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

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.

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.

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.