Hypermobility and autonomic hyperactivity: Relevance for the expression of psychiatric symptoms

Lead Research Organisation: University of Sussex
Department Name: Brighton and Sussex Medical School

Abstract

Our body state influences the way we feel and react to things around us. Pain or hunger can influence our mood, but so too can our state of arousal. Strong emotions such as anxiety and panic are made more intense by the feeling of our heart racing. The way in which people differ physically can affect how much their body reacts and this can influence how likely they are to experience anxiety symptoms. Some of these differences run in families, such as having flexible 'hypermobile' joints (double-jointed) or a tendency to faint at the sight of blood. More people who are double-jointed or who faint experience problems with anxiety or panic than you would expect by chance. Knowing how and why this is the case is important as it may improve ways of treating anxiety and other symptoms, and help doctors pick the right medicines to avoid side effects.

My project will study people attending mental health clinics, to see using questionnaires, how many people may have hypermobile joints, a related condition called PoTS (in which a person's heart race when he/she stands up), or a tendency to faint. I will also see if having these conditions is associated with particular types of mental health symptoms (e.g. anxiety). I will then test a sample of these people to look in more detail at the patterns of bodily response, how aware the people are of these responses, and how this might in some cases lead to anxiety. Lastly, I will use brain scans to show exactly how the brain is responsible for anxiety and other abnormal feelings in people with hypermobile joints. I have already shown that a region involved in fear (called the amygdala) is different in size between people with and without flexible joints. I want to continue working on this and look in the hypermobile patients at the way in which this brain region responds during mildly threatening situations. This will help us understand more why some people develop anxiety disorders. By measuring how the amygdala works together with parts of the brain controlling feelings and arousal, I hope to discover more about which medications or treatments may work best for particular people. Together this important body of work will provide me with a good scientific training in brain-body medicine brain scanning and psychiatry research. This research will be undertaken at the Clinical Imaging Sciences Unit at the University of Sussex within a team of neuroscientists who specialize in brain imaging and the relationship between nerves and the body. Patients will be recruited from Sussex Partnership NHS Foundation Trust.

Technical Summary

This proposal aims to test how common constitutional differences in bodily physiology (namely joint hypermobility, postural tachycardia syndrome (PoTs) and vasovagal syncope (VVS) are linked to the clinical expression of psychiatric symptoms, notably anxiety.
Key aims:
1. To determine the representation of joint hypermobility and autonomic symptoms (PoTs, VVS) amongst psychiatric clinical groups by survey.
2. To further characterize subjects in terms of autonomic function, symptom expression and responses to medication and thus determine if the profile of psychiatric symptoms differ by autonomic profile - e.g. cardiovascular reactivity (heart rate variability, response to orthostatic challenge) and interoceptive sensitivity.
3. To determine if such constitutional/autonomic differences are related to concepts of self representation e.g. differential susceptibility to rubber hand illusion (Tsakiris et al, 2011), response to false bio-feedback (Gray et al, 2009) and performance in anxiety induction experiments (Kalisch et al, 2005)
4. Use findings of above to characterize patterns of vulnerability and resilience to psychiatric symptoms and differential responses to medication to inform better treatments and selection of medication.

In order to acheive these objectives three linked studies will be undertaken:
A) Study 1 (Year 1): survey of 400 psychiatric patients to establish relevance of joint hypermobility and autonomic symptoms (PoTs, VVS) to clinical psychopathology and identify / recruit participants for the mechanistic psychophysiology and imaging studies.
B) Study 2 (Years 1-2): A psychophysiological and behavioural charecterization of hypermobility, PoTs and VVS. Autonomic study of individuals identified above (estimated to be approx 100).
C) Study 3 (Years 2-3): A neuroimaging study of the relationship between hypermobility and clinical anxiety with specific focus on amygdala, autonomic reactivity and interoceptive awareness in 80 individuals.

Planned Impact

The recognition of constitutional and physiological vulnerabilities to psychological symptoms may mitigate the development of mental illness, inform new approaches to intervention and promote well-being, with associated benefits to health, the economy and quality of life. It has the capacity to promote better awareness and understanding of anxiety in research and clinical settings and in the public domain and encourage better access to care. The results of this cross-disciplinary project have the potential for far reaching impact in advancing understanding and treatment in the fields of psychiatry, neuroscience and psychological medicine and will have direct clinical relevance to service users. It will expand our knowledge of the interaction between brain and body in one of the most common and debilitating mental illnesses (anxiety) and encourage further research in the area. It will also increase understanding of one of the most common but poorly understood rheumatological conditions, joint hypermobility.

The potential beneficiaries of this research include patients, their carers, physicians and psychiatrists and ultimately the general public. It will also be particularly relevant to physicians treating medically unexplained symptoms. In the short term (during and within one to two years of the completion of the fellowship) this will help enhanced understanding of how certain bodily states interact in mental illness and the identification of previously unrecognized individual differences that predispose to psychiatric symptoms such as anxiety. This will lead to enhanced, individualized treatment plans including selection of medication and behavioural and psychological therapies. Previous work within our research department has fuelled a proposal to develop a department of psychological medicine in partnership with both the mental and physical health trust, which should have direct impact on both service users and clinicians across a range of disciplines. This work speaks directly to that.

The MRC states that 'the brain is the most complex and least understood organ in the human body,' and has identified mental health as one of its key research themes in its 2010 strategic aims. This project will not only accelerate research into anxiety disorders, but also provide the possibility of effective, individualized treatment, one of the Department of Health key aims in its paper 'No health without mental health.' This paper estimates the annual cost of anxiety disorder at £8.9 billion. In 'Pathways to impact' I set out how I propose to maximize the impact of this project during the lifetime of the grant.

Publications

10 25 50

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Garfinkel SN (2015) The Heart, the Brain, and the Regulation of Emotion. in JAMA psychiatry

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Eccles JA (2015) Neurovisceral phenotypes in the expression of psychiatric symptoms. in Frontiers in neuroscience

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Eccles JA (2012) Brain structure and joint hypermobility: relevance to the expression of psychiatric symptoms. in The British journal of psychiatry : the journal of mental science

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Eccles J (2013) CENTRAL EXPRESSION OF ABNORMAL AND UNEXPLAINED SKIN SENSATIONS in Journal of Neurology, Neurosurgery & Psychiatry

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Eccles J (2014) JOINT HYPERMOBILITY AND AUTONOMIC HYPERACTIVITY: RELEVANCE TO NEURODEVELOPMENTAL DISORDERS in Journal of Neurology, Neurosurgery & Psychiatry

 
Description Action for ME PhD Studentships
Amount £45,000 (GBP)
Organisation Action for M.E. 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2018 
End 06/2021
 
Description Arthritis Research UK programme grant
Amount £250,000 (GBP)
Funding ID 21194 
Organisation Versus Arthritis 
Start 04/2016 
End 04/2019
 
Description CISC Pilot funding
Amount £4,080 (GBP)
Organisation University of Sussex 
Department Brighton and Sussex Medical School
Sector Academic/University
Country United Kingdom
Start 06/2011 
End 06/2013
 
Description MQ Fellows Award
Amount £225,000 (GBP)
Organisation MQ Transforming Mental Health 
Sector Charity/Non Profit
Country United Kingdom
Start 05/2018 
End 05/2021
 
Description Medical Research Council Clinical Research Training Fellowship
Amount £177,000 (GBP)
Funding ID MR/K002643/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 09/2012 
End 09/2015
 
Description Sackler Centre for Consciousness Science
Amount £3,400 (GBP)
Organisation Dr Mortimer and Theresa Sackler Foundation 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2013 
End 06/2014
 
Description Starter Grants for Clinical Lecturers
Amount £30,000 (GBP)
Organisation Academy of Medical Sciences (AMS) 
Sector Charity/Non Profit
Country United Kingdom
Start 02/2017 
End 08/2018
 
Description Travel Bursary
Amount £400 (GBP)
Organisation Royal College of Psychiatrists 
Sector Learned Society
Country United Kingdom
Start 05/2013 
End 06/2013
 
Description Young Investigator Colloquim
Amount $1,000 (USD)
Organisation American Psychosomatic Society 
Sector Learned Society
Country United States
Start 03/2013 
End 03/2014
 
Description Autonomic Unit 
Organisation University College London
Department Autonomic Neuroscience Centre
Country United Kingdom 
Sector Academic/University 
PI Contribution We have given training on psychiatric aspects of joint hypermobility
Collaborator Contribution Training in autonomic function tests. Provision of tool to measure symptoms of autonomic dysfunction. Access to autonomic data in a cohort of healthy volunteers to compare with our data collected in a psychiatric group
Impact 2 abstracts submitted to conferences. One paper in draft.
Start Year 2013
 
Description Collaboration for Brain Fog Proposal 
Organisation Cardiff University
Department Brain Research Imaging Centre (CUBRIC)
Country United Kingdom 
Sector Academic/University 
PI Contribution Collaboration to submit grant proposal to Dysautonomia International to investigate neural mechanisms of Brain Fog
Collaborator Contribution Expertise in Imaging and POTS
Impact Application for grant funding (Dysautonomia International) now in Final Stage ($100,000 USD). Outcome should be known April 2018
Start Year 2017
 
Description Collaboration for Brain Fog Proposal 
Organisation Johns Hopkins University
Department School of Medicine Johns Hopkins
Country United States 
Sector Academic/University 
PI Contribution Collaboration to submit grant proposal to Dysautonomia International to investigate neural mechanisms of Brain Fog
Collaborator Contribution Expertise in Imaging and POTS
Impact Application for grant funding (Dysautonomia International) now in Final Stage ($100,000 USD). Outcome should be known April 2018
Start Year 2017
 
Description Collaboration for Brain Fog Proposal 
Organisation University of Sussex
Department Brighton and Sussex Medical School
Country United Kingdom 
Sector Academic/University 
PI Contribution Collaboration to submit grant proposal to Dysautonomia International to investigate neural mechanisms of Brain Fog
Collaborator Contribution Expertise in Imaging and POTS
Impact Application for grant funding (Dysautonomia International) now in Final Stage ($100,000 USD). Outcome should be known April 2018
Start Year 2017
 
Description IoPPN for ALSPAC data 
Organisation University of Sao Paulo
Department Institute of Psychiatry
Country Brazil 
Sector Academic/University 
PI Contribution Access to data
Collaborator Contribution expertise
Impact no outcomes yet
Start Year 2015
 
Description NAAT 2012 Reported_Colloboration discussion 
Organisation University College London
Department Institute of Neurology
Country United Kingdom 
Sector Academic/University 
PI Contribution Application for succesful grant
Collaborator Contribution Application for successful grant
Impact Co-applications for funding,Successful co-applications for funding
Start Year 2012
 
Description Rheumatology 
Organisation Brighton and Sussex University Hospitals NHS Trust
Country United Kingdom 
Sector Public 
PI Contribution We have bought skills and protocol and equipment
Collaborator Contribution they have provided research nurses and equipment and access to patients
Impact no outputs yet outcome has facilitated testing and recruitment
Start Year 2014
 
Description AMS Youtube Video Anxiety and Hypermobility 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact The AMS interviewed me on my work and this was published on Youtube. It has received over 800 views internationally and has sparked several email conversations
Year(s) Of Engagement Activity 2017
URL https://www.youtube.com/watch?v=Mjo7rdAv5ps
 
Description BBC Radio Sussex Interview 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact I took part in an interview on BBC Radio Sussex about the impact of ME/CFS and Fibromyalgia and discussed our future study. I received over 50 emails expressing interest in taking part as a consequence
Year(s) Of Engagement Activity 2017
 
Description BSMS 10 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact I gave a talk to 100 academics to celebrate 10 years of research at BSMS

Prompted collaboration from other disciplines. Invited to give talk an an international conference
Year(s) Of Engagement Activity 2013
 
Description Brain and body seminar 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact I gave a talk on my research to approx 100 patients/carers and clinicians - sparked debate and prompted questions
Year(s) Of Engagement Activity 2017
 
Description EDS UK conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Participants in your research and patient groups
Results and Impact Talk sparked questions and discussion afterwards including email correspondence

Research participants recruited, email correspondence
Year(s) Of Engagement Activity 2014
 
Description EDS article 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Participants in your research and patient groups
Results and Impact This article was published in the EDS newsletter and online

Prompted contact from many interested patients
Year(s) Of Engagement Activity 2013
 
Description HMSA article 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Participants in your research and patient groups
Results and Impact I wrote an article for the HMSA newsletter.

This prompted contact from interested academic collaborators and also from patients
Year(s) Of Engagement Activity 2013
 
Description Hypermobility Syndromes Association Talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Participants in your research and patient groups
Results and Impact I gave an invited presentation to the Hypermobility Syndrome Association annual member resedential. There were around 200 members (patients and interested professionals in attendance).

Increased awareness of psychiatric manifestions of joint hypermobility. Asked to prepare an article for patient newsletter. Patients have contacted me to see if they can be involved in further research.
Year(s) Of Engagement Activity 2012
 
Description Hypermobility and autonomic dysfunction: insights from bench to bedside, presented British Neuropsychiatric Association, London, March 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact presentation on relationship between anxiety and hypermobility and novel treatment targets
Year(s) Of Engagement Activity 2019
 
Description IoN talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Local
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact I gave a talk to about 25 academic peers/clinicans who are based in my collaborator's group.

Strengthened collaboration
Year(s) Of Engagement Activity 2013
 
Description Joint Hypermobility: Relevance of Nuerodevelopmental conditions: presented EDS Congres, Paris, March 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I gave a talk on the relationship between hypermobility and neurodevelopmental conditions to an international audience
Year(s) Of Engagement Activity 2018
 
Description Joint hypermobility and its relevance to common mental illness in adolescents: a population-based longitudinal study European Association of Psychosomatic Medicine, Verona, June 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact i gave a talk on the relationship between hypermobility in adolescence and subsequent mental illness
Year(s) Of Engagement Activity 2018
 
Description London and SE Hypermobility Club 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Health professionals
Results and Impact 100 professionals who work in fields related to hypermobility attended my talk, which sparked questions and discussions after.

Met with potential collaborators. Asked to write an article for the Ehlers Danlos support group
Year(s) Of Engagement Activity 2012
 
Description Medical School Teaching - Chronic Pain Syndromes in Rheumatology 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Undergraduate students
Results and Impact I teach 4th year undergrate medical students on chronic pain conditions - this is often their only formal exposure to the conditions of joint hypermobility and fibromyalgia whilst undergraduates. This workshop happens each rotation (approx 20 students per rotation, 6 rotations). It is co-delivered with an occupational therapist. It sparks considerable debate and interest
Year(s) Of Engagement Activity 2017,2018
 
Description Poster on autonomic dysfunction and dissociative experiences at APS Conference 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I presented a poster on the relationship between autonomic dysfunction and dissociation to American Psychosomatic Medicine Society to approx 350 audience members. This sparked debate and questions
Year(s) Of Engagement Activity 2017
 
Description Poster on heart rate and psychopathology at APS Conference 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I presented work on the relationship between autonomic function and subsequent psychopathology in adolescence to a conference of approx 350 attendees. This sparked discussion and depbate
Year(s) Of Engagement Activity 2017
 
Description Poster on structural brain correlates of hypermobility to European Psychiatric Association 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I presented a poster on strucutral brain correlates of hypermobility at EPA 2017 to a total audience of approx 500. This sparked questions and debate
Year(s) Of Engagement Activity 2017
 
Description Prize talk at BNPA 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Gave prize talk to BNPA on work related to grant, helped facilitate networking and questions
Year(s) Of Engagement Activity 2014,2016
 
Description Psychosomatic Medicine Teaching 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Undergraduate students
Results and Impact I organise and deliver the psychosomatic medicine afternoon to medical undergraduates - an opportunity to showcase the type of brain body research we are undertaking at BSMS. Each session has approx 40 students (120 over course of year). I introduce them to the concept of hypermobility and demonstrate how to assess for it. It frequently receives good feedback
Year(s) Of Engagement Activity 2017,2018
 
Description Psychosomatic Special Interest Group 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Local
Primary Audience Undergraduate students
Results and Impact I regularly give a talk to approx 70 medical students as part of their psychosomatic medicine special interest session. This prompts much debate and questions

This will help with recruitment of a medical student to assist in taking part of the project further next year
Year(s) Of Engagement Activity 2013,2014,2015,2016
 
Description Talk at NIHR Day at BSMS 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact I gave a talk on my career to the NIHR day at BSMS - approx 100 in the audience. Raised the profile of mental health research, particularly brain-body interactions and sparked questions and debate
Year(s) Of Engagement Activity 2017
 
Description Talk to IoPPN 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Gave a talk to IoPPN about work - led to a collaboration
Year(s) Of Engagement Activity 2015
 
Description Talk to Kent Hypermobility Masterclass 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact I gave a talk at the hypermobility masterclass to about 80 interested practitioners and members of patient organisations. This sparked debate and discuss and forged new networks
Year(s) Of Engagement Activity 2016
 
Description Talk to London and SE Hypermobility Club 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact I delivered a talk on neuroimaging of hypermobility to clinicians and students involved in the management of hypermobility in London and South East. It sparked questions and debate and helped forge new links
Year(s) Of Engagement Activity 2016
 
Description Talk to North East Fatigue Group 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact 40 people attended my talk about relevance of joint hypermobility to psychiatric symptoms, which sparked questions and discussion afterwards and help forge potential new collaborations
Year(s) Of Engagement Activity 2016
 
Description Talk to ReMEMBER (patient organisation) about our research 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact Myself and Prof Davies spoke about our upcoming research and past research to a patient organisation. This sparked questions and discussion and helped with recruitment
Year(s) Of Engagement Activity 2017
 
Description Workshop to Physiotherapists at BSUH 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact I gave a workshop to local physiotherapists about the relationship between joint hypermobility and anxiety. This sparked discussion and debate and raised the profile of the condition amongst clinicians on the front line
Year(s) Of Engagement Activity 2016