Publications

Ratcliff, C. van der Feltz-Cornelis. Conversion disorder/functional neurological disorder – a narrative review on current research into its pathological mechanism. The European Journal of Psychiatry 2020;34:3:143-152, ISSN 0213-6163

Abstract

Background and objectives
Conversion disorder/functional neurological disorder (CD/FND) can be a chronic disorder and has an unknown pathology. This review explored the current level of research and understanding the origin of CD/FND pathology.

Methods
This narrative review collated relevant papers and articles identified by a search in both Scopus and PubMed. Systematic reviews and observational articles focusing on inflammation and childhood trauma were included. Articles that were not in English, case reports, or that included participants from military background, were excluded.

Results
Overall 54 papers were included from an initial search number of 5264. 34 of these articles were identifying and discussing new trends and theories related to the pathophysiology while the remaining 20 were defining the current knowledge of CD/FND. There is no definitively known pathophysiology of FND, with several noted categories of involved being immune system, inflammation and neural changes. Each system and mechanism could either be seen as a direct mechanism of action or an indirect effect from a further unknown mechanism of action. Additionally, there seems to be a lack of coherency between these different proposed theories, with little information bringing them together. Further research may explore whether or not inflammation plays a direct role in the pathophysiology of the disorder, and if a difference in the symptoms is dictated by different inflammatory markers.

Conclusion
Overall this narrative review identified and postulated different mechanisms for the pathology of CD/FND while also discovering where new research should focus.

C. Van Der Feltz-Cornelis, S. Brabyn, S.F. Allen, J. Reilly, C. Clarke, L. de Vroege, S. Gilbody, M. Wittington, D. Lagos. Conversion and neuro-inflammation disorder observational study (CANDO). Protocol of a feasibility study. The European Journal of Psychiatry, 2020;34:3:164-172, ISSN 0213-6163

Abstract

Background
Conversion disorder (CD) or functional neurological disorder (FND) affects at least 764,000 people in the UK per year. As its origin is unknown and treatment has limited effects the condition forms a high individual and societal burden and clinically-unmet need. Research aiming to improve the outlook for people with this condition is urgently required. Exploration of the role of stress response and systemic low-grade inflammation (SLI) in CD/FND is warranted. The first step is to establish the feasibility of identifying, recruiting and assessing a clinical cohort of CD/FND patients for biomarkers of SLI, in addition to objective and subjective measures of stress and related factors.

Methods
The settings are currently clinics and services within the Tees, Esk and Wear Valleys NHS Foundation Trust (TEWV). Phase 1 and phase 3 of our work are described in this paper, assessing the feasibility of assessing a cohort of CD/FND patients. Ethical approval has been granted for this study. The study will use observational measures including a blood sample for assessment of inflammation biomarkers; hair cortisol testing; self-report measures of stress, childhood trauma and health; targeted neurocognitive functioning and psychiatric examination. The findings will be used to inform future phases of our work.

Discussion
Study outcomes will be knowledge about levels of SLI, psychological and cognitive symptoms in patients with CD/FND that is so far largely unknown. Knowledge regarding the feasibility of conducting a study in this population will also be gained. This will enable a comprehensive testing and evaluation of the proposed processes of recruitment, retention and data collection. This is hoped to lay the groundwork for future work leading to the development of novel treatments for CD/FND patients.

Registration
researchregistry.com researchregistry5289

van der Feltz-Cornelis C, Brabyn S, Ratcliff J, Varley D, Allgar V, Gilbody S, Clarke C, Lagos D. Assessment of cytokines, microRNA and patient related outcome measures in conversion disorder/functional neurological disorder (CD/FND): The CANDO clinical feasibility study. Brain Behav Immun Health. 2021 Feb 24;13:100228. doi: 10.1016/j.bbih.2021.100228. PMID: 34589743; PMCID: PMC8474571.

Abstract

Background
Conversion disorder/functional neurological disorder (CD/FND) occurs often in neurological settings and can lead to long-term distress, disability and demand on health care services. Systemic low-grade inflammation might play a role, however, the pathogenic mechanism is still unknown.

Aim
1) To explore the feasibility to establish and assess a cohort of CD/FND with motor symptoms, involving persons with lived experience (PPI).

2) To generate proof of concept regarding a possible role for cytokines, microRNA, cortisol levels and neurocognitive symptoms in patients with motor CD/FND.

Method: Feasibility study.

Results
The study showed active involvement of patients despite high clinical illness burden and disability, neurocognitive symptoms, childhood adverse experiences (ACE) and current life events. The study provided valuable knowledge regarding the feasibility of conducting a study in these patients that will inform future study phases. In the sample there were elevated levels of IL6, IL12, IL17A, IFNg, TNFa and VEGF-a, suggesting systemic low-grade inflammation. Also, microRNAs involved in inflammation and vascular inflammation were correlated with TNFa and VEGFa respectively, suggesting proof of concept for an epigenetic mechanism. Owing to the COVID-19 outbreak, the patient sample was limited to 15 patients.

Conclusion
It is a novelty that this study is conducted in the clinical setting. This innovative, translational study explores stress-related SLI in CD/FND patients and the feasibility of a larger project aiming to develop new treatments for this vulnerable population. Given the positive findings, there is scope to conduct further research into the mechanism of disease in CD/FND.

See all publications of the CANDO study