Links between Functional Neurological Disorder / Functional Seizures and abnormalities of the immune system

Functional Neurological Disorder (FND) causes symptoms such as seizures, paralysis, loss of sensation and cognitive problems without any signs of obvious damage or chemical abnormality. Although traditionally classified as a “mental” (“conversion”) disorder, recent large studies have shown that this diagnosis is associated with a 3-6 times greater mortality risk than found in people of the same age and sex. The difference in mortality between patients with FND / FS and others seems to be explained by increased rates of a broad range of medical disorders including cerebrovascular disease, pulmonary disease and cancer.

Previous research in patients with Posttraumatic Stress Disorder (PTSD) and depression suggests that chronic “silent” inflammation, and early aging of the immune system could explain similar reductions in life expectancy associated with these diagnoses. We think that excess inflammation, accelerated aging and reduced immune efficiency may also contribute to the excess deaths observed in patients with FND /FS. We expect changes in the immune cells of patients to mimic those of the natural aging of the immune system but to happen earlier in life. A better understanding of the biological causes of FND could improve the management of this disorder in the future.

We would like to study links between FND / FS and abnormalities of the immune system in patients with this disorder accessing psychological treatment for this condition from the internationally recognised Neuropsychotherapy Service based at Sheffield Teaching Hospitals NHS Foundation Trust. This PhD project will be conducted over a period of 3.5 years. We will use questionnaires and blood tests to investigate samples of 30 FND/FS patients and 30 healthy controls. We will analyse associations of:

a) mental health status,

b) life-time traumatic stress load,

c) life-style (diet, nutrient intake, physical exercise, smoking),

d) immunological markers of accelerated aging of the immune system, and e) a physical marker of current stress (heart rate variability analysis). We will collect samples from patients before and after psychotherapy.

Building on the international reputation Sheffield has in the fields of FND (MR/CG) and immunological research / cell signalling (EKT), this project will benefit from additional supervision from Professor Iris Kolassa, a biopsychologist and psychotherapist based at Ulm University, Germany, with extensive research experience in stress and trauma- spectrum disorders such as PTSD and depression, and an internationally leading expertise on the role of mitochondrial biopsychology in mental health research.In this project, we will focus on the exploration of accelerated aging of the immune system, as measured by declining monocyte function in patients with FND / FS. We will explore links between the life experiences and physical and mental health state of patients with FND / FS, their biographical and immunological age. We will also collect data allowing us to explore relationship between activations of the autonomic nervous and immune system as well as samples which will enable us to study the possible role of chronic (“silent”) inflammation in FND/FS in future research. Analyses will include cross-sectional comparisons between patients and controls, correlations between self-report / autonomic function and immunological measures and longitudinal comparisons exploring potential treatment-related changes.

Laboratory sample processing will involve:

– Analysis of monocyte populations (CD14+ and ±CD16 expressing populations) in patient blood by Flow cytometry, as well as soluble inflammatory markers (IL6, hsCRP).

– Characterisation of the capacity of blood-isolated monocytes for chemotactic migration and phagocytosis, functions that we have shown to substantially decline in otherwise healthy humans by their fifties. Expression of master-regulators (MYC) and effectors we have shown to be dysregulated during aging (ITGA2B, ATP8B1, STAB2) will be assessed by qRT-PCR.

– Separation and storage of serum from all participants will be stored for future research focussing on the level of immune activation in patients with FND / FS.

This research will be completed at the University of Sheffield and in the Royal Hallamshire Hospital. The project should be suitable for candidates with an undergraduate backgroundin psychology, neuro- or biomedical science. Candidates will be supported in acquiring the necessary laboratory and analytic skills for this project.

Entry Requirements:

Candidates must have a first or upper second class honours degree or significant research experience.

How to apply:

Please complete a University Postgraduate Research Application form available here: http://www.shef.ac.uk/postgraduate/research/apply