Evidence-Based Reviews

Anxiety and joint hypermobility: An unexpected association

Current Psychiatry. 2018 April;17(4):15-21

References

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2. Hakim A, Grahame R. Joint hypermobility. Best Pract Res Clin Rheumatol. 2003;17(6):989-1004.
3. Hakim AJ, Grahame R. Non-musculoskeletal symptoms in joint hypermobility syndrome. Indirect evidence for autonomic dysfunction? Rheumatology (Oxford). 2004;43(9):1194-1195.
4. Grahame R, Hakim AJ. Hypermobility. Curr Opin Rheumatol. 2008;20(1):106-110.
5. Castori M. Ehlers-Danlos syndrome, hypermobility type: an underdiagnosed hereditary connective tissue disorder with mucocutaneous, articular, and systemic manifestations. ISRN Dermatol. 2012;2012:751768. doi: 10.5402/2012/751768.
6. Bulbena A, Baeza-Velasco C, Bulbena-Cabré A, et al. Psychiatric and psychological aspects in the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017;175(1):237-245.
7. Bulbena A, Duro JC, Mateo A, et al. Joint hypermobility syndrome and anxiety disorders. Lancet. 1988;332(8612):694.
8. Bulbena-Cabré A, Pailhez G, Cabrera A, et al. Body perception in a sample of nonclinical youngsters with joint hypermobility. Ansiedad y Estrés. 2017;23(2-3):99-103.
9. Martín-Santos R, Bulbena A, Porta M, et al. Association between joint hypermobility syndrome and panic disorder. Am J Psychiatry. 1998;155(11):1578-1583.
10. Bulbena A, Agulló A, Pailhez G, et al. Is joint hypermobility related to anxiety in a nonclinical population also? Psychosomatics. 2004;45(5):432-437.
11. Bulbena-Cabré A, Baeza-Velasco C, Pailhez G, et al. Psicopatología de la hiperlaxitud articular [in Spanish]. Cuadernos de Neuropsicología/Panamerican Journal of Neuropsychology 2016;10(3):61-70.
12. Bulbena‐Cabré A, Rojo C, Pailhez G, et al. Joint hypermobility is also associated with anxiety disorders in the elderly population. Int J Geriatr Psychiatry. 2018;33(1):e113-e119.
13. Bulbena A, Pailhez G, Bulbena-Cabré A, et al. Joint hypermobility, anxiety and psychosomatics: two and a half decades of progress toward a new phenotype. Adv Psychosom Med. 2015;34:143-157.
14. Smith TO, Easton V, Bacon H, et al. The relationship between benign joint hypermobility syndrome and psychological distress: a systematic review and meta-analysis. Rheumatology (Oxford). 2014;53(1):114-122.
15. Cederlöf M, Larsson H, Lichtenstein P, et al. Nationwide population-based cohort study of psychiatric disorders in individuals with Ehlers-Danlos syndrome or hypermobility syndrome and their siblings. BMC Psychiatry. 2016;16(1):207.
16. Gratacòs M, Nadal M, Martín-Santos R, et al. A polymorphic genomic duplication on human chromosome 15 is a susceptibility factor for panic and phobic disorders. Cell. 2001;106(3):367-379.
17. Tabiner M, Youings S, Dennis N, A et al. Failure to find DUP25 in patients with anxiety disorders, in control individuals, or in previously reported positive control cell lines. Am J Hum Genet. 2003;72(3):535-538.
18. Henrichsen CN, Delorme R, Boucherie M, et al. No association between DUP25 and anxiety disorders. Am J Med Genet B Neuropsychiatr Genet. 2004;128B(1):80-83.
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20. Mallorqui-Bagué N, Garfinkel SN, Engels M, et al. Neuroimaging and psychophysiological investigation of the link between anxiety, enhanced affective reactivity and interoception in people with joint hypermobility. Front Psychol. 2014;5:1162. doi: 10.3389/fpsyg.2014.01162.
21. Critchley HD, Harrison NA. Visceral influences on brain and behavior. Neuron. 2013;77(4):624-638.
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Biologic hypotheses that have been proposed to explain the link between anxiety and JHS/hEDS are described in the Box^6,16-28.

Box
What underlying mechanisms link anxiety and joint hypermobility?

Interestingly, both anxiety and joint hypermobility syndrome/Ehlers-Danlos type 3-hypermobile type (JHS/hEDS) are often underdiagnosed and undertreated, and have similar prevalence in the general population. While it is possible that some psychiatric symptoms can be a consequence of adaptation and difficulties in dealing with chronic illnesses, biologic hypotheses have been considered to explain the association between JHS/hEDS and anxiety. The most accepted biologic hypotheses include:

genetic risks
interoceptive sensitivity
somatosensory amplification
emotion processing variances
autonomic nervous system dysfunction.

A duplication of chromosome 15 (DUP-25) was found in patients with both JHS/hEDS and an anxiety disorder,¹⁶ but to date, this finding has not been replicated.^17,18 The fact that both conditions are highly heritable suggests high likelihood of a genetic linkage. Other theories about the neural connections between mind and body have been proposed. Brain and body are intrinsically and dynamically coupled; perceptions, emotions, and cognitions respond to and change the state of the body.¹⁹ In this sense, body perception and dysautonomia have gained recognition.

Patients with JHS/hEDS have higher interoception,²⁰ meaning greater signaling and perception of internal bodily sensations. This is in line with Critchley's hypothesis, in which he describes the influence of visceral inputs over thoughts, feelings, and behavior.²¹ Consistent with Critchley's views, Porges described the Polyvagal Theory,²² which is phylogenetic approach relating the autonomic nervous system to behavior. Atypical body awareness is a feature of multiple disorders, including anxiety, depression, and JHS/hEDS.^19,23-25 Interestingly, a recent neuroimaging study found that interception sensitivity mediated the relationship between anxiety and hypermobility.²⁰

JHS/hEDS patients have greater exteroception (perception of environment), nocioception (pain perception), and somatosensory amplification.^6,26 At the same time, they also have decreased proprioception,²⁷ which could explain the coordination difficulties they experience. Neuroimaging studies have confirmed that individuals with JHS/hEDS have structural differences in key emotion processing regions, notably affecting the amygdala bilaterally.²⁸

Together, these findings increase our understanding about the mechanisms through which vulnerability to anxiety disorders and somatic symptoms arises in certain patients.

Continue to: How JHS/hEDS is diagnosed

Anxiety and joint hypermobility: An unexpected association

References

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