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Symptoms of posttraumatic stress disorder in patients with functional neurological symptom disorder
Journal Pre-proof Symptoms of posttraumatic stress disorder in patients with functional neurological symptom disorder
M.A. Cordelia Gray, Alex Calderbank, Joy Adewusi, Rhiannon Hughes, Markus Reuber PII:
S0022-3999(19)30449-0
DOI:
https://doi.org/10.1016/j.jpsychores.2019.109907
Reference:
PSR 109907
To appear in:
Journal of Psychosomatic Research
Received date:
15 April 2019
Revised date:
16 December 2019
Accepted date:
16 December 2019
Please cite this article as: M.A. Cordelia Gray, A. Calderbank, J. Adewusi, et al., Symptoms of posttraumatic stress disorder in patients with functional neurological symptom disorder, Journal of Psychosomatic Research(2019), https://doi.org/10.1016/ j.jpsychores.2019.109907
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© 2019 Published by Elsevier.
Journal Pre-proof Symptoms of Posttraumatic Stress Disorder in patients with Functional Neurological Symptom Disorder Short Running Head: PTSD in FNSD Cordelia Gray M.A. a,b, Alex Calderbank, Joy Adewusi MSc, Rhiannon Hughes b MSc, Markus Reuberb PhD a
Neurology Psychotherapy Service, Sheffield Teaching Hospital, Sheffield, UK
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Academic Neurology Unit, University of Sheffield, Sheffield, UK
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Cordelia Gray, Neurology Psychotherapy Service, 12 Claremont Crescent, Sheffield, S10 2TA, [email protected], 0114 226 5018.Fax: 0114 271 3999
Journal Pre-proof Abstract Objective: To describe prevalence and relevance of Post-Traumatic Stress Disorder (PTSD) symptoms in Functional Neurological Symptom Disorder (FNSD) and explore differences in PTSD symptom scores between subgroups with Psychogenic Non-Epileptic Seizures (PNES) or other FNSD.
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Methods: This cross-sectional study evaluated data from 430 consecutive patients referred to a specialist psychotherapy service (69.3% female, 56% with PNES/44% with other FNSD). We analysed self-reported symptoms of Post-Traumatic Stress Disorder (PTSD Civilian Checklist, PCL-C), depression (PHQ-9), anxiety (GAD-7), physical symptoms (PHQ15), social functioning (WSAS), and health related quality of life (SF-36). Relationships between PTSD scores, diagnosis and other measures were examined. Independent associations of PTSD scores were identified using multilinear regression.
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Results: Symptom scores likely to indicate clinical PTSD were reported by 60.7% of patients with no difference between PNES and FNSD subgroups. Those potentially symptomatic of PTSD were less likely to be living with a partner OR 2.95 (95% CI 1.83-4.04), or to be in employment OR 2.23 (95% CI 1.46-3.41) than asymptomatic patients. There were higher levels of anxiety (r=0.62), depression (r=0.63) and somatic symptoms (r=0.45) and lower quality of life scores (r = 0.48) in patients PTSD symptoms (p<0.0001 for all comparisons). Anxiety, depression and somatic symptoms made independent contributions to the variance of PTSD symptoms.
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Conclusion: There is a high prevalence of PTSD symptoms in patient with FNSD regardless of whether they have PNES. Trauma and PTSD symptoms are negatively correlated with quality of life. Self-report instruments for anxiety, depression and somatic symptoms may predict the presence of PTSD.
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Keywords: Post Traumatic Stress Disorder, Functional Neurological Symptom Disorder, Psychogenic Non-Epileptic Seizures, anxiety, depression, trauma
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Introduction: Functional neurological symptom disorders (FNSD) are one of the most common reasons for referral to a neurological outpatient clinic 1. Functional neurological symptoms are as disabling as similar symptoms attributable to structurally or physiologically explained pathologies but associated with more psychiatric comorbidities 2,3.
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Historically, two key criteria had to be met before a diagnosis of conversion disorder (the name for FNSD in DSM-4) could be made: 1) neurological symptoms could not be explained by neurological disease, and 2) a precipitant likely to have caused significant distress such as a traumatic life event or a personal dilemma had to be identified 4. The interpretation of FNSD as a physical manifestation of distress is supported by many studies demonstrating a higher frequency of child- or adulthood traumatic life events in FNSD patients compared to healthy or disease controls 5. However, despite increased rates of trauma across different patient populations with FNSD 2, some patients with otherwise typical manifestations of FNSD do not report any potential stressors in their lives 5. Reflecting the development of recent thought about FNSD and in order to allow clinicians to formulate a diagnosis in such circumstances, the DSM-5 has therefore dropped the mandatory diagnostic criterion of a psychological precipitant. The diagnosis of FNSD is now based on neurologically defined criteria such as the observation of incompatibility between illness manifestation and recognised neurological or medical condition 6, e.g. the presence of Hoover’s sign in patients with unilateral leg weakness or resistance to eye opening during a seizure 3.
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Nevertheless, previous trauma continues to be an important aetiological factor in modern accounts of FNSD 5, 7, 8, and it is a matter of continuing debate whether the inability of some patients’ to recall potentially relevant distressing experiences means that they never occurred, that they are unwilling or unable to recall them, or that the methods used to capture this information are inadequate 3.
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The aim of the current study is to explore the potential relevance of previous trauma in patients with FNSD by examining the prevalence and clinical significance of symptoms characterising Post Traumatic Stress Disorder (PTSD). In addition to using these symptoms as an indirect indication of the possible relevance of trauma in FNSD, our study examines whether differences in the levels of PTSD symptoms could account for some of the phenomenological and aetiological differences which have been described between subtypes of FNSD, namely those with seizure-like presentations (Psychogenic Non-epileptic Seizures, PNES) and other manifestations 2,9,10. This exploration is intended to contribute to the on-going debate about whether it makes more sense to consider different presentations as distinct entities or to approach them as minor variants of FNSD 11. Last but not least this study explores whether self-report instruments commonly used for routine anxiety and depression screening in neurological patient populations could be used to predict the presence of PTSD symptoms. Method: Subjects and recruitment
Journal Pre-proof Patients contributing to this study were referred consecutively to a team of six psychotherapists and one psychotherapy manager working within the Department of Neurology at the Royal Hallamshire Hospital (RHH), Sheffield, United Kingdom, between October 2015 and October 2017. Referrals were made by fully trained Consultant Neurologists working for neurology service for adults (over 16 years old). The neurologists based at RHH reach out to hospitals in surrounding towns and are the sole service provider in their medical speciality for the population of South Yorkshire (population 1.39 million). Neurologists were encouraged to refer all patients diagnosed with FNSD and willing to access psychotherapy with the following exceptions: 1. Patients with serious on-going psychiatric problems.
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2. Patients who are currently suicidal (e.g. persistent suicidal urges, making plans etc.) or who have had a suicide attempt in the last year. 3. Patients who are currently receiving psychotherapy elsewhere.
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4. Patients who have already had two episodes of treatment from this service.
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5. Patients who are currently dependent on alcohol or opiate drugs.
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Referrals for these patients were rejected because they initially require intervention from other treatment providers. In the United Kingdom, National Health Service (NHS) patients are referred to Neurologists by General Practitioners or Emergency Physicians based on clinical need and have access to neurological assessment, investigations and treatment free of charge. Similarly, access to psychotherapy is provided on the basis of clinical need, and treatment is provided without the need for payment or insurance.
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Prior to receiving their initial appointment with the psychotherapy service, patients are routinely asked to complete a series of questionnaires to provide a baseline account of their symptoms and level of impairment and to indicate that they are keen to opt in to psychological intervention (see below). Clinical data was extracted from hospital administration systems. Diagnoses (FNSD, PNES) were formulated by referring neurologists on the basis of all available clinical data focusing on positive signs rather than the exclusion of other neurological disorders (including through video-EEG recordings of typical events in those with PNES). PNES was conceptualised as a subtype of FNSD. For some analyses, patients were split into subgroups with PNES or “other FNSD”. Patients with a diagnosis of PNES with additional other FNSD symptoms were included in the PNES group. No patients with mixed epilepsy/PNES were included. Apart from PNES, the range of FNSD symptoms included weakness, abnormal movement, swallowing symptoms, speech symptom, sensory loss, visual, olfactory or hearing disturbance. Almost all patients had more than one symptom. Routine baseline clinical measures: Demographic Questionnaire A simple demographic questionnaire was developed for the study to collect information about gender, marital status, employment status and education level.
Journal Pre-proof Post-Traumatic Stress Disorder Civilian Checklist (PCL-C) The PCL-C is a 17-item Likert self-report questionnaire that aims to identify PTSD and quantify its resultant symptoms 12. The 17 items reflect the DSM-IV PTSD symptoms criteria. Symptom severity is rated on Likert scales ranging from 1-5 and a score is computed by summing the responses 13. There are 3 types of the checklist – PCL - Military, Civilian and specific trauma. The PCL-C has shown good internal consistency in 14 studies in clinical and non-clinical settings including among patients with severe mental illness 12.
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In line with guidance from the National Centre for PTSD (USA) those with a PCL-C score ≥45 were considered “symptomatic” while those with a score below this level were considered “asymptomatic”14. While being “symptomatic” of PTSD does not equate to a clinical diagnosis of PTSD the relatively high cut off point of ≥45 is the level recommended for mental health rather than neurological settings and may thus underestimate the true prevalence of clinical PTSD diagnoses in this patient sample 14. In light of this we refer to patients with a score ≥45 as being potentially symptomatic of PTSD throughout the paper.
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Generalised Anxiety Disorder (GAD-7)
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The GAD-7 is a 7-item self-report anxiety questionnaire assessing anxiety symptoms experienced over the course of the past two weeks with a maximum score of 21 15. The reliability and validity of the GAD-7 have been tested and supported by a number of studies in both the general population and patients with psychopathology16-18. The seven items of the GAD-7 were combined to produce a total score (higher score reflects higher anxiety levels) out of 21. A score of ≥15 was interpreted as a marker of severe anxiety 15 and is the cut off used for this paper.
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Patient Health Questionnaire -9 (PHQ-9)
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The PHQ-9 is a nine item self-report questionnaire measuring symptoms of Major Depressive Disorder over the past two weeks with a maximum score of 27 19. The PHQ-9 has a sensitivity of 88% and a specificity of 88% for Major Depression. The PHQ-9 is a widely used clinical measure and has been administered to patients with PNES 20. A score of ≥15 was considered as indicative of moderately severe depression and is the cut off used for this paper 19. Patient Health Questionnaire -15 (PHQ-15) The PHQ-15 is a 15-item self-report questionnaire assessing the frequency and severity of somatic symptoms experienced over the last four weeks with a maximum score of 30 21. The PHQ-15 has previously been administered to patients with PNES and other types of FNSD. High severity levels of somatic symptoms would be indicated by a score of 15 and above and is the cut off used for this paper 17,18. Work and Social Adjustment Scale (WSAS) The WSAS is a 5-item measure of impaired functioning attributable to a particular problem or disease 22. The scale assesses impairment in five areas including work, home management, social leisure activities, private leisure activities, family and relationships, with higher values indicating greater impairment. The WSAS has been established as a valid, reliable, and sensitive measure in a number of different physical and psychiatric disorders 8, 23-25.
Journal Pre-proof The scores in the five items were combined into a total score, which was found to have acceptable internal consistency reliability. The lower the score the better the quality of life. Short Form 36 (SF-36)
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The Short Form 36-Item Health Survey (Version 2.0) (SF-36) is a widely-used and wellvalidated self-report measure of health related quality of life (HRQoL) consisting of 36 items 26, 27 . The SF-36 comprises a set of quality of life items that are used to address health concepts in 8 sub-scales (physical functioning; physical role limitations, bodily pain; general health perceptions; vitality, social role functioning, emotional role functioning, mental health/emotional well-being and perceived change in health status over the last year). Scores were analysed according to the procedure for the RAND SF-36. Each item score is positively measured such that higher scores constitute better health-related quality of life. The SF-36 scales can be combined to obtain two summary measures; these are the Physical Health Component score and the Mental Health Component score 28, 29.
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Statistical Analysis
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All questionnaire data were scored, and missing data handled according to the respective questionnaire scoring manuals. Data was analysed using SPSS (version 24; SPSS Inc., Chicago, IL, U.S.A.). Distribution was assessed for normality using the Shapiro-Wilk test. As almost all scores were not normally distributed, non-parametric tests were used throughout. Frequencies and descriptive statistics were examined for each variable. Comparisons between the two patient groups were made using Mann Whitney U test for continuous data and effect sizes were calculated and reported as r-values. Chi squared tests were used for categorical/nominal data and odds ratios were calculated. Spearman’s rho correlations were calculated to examine relations between PCL-C scores, diagnoses and the other measures. Significant Spearman’s rho correlation coefficients of >0.3 were interpreted as showing a moderate to high correlation 30. Statistically significant correlations were entered into a multilinear regression model for continuous data to explore whether psychopathological variables could be used to predict the PTSD symptom score. We controlled for other variables using hierarchical linear regression and determined the amount of variance in PTSD score explained by the variables of interest. The validity of the assumptions of linear regression was tested through visual inspection of histograms of standardized residual and P-P plots of expected against observed cumulative probabilities; visual inspection of scatter plots of predicted against observed standardized residuals; and assessing for multicollinearity using Variance Inflation Factors for all independent variables. We identified potential outlying results by calculating standardised residuals and Cook’s distances for all data points. Cronbach’s alpha was calculated for all self-report questionnaires as a measure of internal consistency. Regulatory Approval The data, which form the basis of this report, were collected as part of the routine evaluation of our psychotherapy service required by the funders of the service. The service evaluation was approved by the Clinical Effectiveness Unit of Sheffield Teaching Hospitals NHS Foundation Trust and conducted in full compliance with UK research governance regulations.
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Results:
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Table 1 summarises demographics and clinical characteristics of our study population. Our cohort comprised 430 patients with a diagnosis of FNSD, of whom 241 (56.0%) had PNES. The mean PCL score for the whole cohort was 51. Of the whole group, 261 (60.7%) had PCL-C scores above the cut off of 45 deemed potentially symptomatic of PTSD. There were significant differences between the potentially symptomatic PTSD and asymptomatic groups in terms of cohabitation (fewer people in the symptomatic group were living with a partner) OR 2.95 (95% CI 1.83-4.04) and economic activity (fewer individuals in the symptomatic group were economically active) OR 2.23 (95% CI 1.46-3.41).The levels of PTSD symptoms reported by those in the FNSD and PNES groups did not differ significantly (p=0.28), with high PCL-C scores found in both populations.
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FNSD Patients above the clinical PTSD cut-off self-reported significantly more distress and greater impairment on all of the measures used apart from SF36 for physical functioning. Those with a PCL score below 45 had significantly lower levels of somatic symptoms, anxiety and depression than the potentially symptomatic group (see Table 2). All self-report measures used in this study had high levels of iinternal consistency (see table 3).
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Tables 2 & 3 near here
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Anxiety (GAD-7), depression (PHQ-9), somatisation (PHQ-15), disease-related social dysfunction (WSAS) and mental HRQoL (SF36-MCS) showed high levels of correlation with PTSD symptom burden (PCL-C score) across the whole FND patient group (see Table 4 – Spearman Rho correlation coefficients and significance).
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We sought to explore further whether these variables made independent contributions to the variance of the PTSD symptom burden when controlling for demographic variables (age, gender, marital status, employment status, and diagnosis). Using the PCL-C score as the independent variable and demographic variables as predictors for the first step of the hierarchical regression, the psychological variables were added as the second step. Demographic and psychological variables were independently associated with the PCL-C score (ANOVA for omnibus test of model coefficients, p<0.001). Psychological variables explained an additional 59.5% of the variance in PCL-C score (ΔR2 = 0.595, p<0.001) after controlling for demographic variables. In our final model, relationship status, GAD-7 score, PHQ-9 score, and PHQ-15 score were all significantly and independently associated with the level of PTSD symptoms (PCL-C score). Full details of the model and regression coefficients are provided in Table 5.
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Discussion
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Sixty percent of our large consecutive cohort of patients with FNSD were potentially symptomatic of PTSD as determined by a PCL-C score of ≥45. A high PTSD symptom burden was associated with decreased quality of life, high levels of distress, anxiety, depression and poor social functioning. This suggests that PTSD symptoms matter to the wellbeing of individuals with FNSD; although further research needs to be done to clarify the direction of causality. The mean PTSD symptom burden level in this population (51) was much higher than that in studies of non-clinical populations, such as university staff or students where means of 29 were found 13,31. In a study exploring the prevalence of PTSD in patients with chronic and severe mental health Cusack et al. [2006] found that, although 87% of patients with severe mental illness reported previous trauma, only 30% of these patients had sufficiently severe post traumatic symptoms to pass their threshold of potential clinical PTSD of 40. When the cut off was increased to 50 only 19% met this criterion 32. The mean PCL score in their population was 35.5, i.e. much lower than in our population.
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The high PCL scores in our patient group may indicate a clinically important difference in psychological coping mechanisms between those with FNSD and patients with other severe mental health illness. Alternatively, symptoms of FNSD could overlap with those typically associated with PTSD. Indeed, FNSD has been interpreted as ‘somatic dissociation’, for instance Fizman et al. (2004) described two subtypes of PTSD and suggested ‘PNES could be understood as a clinical expression of the dissociative subtype of PTSD’ 9. Gupta also alluded to PNES being a specific coping mechanism when he described dissociation in the context of conversion as a ‘regulatory state involved in coping with extreme arousal in PTSD through the hyper-inhibition of the limbic regions.’ 33.
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The levels of PTSD symptoms in our patient cohort were as high in those with PNES as they were in those with other manifestations of FNSD. The lack of a difference in PTSD symptom levels between these two FNSD subgroups is at variance with the findings of some previous studies which found that patients with PNES are likely to be more traumatised 2, 34-38 and suggested important aetiological differences between FNSD and PNES 39-42. However, other studies have shown that patients with ‘Psychogenic Movement Disorders’ (PMD) show clinical overlap with those with PNES in that both groups have similar psychological profiles characterised by increased somatisation, depression and anxiety ratings ,10,11,43, 44. In fact, Hopp et al. concluded that PNES and PMD were so similar that ‘diagnosing and treating PNES and PMD as two separate processes may be detrimental to progress in understanding and managing these challenging disorders’ 39. Despite the fact that our findings are based on a large consecutive FNSD patient cohort, the failure of the current study to demonstrate higher levels of PTSD symptoms in the subgroup with PNES may be the result of patient selection bias. Although neurologists were able to refer any patient with FNSD to the departmental psychotherapy service, they may preferentially have referred patients with a history of trauma. It is also possible that patients with no PTSD symptoms were less likely than those with such symptoms to accept the referral for psychotherapy or to express an interest in the offer of psychological treatment by
Journal Pre-proof returning the baseline questionnaires. Regardless of the possible effects of selection bias, our findings clearly demonstrate a high prevalence of symptoms likely to indicate previous traumatisation across the whole FNSD patient group regardless of predominant neurological manifestations. Given that screening for PTSD is highly unusual in neurological settings, we explored to what extent other patient characteristics can help to predict a high PCL-C score. The linear regression analysis suggests that relationship status, anxiety, depression and PHQ15 scores significantly predicted potentially symptomatic PTSD and explained nearly 60% of the variance. This close relationship between symptoms of anxiety and depression and PTSD symptoms suggests that high scores on anxiety or depression screening instruments should alert clinicians to the possible presence of PTSD in those with FNSD.
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Other studies have described the overlap between depression, anxiety and PTSD symptoms reflected in our data 44-49. In a study of 500 people recruited from community organisations and clinics, higher levels of trauma and adversity over a lifetime were associated with more severe somatic and depressive symptoms 50. In a longitudinal study of men who had experienced childhood sexual abuse (CSA), CSA was positively related to both depressive and somatic symptoms 51. Elhai et al. found that 48-55% of participants with a history of PTSD also met the criteria for a major depressive disorder 52. There is overlap between criteria for depression and the ‘dysphoria’ symptoms in the diagnostic criteria for PTSD 46, 48. However, even with amendments to the criteria to account for this overlap, rates of depression and anxiety were still high in those with PTSD 47. Our cross-sectional study design does not allow us to come to any conclusions about the direction of the relationship between these variables and it remains unclear which precipitates the other. However, all interact and are capable of causing significant distress.
Limitations
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The fact that patients with potentially symptomatic PTSD were statistically less likely to be living with a partner than those without high PTSD symptom levels and were also less likely to be in paid employment may simply be a reflection of the severity of their symptoms. However, previous research in patients with PNES suggests that traumatisation (especially in early life) is also linked to problems with attachment and emotional processing in this patient group which may have reduced their ability to sustain stable personal relationships and employment 53.
This study had several limitations. This service evaluation benefits from truly consecutive case identification, i.e. “a real life’ setting and very large patient numbers. However, our study is based on routine data and procedures, including clinical diagnoses rather than diagnoses based on research criteria. Having said this, patients were only included in this study when fully trained consultant neurologists with an interest in functional disorders and PNES had arrived at these diagnoses with sufficient certainty to recommend psychotherapy and to withdraw any treatments for alternative diagnoses considered erroneous (such an incorrect diagnosis of epilepsy in a person with PNES). In line with clinical practice in the UK, about 40% of PNES diagnoses at our centre are based video-EEG documented seizures, but diagnoses will also have been made on the basis of home video recordings or the observation of seizures by clinicians in conjunction with other test findings available (such as brain imaging or interictal EEG findings 54.
Journal Pre-proof Our case identification method means that no selection bias was introduced through consenting procedures. Psychotherapy could be offered to all patients referred, with no financial restrictions or conditions, and our service is the only public provider of psychotherapy for FNSD in the area we serve. However, all data analysed were provided by patients who had been referred to a psychotherapy service, and we cannot be sure whether neurologists were more likely to refer particular subgroups of FNSD patients (for instance those with high levels of trauma).
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Importantly, we made no attempt to measure trauma directly. Instead we make inferences about previous trauma on the basis of symptoms typically attributed to PTSD. Further, while our characterisation of a subgroup potentially symptomatic of PTSD is likely to have identified patients meeting the criteria for a clinical diagnosis of PTSD, the gold standard examination for PTSD would have involved an interview with a trained professional 5 rather than the questionnaire used in this study. Although all patients seen for psychotherapy in our service would have provided a detailed personal and medical history during their treatment, and accounts of traumatic experiences would have been sought by therapists, these data were not captured prospectively in a standardised form throughout the period described in this paper. When this information was captured in a methodical fashion among patients with FNSD referred to our service between January 2003 and December 2004, 20.3% of all patients had experienced relevant sexual and 72.9% non-sexual trauma prior to developing FNSD 2. What is more, the PCL-C is a well-validated instrument, and we used a conservative measure of 45 as a cut-off of potentially symptomatic PTSD. Nevertheless, there is debate about the value of this measure as a diagnostic tool: Whereas Wilkins et al. suggest that the PCL-C may overestimate the prevalence of PTSD and argue that the overlap with symptoms of anxiety and depression makes it hard to differentiate which symptoms are specifically related to PTSD 12, Ruggerio et al. point out that, as the questionnaire included diagnostic criteria B, C & D of the DSM-IV for PTSD, it ‘may yield information that has a greater predictive value on a diagnostic level’ 13.
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Next, our findings are based on patients referred to a single NHS Neurosciences treatment provider. This limits generalisability, although patients were referred by over 20 different neurologists from a range of neurological clinic settings in secondary and tertiary care centres served by specialists based at RHH. Further limitations of the dataset available for this study include the absence of information allowing a more fine-grained subdifferentiation of FNSD presentations, and a standardised measure of dissociation. Conclusion Despite these limitations, the data demonstrate the high prevalence of PTSD symptoms in patients with FNSD, adding to the evidence of a link between trauma and the development of FNSD. Trauma and PTSD symptoms were negatively correlated with the quality of life of patients with FNSD and associated with other psychiatric comorbidities such as anxiety and depression. High levels of anxiety and depression were independently associated with higher levels of PTSD symptoms and screening instruments for anxiety and depression could therefore indicate which individuals would be at high risk of PTSD. Practitioners
Journal Pre-proof working with this client group need to be capable of screening for trauma and managing trauma in the treatment. 'All authors have completed the Unified Competing Interest form at http://www.icmje.org/coi_disclosure.pdf and declare that : The authors have no competing
interests to report. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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All listed authors have approved the submission of the manuscript to the journal, there are no other published, submitted or proposed papers reporting the same or overlapping data.
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25. Cella M, Sharpe M, Chalder T. Measuring disability in patients with chronic fatigue syndrome: reliability and validity of the Work and Social Adjustment Scale. Journal of Psychosomatic Research. 2011;71(3):124-128. 26. Brazier J, Harper R, Jones N, O'Cathain A, Thomas K, Usherwood T et al. Validating the SF-36 health survey questionnaire: new outcome measure for primary care. BMJ. 1992;305(6846):160 164. 27. McHorney C, Ware J, Rachel Lu J, Sherbourne C. The MOS 36-ltem Short-Form Health Survey (SF-36): III. Tests of Data Quality, Scaling Assumptions, and Reliability Across Diverse Patient Groups. Medical Care. 1994;32(1):40-66. 28. Ware J. SF-36 physical and mental health summary scales: a user’s manual. Boston, MA: Health Assessment Lab, New England Medical Center.; 1999. 29. Ware J. SF-36 Health Survey Update. Spine. 2000;25(24):3130-3139. 30. Mukaka M. Statistics corner: A guide to appropriate use of correlation coefficient in medical research. Malawi Medicine Journal. 2012;24(3):69-71. 31 Conybeare D, Behar E, Solomon A, Newman M, Borkovec T. The PTSD Checklist-Civilian Version: Reliability, Validity, and Factor Structure in a Nonclinical Sample. Journal of Clinical Psychology. 2012;68(6):699-713.
Journal Pre-proof 32. Cusack K, Grubaugh A, Knapp R, Frueh B. Unrecognized Trauma and PTSD among Public Mental Health Consumers with Chronic and Severe Mental Illness. Community Mental Health Journal. 2006;42(5):487-500. 33. Gupta M. Review of somatic symptoms in post-traumatic stress disorder. International Review of Psychiatry. 2013;25(1):86-99. 34. Keynejad R, Frodl T, Kanaan R, Pariante C, Reuber M, Nicholson T. Stress and functional neurological disorders: mechanistic insights. Journal of Neurology, Neurosurgery & Psychiatry. 2018;:jnnp-2018-318297. 35. Akyuz G, Kugu N, Akyuz A, Dogan O. Dissociation and childhood abuse history in epileptic and pseudoseizure patients. Epileptic Disorders. 2004;6(3):187-92.
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36. Kaplan M, Dwivedi A, Privitera M, Isaacs K, Hughes C, Bowman M. Comparisons of childhood trauma, alexithymia, and defensive styles in patients with psychogenic non-epileptic seizures vs. epilepsy: Implications for the etiology of conversion disorder. Journal of Psychosomatic Research. 2013;75(2):142-146.
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37. Ozcetin A, Belli H, Ertem U, Bahcebasi T, Ataoglu A, Canan F. Childhood trauma and dissociation in women with pseudoseizure-type conversion disorder. Nordic Journal of Psychiatry. 2009;:1-7.
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38. Salmon P, Al-Marzooqi S, Baker G, Reilly J. Childhood Family Dysfunction and Associated Abuse in Patients With Nonepileptic Seizures. Psychosomatic Medicine. 2003;65(4):695-700.
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39. Kanaan RAA, Duncan R, Goldstein LH, Jankovic J, Cavanna AE. Are psychogenic non-epileptic seizures just another symptom of conversion disorder? J Neurol Neurosurg Psychiatry. 2017;88(5):425–9.
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40. Ekanayake V, Kranick S, Lafaver K, Naz A, Frank A, Lafrance WC, et al. Personality traits in psychogenic nonepileptic seizures ( PNES ) and psychogenic movement disorder ( PMD ): Neuroticism and perfectionism. J Psychosom Res [Internet]. 2017;97 (November 2016):23–9.
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41. Jalilianhasanpour R, Williams B, Gilman I, Burke MJ, Glass S, Fricchione GL, et al. Resilience linked to personality dimensions, alexithymia and affective symptoms in motor functional neurological disorders. J Psychosom Res [Internet]. 2018;107(February):55–61. 42. Matin N, Young SS, Williams B, Lafrance WC, King JN, Caplan D, et al. Neuropsychiatric associations with gender, illness duration, work disability, and motor subtype in a U.S. functional neurological disorders clinic population. J Neuropsychiatry Clin Neurosci. 2017;29(4):375–82.
43. Hopp J, Anderson K, Krumholz A, Gruber-Baldini A, Shulman L. Psychogenic seizures and psychogenic movement disorders: Are they the same patients?. Epilepsy & Behavior. 2012;25(4):666-669. 44. Kranick S, Ekanayake V, Martinez V, Ameli R, Hallett M, Voon V. Psychopathology and psychogenic movement disorders. Movement Disorders. 2011;26(10):1844-1850.
45. Lockwood E, Forbes D. Posttraumatic Stress Disorder and Comorbidity: Untangling the Gordian Knot. Psychological Injury and Law. 2014;7(2):108-121. 46. Rosen G, Lilienfeld S. Posttraumatic stress disorder: An empirical evaluation of core assumptions. Clinical Psychology Review. 2008;28(5):837-868.
Journal Pre-proof 47. Van Emmerik A, Kamphuis J. Testing a DSM-5 reformulation of posttraumatic stress disorder: Impact on prevalence and comorbidity among treatment-seeking civilian trauma survivors. Journal of Traumatic Stress. 2011;24(2):213-217. 48. Spitzer R, First M, Wakefield J. Saving PTSD from itself in DSM-V. Journal of Anxiety Disorders. 2007;21(2):233-241. 49. Elhai J, Contractor A, Tamburrino M, Fine T, Cohen G, Shirley E et al. Structural relations between DSM-5 PTSD and major depression symptoms in military soldiers. Journal of Affective Disorders. 2015;175:373-378. 50. Loeb T, Joseph N, Wyatt G, Zhang M, Chin D, Thames A et al. Predictors of somatic symptom severity: The role of cumulative history of trauma and adversity in a diverse community sample. Psychological Trauma: Theory, Research, Practice, and Policy. 2018;10(5):491-498.
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51. Easton S, Kong J. Mental health indicators fifty years later: A population-based study of men with histories of child sexual abuse. Child Abuse & Neglect. 2017;63:273-283.
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52. Elhai J, Grubaugh A, Kashdan T, Frueh B. Empirical Examination of a Proposed Refinement to DSM-IV Posttraumatic Stress Disorder Symptom Criteria Using the National Comorbidity Survey Replication Data. The Journal of Clinical Psychiatry. 2008;69(4):597-602.
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53. Holman N, Kirkby A, Duncan S, Brown R. Adult attachment style and childhood interpersonal trauma in non-epileptic attack disorder. Epilepsy Research. 2008;79(1):84-89.
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54. Mayor, R.; Smith, P.; Reuber, M. Management of patients with Nonepileptic Attack Disorder in the United Kingdom: a survey of healthcare professionals. Epilepsy and Behavior. 2011;21,402-06.
Table 1. Patient demographics Total Population
Symptomatic
Asymptomatic
Significance
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N Age in years (SD)
430 42.1 (15.7)
261 41.3 (15.1)
162 42.7 (15.6)
122 (28.4) 298 (69.3)
75 (28.7) 181 (69.3)
45 (27.7) 115 (71.0)
Gender b
238 (55.3) 189 (44.0)
133 (49.0) 128 (51.0)
107 (66.0) 54 (33.3)
<.001 ( 2= 12.24)
<.001 ( 2= 14.10)
241 (56) 189 (44)
151 (57.9) 110 (42.1)
68 (42.0) 85 (52.5)
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67 (25.1) 187 (71.6)
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137 (31.6) 276 (64.2)
85 (52.5) 77 (47.5)
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Male (%) Female (%) Marital Status b Living with Partner (%) Not partner (%) Employment Status b Employed (%) Unemployed (%) Coded Diagnosis PNES (%) Other FNSD (%)
0.40 (z=-.84) 0.84 ( 2= 0.35)
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Abbreviations: PNES = Psy chogenic Non-Epileptic Seizures, FNSD = Functional Neurological Sy mptom Disorder. Sy mptomatic PTSD subgroup def ined by PTSD-C score ≥ 45, see methods section f or details.
b
Missing Data: Gender-10 (2.3%), Marital status-3 (0.7%), employ ment status-17 (4.0%).
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a
0.28 ( 2= 1.18)
Journal Pre-proof Table 2 – Comparison of median scores of the main measures of interest for the whole population, symptomatic PTSD and asymptomatic patient groups Symptomatic of PTSD 261 64 (40, 45-85)
Asymptomatic
Significance
169 30 (27, 17-44)
31 (40, 0-40)
21.5 (40, 0-40)
PHQ-15 15 (29, 0-29)
18 (28, 1-29)
11 (25, 0-25)
GAD-7 15 (21, 0-21)
18 (21, 0-21)
6 (21, 0-21)
PHQ-9 18 (27, 0-27)
21 (27, 0-27)
P (Z, r) <0.001 (-17.30, 0.83) <0.001 (-6.17, 0.30) <0.001 (-9.34, 0.45) <0.001 (-12.91, 0.62) < 0.001 (-13.11, 0.63)
10.5 (25, 0-25)
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N 430 PCL-C Median a 52 (85, 17-85) (range, minimum to maximum) WSAS 27 (40, 0-40)
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Measure Whole population
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SF36 a
PCS 27.1 (61.5, 6.8-68.3)
24.3 (53.5) (3.7-57.1) 27.7 (60, 8.468.3)
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MCS 28.5 (62.6, 3.7-66.3)
41 (54.7, 11.666.3) 27.7 (59.4, 6.866.2)
<0.001 (-9.98, 0.48) .93 (-0.09, 0.00)
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Missing Data: PCL – 7 (1.6%), SF36 – 36 (8.4%).
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Abbreviations: PCL-C = Post-Traumatic Stress Disorder Civilian Checklist, WSAS = Work and Social Adjustment Scale, PHQ-15 = Patient Health Questionnaire 15, GAD-7 = Generalised Anxiety Disorder 7. PHQ-9 = Patient Health Questionnaire 9, SF36 = Short Form 36, MCS = Mental Component Score, PCS = Physical Component Score.
Journal Pre-proof Table 3 – Internal Consistency for Self-Report Measures Cronbach’s Alpha
Measure Number of Items PCL-C 17
.94
PHQ-9 9
.89
GAD-7 7
.93
PHQ-15 15
.82
WSAS 5
.87
SF36 a 8
.82
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8 Standardised SF36 subscales were used to calculate internal consistency
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Abbreviations: PCL-C = Post-Traumatic Stress Disorder Civilian Checklist, WSAS = Work and Social Adjustment Scale, PHQ-15 = Patient Health Questionnaire 15, GAD-7 = Generalised Anxiety Disorder 7. PHQ-9 = Patient Health Questionnaire 9, MCS = Mental Component Score, PCS = Physical Component Score
Journal Pre-proof Table 4 –Correlations between self-report measures across the whole FNSD group Measures PCL-Ca
PCL-C
PHQ-9
GAD-7
PHQ-15
WSAS
SF36
SF36
MCS
PCS
-
PHQ-9 .747*
-
GAD-7 .743*
.744*
-
PHQ-15 .585*
.616*
.555*
-
.448*
.570*
.447*
.479*
-
MCS*
-.578*
-.641*
-.611*
-.360*
-.372*
-
PCS*
-.029
-.172*
-.034
-.331*
-.461*
-.225*
-
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WSAS
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Abbreviations: PCL-C = Post-Traumatic Stress Disorder Civilian Checklist, WSAS = Work and Social Adjustment Scale, PHQ-15 = Patient Health Questionnaire 15, GAD-7 = Generalised Anxiety Disorder 7. PHQ-9 = Patient Health Questionnaire 9, MCS = Mental Component Score, PCS = Physical Component Score. Missing Data: PCL – 7 (1.6%), SF36 – 36 (8.4%).
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* Correlation is signif icant at the lev el of P <0.01.
Journal Pre-proof Table 5 - Linear Regression Predicting PCL-C score Model Standardised 1
95% CI (lower – upper bound)
Sig. dif.
(constant)
33.6 - 59.2
Age -.044
.41
-0.1 – 0.1
Gender -.005
.92
-3.9 – 3.5
<.001
-10.0 – -2.4
<.001
4.6 – 12.5
.40
-2.1 – 5.4
Marital Status -.165 Employment Status .217 Diagnosis .044
16.6 – 36.5
.92
Gender -.026
.40
Marital Status -.117
PHQ9 .360
-1.8 – 2.8
P < .001
0.7 – 1.3
.23
-0.2 – 0.1
P < .001
0.6 – 1.2
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SF36 MCS -.053
-4.1 – 1.2
.70
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GAD7 .331
-6.7 – -2.1
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.27
Diagnosis .012
PHQ15 .173
-3.2 – 1.3
P < .001
Employment Status -.037
WSAS .010
-0.1 – 0.1
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Age -.003
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(constant)
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2
.79
-0.1 – 0.1
P < .001
0.3 – 0.8
2
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Abbreviations: WSAS = Work and Social Adjustment Scale, PHQ-15 = Patient Health Questionnaire 15, GAD-7 = Generalised Anxiety Disorder 7. PHQ-9 = Patient Health Questionnaire 9, SF36 MCS = Short Form 36 Mental Component Score. Note: ΔR = 0.595, p<0.001
Journal Pre-proof Symptoms of Post-Traumatic Stress Disorder (PTSD) in patients with Functional Neurological Symptom Disorder (FNSD)
Highlights of paper:
60% with Functional Neurological Symptom Disorder (FNSD) had high PTSD symptom burden
No difference in levels of PTSD symptoms between Psychogenic Non Epileptic Seizures (PNES) and other FNSD Those with potentially Symptomatic PTSD had lower quality of life, more likely to be single or not
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High levels of anxiety and depression were independently associated with higher levels o f PTSD
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symptoms
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working
M.A. Cordelia Gray, Alex Calderbank, Joy Adewusi, Rhiannon Hughes, Markus Reuber PII:
S0022-3999(19)30449-0
DOI:
https://doi.org/10.1016/j.jpsychores.2019.109907
Reference:
PSR 109907
To appear in:
Journal of Psychosomatic Research
Received date:
15 April 2019
Revised date:
16 December 2019
Accepted date:
16 December 2019
Please cite this article as: M.A. Cordelia Gray, A. Calderbank, J. Adewusi, et al., Symptoms of posttraumatic stress disorder in patients with functional neurological symptom disorder, Journal of Psychosomatic Research(2019), https://doi.org/10.1016/ j.jpsychores.2019.109907
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
© 2019 Published by Elsevier.
Journal Pre-proof Symptoms of Posttraumatic Stress Disorder in patients with Functional Neurological Symptom Disorder Short Running Head: PTSD in FNSD Cordelia Gray M.A. a,b, Alex Calderbank, Joy Adewusi MSc, Rhiannon Hughes b MSc, Markus Reuberb PhD a
Neurology Psychotherapy Service, Sheffield Teaching Hospital, Sheffield, UK
b
Academic Neurology Unit, University of Sheffield, Sheffield, UK
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Cordelia Gray, Neurology Psychotherapy Service, 12 Claremont Crescent, Sheffield, S10 2TA, [email protected], 0114 226 5018.Fax: 0114 271 3999
Journal Pre-proof Abstract Objective: To describe prevalence and relevance of Post-Traumatic Stress Disorder (PTSD) symptoms in Functional Neurological Symptom Disorder (FNSD) and explore differences in PTSD symptom scores between subgroups with Psychogenic Non-Epileptic Seizures (PNES) or other FNSD.
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Methods: This cross-sectional study evaluated data from 430 consecutive patients referred to a specialist psychotherapy service (69.3% female, 56% with PNES/44% with other FNSD). We analysed self-reported symptoms of Post-Traumatic Stress Disorder (PTSD Civilian Checklist, PCL-C), depression (PHQ-9), anxiety (GAD-7), physical symptoms (PHQ15), social functioning (WSAS), and health related quality of life (SF-36). Relationships between PTSD scores, diagnosis and other measures were examined. Independent associations of PTSD scores were identified using multilinear regression.
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Results: Symptom scores likely to indicate clinical PTSD were reported by 60.7% of patients with no difference between PNES and FNSD subgroups. Those potentially symptomatic of PTSD were less likely to be living with a partner OR 2.95 (95% CI 1.83-4.04), or to be in employment OR 2.23 (95% CI 1.46-3.41) than asymptomatic patients. There were higher levels of anxiety (r=0.62), depression (r=0.63) and somatic symptoms (r=0.45) and lower quality of life scores (r = 0.48) in patients PTSD symptoms (p<0.0001 for all comparisons). Anxiety, depression and somatic symptoms made independent contributions to the variance of PTSD symptoms.
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Conclusion: There is a high prevalence of PTSD symptoms in patient with FNSD regardless of whether they have PNES. Trauma and PTSD symptoms are negatively correlated with quality of life. Self-report instruments for anxiety, depression and somatic symptoms may predict the presence of PTSD.
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Keywords: Post Traumatic Stress Disorder, Functional Neurological Symptom Disorder, Psychogenic Non-Epileptic Seizures, anxiety, depression, trauma
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Introduction: Functional neurological symptom disorders (FNSD) are one of the most common reasons for referral to a neurological outpatient clinic 1. Functional neurological symptoms are as disabling as similar symptoms attributable to structurally or physiologically explained pathologies but associated with more psychiatric comorbidities 2,3.
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Historically, two key criteria had to be met before a diagnosis of conversion disorder (the name for FNSD in DSM-4) could be made: 1) neurological symptoms could not be explained by neurological disease, and 2) a precipitant likely to have caused significant distress such as a traumatic life event or a personal dilemma had to be identified 4. The interpretation of FNSD as a physical manifestation of distress is supported by many studies demonstrating a higher frequency of child- or adulthood traumatic life events in FNSD patients compared to healthy or disease controls 5. However, despite increased rates of trauma across different patient populations with FNSD 2, some patients with otherwise typical manifestations of FNSD do not report any potential stressors in their lives 5. Reflecting the development of recent thought about FNSD and in order to allow clinicians to formulate a diagnosis in such circumstances, the DSM-5 has therefore dropped the mandatory diagnostic criterion of a psychological precipitant. The diagnosis of FNSD is now based on neurologically defined criteria such as the observation of incompatibility between illness manifestation and recognised neurological or medical condition 6, e.g. the presence of Hoover’s sign in patients with unilateral leg weakness or resistance to eye opening during a seizure 3.
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Nevertheless, previous trauma continues to be an important aetiological factor in modern accounts of FNSD 5, 7, 8, and it is a matter of continuing debate whether the inability of some patients’ to recall potentially relevant distressing experiences means that they never occurred, that they are unwilling or unable to recall them, or that the methods used to capture this information are inadequate 3.
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The aim of the current study is to explore the potential relevance of previous trauma in patients with FNSD by examining the prevalence and clinical significance of symptoms characterising Post Traumatic Stress Disorder (PTSD). In addition to using these symptoms as an indirect indication of the possible relevance of trauma in FNSD, our study examines whether differences in the levels of PTSD symptoms could account for some of the phenomenological and aetiological differences which have been described between subtypes of FNSD, namely those with seizure-like presentations (Psychogenic Non-epileptic Seizures, PNES) and other manifestations 2,9,10. This exploration is intended to contribute to the on-going debate about whether it makes more sense to consider different presentations as distinct entities or to approach them as minor variants of FNSD 11. Last but not least this study explores whether self-report instruments commonly used for routine anxiety and depression screening in neurological patient populations could be used to predict the presence of PTSD symptoms. Method: Subjects and recruitment
Journal Pre-proof Patients contributing to this study were referred consecutively to a team of six psychotherapists and one psychotherapy manager working within the Department of Neurology at the Royal Hallamshire Hospital (RHH), Sheffield, United Kingdom, between October 2015 and October 2017. Referrals were made by fully trained Consultant Neurologists working for neurology service for adults (over 16 years old). The neurologists based at RHH reach out to hospitals in surrounding towns and are the sole service provider in their medical speciality for the population of South Yorkshire (population 1.39 million). Neurologists were encouraged to refer all patients diagnosed with FNSD and willing to access psychotherapy with the following exceptions: 1. Patients with serious on-going psychiatric problems.
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2. Patients who are currently suicidal (e.g. persistent suicidal urges, making plans etc.) or who have had a suicide attempt in the last year. 3. Patients who are currently receiving psychotherapy elsewhere.
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4. Patients who have already had two episodes of treatment from this service.
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5. Patients who are currently dependent on alcohol or opiate drugs.
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Referrals for these patients were rejected because they initially require intervention from other treatment providers. In the United Kingdom, National Health Service (NHS) patients are referred to Neurologists by General Practitioners or Emergency Physicians based on clinical need and have access to neurological assessment, investigations and treatment free of charge. Similarly, access to psychotherapy is provided on the basis of clinical need, and treatment is provided without the need for payment or insurance.
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Prior to receiving their initial appointment with the psychotherapy service, patients are routinely asked to complete a series of questionnaires to provide a baseline account of their symptoms and level of impairment and to indicate that they are keen to opt in to psychological intervention (see below). Clinical data was extracted from hospital administration systems. Diagnoses (FNSD, PNES) were formulated by referring neurologists on the basis of all available clinical data focusing on positive signs rather than the exclusion of other neurological disorders (including through video-EEG recordings of typical events in those with PNES). PNES was conceptualised as a subtype of FNSD. For some analyses, patients were split into subgroups with PNES or “other FNSD”. Patients with a diagnosis of PNES with additional other FNSD symptoms were included in the PNES group. No patients with mixed epilepsy/PNES were included. Apart from PNES, the range of FNSD symptoms included weakness, abnormal movement, swallowing symptoms, speech symptom, sensory loss, visual, olfactory or hearing disturbance. Almost all patients had more than one symptom. Routine baseline clinical measures: Demographic Questionnaire A simple demographic questionnaire was developed for the study to collect information about gender, marital status, employment status and education level.
Journal Pre-proof Post-Traumatic Stress Disorder Civilian Checklist (PCL-C) The PCL-C is a 17-item Likert self-report questionnaire that aims to identify PTSD and quantify its resultant symptoms 12. The 17 items reflect the DSM-IV PTSD symptoms criteria. Symptom severity is rated on Likert scales ranging from 1-5 and a score is computed by summing the responses 13. There are 3 types of the checklist – PCL - Military, Civilian and specific trauma. The PCL-C has shown good internal consistency in 14 studies in clinical and non-clinical settings including among patients with severe mental illness 12.
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In line with guidance from the National Centre for PTSD (USA) those with a PCL-C score ≥45 were considered “symptomatic” while those with a score below this level were considered “asymptomatic”14. While being “symptomatic” of PTSD does not equate to a clinical diagnosis of PTSD the relatively high cut off point of ≥45 is the level recommended for mental health rather than neurological settings and may thus underestimate the true prevalence of clinical PTSD diagnoses in this patient sample 14. In light of this we refer to patients with a score ≥45 as being potentially symptomatic of PTSD throughout the paper.
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Generalised Anxiety Disorder (GAD-7)
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The GAD-7 is a 7-item self-report anxiety questionnaire assessing anxiety symptoms experienced over the course of the past two weeks with a maximum score of 21 15. The reliability and validity of the GAD-7 have been tested and supported by a number of studies in both the general population and patients with psychopathology16-18. The seven items of the GAD-7 were combined to produce a total score (higher score reflects higher anxiety levels) out of 21. A score of ≥15 was interpreted as a marker of severe anxiety 15 and is the cut off used for this paper.
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Patient Health Questionnaire -9 (PHQ-9)
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The PHQ-9 is a nine item self-report questionnaire measuring symptoms of Major Depressive Disorder over the past two weeks with a maximum score of 27 19. The PHQ-9 has a sensitivity of 88% and a specificity of 88% for Major Depression. The PHQ-9 is a widely used clinical measure and has been administered to patients with PNES 20. A score of ≥15 was considered as indicative of moderately severe depression and is the cut off used for this paper 19. Patient Health Questionnaire -15 (PHQ-15) The PHQ-15 is a 15-item self-report questionnaire assessing the frequency and severity of somatic symptoms experienced over the last four weeks with a maximum score of 30 21. The PHQ-15 has previously been administered to patients with PNES and other types of FNSD. High severity levels of somatic symptoms would be indicated by a score of 15 and above and is the cut off used for this paper 17,18. Work and Social Adjustment Scale (WSAS) The WSAS is a 5-item measure of impaired functioning attributable to a particular problem or disease 22. The scale assesses impairment in five areas including work, home management, social leisure activities, private leisure activities, family and relationships, with higher values indicating greater impairment. The WSAS has been established as a valid, reliable, and sensitive measure in a number of different physical and psychiatric disorders 8, 23-25.
Journal Pre-proof The scores in the five items were combined into a total score, which was found to have acceptable internal consistency reliability. The lower the score the better the quality of life. Short Form 36 (SF-36)
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The Short Form 36-Item Health Survey (Version 2.0) (SF-36) is a widely-used and wellvalidated self-report measure of health related quality of life (HRQoL) consisting of 36 items 26, 27 . The SF-36 comprises a set of quality of life items that are used to address health concepts in 8 sub-scales (physical functioning; physical role limitations, bodily pain; general health perceptions; vitality, social role functioning, emotional role functioning, mental health/emotional well-being and perceived change in health status over the last year). Scores were analysed according to the procedure for the RAND SF-36. Each item score is positively measured such that higher scores constitute better health-related quality of life. The SF-36 scales can be combined to obtain two summary measures; these are the Physical Health Component score and the Mental Health Component score 28, 29.
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Statistical Analysis
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All questionnaire data were scored, and missing data handled according to the respective questionnaire scoring manuals. Data was analysed using SPSS (version 24; SPSS Inc., Chicago, IL, U.S.A.). Distribution was assessed for normality using the Shapiro-Wilk test. As almost all scores were not normally distributed, non-parametric tests were used throughout. Frequencies and descriptive statistics were examined for each variable. Comparisons between the two patient groups were made using Mann Whitney U test for continuous data and effect sizes were calculated and reported as r-values. Chi squared tests were used for categorical/nominal data and odds ratios were calculated. Spearman’s rho correlations were calculated to examine relations between PCL-C scores, diagnoses and the other measures. Significant Spearman’s rho correlation coefficients of >0.3 were interpreted as showing a moderate to high correlation 30. Statistically significant correlations were entered into a multilinear regression model for continuous data to explore whether psychopathological variables could be used to predict the PTSD symptom score. We controlled for other variables using hierarchical linear regression and determined the amount of variance in PTSD score explained by the variables of interest. The validity of the assumptions of linear regression was tested through visual inspection of histograms of standardized residual and P-P plots of expected against observed cumulative probabilities; visual inspection of scatter plots of predicted against observed standardized residuals; and assessing for multicollinearity using Variance Inflation Factors for all independent variables. We identified potential outlying results by calculating standardised residuals and Cook’s distances for all data points. Cronbach’s alpha was calculated for all self-report questionnaires as a measure of internal consistency. Regulatory Approval The data, which form the basis of this report, were collected as part of the routine evaluation of our psychotherapy service required by the funders of the service. The service evaluation was approved by the Clinical Effectiveness Unit of Sheffield Teaching Hospitals NHS Foundation Trust and conducted in full compliance with UK research governance regulations.
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Results:
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Table 1 summarises demographics and clinical characteristics of our study population. Our cohort comprised 430 patients with a diagnosis of FNSD, of whom 241 (56.0%) had PNES. The mean PCL score for the whole cohort was 51. Of the whole group, 261 (60.7%) had PCL-C scores above the cut off of 45 deemed potentially symptomatic of PTSD. There were significant differences between the potentially symptomatic PTSD and asymptomatic groups in terms of cohabitation (fewer people in the symptomatic group were living with a partner) OR 2.95 (95% CI 1.83-4.04) and economic activity (fewer individuals in the symptomatic group were economically active) OR 2.23 (95% CI 1.46-3.41).The levels of PTSD symptoms reported by those in the FNSD and PNES groups did not differ significantly (p=0.28), with high PCL-C scores found in both populations.
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FNSD Patients above the clinical PTSD cut-off self-reported significantly more distress and greater impairment on all of the measures used apart from SF36 for physical functioning. Those with a PCL score below 45 had significantly lower levels of somatic symptoms, anxiety and depression than the potentially symptomatic group (see Table 2). All self-report measures used in this study had high levels of iinternal consistency (see table 3).
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Tables 2 & 3 near here
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Anxiety (GAD-7), depression (PHQ-9), somatisation (PHQ-15), disease-related social dysfunction (WSAS) and mental HRQoL (SF36-MCS) showed high levels of correlation with PTSD symptom burden (PCL-C score) across the whole FND patient group (see Table 4 – Spearman Rho correlation coefficients and significance).
Tables 4 near here
We sought to explore further whether these variables made independent contributions to the variance of the PTSD symptom burden when controlling for demographic variables (age, gender, marital status, employment status, and diagnosis). Using the PCL-C score as the independent variable and demographic variables as predictors for the first step of the hierarchical regression, the psychological variables were added as the second step. Demographic and psychological variables were independently associated with the PCL-C score (ANOVA for omnibus test of model coefficients, p<0.001). Psychological variables explained an additional 59.5% of the variance in PCL-C score (ΔR2 = 0.595, p<0.001) after controlling for demographic variables. In our final model, relationship status, GAD-7 score, PHQ-9 score, and PHQ-15 score were all significantly and independently associated with the level of PTSD symptoms (PCL-C score). Full details of the model and regression coefficients are provided in Table 5.
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Discussion
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Sixty percent of our large consecutive cohort of patients with FNSD were potentially symptomatic of PTSD as determined by a PCL-C score of ≥45. A high PTSD symptom burden was associated with decreased quality of life, high levels of distress, anxiety, depression and poor social functioning. This suggests that PTSD symptoms matter to the wellbeing of individuals with FNSD; although further research needs to be done to clarify the direction of causality. The mean PTSD symptom burden level in this population (51) was much higher than that in studies of non-clinical populations, such as university staff or students where means of 29 were found 13,31. In a study exploring the prevalence of PTSD in patients with chronic and severe mental health Cusack et al. [2006] found that, although 87% of patients with severe mental illness reported previous trauma, only 30% of these patients had sufficiently severe post traumatic symptoms to pass their threshold of potential clinical PTSD of 40. When the cut off was increased to 50 only 19% met this criterion 32. The mean PCL score in their population was 35.5, i.e. much lower than in our population.
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The high PCL scores in our patient group may indicate a clinically important difference in psychological coping mechanisms between those with FNSD and patients with other severe mental health illness. Alternatively, symptoms of FNSD could overlap with those typically associated with PTSD. Indeed, FNSD has been interpreted as ‘somatic dissociation’, for instance Fizman et al. (2004) described two subtypes of PTSD and suggested ‘PNES could be understood as a clinical expression of the dissociative subtype of PTSD’ 9. Gupta also alluded to PNES being a specific coping mechanism when he described dissociation in the context of conversion as a ‘regulatory state involved in coping with extreme arousal in PTSD through the hyper-inhibition of the limbic regions.’ 33.
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The levels of PTSD symptoms in our patient cohort were as high in those with PNES as they were in those with other manifestations of FNSD. The lack of a difference in PTSD symptom levels between these two FNSD subgroups is at variance with the findings of some previous studies which found that patients with PNES are likely to be more traumatised 2, 34-38 and suggested important aetiological differences between FNSD and PNES 39-42. However, other studies have shown that patients with ‘Psychogenic Movement Disorders’ (PMD) show clinical overlap with those with PNES in that both groups have similar psychological profiles characterised by increased somatisation, depression and anxiety ratings ,10,11,43, 44. In fact, Hopp et al. concluded that PNES and PMD were so similar that ‘diagnosing and treating PNES and PMD as two separate processes may be detrimental to progress in understanding and managing these challenging disorders’ 39. Despite the fact that our findings are based on a large consecutive FNSD patient cohort, the failure of the current study to demonstrate higher levels of PTSD symptoms in the subgroup with PNES may be the result of patient selection bias. Although neurologists were able to refer any patient with FNSD to the departmental psychotherapy service, they may preferentially have referred patients with a history of trauma. It is also possible that patients with no PTSD symptoms were less likely than those with such symptoms to accept the referral for psychotherapy or to express an interest in the offer of psychological treatment by
Journal Pre-proof returning the baseline questionnaires. Regardless of the possible effects of selection bias, our findings clearly demonstrate a high prevalence of symptoms likely to indicate previous traumatisation across the whole FNSD patient group regardless of predominant neurological manifestations. Given that screening for PTSD is highly unusual in neurological settings, we explored to what extent other patient characteristics can help to predict a high PCL-C score. The linear regression analysis suggests that relationship status, anxiety, depression and PHQ15 scores significantly predicted potentially symptomatic PTSD and explained nearly 60% of the variance. This close relationship between symptoms of anxiety and depression and PTSD symptoms suggests that high scores on anxiety or depression screening instruments should alert clinicians to the possible presence of PTSD in those with FNSD.
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Other studies have described the overlap between depression, anxiety and PTSD symptoms reflected in our data 44-49. In a study of 500 people recruited from community organisations and clinics, higher levels of trauma and adversity over a lifetime were associated with more severe somatic and depressive symptoms 50. In a longitudinal study of men who had experienced childhood sexual abuse (CSA), CSA was positively related to both depressive and somatic symptoms 51. Elhai et al. found that 48-55% of participants with a history of PTSD also met the criteria for a major depressive disorder 52. There is overlap between criteria for depression and the ‘dysphoria’ symptoms in the diagnostic criteria for PTSD 46, 48. However, even with amendments to the criteria to account for this overlap, rates of depression and anxiety were still high in those with PTSD 47. Our cross-sectional study design does not allow us to come to any conclusions about the direction of the relationship between these variables and it remains unclear which precipitates the other. However, all interact and are capable of causing significant distress.
Limitations
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The fact that patients with potentially symptomatic PTSD were statistically less likely to be living with a partner than those without high PTSD symptom levels and were also less likely to be in paid employment may simply be a reflection of the severity of their symptoms. However, previous research in patients with PNES suggests that traumatisation (especially in early life) is also linked to problems with attachment and emotional processing in this patient group which may have reduced their ability to sustain stable personal relationships and employment 53.
This study had several limitations. This service evaluation benefits from truly consecutive case identification, i.e. “a real life’ setting and very large patient numbers. However, our study is based on routine data and procedures, including clinical diagnoses rather than diagnoses based on research criteria. Having said this, patients were only included in this study when fully trained consultant neurologists with an interest in functional disorders and PNES had arrived at these diagnoses with sufficient certainty to recommend psychotherapy and to withdraw any treatments for alternative diagnoses considered erroneous (such an incorrect diagnosis of epilepsy in a person with PNES). In line with clinical practice in the UK, about 40% of PNES diagnoses at our centre are based video-EEG documented seizures, but diagnoses will also have been made on the basis of home video recordings or the observation of seizures by clinicians in conjunction with other test findings available (such as brain imaging or interictal EEG findings 54.
Journal Pre-proof Our case identification method means that no selection bias was introduced through consenting procedures. Psychotherapy could be offered to all patients referred, with no financial restrictions or conditions, and our service is the only public provider of psychotherapy for FNSD in the area we serve. However, all data analysed were provided by patients who had been referred to a psychotherapy service, and we cannot be sure whether neurologists were more likely to refer particular subgroups of FNSD patients (for instance those with high levels of trauma).
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Importantly, we made no attempt to measure trauma directly. Instead we make inferences about previous trauma on the basis of symptoms typically attributed to PTSD. Further, while our characterisation of a subgroup potentially symptomatic of PTSD is likely to have identified patients meeting the criteria for a clinical diagnosis of PTSD, the gold standard examination for PTSD would have involved an interview with a trained professional 5 rather than the questionnaire used in this study. Although all patients seen for psychotherapy in our service would have provided a detailed personal and medical history during their treatment, and accounts of traumatic experiences would have been sought by therapists, these data were not captured prospectively in a standardised form throughout the period described in this paper. When this information was captured in a methodical fashion among patients with FNSD referred to our service between January 2003 and December 2004, 20.3% of all patients had experienced relevant sexual and 72.9% non-sexual trauma prior to developing FNSD 2. What is more, the PCL-C is a well-validated instrument, and we used a conservative measure of 45 as a cut-off of potentially symptomatic PTSD. Nevertheless, there is debate about the value of this measure as a diagnostic tool: Whereas Wilkins et al. suggest that the PCL-C may overestimate the prevalence of PTSD and argue that the overlap with symptoms of anxiety and depression makes it hard to differentiate which symptoms are specifically related to PTSD 12, Ruggerio et al. point out that, as the questionnaire included diagnostic criteria B, C & D of the DSM-IV for PTSD, it ‘may yield information that has a greater predictive value on a diagnostic level’ 13.
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Next, our findings are based on patients referred to a single NHS Neurosciences treatment provider. This limits generalisability, although patients were referred by over 20 different neurologists from a range of neurological clinic settings in secondary and tertiary care centres served by specialists based at RHH. Further limitations of the dataset available for this study include the absence of information allowing a more fine-grained subdifferentiation of FNSD presentations, and a standardised measure of dissociation. Conclusion Despite these limitations, the data demonstrate the high prevalence of PTSD symptoms in patients with FNSD, adding to the evidence of a link between trauma and the development of FNSD. Trauma and PTSD symptoms were negatively correlated with the quality of life of patients with FNSD and associated with other psychiatric comorbidities such as anxiety and depression. High levels of anxiety and depression were independently associated with higher levels of PTSD symptoms and screening instruments for anxiety and depression could therefore indicate which individuals would be at high risk of PTSD. Practitioners
Journal Pre-proof working with this client group need to be capable of screening for trauma and managing trauma in the treatment. 'All authors have completed the Unified Competing Interest form at http://www.icmje.org/coi_disclosure.pdf and declare that : The authors have no competing
interests to report. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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All listed authors have approved the submission of the manuscript to the journal, there are no other published, submitted or proposed papers reporting the same or overlapping data.
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45. Lockwood E, Forbes D. Posttraumatic Stress Disorder and Comorbidity: Untangling the Gordian Knot. Psychological Injury and Law. 2014;7(2):108-121. 46. Rosen G, Lilienfeld S. Posttraumatic stress disorder: An empirical evaluation of core assumptions. Clinical Psychology Review. 2008;28(5):837-868.
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Table 1. Patient demographics Total Population
Symptomatic
Asymptomatic
Significance
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N Age in years (SD)
430 42.1 (15.7)
261 41.3 (15.1)
162 42.7 (15.6)
122 (28.4) 298 (69.3)
75 (28.7) 181 (69.3)
45 (27.7) 115 (71.0)
Gender b
238 (55.3) 189 (44.0)
133 (49.0) 128 (51.0)
107 (66.0) 54 (33.3)
<.001 ( 2= 12.24)
<.001 ( 2= 14.10)
241 (56) 189 (44)
151 (57.9) 110 (42.1)
68 (42.0) 85 (52.5)
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137 (31.6) 276 (64.2)
85 (52.5) 77 (47.5)
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Male (%) Female (%) Marital Status b Living with Partner (%) Not partner (%) Employment Status b Employed (%) Unemployed (%) Coded Diagnosis PNES (%) Other FNSD (%)
0.40 (z=-.84) 0.84 ( 2= 0.35)
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Abbreviations: PNES = Psy chogenic Non-Epileptic Seizures, FNSD = Functional Neurological Sy mptom Disorder. Sy mptomatic PTSD subgroup def ined by PTSD-C score ≥ 45, see methods section f or details.
b
Missing Data: Gender-10 (2.3%), Marital status-3 (0.7%), employ ment status-17 (4.0%).
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0.28 ( 2= 1.18)
Journal Pre-proof Table 2 – Comparison of median scores of the main measures of interest for the whole population, symptomatic PTSD and asymptomatic patient groups Symptomatic of PTSD 261 64 (40, 45-85)
Asymptomatic
Significance
169 30 (27, 17-44)
31 (40, 0-40)
21.5 (40, 0-40)
PHQ-15 15 (29, 0-29)
18 (28, 1-29)
11 (25, 0-25)
GAD-7 15 (21, 0-21)
18 (21, 0-21)
6 (21, 0-21)
PHQ-9 18 (27, 0-27)
21 (27, 0-27)
P (Z, r) <0.001 (-17.30, 0.83) <0.001 (-6.17, 0.30) <0.001 (-9.34, 0.45) <0.001 (-12.91, 0.62) < 0.001 (-13.11, 0.63)
10.5 (25, 0-25)
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N 430 PCL-C Median a 52 (85, 17-85) (range, minimum to maximum) WSAS 27 (40, 0-40)
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Measure Whole population
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PCS 27.1 (61.5, 6.8-68.3)
24.3 (53.5) (3.7-57.1) 27.7 (60, 8.468.3)
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MCS 28.5 (62.6, 3.7-66.3)
41 (54.7, 11.666.3) 27.7 (59.4, 6.866.2)
<0.001 (-9.98, 0.48) .93 (-0.09, 0.00)
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Missing Data: PCL – 7 (1.6%), SF36 – 36 (8.4%).
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Abbreviations: PCL-C = Post-Traumatic Stress Disorder Civilian Checklist, WSAS = Work and Social Adjustment Scale, PHQ-15 = Patient Health Questionnaire 15, GAD-7 = Generalised Anxiety Disorder 7. PHQ-9 = Patient Health Questionnaire 9, SF36 = Short Form 36, MCS = Mental Component Score, PCS = Physical Component Score.
Journal Pre-proof Table 3 – Internal Consistency for Self-Report Measures Cronbach’s Alpha
Measure Number of Items PCL-C 17
.94
PHQ-9 9
.89
GAD-7 7
.93
PHQ-15 15
.82
WSAS 5
.87
SF36 a 8
.82
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8 Standardised SF36 subscales were used to calculate internal consistency
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Abbreviations: PCL-C = Post-Traumatic Stress Disorder Civilian Checklist, WSAS = Work and Social Adjustment Scale, PHQ-15 = Patient Health Questionnaire 15, GAD-7 = Generalised Anxiety Disorder 7. PHQ-9 = Patient Health Questionnaire 9, MCS = Mental Component Score, PCS = Physical Component Score
Journal Pre-proof Table 4 –Correlations between self-report measures across the whole FNSD group Measures PCL-Ca
PCL-C
PHQ-9
GAD-7
PHQ-15
WSAS
SF36
SF36
MCS
PCS
-
PHQ-9 .747*
-
GAD-7 .743*
.744*
-
PHQ-15 .585*
.616*
.555*
-
.448*
.570*
.447*
.479*
-
MCS*
-.578*
-.641*
-.611*
-.360*
-.372*
-
PCS*
-.029
-.172*
-.034
-.331*
-.461*
-.225*
-
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WSAS
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Abbreviations: PCL-C = Post-Traumatic Stress Disorder Civilian Checklist, WSAS = Work and Social Adjustment Scale, PHQ-15 = Patient Health Questionnaire 15, GAD-7 = Generalised Anxiety Disorder 7. PHQ-9 = Patient Health Questionnaire 9, MCS = Mental Component Score, PCS = Physical Component Score. Missing Data: PCL – 7 (1.6%), SF36 – 36 (8.4%).
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* Correlation is signif icant at the lev el of P <0.01.
Journal Pre-proof Table 5 - Linear Regression Predicting PCL-C score Model Standardised 1
95% CI (lower – upper bound)
Sig. dif.
(constant)
33.6 - 59.2
Age -.044
.41
-0.1 – 0.1
Gender -.005
.92
-3.9 – 3.5
<.001
-10.0 – -2.4
<.001
4.6 – 12.5
.40
-2.1 – 5.4
Marital Status -.165 Employment Status .217 Diagnosis .044
16.6 – 36.5
.92
Gender -.026
.40
Marital Status -.117
PHQ9 .360
-1.8 – 2.8
P < .001
0.7 – 1.3
.23
-0.2 – 0.1
P < .001
0.6 – 1.2
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SF36 MCS -.053
-4.1 – 1.2
.70
Pr
GAD7 .331
-6.7 – -2.1
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.27
Diagnosis .012
PHQ15 .173
-3.2 – 1.3
P < .001
Employment Status -.037
WSAS .010
-0.1 – 0.1
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Age -.003
f
(constant)
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2
.79
-0.1 – 0.1
P < .001
0.3 – 0.8
2
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Abbreviations: WSAS = Work and Social Adjustment Scale, PHQ-15 = Patient Health Questionnaire 15, GAD-7 = Generalised Anxiety Disorder 7. PHQ-9 = Patient Health Questionnaire 9, SF36 MCS = Short Form 36 Mental Component Score. Note: ΔR = 0.595, p<0.001
Journal Pre-proof Symptoms of Post-Traumatic Stress Disorder (PTSD) in patients with Functional Neurological Symptom Disorder (FNSD)
Highlights of paper:
60% with Functional Neurological Symptom Disorder (FNSD) had high PTSD symptom burden
No difference in levels of PTSD symptoms between Psychogenic Non Epileptic Seizures (PNES) and other FNSD Those with potentially Symptomatic PTSD had lower quality of life, more likely to be single or not
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High levels of anxiety and depression were independently associated with higher levels o f PTSD
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symptoms
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working