13 Hypermobility and autonomic dysfunction: insights from bench to bedside

Abstract

Dr Jessica Eccles trained in medicine at University of Cambridge and University of Oxford, completing a BA in The History and Philosophy of Science, sparking a keen interest in philosophy of mind and brain-body interactions. Since graduation from medical school has pursued a combined academic clinical path at Brighton and Sussex Medical School. As an MRC Clinical Research Training Fellow she recently completed her PhD in the relationship between joint hypermobility, autonomic dysfunction and psychiatric symptoms and is now an NIHR Clinical Lecturer. She is currently working on an Academy of Medical Sciences grant to explore neural connectivity in hypermobility using leading edge Human Connectome Project techniques and has recently been awarded a MQ Arthritis Research UK Fellows Award to conduct a randomised clinical trial of a new targeted treatment for anxiety in hypermobility. Dr Eccles has also been awarded a grant from Dysautonomia International and will be working with Profs Critchley, Cercignani, Rowe, Murphy and Drs Nagai, Asslanni, Iodice and Giovanni to explore multi-modal correlates of ‘brain fog’ in Postural Tachycardia Syndrome. Dr Eccles is working with Profs Davies, Harrison, Cercignani, Critchley and Dr Tarzi to explore brain- body interactions in Fibromyalgia and ME/CFS. This involves autonomics, inflammatory and cytokine markers, brain imaging and genomics. This work is funded by Versus Arthritis and Action for ME Alongside clinical academic colleagues at BSMS, Prof Harrison and Dr Colasanti. Joint hypermobility is a common, yet poorly recognised variant of connective tissue affecting up to 20% of the population. Hypermobility is a cardinal feature of Hyermobility Spectrum Disorder (HSD) and hypermobile Ehlers Danlos Syndrome (hEDS), inherited disorders of connective tissue. Individuals with joint hypermobility are over represented in panic, anxiety and neurodevelopmental populations and are prone to dysautonomia, typically postural tachycardia syndrome (PoTS), in which there is a phenomenological overlap with anxiety disorder. Interestingly differences in brain structure and function have been described in hypermobility in regions associated with emotional processing, including amygdala and insula. Individuals with joint hypermobility are more likely to experience severe chronic widespread pain, and many have co-morbid rheumatic conditions. A data-driven theoretical model linking joint hypermobility to psychiatric disorder is proposed, characterised by aberrant autonomic control and central representation, grounded in current theoretical models that seek to frame emotion as interoceptive inference, using leading-edge predictive coding approaches. Ultimately this approach has considerable relevance to personalised psychiatric medicine in this disorder and greater understanding of brain-body mechanisms underpinning neuropsychiatric states.