis is presented in supplementary Fig. 1. It shows asymmetry, which could indicate publication bias. However, this plot also includes a study (Demartini et alReference Demartini, Goeta, Barbieri, Ricciardi, Canevini and Turner56) identified in sensitivity analyses as a potential outlier. When this study was removed, the prediction interval shifted to above zero (0.47–3.31, g = 1.80, 95% CI 1.25–2.34, I 2 = 75%), although heterogeneity between studies was only reduced to 75%. Supplementary Figs 2 and 3 shows the forest and funnel plots when Demartini et al is removed. In the original meta-analysis, all studies were case–control, five were at high risk of bias and four were at low risk of bias (Demartini et al gave data for participants with motor symptoms and seizures). A meta-regression showed that the studies’ risk of bias category is not a significant effect size predictor (P = 0.50). All studies included in all meta-analyses were case–control studies because of our data inclusion principles outlined in the Methods section above.

Fig. 2 Somatoform dissociation scores in samples with functional neurological disorder (FND) compared with healthy controls. SDQ, Somatoform Dissociation Questionnaire; Low, low risk of bias; High, high risk of bias.

Psychoform dissociation: all samples with FND versus healthy, neurological and psychiatric controls

Figure 3 presents results of the mixed-effects model meta-analysis investigating dissociative symptom scale scores (combined psychoform dissociation measure) in all samples with FND (FND-seizures, FND-motor, FND-sensory, mixed) compared with healthy, psychiatric or neurological controls (k = 36, n = 3031). Overall, the test between control subgroups was not significant (Q(2) = 5.77, P = 0.056). The FND groups showed a significant effect towards increasing psychoform dissociation compared with healthy controls (g = 0.90, 95% CI 0.66–1.14, I 2 = 70%) and neurological controls (g = 0.56, 95% CI 0.19–0.92, I 2 = 67%). Psychiatric controls also showed an effect towards lower dissociation scores compared with the FND groups but heterogeneity was very high (g = 0.35, 95% CI 0.24–0.95, I2 = 90%), suggesting that, across studies, the psychiatric samples were too dissimilar for interpretation at this stage. A funnel plot of data available for this meta-analysis is given in supplementary Fig. 4. It shows some smaller studies with large effect sizes, which might indicate some publication bias. All studies in this analysis were case–control, 21 data comparisons were from studies with high risk of bias, and the final 15 were from studies with low risk of bias. A meta-regression showed no significant effect of the studies’ risk of bias category (P = 0.97).

Fig. 3 Psychoform dissociation scores in samples with functional neurological disorder (FND) compared with healthy (HC), psychiatric (PSYCH) and neurological (NEURO) controls. Low, low risk of bias; High, high risk of bias.

Psychoform dissociation: FND subgroups (FND-seizures, FND-motor) versus healthy controls

Figure 4 presents data from the mixed-effects model meta-analysis for the subgroups FND-seizures and FND-motor (k = 14, n = 799). Four valid data comparisons were available for healthy controls and FND-motor samples and ten for FND-seizures. The FND-seizures group showed a significant effect of increasing psychoform dissociation compared with the FND-motor group (Q(1) = 5.44, P = 0.020). As there were only four data points available for the FND-motor group, compared with ten for FND-seizures group, we checked results assuming common heterogeneity (τ 2 = 0.071) and the effect remained significant (P = 0.020).

Fig. 4 Psychoform dissociation scores in samples with seizure symptoms and motor symptoms of functional neurological disorder (FND) compared with healthy controls. Low, low risk of bias; High, high risk of bias.

The effect of FND-seizures on increasing psychoform dissociation was significant compared with healthy controls, with a large effect size (g = 0.94, 95% CI 0.65–1.22). There was also an effect towards greater dissociation scores in the FND-motor group compared with healthy controls; however, this was a smaller effect compared with that for FND-seizures (g = 0.40, 95% CI −0.18 to 1.00). Estimates of between-study heterogeneity ranged from 53.7% for FND-motor to 42% for FND-seizures and was 58.3% overall; therefore, we can be confident that each group represents the target population. A funnel plot of data available for this meta-analysis is given in supplementary Fig. 5. As above, it shows a study with a large effect size, despite large standard error.Reference Mousa, Latchford, Weighall, Nash, Murray-Leslie and Reuber82 All studies included were case–control. Data comparisons were available from six studies at high risk of bias and eight at low risk of bias. A meta-regression showed no significant effect of the studies’ risk of bias category (P = 0.81).

Discussion

This review presents evidence that dissociation is an important feature of FND. In relation to the three aims of this study, our principal findings are as follows. First, that FND frequently involves comorbid dissociative disorders. Second, psychoform and somatoform dissociative symptoms are commonly present in FND and appear to vary with FND presentation. Third, we found several potential biological and clinical associations of dissociation in FND that merit further exploration.

Dissociative disorders are common comorbidities in FND

Fewer studies than expected commented on comorbid dissociative disorders in FND samples. In the nine studies that did, the proportion of participants with FND found to have comorbid dissociative disorder ranged considerably, from 8% to 80%.Reference Yayla, Bakım, Tankaya, Ozer, Karamustafalioglu and Ertekin14,Reference Litwin and Cardeña41Reference Tezcan, Atmaca, Kuloglu, Gecici, Buyukbayram and Tutkun48 The most common dissociative disorder diagnosed was dissociative disorder not otherwise specified (DDNOS) – a subtype previously highlighted as being the most prevalent in epidemiological studies.Reference Şar, Akyüz and Doğan121,Reference Spitzer, Liss, Dudeck, Orlob, Gillner and Hamm122 When compared with prevalence rates reported for the general population, dissociative disorder rates are higher in FND groups. A review of dissociative disorder prevalence rates in community and clinical samples suggested an overall lifetime prevalence of 10%.Reference Sar123 Similarly, a recent meta-analysis of college student populations (n = 31 905) reported an overall prevalence of 11%.Reference Kate, Hopwood and Jamieson124 Prevalence of dissociative disorder might be higher in clinical populations; for example, Foote and colleagues observed an overall prevalence of 29% in 82 consecutive out-patient psychiatric clinic attendees, and Ross et al observed considerably higher lifetime prevalence in in-patients (28–44.5%).Reference Foote, Smolin, Kaplan, Legatt and Lipschitz125,Reference Ross, Duffy and Ellason126 A separate study found that general psychiatric in-patients were more likely to have a comorbid dissociative disorder if they scored above 30 on the DES, with patients in this bracket having a prevalence of up to 80%.Reference Tutkun, Sar, Yargiç, Ozpulat, Yanik and Kiziltan127 The majority of studies reviewed here reported prevalence rates within the clinical range observed by Ross et al, and in some cases considerably higher. However, two of the included studiesReference Marchetti, Kurcgant, Neto, Von Bismark and Fiore42,Reference Moene, Spinhoven, Hoogduin, Sandyck and Roelofs45 had prevalence rates of 10% or lower, commensurate with the prevalence rate of dissociative disorders in the general population.Reference Sar123,Reference Kate, Hopwood and Jamieson124

The prevalence of dissociative disorders seen in the samples with FND presented in this review supports the notion that FND and dissociative disorders might share similar mechanisms and aetiology (e.g. traumatic experiences, chronic/severe stressors), in addition to symptoms, supporting the classification of FND as a dissociative disorder in the ICD.2,Reference Brown, Cardeña, Nijenhuis, Sar and van der Hart4 Given that dissociative disorders are prevalent in other psychiatric populations,Reference Foote, Smolin, Kaplan, Legatt and Lipschitz125,Reference Ross, Duffy and Ellason126 dissociation as an explanatory mechanism for other mental disorders merits exploration. For FND, this proximity invites questions about treatment options and whether some people with FND would benefit from treatments that target dissociative disorders and symptoms, including those currently being evaluated in FND such as eye movement desensitisation and reprocessing (EMDR)Reference Cope128Reference Cope, Mountford, Smith and Agrawal131 and dynamic psychotherapies.Reference Malda Castillo, Beton, Coman, Howell, Burness and Martlew132,Reference Russell, Abbass, Allder, Kisely, Pohlmann-Eden and Town133

Dissociative symptoms are elevated in FND and vary by subgroup

Dissociative symptoms, as measured through validated scales, ranged widely in the FND samples. However, most studies reported elevated dissociative symptom scores in FND samples that were above clinical cut-off scores and/or the scores reported for comparison groups. Elevated scores were observed for both psychoform and somatoform manifestations of dissociation.

The DES was the most used measure of psychoform dissociation. DES scores have recently been meta-analysed in psychiatric populations.Reference Lyssenko, Schmahl, Bockhacker, Vonderlin, Bohus and Kleindienst3 In that meta-analysis, the mean DES score for FND was reported at 25.6, based on 20 studies, and dissociative disorders had a mean score of 38.9;Reference Lyssenko, Schmahl, Bockhacker, Vonderlin, Bohus and Kleindienst3 11 studies from our review reported mean or median scores higher than this, and 4 reported scores above the mean score for dissociative disorders. We found 11 studies that used other psychoform dissociation scales (e.g. CADSS, MDI, CDS) – the majority of FND groups scored higher on these dissociative measures when compared with controls.

In our subgroup meta-analysis investigating psychoform dissociation in FND groups versus different control groups, a large effect towards higher dissociation scores was found in the FND groups compared with healthy controls. This effect was also observed in the comparison with neurological controls, but of a medium effect size. High heterogeneity prevents us from confirming an effect between FND groups and psychiatric controls. The last finding may have been affected by the amalgamation of multiple psychiatric populations into one group. Four out of eight studies included a mixed psychiatric control group, while the remaining four involved somatisation, eating disorder, chronic pain and depression.

The SDQ-20 was the next most used dissociative symptom scale, and the only ‘pure’ measure of somatoform dissociation. Mean SDQ-20 scores in samples with dissociative disorder have been reviewed previously, observing mean scores >30 for FND samples, >43 for DDNOS and DPDR samples and >50 for DID samples.Reference Nijenhuis134 Using these as a reference, FND samples (of a total of 25) endorsed mean or median SDQ-20 scores >30, supporting the view that compartmentalisation is a significant feature of FND. Our meta-analysis comparing SDQ scores in people with FND and healthy controls displayed high heterogeneity between studies (Fig. 2); however, the prediction interval shows that research in this area has generally found people with FND to exhibit higher somatoform dissociation than healthy controls. Only the comparison from Demartini et alReference Demartini, Goeta, Barbieri, Ricciardi, Canevini and Turner56 involving participants with FND-seizures compared with healthy controls showed a non-significant effect. Sensitivity analyses suggested that this study was an outlier, and removing it shifted the prediction interval to greater than zero, indicating that future studies are likely to find the same pattern of results. Despite this, large heterogeneity remained (75%), meaning it is likely that the FND samples contained important subgroup populations that would need to be studied before effect size estimates could be interpreted. However, subgroup analysis was not possible as there were fewer than ten studies.

Our results suggested that there might be different dissociative symptom profiles across FND subgroups, specifically elevated psychoform dissociation in FND-seizures and greater somatoform dissociation in FND-motor samples. Guz and colleagues,Reference Guz, Doganay, Ozkan, Colak, Tomac and Sarisoy66 for example, reported the highest DES scores in an FND-seizures sample (mean score 27) relative to FND-motor (mean 12) and FND-sensory samples (mean 7). Nearly all of the FND-motor sample DES scores were comparable to the aforementioned mean scores of non-clinical populations, or substantially lower.Reference Van IJzendoorn and Schuengel135 Only in Tezcan and colleagues’ study did an FND-motor group exhibit high psychoform dissociation (mean DES = 25).Reference Tezcan, Atmaca, Kuloglu, Gecici, Buyukbayram and Tutkun48 Demartini and colleagues directly compared FND-seizures and FND-motor groups and noted an inverse relationship between DES and SDQ-20 scores in the two groups (FND-seizures mean DES = 17.2, mean SDQ-20 = 23.3; FND-motor mean DES = 7.9, mean SDQ-20 = 44.9).Reference Demartini, Goeta, Barbieri, Ricciardi, Canevini and Turner56 This observation was not totally consistent; some FND-seizures groups scored highly on the SDQ-20 (median SDQ-20 = 34 in Pick et alReference Pick, Mellers and Goldstein90; mean SDQ-20 = 38 in Koreki et alReference Koreki, Garfkinel, Mula, Agrawal, Cope and Eilon76), with no clear methodological differences that could account for this.

Significantly higher SDQ-20 scores in an FND-seizures sample relative to epilepsy controls were reported in a study in which the DES and CDS were unable to differentiate participants with FND from controls.Reference Lawton, Baker and Brown136 The authors argued therefore that compartmentalisation symptoms are more characteristic of FND-seizures, whereas detachment symptoms are less prominent. In our review, the highest DIS-Q score was also in an FND-seizures group.Reference Ozcetin, Belli, Ertem, Bahcebasi, Ataoglu and Canan85 Perhaps, therefore, these results indicate that people with the FND-seizures subtype have a greater overall tendency to dissociate in general, with respect to both somatoform and psychoform symptoms. The discrepant findings noted here require further examination in additional studies using measures of both somatoform and psychoform dissociation in FND-seizures and FND-motor samples.

A potential explanation of the observed trends is that FND motor symptoms are indeed comparable to so-called somatoform dissociative symptoms, whereas psychoform dissociative symptoms are more common in people with FND-seizures. Indeed, the SDQ-20 contains several items that map directly onto FND motor symptoms, whereas there is only one item regarding attacks resembling seizures. One of the developers of the SDQ-20 has already called for physical ‘conversion’ symptoms to be relabelled as somatoform dissociative symptoms.Reference Nijenhuis134

Several limitations affect the generalisability of the observations outlined above. The majority of studies that addressed FND subtypes focused on FND-seizures; very few studies specified the FND subtype and most involved people with FND endorsing multiple symptoms. There were only three studies presenting FND-sensory or ‘mixed’ (F44.6 and F44.7 respectively) subtype specific scoresReference Tezcan, Atmaca, Kuloglu, Gecici, Buyukbayram and Tutkun48,Reference Guz, Doganay, Ozkan, Colak, Tomac and Sarisoy66,Reference Spitzer, Spelsberg, Grabe, Mundt and Freyberger97 and our subgroup meta-analysis indicated that FND-seizures groups exhibited different levels of psychoform dissociation from FND-motor groups. This meta-analysis indicates the need for more FND-motor and healthy control comparisons. Importantly, future studies should examine closely the effect on SDQ-20 total scores of items pertaining to the particular FND symptoms experienced by each respondent. One methodological solution is to rerun analyses excluding items that resemble FND symptoms common in the sample under investigation.

Although the DES and SDQ-20 scales were the most commonly used dissociation scales, most studies did not administer both and thus did not screen for both types of dissociative symptoms. It has been suggested that rather than existing as a general attribute, dissociation represents a diverse and not necessarily connected cluster of symptoms; consequently, scales such as the MDI, which measure specific psychoform dissociative symptoms such as depersonalisation and identity dissociation, might be more valuable for assessing dissociative symptom profiles.Reference Briere, Weathers and Runtz137 Reporting bias, and additionally recall bias, are also potential limitations of self-report scales, which may be mitigated by use of scales that are clinician-administered and/or state-based, such as the CADSS.

The large values for measures of dispersion seen across the studies indicate that although some individuals with FND report elevated dissociative tendencies, there are some who appear less affected by dissociation. If specific FND presentations present with different types of dissociative symptoms, as suggested by our results, then omission of measures of psychoform and/or somatoform dissociation might result in falsely low or unrepresentative results. However, another interpretation is that dissociative symptoms, although common, are not a ubiquitous feature of FND. More studies that administer both psychoform and somatoform dissociative scales to people with various FND subtypes will help to establish more concretely whether the observed trends represent the population.

Biological associations of dissociation in FND

Little is known about the biological processes underlying pathological dissociation. Roydeva & ReindersReference Roydeva and Reinders15 recently systematically reviewed studies exploring potential biomarkers associated with pathological dissociation transdiagnostically, including dissociative disorders, FND, and affective, personality and stress-related disorders.Reference Roydeva and Reinders15 Increased neural activity was observed in several brain regions in the dissociative groups relative to healthy or clinical control groups, in both resting-state and task-based functional neuroimaging studies. This was consistent in regions of the prefrontal cortex, insula and ACC – findings also reported by Drane et al in a previous reviewReference Drane, Fani, Hallett, Khalsa, Perez and Roberts138 and in models of dissociation in specific disorders, including PTSD and DID.Reference Lanius, Vermetten, Loewenstein, Brand, Schmahl and Bremner139,Reference Reinders, Willemsen, den Boer, Vos, Veltman and Loewenstein140

Trends in connectivity alterations included increased connectivity from amygdala seed regions to prefrontal cortex (e.g. dorsolateral, medial, orbitofrontal), precuneus and superior parietal cortex. In addition, structural imaging studies found evidence of volumetric reductions in several regions in the dissociative groups, including the hippocampus, thalamus and basal ganglia. Other trends included a negative correlation between tumour necrosis factor alpha and dissociative symptoms, and a positive correlation with interleukin 6, raising questions about an interaction between inflammation and dissociative symptoms;Reference Roydeva and Reinders15 however, this process may be mediated by other comorbid disorders, such as depression.Reference Osimo, Pillinger, Rodriguez, Khandaker, Pariante and Howes141 Further research is needed to better understand the neurobiological basis of dissociative symptoms and disorders.

Our review found a noticeably smaller number of studies examining the relationships between biological factors and dissociative symptoms in people with FND when compared with the Roydeva & Reinders review.Reference Roydeva and Reinders15 This is likely due to differing study inclusion criteria; we specified that our studies describe dissociative symptoms or comorbid disorders with validated measures in people with FND, whereas the aforementioned review accepted diagnosis of FND alone as a marker of dissociation. Despite this disparity, there were some common trends noted: three of the identified studies from our review shared consistent findings with some of the reports of altered neural circuitry described above.Reference Perez, Matin, Williams, Tanev, Makris and LaFrance88,Reference van der Kruijs, Jagannathan, Bodde, Besseling, Lazeron and Vonck102,Reference van der Kruijs, Bodde, Vaessen, Lazeron, Vonck and Boon118 Volumetric and functional connectivity changes were observed within several brain regions, including the ACC – a region implicated in action planning, decision-making and empathy-related responses. The ACC is consistently highlighted as an area of interest in FND studies.Reference Drane, Fani, Hallett, Khalsa, Perez and Roberts138,Reference Perez, Nicholson, Asadi-Pooya, Bègue, Butler and Carson142,Reference Ospina, Jalilianhasanpour and Perez143 Increased functional connectivity and neural activity within this cortical region, among several other related regions described earlier, has been advocated as a potential biomarker for pathological dissociation and for FND.Reference Drane, Fani, Hallett, Khalsa, Perez and Roberts138,Reference Wegrzyk, Kebets, Richiardi, Galli, de Ville and Aybek144 Whether these demonstrable alterations in neural circuitry can be translated into an in vivo biomarker of disorder severity or response to treatment remains to be explored. Studies applying this method have shared promising results.Reference Faul, Knight, Espay, Depue and LaFaver145,Reference Espay, Ries, Maloney, Vannest, Neefus and Dwivedi146

Two relevant studies from Labate and colleagues could not be included in this review as they did not meet our inclusion criteria.Reference Labate, Cerasa, Mula, Mumoli, Gioia and Aguglia147,Reference Labate, Martino, Caligiuri, Fortunato, Bruni and Segura-Garcia148 The first reported on cortical thinning in similar brain regions, using voxel-based morphometry and cortical thickness MRI techniques.Reference Labate, Cerasa, Mula, Mumoli, Gioia and Aguglia147 Significant loss of grey matter volume in participants with FND-seizures was observed in primary motor and premotor cortices, the supplementary motor area and the ACC.Reference Labate, Cerasa, Mula, Mumoli, Gioia and Aguglia147 Thickness alterations in these regions of interest were not associated with dissociation (on DES and SDQ scores); however, SDQ scores were significantly negatively associated with reduced cortical thickness in the left inferior frontal gyrus and the left central sulcus.Reference Labate, Cerasa, Mula, Mumoli, Gioia and Aguglia147 The second, more recent, study contrasted similar brain regions of interest in subgroups of healthy participants and participants with depression and FND-seizures.Reference Labate, Martino, Caligiuri, Fortunato, Bruni and Segura-Garcia148 Relative to healthy controls, both the depression and FND-seizures subgroups had noticeable thinning of the ACC and lateral orbitofrontal cortext on MRI. Although this was more pronounced in participants with depression, a significant positive relationship between SDQ scores and morphological changes in the right medial orbitofrontal cortext was observed.Reference Labate, Martino, Caligiuri, Fortunato, Bruni and Segura-Garcia148

Other biological findings were more variable. Two studies measured skin conductance levels in people with FND, with inconsistent results.Reference Herrero, Tarrada, Haffen, Mignot, Sense and Schwan70,Reference Pick, Rojas-Aguiluz, Butler, Mulrenan, Nicholson and Goldstein89 These inconsistent findings are similar to those previously reported in Drane et al's review.Reference Drane, Fani, Hallett, Khalsa, Perez and Roberts138 One possible explanation is that in FND, interoceptive impairments lead to a discordance between subjective and autonomic responses. This is reflected further in other studies that have reported impaired interoceptive accuracy of people with FND.Reference Demartini, Goeta, Barbieri, Ricciardi, Canevini and Turner56,Reference Demartini, Goeta, Romito, Anselmetti, Bertelli and D'Agostino57,Reference Koreki, Garfkinel, Mula, Agrawal, Cope and Eilon76,Reference Pick, Rojas-Aguiluz, Butler, Mulrenan, Nicholson and Goldstein89 Owing to the limited number of studies found and the variety of objective measures, a meta-analysis was not possible for the biological associations of dissociation in FND.

Clinical features associated with dissociation in FND

Several studies in this review offer compelling evidence in support of using dissociative tendencies, symptoms or comorbidity as a potential prognostic marker in FND. Many of these studies pertained to the FND-seizures subtype. Severity or frequency of seizure symptoms, and presence of ongoing seizures relative to remission states, were seen in people with FND who reported greater degrees of dissociative symptoms.Reference Bodde, Janssen, Theuns, Vanhoutvin, Boon and Aldenkamp51,Reference Kuyk, Siffels, Bakvis and Swinkels78,Reference Martino, Bruni, Labate, Vasta, Cerasa and Borzì80,Reference O'Brien, Fortune, Dicker, O'Hanlon, Cassidy and Delanty87,Reference Reuber, House, Pukrop, Bauer and Elger93,Reference Walther, Volbers, Erdmann, Dogan Onugoren, Gollwitzer and Kasper103 Quality of life in people with FND-seizures was also reportedly affected by degree of dissociation, even after controlling for a number of other factors.Reference Mitchell, Ali and Cavanna81,Reference Gagny, Grenevald, El-Hage, Chrusciel, Sanchez and Schwan115 Other studies observed varying severity of presentation with level of dissociation in general FND populations. The concerning link between dissociative symptoms and suicide has been established previously in psychiatric samples.Reference Calati, Bensassi and Courtet26,Reference Güleç, Ýnanç, Yanartaþ, Üzer and Güleç68,Reference Kılıç, Coşkun, Bozkurt, Kaya and Zoroğlu149 More longitudinal studies could therefore be helpful to further establish the link between dissociative symptoms and FND severity or quality of life.

Several studies observed that alexithymia and emotion dysregulation were associated with dissociation severity in FND participants.Reference Brown, Bouska, Frow, Kirkby, Baker and Kemp53,Reference Del Río-Casanova, González-Vázquez, Justo, Andrade, Páramo and Brenlla55,Reference Kienle, Rockstroh, Bohus, Fiess, Huffziger and Steffen-Klatt75 Number of FND symptoms, earlier onset of symptoms and likelihood of symptom severity requiring in-patient management were also predicted, to a degree, by dissociative symptoms.Reference Yayla, Bakım, Tankaya, Ozer, Karamustafalioglu and Ertekin14,Reference Moene, Spinhoven, Hoogduin, Sandyck and Roelofs45,Reference Roelofs, Hoogduin, Keijsers, Näring, Moene and Sandijck46 Other findings included elevated general psychopathology and psychiatric comorbidity in FND participants with greater dissociative tendencies.Reference Yayla, Bakım, Tankaya, Ozer, Karamustafalioglu and Ertekin14,Reference van der Hoeven, Broersma, Pijnenborg, Koops, van Laar and Stone101

Taken together, these findings have important clinical implications. Dissociation scales might provide a novel means of categorising FND severity, prognosis and guiding treatment. Reflecting this notion, some of the studies in this review adopted the SDQ-20 specifically as a marker of FND severity.Reference Kienle, Rockstroh, Bohus, Fiess, Huffziger and Steffen-Klatt75,Reference Steffen-Klatt, Fiess, Beckha, Schmidt and Rockstroh99 It might be beneficial to measure psychoform or somatoform dissociative symptoms as an outcome for FND in future studies. In addition, high scores on dissociation measures in people with FND also reporting previous trauma might indicate the presence of post-traumatic symptoms,Reference Pick, Mellers and Goldstein90 which would need to be addressed specifically in any effective clinical intervention. The associations between traumatic experiences, dissociative and post-traumatic symptoms in FND are important and understudied; although this unfortunately goes beyond the scope of this paper, it merits further exploration in future studies.

Strengths and limitations of the review

Our review has several strengths. First, we have comprehensively summarised existing data on both dissociative disorders and dissociative symptoms across different FND symptom types, and our subgroup analyses have highlighted potentially important subgroup differences. We also included studies that used a range of validated dissociation measures, ensuring that our review captured as much of the existing data as possible and providing insights into the relative prevalence of different types of dissociative symptoms (e.g. detachment, compartmentalisation) in the FND samples. Our findings have also indicated several important directions for future research on biological mechanisms and clinical implications of dissociation in FND.

We acknowledge some limitations in the methods used. Regarding the search strategy, terms for cognitive FND symptoms were not included because we designed the search strategy in 2019, before these symptoms were formally classified as FND in ICD-11. Overall, the meta-analyses indicated a general problem of large heterogeneity between studies, which limits the certainty with which some conclusions can be drawn. This is especially evident in the neurological and psychiatric control groups, which each subsumed several different clinical disorders. In addition to this, funnel plots all showed asymmetry within the data. There are cases of small studies reporting a large effect size and large standard error, which is a potential indictor of publication bias. However, this could also be reflective of the high heterogeneity and the presence of outliers. We were also unable to explore the influence of associated risk factors such as trauma on dissociation scores in the meta-analysis, which might be of value in future. Generally, there were only a small number of studies that investigated the relationship between dissociation scores and biological measures, with inconsistent findings on several measures. Finally, although we excluded any study that stated that participants with FND had comorbid neurological disorders, not all studies explicitly declared this (or that comorbid neurological disorders were excluded), and therefore there is a possibility that some of the data included may have not been FND-specific.

Future directions and clinical implications

The findings presented here indicate that dissociation is a pervasive and clinically relevant feature in FND, also lending support to the view that dissociation is a possible underlying mechanism. Further research is needed to examine more rigorously the role of dissociative processes in the generation of FND symptoms, with methods designed to examine causal hypotheses. Improved understanding of the role of dissociation in FND will have implications for diagnosis and classification, with potential to facilitate resolution of the discrepancy between the ICD-11 and DSM-5 classifications.

Despite the considerable literature reviewed here, few studies investigated the potentially differing degrees of psychoform and somatoform dissociation in different FND subtypes. Furthermore, few studies explicitly sought to examine the distinction between compartmentalisation and detachment subtypes of dissociation in FND subgroups. More studies should closely examine these different forms of dissociation, their underlying aetiological and neurobiological basis, and how they relate to the occurrence of core FND symptoms such as seizure, motor, cognitive and sensory symptoms.

From a clinical perspective, this review highlighted several possible implications. To accurately capture all of the symptomatology and experiences of patients with FND, clinicians might consider screening for both somatoform and psychoform dissociative symptoms, as they are evidently overexpressed in this population and are associated with adverse clinical features and outcomes. For individuals with FND who report significant dissociation, a dedicated clinical interview to assess possible comorbid dissociative disorders would be another consideration, as would be a more detailed screening for past trauma and possible post-traumatic symptoms.

A key research question is whether level of dissociative symptoms could constitute a prognostic indicator of FND severity. Lastly, there are some appreciable potential biomarkers of dissociation that, if explored further, could aid in understanding how this process occurs and potentially act as guides to monitoring treatment efficacy and/or developing novel treatments for the disorder.

Supplementary material

Supplementary material is available online at https://doi.org/10.1192/bjo.2022.597.

Data availability

Data availability is not applicable to this article as no new data were created or analysed in this study.

Author contributions

M.C.C. contributed to developing the research question and design of the review, conducted the systematic searches, screened the articles, extracted and tabulated the results, carried out the qualitative synthesis and wrote the first draft of the manuscript. A.S. conducted the updated searches, screened and tabulated the additional results, designed and conducted the meta-analysis, wrote the meta-analysis sections of the manuscript, carried out the quality ratings and contributed to writing several sections of the manuscript. M.R.-A. contributed to screening and tabulating search results, completed quality ratings and formatted the references. E.C. and L.H.G. contributed to developing the design of the review and were involved in reviewing and editing drafts of the manuscript. A.A.T.S.R. and T.R.N. contributed to reviewing and editing the manuscript. S.P. formulated the original research question(s) and overall design of the review, supervised the systematic review and meta-analysis, screened titles and abstracts, and contributed to writing and editing the manuscript.

Funding

This paper represents research part-funded by the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust, King's College London (T.R.N., L.H.G., S.P., A.A.T.S.R.) and the Medical Research Council (S.P.). The views expressed in this publication are those of the authors and not necessarily those of the National Health Service, the NIHR, the MRC or the Department of Health and Social Care.

Declaration of interest

None.

Appendix

Dissociation and functional neurological disorder terms used in the database search. The categories ‘dissociation’ and ‘functional neurological disorder’ were combined with ‘AND’; the list of terms within each category were combined with ‘OR’:

Dissociation terms

Dissociative

Dissociation

Depersonali*tion

Dereali*ation

Detachment

Compartmentali*ation

Functional neurological disorder terms

Functional neurological

Functional motor

Functional weakness

Conversion disorder

Psychogenic

Non*epileptic

Dissociative seizure

Hysteri*

Footnotes

*

Joint first authors.

References

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (5th edn) (DSM-5). American Psychiatric Association, 2013.Google Scholar
World Health Organization. ICD-11: International Classification of Diseases 11th Revision . WHO, 2019.Google Scholar
Lyssenko, L, Schmahl, C, Bockhacker, L, Vonderlin, R, Bohus, M, Kleindienst, N. Dissociation in psychiatric disorders: a meta-analysis of studies using the Dissociative Experiences Scale. Am J Psychiatry 2018; 175: 3746.10.1176/appi.ajp.2017.17010025CrossRefGoogle ScholarPubMed
Brown, RJ, Cardeña, E, Nijenhuis, E, Sar, V, van der Hart, O. Should conversion disorder be reclassified as a dissociative disorder in DSM–V? Psychosomatics 2007; 48: 369–78.CrossRefGoogle ScholarPubMed
Brown, RJ, Reuber, M. Psychological and psychiatric aspects of psychogenic non-epileptic seizures (PNES): a systematic review. Clin Psychol Rev 2016; 45: 157–82.CrossRefGoogle ScholarPubMed
Cardeña, E, Carlson, E. Acute stress disorder revisited. Annu Rev Clin Psychol 2011; 7: 245–67.CrossRefGoogle Scholar
Dell, PF. Dissociative phenomenology of dissociative identity disorder. J Nerv Ment Dis 2002; 190: 10–5.10.1097/00005053-200201000-00003CrossRefGoogle ScholarPubMed
Medford, N, Baker, D, Hunter, E, Sierra, M, Lawrence, E, Phillips, ML, et al. Chronic depersonalization following illicit drug use: a controlled analysis of 40 cases. Addiction 2003; 98: 1731–6.CrossRefGoogle ScholarPubMed
Romero-López, MJ. A review of the dissociative disorders: from multiple personality disorder to the posttraumatic stress. Anales de Psicol 2016; 32: 448–56.10.6018/analesps.32.2.218301CrossRefGoogle Scholar
Hunter, E, Phillips, ML, Chalder, T, Sierra, M, David, AS. Depersonalisation disorder: a cognitive–behavioural conceptualisation. Behav Res Ther 2003; 41: 1451–67.CrossRefGoogle ScholarPubMed
Ross, CA, Joshi, S, Currie, R. Dissociative experiences in the general population. Am J Psychiatry 1990; 147: 1547–52.Google ScholarPubMed
Hendrickson, R, Popescu, A, Ghearing, G, Bagic, A. Thoughts, emotions, and dissociative features differentiate patients with epilepsy from patients with psychogenic nonepileptic spells (PNESs). Epilepsy Behav 2015; 51: 158–62.10.1016/j.yebeh.2015.07.016CrossRefGoogle ScholarPubMed
Spiegel, D. Dissociation in the DSM5. J Trauma Dissociation 2010; 11: 261–5.CrossRefGoogle ScholarPubMed
Yayla, S, Bakım, B, Tankaya, O, Ozer, OA, Karamustafalioglu, O, Ertekin, H, et al. Psychiatric comorbidity in patients with conversion disorder and prevalence of dissociative symptoms. J Trauma Dissociation 2015; 16: 2938.10.1080/15299732.2014.938214CrossRefGoogle ScholarPubMed
Roydeva, MI, Reinders, AA. Biomarkers of pathological dissociation: a systematic review. Neurosci Biobehav Rev 2021; 123: 120202.CrossRefGoogle ScholarPubMed
Treise, C, Perez, J. The role of dissociative compartmentalization in difficult-to-treat psychotic phenomena. Front Psychol 2021; 12: 1093.CrossRefGoogle ScholarPubMed
Cardeña, E, Gušić, S, Cervin, M. A network analysis to identify associations between PTSD and dissociation among teenagers. J Trauma Dissociation [Epub ahead of print] 22 Oct 2021. Available from: https://doi.org/10.1080/15299732.2021.1989122.Google ScholarPubMed
Schimmenti, A, Sar, V. A correlation network analysis of dissociative experiences. J Trauma Dissociation 2019; 20: 402–19.CrossRefGoogle ScholarPubMed
Holmes, EA, Brown, RJ, Mansell, W, Fearon, RP, Hunter, EC, Frasquilho, F, et al. Are there two qualitatively distinct forms of dissociation? A review and some clinical implications. Clin Psychol Rev 2005; 25(1): 123.CrossRefGoogle ScholarPubMed
Nijenhuis, ER, Spinhoven, P, Van Dyck, R, Van der Hart, O, Vanderlinden, J. The development and psychometric characteristics of the Somatoform Dissociation Questionnaire (SDQ-20). J Nerv Ment Dis 1996; 184: 688–94.10.1097/00005053-199611000-00006CrossRefGoogle ScholarPubMed
van der Boom, KJ, van den Hout, MA, Huntjens, RJC. Psychoform and somatoform dissociation, traumatic experiences, and fantasy proneness in somatoform disorders. Pers Individ Dif 2010; 48: 447–51.CrossRefGoogle Scholar
Bernstein, EM. Development, Reliability and Validity of a Dissociation Scale (Derealization, Depersonalization, Test Construction). American University, 1986.Google Scholar
Hansen, M, Ross, J, Armour, C. Evidence of the dissociative PTSD subtype: a systematic literature review of latent and class and profile analytic studies of PTSD. J Affect Disord 2017; 213: 5969.CrossRefGoogle ScholarPubMed
Burton, MS, Feeny, NC, Connell, AM, Zoellner, LA. Exploring evidence of a dissociative subtype in PTSD: baseline symptom structure, etiology, and treatment efficacy for those who dissociate. J Consult Clin Psychol 2018; 86: 439–51.CrossRefGoogle ScholarPubMed
Huijstee, JV, Vermetten, E. The dissociative subtype of post-traumatic stress disorder: research update on clinical and neurobiological features. Behav Neurobiol PTSD 2017; 38: 229–48.CrossRefGoogle Scholar
Calati, R, Bensassi, I, Courtet, P. The link between dissociation and both suicide attempts and non-suicidal self-injury: meta-analyses. Psychiatry Res 2017; 251: 103–14.CrossRefGoogle ScholarPubMed
Langeland, W, Jepsen, EKK, Brand, BL, Kleven, L, Loewenstein, RJ, Putnam, FW, et al. The economic burden of dissociative disorders: a qualitative systematic review of empirical studies. Psychol Trauma 2020; 12(7): 730–8.CrossRefGoogle ScholarPubMed
Brière, J. MDI, Multiscale Dissociation Inventory: Professional Manual. Psychological Assessment Resources, 2002.Google Scholar
Bremner, JD, Krystal, JH, Putnam, FW, Southwick, SM, Marmar, C, Charney, DS, et al. Measurement of dissociative states with the Clinician-Administered Dissociative States Scale (CADSS). J Trauma Stress 1998; 11: 125–36.10.1023/A:1024465317902CrossRefGoogle ScholarPubMed
Vanderlinden, J, Van Dyck, R, Vandereycken, W, Vertommen, H, Verkes, RJ et al. The Dissociation Questionnaire (DIS-Q): development and characteristics of a new self-report questionnaire. Clin Psychol Psychother 1993; 1: 21–7.10.1002/cpp.5640010105CrossRefGoogle Scholar
Steinberg, M, Rounsaville, B, Cicchetti, DV. The Structured Clinical Interview for DSM-III-R Dissociative Disorders: preliminary report on a new diagnostic instrument. Am J Psychiatry 1990; 147: 7682.Google ScholarPubMed
Moskalewicz, A, Oremus, M. No clear choice between Newcastle–Ottawa scale and appraisal tool for cross-sectional studies to assess methodological quality in cross-sectional studies of health-related quality of life and breast cancer. J Clin Epidemiol 2020; 120: 94103.CrossRefGoogle ScholarPubMed
Higgins, JPT, Li, T, Deeks, J. Obtaining standard errors from confidence intervals and P values: absolute (difference) measures. In Cochrane Handbook for Systematic Reviews of Interventions, version 6.3 (updated February 2022) (eds Higgins, JPT, Thomas, J, Chandler, J, Cumpston, M, Li, T, Page, MJ, Welch, VA): Ch. 6.3.1. Cochrane, 2022 (https://training.cochrane.org/handbook/current/chapter-06#section-6-3-1).Google Scholar
Viechtbauer, W. Bias and efficiency of meta-analytic variance estimators in the random-effects model. J Educ Behav Stat 2005; 30: 261–93.CrossRefGoogle Scholar
Hartung, J, Knapp, G. An alternative test procedure for meta-analysis. In Meta-analysis: New Developments and Applications in Medical and Social Sciences (eds Schulze, R, Holling, H, Böhning, D): 5369. Hogrefe & Huber Publishers, 2003.Google Scholar
Balduzzi, S, Rücker, G, Schwarzer, G. How to perform a meta-analysis with R: a practical tutorial. Evid Based Ment Health 2019; 22: 153–60.CrossRefGoogle Scholar
Harrer, M, Cuijpers, P, Furukawa, T, Ebert, D et al. Doing Meta-Analysis With R: A Hands-On Guide. CRC Press, 2021.10.1201/9781003107347CrossRefGoogle Scholar
Cochran, WG. The combination of estimates from different experiments. Biometrics 1954; 10: 101–29.CrossRefGoogle Scholar
Higgins, JP, Thompson, SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21: 1539–58.CrossRefGoogle ScholarPubMed
Wells, GA, Shea, B, O'Connell, D, Peterson, J, Welch, V, Losos, M, et al. The Newcastle–Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses. The Ottawa Hospital Research Institute, 2000 (https://www.ohri.ca//programs/clinical_epidemiology/oxford.asp).Google Scholar
Litwin, R, Cardeña, E. Demographic and seizure variables, but not hypnotizability or dissociation, differentiated psychogenic from organic seizures. J Trauma Dissociation 2001; 1: 99122.CrossRefGoogle Scholar
Marchetti, RL, Kurcgant, D, Neto, JG, Von Bismark, MA, Fiore, LA. Evaluating patients with suspected nonepileptic psychogenic seizures. J Neuropsychiatry Clin Neurosci 2009; 21: 292–8.CrossRefGoogle ScholarPubMed
Akyüz, F, Gökalp, PG, Erdiman, S, Oflaz, S, Karşidağ, Ç. Conversion disorder comorbidity and childhood trauma. Noro Psikiyatr Ars 2017; 54: 1520.CrossRefGoogle ScholarPubMed
Baillés, E, Pintor, L, Fernandez-Egea, E, Torres, X, Matrai, S, De Pablo, J, et al. Psychiatric disorders, trauma, and MMPI profile in a Spanish sample of nonepileptic seizure patients. Gen Hosp Psychiatry 2004; 26: 310–5.CrossRefGoogle Scholar
Moene, FC, Spinhoven, P, Hoogduin, K, Sandyck, P, Roelofs, K et al. Hypnotizability, dissociation and trauma in patients with a conversion disorder: an exploratory study. Clin Psychol Psychother 2001; 8: 400–10.CrossRefGoogle Scholar
Roelofs, K, Hoogduin, KA, Keijsers, GP, Näring, GW, Moene, FC, Sandijck, P. Hypnotic susceptibility in patients with conversion disorder. J Abnorm Psychol 2002; 111: 390–5.CrossRefGoogle ScholarPubMed
Scévola, L, Teitelbaum, J, Oddo, S, Centurión, E, Loidl, CF, Kochen, S, et al. Psychiatric disorders in patients with psychogenic nonepileptic seizures and drug-resistant epilepsy: a study of an Argentine population. Epilepsy Behav 2013; 29: 155–60.CrossRefGoogle ScholarPubMed
Tezcan, E, Atmaca, M, Kuloglu, M, Gecici, O, Buyukbayram, A, Tutkun, H. Dissociative disorders in Turkish inpatients with conversion disorder. Compr Psychiatry 2003; 44: 324–30.CrossRefGoogle ScholarPubMed
Akyuz, G, Kugu, N, Akyuz, A, Dogan, O. Dissociation and childhood abuse history in epileptic and pseudoseizure patients. Epileptic Disord 2004; 6: 187–92.Google ScholarPubMed
Alper, K, Devinsky, O, Perrine, K, Luciano, D, Vazquez, B, Pacia, S, et al. Dissociation in epilepsy and conversion nonepileptic seizures. Epilepsia 1997; 38: 991–7.CrossRefGoogle ScholarPubMed
Bodde, NM, Janssen, AM, Theuns, C, Vanhoutvin, JF, Boon, PA, Aldenkamp, AP. Factors involved in the long-term prognosis of psychogenic nonepileptic seizures. J Psychosom Res 2007; 62: 545–51.CrossRefGoogle ScholarPubMed
Boesten, N, Myers, L, Wijnen, B. Quality of life and psychological dysfunction in traumatized and nontraumatized patients with psychogenic nonepileptic seizures (PNES). Epilepsy Behav 2019; 92: 341–4.CrossRefGoogle ScholarPubMed
Brown, RJ, Bouska, JF, Frow, A, Kirkby, A, Baker, GA, Kemp, S, et al. Emotional dysregulation, alexithymia, and attachment in psychogenic nonepileptic seizures. Epilepsy Behav 2013; 29: 178–83.CrossRefGoogle ScholarPubMed
Cope, SR, Smith, JG, King, T, Agrawal, N. Evaluation of a pilot innovative cognitive-behavioral therapy-based psychoeducation group treatment for functional non-epileptic attacks. Epilepsy Behav 2017; 70(Pt A): 238–44.CrossRefGoogle ScholarPubMed
Del Río-Casanova, L, González-Vázquez, AI, Justo, A, Andrade, V, Páramo, M, Brenlla, J, et al. The role of emotion dysregulation in conversion disorder. Act Esp Psiquiatr 2018; 46: 92103.Google ScholarPubMed
Demartini, B, Goeta, D, Barbieri, V, Ricciardi, L, Canevini, MP, Turner, K, et al. Psychogenic non-epileptic seizures and functional motor symptoms: a common phenomenology? J Neurol Sci 2016; 368: 4954.10.1016/j.jns.2016.06.045CrossRefGoogle ScholarPubMed
Demartini, B, Goeta, D, Romito, L, Anselmetti, S, Bertelli, S, D'Agostino, A, et al. Anorexia nervosa and functional motor symptoms: two faces of the same coin? J Neuropsychiatry Clin Neurosci 2017; 29: 383–90.CrossRefGoogle ScholarPubMed
Ekanayake, V, Kranick, S, LaFaver, K, Naz, A, Frank Webb, A, LaFrance, WC Jr, et al. Personality traits in psychogenic nonepileptic seizures (PNES) and psychogenic movement disorder (PMD): neuroticism and perfectionism. J Psychosom Res 2017; 97: 23–9.CrossRefGoogle ScholarPubMed
Espirito-Santo, HMA, Pio-Abreu, JL. Dissociative disorders and other psychopathological groups: exploring the differences through the somatoform dissociation questionnaire (SDQ-20). Braz J Psychiatry 2007; 29: 354–8.CrossRefGoogle Scholar
Espirito-Santo, H, Pio-Abreu, JL. Psychiatric symptoms and dissociation in conversion, somatization and dissociative disorders. Aust N Z J Psychiatry 2009; 43: 270–6.CrossRefGoogle ScholarPubMed
Evren, C, Can, S. Clinical correlates of dissociative tendencies in male soldiers with conversion disorder. Isr J Psychiatry Relat Sci 2007; 44: 33.Google ScholarPubMed
Gerhardt, C, Hamouda, K, Irorutola, F, Rose, M, Hinkelmann, K, Buchheim, A, et al. Insecure and unresolved/disorganized attachment in patients with psychogenic nonepileptic seizures. J Acad Consult Liaison Psychiatry 2021; 62: 337–44.CrossRefGoogle ScholarPubMed
Goldstein, LH, Drew, C, Mellers, J, Mitchell-O'Malley, S, Oakley, DA. Dissociation, hypnotizability, coping styles and health locus of control: characteristics of pseudoseizure patients. Seizure 2000; 9(5): 314–22.CrossRefGoogle ScholarPubMed
Goldstein, LH, Mellers, JD. Ictal symptoms of anxiety, avoidance behaviour, and dissociation in patients with dissociative seizures. J Neurol Neurosurg Psychiatry 2006; 77: 616–21.CrossRefGoogle ScholarPubMed
González-Vázquez, AI, Del Río-Casanova, L, Seijo-Ameneiros, N, Cabaleiro-Fernández, P, Seoane-Pillado, T, Justo-Alonso, A, et al. Validity and reliability of the Spanish version of the Somatoform Dissociation Questionnaire (SDQ-20). Psicothema 2017; 29: 275–80.Google ScholarPubMed
Guz, H, Doganay, Z, Ozkan, A, Colak, E, Tomac, A, Sarisoy, G. Conversion disorder and its subtypes: a need for a reclassification. Nord J Psychiatry 2003; 57: 377–81.CrossRefGoogle ScholarPubMed
Guz, H, Doganay, Z, Ozkan, A, Colak, E, Tomac, A, Sarisoy, G. Conversion and somatization disorders; dissociative symptoms and other characteristics. J Psychosom Res 2004; 56: 287–91.CrossRefGoogle ScholarPubMed
Güleç, MY, Ýnanç, L, Yanartaþ, Ö, Üzer, A, Güleç, H. Predictors of suicide in patients with conversion disorder. Compr Psychiatry 2014; 55: 457–62.CrossRefGoogle ScholarPubMed
Hammond-Tooke, GD, Grajeda, FT, Macrorie, H, Franz, EA. Response inhibition in patients with functional neurological symptom disorder. J Clin Neurosci 2018; 56: 3843.CrossRefGoogle ScholarPubMed
Herrero, H, Tarrada, A, Haffen, E, Mignot, T, Sense, C, Schwan, R, et al. Skin conductance response and emotional response in women with psychogenic non-epileptic seizures. Seizure 2020; 81: 123–31.10.1016/j.seizure.2020.07.028CrossRefGoogle ScholarPubMed
Holper, S, Foster, E, Lloyd, M, Rayner, G, Rychkova, M, Ali, R, et al. Clinical predictors of discordance between screening tests and psychiatric assessment for depressive and anxiety disorders among patients being evaluated for seizure disorders. Epilepsia 2021; 62: 1170–83.CrossRefGoogle ScholarPubMed
Irorutola, F, Gerhardt, C, Hamouda, K, Rose, M, Hinkelmann, K, Senf-Beckenbach, P. Emotional and cognitive empathy in patients with non-epileptic seizures. Seizure 2020; 81: 280–6.CrossRefGoogle ScholarPubMed
Jalilianhasanpour, R, Ospina, JP, Williams, B, Mello, J, MacLean, J, Ranford, J, et al. Secure attachment and depression predict 6-month outcome in motor functional neurological disorders: a prospective pilot study. Psychosomatics 2019; 60: 365–75.CrossRefGoogle ScholarPubMed
Jungilligens, J, Ospina, JP, Williams, B, Mello, J, MacLean, J, Ranford, J, et al. Impaired emotional and behavioural awareness and control in patients with dissociative seizures. Psychol Med 2020; 50: 2731–9.CrossRefGoogle ScholarPubMed
Kienle, J, Rockstroh, B, Bohus, M, Fiess, J, Huffziger, S, Steffen-Klatt, A. Somatoform dissociation and posttraumatic stress syndrome - two sides of the same medal? A comparison of symptom profiles, trauma history and altered affect regulation between patients with functional neurological symptoms and patients with PTSD. BMC Psychiatry 2017; 17(1): 248.10.1186/s12888-017-1414-zCrossRefGoogle ScholarPubMed
Koreki, A, Garfkinel, SN, Mula, M, Agrawal, N, Cope, S, Eilon, T, et al. Trait and state interoceptive abnormalities are associated with dissociation and seizure frequency in patients with functional seizures. Epilepsia 2020; 61: 1156–65.CrossRefGoogle ScholarPubMed
Kranick, S, Ekanayake, V, Martinez, V, Ameli, R, Hallett, M, Voon, V. Psychopathology and psychogenic movement disorders. Mov Disord 2011; 26: 1844–50.CrossRefGoogle ScholarPubMed
Kuyk, J, Siffels, MC, Bakvis, P, Swinkels, WA. Psychological treatment of patients with psychogenic non-epileptic seizures: an outcome study. Seizure 2008; 17: 595603.CrossRefGoogle ScholarPubMed
Martino, I, et al. Psychopathological constellation in patients with PNES: a new hypothesis. Epilepsy Behav 2018; 78: 297301.CrossRefGoogle ScholarPubMed
Martino, I, Bruni, A, Labate, A, Vasta, R, Cerasa, A, Borzì, G, et al. The impact of sexual abuse on psychopathology of patients with psychogenic nonepileptic seizures. Neurol Sci 2021; 42: 1423–8.CrossRefGoogle ScholarPubMed
Mitchell, JW, Ali, F, Cavanna, AE. Dissociative experiences and quality of life in patients with non-epileptic attack disorder. Epilepsy Behav 2012; 25: 307–12.CrossRefGoogle ScholarPubMed
Mousa, S, Latchford, G, Weighall, A, Nash, H, Murray-Leslie, R, Reuber, M, et al. Evidence of objective sleep impairment in nonepileptic attack disorder: a naturalistic prospective controlled study using actigraphy and daily sleep diaries over six nights. Epilepsy Behav 2021; 117: 107867.CrossRefGoogle ScholarPubMed
Myers, L, Trobliger, R, Bortnik, K, Zeng, R, Saal, E, Lancman, M. Psychological trauma, somatization, dissociation, and psychiatric comorbidities in patients with psychogenic nonepileptic seizures compared with those in patients with intractable partial epilepsy. Epilepsy Behav 2019; 92: 108–13.CrossRefGoogle ScholarPubMed
Nisticò, V, Caputo, G, Tedesco, R, Marzorati, A, Ferrucci, R, Priori, A, et al. Dissociation during Mirror Gazing Test in psychogenic nonepileptic seizures and functional movement disorders. Epilepsy Behav 2020; 112: 107368.CrossRefGoogle ScholarPubMed
Ozcetin, A, Belli, H, Ertem, U, Bahcebasi, T, Ataoglu, A, Canan, F. Childhood trauma and dissociation in women with pseudoseizure-type conversion disorder. Nord J Psychiatry 2009; 63: 462–8.10.3109/08039480903029728CrossRefGoogle ScholarPubMed
Ozdemir, PG, Gur, T, Cokluk, E, Isik, M, Tapan, S. Vitamin B12, folate levels and somatoform dissociation in conversion disorder. J Pak Med Assoc 2020; 70: 1758–61.Google ScholarPubMed
O'Brien, FM, Fortune, GM, Dicker, P, O'Hanlon, E, Cassidy, E, Delanty, N, et al. Psychiatric and neuropsychological profiles of people with psychogenic nonepileptic seizures. Epilepsy Behav 2015; 43: 3945.CrossRefGoogle ScholarPubMed
Perez, DL, Matin, N, Williams, B, Tanev, K, Makris, N, LaFrance, WC Jr, et al. Cortical thickness alterations linked to somatoform and psychological dissociation in functional neurological disorders. Hum Brain Mapp 2018; 39: 428–39.CrossRefGoogle ScholarPubMed
Pick, S, Rojas-Aguiluz, M, Butler, M, Mulrenan, H, Nicholson, TR, Goldstein, LH. Dissociation and interoception in functional neurological disorder. Cogn Neuropsychiatry 2020; 25: 294311.CrossRefGoogle ScholarPubMed
Pick, S, Mellers, JD, Goldstein, LH. Dissociation in patients with dissociative seizures: relationships with trauma and seizure symptoms. Psychol Med 2017; 47: 1215–29.CrossRefGoogle ScholarPubMed
Proença, IC, Castro, LH, Jorge, CL, Marchetti, RL. Emotional trauma and abuse in patients with psychogenic nonepileptic seizures. Epilepsy Behav 2011; 20: 331–3.CrossRefGoogle ScholarPubMed
Reedijk, WB, van Rijn, MA, Roelofs, K, Tuijl, JP, Marinus, J, van Hilten, JJ. Psychological features of patients with complex regional pain syndrome type I related dystonia. Mov Disord 2008; 23: 1551–9.CrossRefGoogle ScholarPubMed
Reuber, M, House, AO, Pukrop, R, Bauer, J, Elger, CE. Somatization, dissociation and general psychopathology in patients with psychogenic non-epileptic seizures. Epilepsy Res 2003; 57: 159–67.CrossRefGoogle ScholarPubMed
Reuber, M, Pukrop, R, Mitchell, AJ, Bauer, J, Elger, CE. Clinical significance of recurrent psychogenic nonepileptic seizure status. J Neurol 2003; 250: 1355–62.CrossRefGoogle ScholarPubMed
Roelofs, K, Keijsers, GP, Hoogduin, KA, Näring, GW, Moene, FC. Childhood abuse in patients with conversion disorder. Am J Psychiatry 2002; 159: 1908–13.CrossRefGoogle ScholarPubMed
Spinhoven, P, Roelofs, K, Moene, F, Kuyk, J, Nijenhuis, E, Hoogduin, K, et al. Trauma and dissociation in conversion disorder and chronic pelvic pain. Int J Psychiatry Med 2004; 34: 305–18.CrossRefGoogle ScholarPubMed
Spitzer, C, Spelsberg, B, Grabe, HJ, Mundt, B, Freyberger, HJ. Dissociative experiences and psychopathology in conversion disorders. J Psychosom Res 1999; 46: 291–4.CrossRefGoogle ScholarPubMed
Steffen, A, Fiess, J, Schmidt, R, Rockstroh, B. “That pulled the rug out from under my feet!” – adverse experiences and altered emotion processing in patients with functional neurological symptoms compared to healthy comparison subjects. BMC Psychiatry 2015; 15: 133.CrossRefGoogle ScholarPubMed
Steffen-Klatt, A, Fiess, J, Beckha, J, Schmidt, R, Rockstroh, B. The impact of adverse childhood experience on symptom severity in patients with functional neurological symptom disorder (FNSD). Ment Health Prev 2019; 13: 169–75.CrossRefGoogle Scholar
Stins, JF, Kempe, CL, Hagenaars, MA, Beek, PJ, Roelofs, K. Attention and postural control in patients with conversion paresis. J Psychosom Res 2015; 78: 249–54.CrossRefGoogle ScholarPubMed
van der Hoeven, RM, Broersma, M, Pijnenborg, GH, Koops, EA, van Laar, T, Stone, J, et al. Functional (psychogenic) movement disorders associated with normal scores in psychological questionnaires: a case control study. J Psychosom Res 2015; 79: 190–4.CrossRefGoogle ScholarPubMed
van der Kruijs, SJ, Jagannathan, SR, Bodde, NM, Besseling, RM, Lazeron, RH, Vonck, KE, et al. Resting-state networks and dissociation in psychogenic non-epileptic seizures. J Psychiatr Res 2014; 54: 126–33.CrossRefGoogle ScholarPubMed
Walther, K, Volbers, B, Erdmann, L, Dogan Onugoren, M, Gollwitzer, S, Kasper, BS, et al. Psychological long-term outcome in patients with psychogenic nonepileptic seizures. Epilepsia 2019; 60: 669–78.CrossRefGoogle ScholarPubMed
Williams, B, Ospina, JP, Jalilianhasanpour, R, Fricchione, GL, Perez, DL. Fearful attachment linked to childhood abuse, alexithymia, and depression in motor functional neurological disorders. J Neuropsychiatry Clin Neurosci 2019; 31: 65–9.CrossRefGoogle ScholarPubMed
Wood, BL, McDaniel, S, Burchfiel, K, Erba, G. Factors distinguishing families of patients with psychogenic seizures from families of patients with epilepsy. Epilepsia 1998; 39: 432–7.CrossRefGoogle ScholarPubMed
Xue, Q, Wang, ZY, Xiong, XC, Tian, CY, Wang, YP, Xu, P. Altered brain connectivity in patients with psychogenic non-epileptic seizures: a scalp electroencephalography study. J Int Med Res 2013; 41: 1682–90.CrossRefGoogle ScholarPubMed
Carlson, E, Putnam, FW, Ross, CA, Torem, M, Coons, P, Dill, DL, et al. Validity of the Dissociative Experiences Scale in screening for multiple personality disorder: a multicenter study. Am J Psychiatry 1993; 150: 1030–6.Google ScholarPubMed
Briere, J. Trauma Symptom Inventory-2: Professional Manual. PAR, 2011.Google Scholar
Sierra, M, Berrios, GE. The Cambridge Depersonalisation Scale: a new instrument for the measurement of depersonalisation. Psychiatry Res 2000; 93: 153–64.CrossRefGoogle Scholar
Sanders, S. The perceptual alteration scale: a scale measuring dissociation. Am J Clin Hypn 1986; 29: 95102.CrossRefGoogle ScholarPubMed
Kennedy, F, Clarke, S, Stopa, L, Bell, L, Rouse, H, Ainsworth, C, et al. Towards a cognitive model and measure of dissociation. J Behav Ther Exp Psychiatry 2004; 35: 2548.CrossRefGoogle ScholarPubMed
Freyberger, HJ, Spitzer, C, Stieglitz, RD, Kuhn, G, Magdeburg, N, Bernstein-Carlson, E. Fragebogen zu dissoziativen Symptomen (FDS). deutsche adaptation, reliabilität und validität der Amerikanischen Dissociative Experience Scale (DES) [Questionnaire on dissociative symptoms. German adaptation, reliability and validity of the American Dissociative Experience Scale (DES)]. Psychother Psychosom Med Psychol 1998; 48: 223–9.Google ScholarPubMed
Nijenhuis, ER. The scoring and interpretation of the SDQ-20 and SDQ-5. Act Nerv Super (Praha) 2010; 52: 24–8.CrossRefGoogle Scholar
Gratz, KL, Roemer, L. Multidimensional assessment of emotion regulation and dysregulation: development, factor structure, and initial validation of the difficulties in emotion regulation scale. J Psychopathol Behav Assess 2004; 26: 4154.CrossRefGoogle Scholar
Gagny, M, Grenevald, L, El-Hage, W, Chrusciel, J, Sanchez, S, Schwan, R, et al. Explanatory factors of quality of life in psychogenic non-epileptic seizure. Seizure 2021; 84: 613.CrossRefGoogle ScholarPubMed
Devinsky, O, Vickrey, BG, Cramer, J, Perrine, K, Hermann, B, Meador, K, et al. Development of the Quality of Life in Epilepsy Inventory. Epilepsia 1995; 36: 1089–104.CrossRefGoogle ScholarPubMed
Kienle, J, Rockstroh, B, Fiess, J, Schmidt, R, Popov, T, Steffen-Klatt, A. Variation of functional neurological symptoms and emotion regulation with time. Front Psychiatry 2018; 9: 35.CrossRefGoogle ScholarPubMed
van der Kruijs, SJ, Bodde, NM, Vaessen, MJ, Lazeron, RH, Vonck, K, Boon, P, et al. Functional connectivity of dissociation in patients with psychogenic non-epileptic seizures. J Neurol Neurosurg Psychiatry 2012; 83: 239–47.CrossRefGoogle ScholarPubMed
Boucsein, W. Electrodermal Activity. Springer Science & Business Media, 2012.CrossRefGoogle Scholar
Krüger, C, Mace, CJ. Psychometric validation of the state scale of dissociation (SSD). Psychol Psychother 2002; 75: 3351.CrossRefGoogle ScholarPubMed
Şar, V, Akyüz, G, Doğan, O. Prevalence of dissociative disorders among women in the general population. Psychiatry Res 2007; 149: 169–76.CrossRefGoogle ScholarPubMed
Spitzer, C, Liss, H, Dudeck, M, Orlob, S, Gillner, M, Hamm, A, et al. Dissociative experiences and disorders in forensic inpatients. Int J Law Psychiatry 2003; 26: 281–8.CrossRefGoogle ScholarPubMed
Sar, V. Epidemiology of dissociative disorders: an overview. Epidemiol Res Int 2011; 404538.10.1155/2011/404538CrossRefGoogle Scholar
Kate, M-A, Hopwood, T, Jamieson, G. The prevalence of dissociative disorders and dissociative experiences in college populations: a meta-analysis of 98 studies. J Trauma Dissociation 2020; 21: 1661.CrossRefGoogle ScholarPubMed
Foote, B, Smolin, Y, Kaplan, M, Legatt, ME, Lipschitz, D. Prevalence of dissociative disorders in psychiatric outpatients. Am J Psychiatry 2006; 163: 623–9.CrossRefGoogle ScholarPubMed
Ross, CA, Duffy, CM, Ellason, JW. Prevalence, reliability and validity of dissociative disorders in an inpatient setting. J Trauma Dissociation 2002; 3: 717.CrossRefGoogle Scholar
Tutkun, H, Sar, V, Yargiç, LI, Ozpulat, T, Yanik, M, Kiziltan, E. Frequency of dissociative disorders among psychiatric inpatients in a Turkish university clinic. Am J Psychiatry 1998; 155: 800–5.Google Scholar
Cope, SR. EMDR as an adjunctive psychological therapy for patients with functional neurological disorder: illustrative case examples. J EMDR Prac Res 2020; 2: 7689.CrossRefGoogle Scholar
Fine, CG, Berkowitz, AS. The wreathing protocol: the imbrication of hypnosis and EMDR in the treatment of dissociative identity disorder and other dissociative responses. Am J Clin Hypn 2001; 43: 275–90.CrossRefGoogle ScholarPubMed
International Society for the Study of Trauma and Dissociation. Guidelines for Treating Dissociative Identity Disorder in Adults, Third Revision. J Trauma Dissociation 2011; 12: 115–87.CrossRefGoogle Scholar
Cope, SR, Mountford, L, Smith, JG, Agrawal, N et al. EMDR to treat functional neurological disorder: a review. J EMDR Prac Res 2018; 3: 118–32.CrossRefGoogle Scholar
Malda Castillo, J, Beton, E, Coman, C, Howell, B, Burness, C, Martlew, J, et al. Three sessions of intensive short-term dynamic psychotherapy (ISTDP) for patients with dissociative seizures: a pilot study. Psychoanal Psychother 2022; 36: 81–104.CrossRefGoogle Scholar
Russell, LA, Abbass, AA, Allder, SJ, Kisely, S, Pohlmann-Eden, B, Town, JM. A pilot study of reduction in healthcare costs following the application of intensive short-term dynamic psychotherapy for psychogenic nonepileptic seizures. Epilepsy Behav 2016; 63: 17–9.CrossRefGoogle ScholarPubMed
Nijenhuis, ER. Somatoform dissociation: major symptoms of dissociative disorders. J Trauma Dissociation 2001; 1(4): 732.CrossRefGoogle Scholar
Van IJzendoorn, MH, Schuengel, C. The measurement of dissociation in normal and clinical populations: meta-analytic validation of the Dissociative Experiences Scale (DES). Clin Psychol Rev 1996; 16: 365–82.CrossRefGoogle Scholar
Lawton, G, Baker, GA, Brown, RJ. Comparison of two types of dissociation in epileptic and nonepileptic seizures. Epilepsy Behav 2008; 13: 333–6.CrossRefGoogle ScholarPubMed
Briere, J, Weathers, FW, Runtz, M. Is dissociation a multidimensional construct? Data from the multiscale dissociation inventory. J Trauma Stress 2005; 18: 221–31.CrossRefGoogle ScholarPubMed
Drane, DL, Fani, N, Hallett, M, Khalsa, SS, Perez, DL, Roberts, NA. A framework for understanding the pathophysiology of functional neurological disorder. CNS Spectr [Epub ahead of print] 4 Sep 2021. Available from: https://doi.org/10.1017/S1092852920001789.CrossRefGoogle Scholar
Lanius, RA, Vermetten, E, Loewenstein, RJ, Brand, B, Schmahl, C, Bremner, JD, et al. Emotion modulation in PTSD: clinical and neurobiological evidence for a dissociative subtype. Am J Psychiatry 2010; 167: 640–7.CrossRefGoogle ScholarPubMed
Reinders, AATS, Willemsen, AT, den Boer, JA, Vos, HP, Veltman, DJ, Loewenstein, RJ. Opposite brain emotion-regulation patterns in identity states of dissociative identity disorder: a PET study and neurobiological model. Psychiatry Res 2014; 223: 236–43.CrossRefGoogle ScholarPubMed
Osimo, EF, Pillinger, T, Rodriguez, IM, Khandaker, GM, Pariante, CM, Howes, OD. Inflammatory markers in depression: a meta-analysis of mean differences and variability in 5,166 patients and 5,083 controls. Brain, Behavior, and Immunity 2020; 87: 901–9.CrossRefGoogle ScholarPubMed
Perez, DL, Nicholson, TR, Asadi-Pooya, AA, Bègue, I, Butler, M, Carson, AJ, et al. Neuroimaging in functional neurological disorder: state of the field and research agenda. Neuroimage 2021; 30: 102623.CrossRefGoogle ScholarPubMed
Ospina, JP, Jalilianhasanpour, R, Perez, DL. The role of the anterior and midcingulate cortex in the neurobiology of functional neurologic disorder. Handb Clin Neurol 2019; 166: 267–79.CrossRefGoogle ScholarPubMed
Wegrzyk, J, Kebets, V, Richiardi, J, Galli, S, de Ville, DV, Aybek, S. Identifying motor functional neurological disorder using resting-state functional connectivity. Neuroimage 2018; 17: 163–8.CrossRefGoogle ScholarPubMed
Faul, L, Knight, LK, Espay, AJ, Depue, BE, LaFaver, K. Neural activity in functional movement disorders after inpatient rehabilitation. Psychiatry Res 2020; 303: 111125.CrossRefGoogle ScholarPubMed
Espay, AJ, Ries, S, Maloney, T, Vannest, J, Neefus, E, Dwivedi, AK, et al. Clinical and neural responses to cognitive behavioral therapy for functional tremor. Neurology 2019; 93: e1787–98.CrossRefGoogle ScholarPubMed
Labate, A, Cerasa, A, Mula, M, Mumoli, L, Gioia, MC, Aguglia, U, et al. Neuroanatomic correlates of psychogenic nonepileptic seizures: a cortical thickness and VBM study. Epilepsia 2012; 53: 377–85.CrossRefGoogle ScholarPubMed
Labate, A, Martino, I, Caligiuri, ME, Fortunato, F, Bruni, A, Segura-Garcia, C, et al. Orbito-frontal thinning together with a somatoform dissociation might be the fingerprint of PNES. Epilepsy Behav 2021; 121(Pt A): 108044.CrossRefGoogle ScholarPubMed
Kılıç, F, Coşkun, M, Bozkurt, H, Kaya, İ, Zoroğlu, S. Self-injury and suicide attempt in relation with trauma and dissociation among adolescents with dissociative and non-dissociative disorders. Psychiatry Invest 2017; 14: 172–8.CrossRefGoogle ScholarPubMed
Figure 0

Table 1 Example dissociation symptom rating scales

Figure 1

Fig. 1 PRISMA flowchart. FND, functional neurological disorder.

Figure 2

Table 2 Subset of studies reporting on rates of comorbid dissociative disorders in samples with functional neurological disorder (FND)

Figure 3

Table 3 Dissociative symptom scale scores in samples with functional neurological disorder (FND)

Figure 4

Table 4 Studies reporting biological correlates of dissociation in functional neurological disorder (FND)

Figure 5

Fig. 2 Somatoform dissociation scores in samples with functional neurological disorder (FND) compared with healthy controls. SDQ, Somatoform Dissociation Questionnaire; Low, low risk of bias; High, high risk of bias.

Figure 6

Fig. 3 Psychoform dissociation scores in samples with functional neurological disorder (FND) compared with healthy (HC), psychiatric (PSYCH) and neurological (NEURO) controls. Low, low risk of bias; High, high risk of bias.

Figure 7

Fig. 4 Psychoform dissociation scores in samples with seizure symptoms and motor symptoms of functional neurological disorder (FND) compared with healthy controls. Low, low risk of bias; High, high risk of bias.

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