Abstract
Ehlers–Danlos syndromes (EDS) are a heterogeneous group of hereditary connective tissue disorders characterized by joint hypermobility, widespread musculoskeletal pain and tissue fragility. Psychiatric disorders and psychosocial impairment are common, yet poorly characterized, findings in EDS patients. We investigated the frequency and types of psychiatric disorders and their relationship to systemic manifestations in a cohort of 106 classic and hypermobility type EDS patients. In this retrospective study, extensive medical chart review was performed for patients referred at two genetics clinics who were diagnosed with EDS. Statistical analysis was undertaken to determine the frequency of psychiatric disorders and association with systemic findings. Psychiatric disorders were found in 42.5 % of the EDS cohort, with 22.7 % of patients affected with 2 or more psychiatric diagnoses. Anxiety and depression were most commonly reported, with frequencies of 23.6 and 25.5 %, respectively. A variety of other psychiatric diagnoses were also identified. Abdominal pain [odds ratio (OR) 7.38], neuropathic pain (OR 4.07), migraines (OR 5.21), joint pain (OR 2.85) and fatigue (OR 5.55) were significantly associated with the presence of a psychiatric disorder. The presence of any pain symptom was significantly associated with having a psychiatric disorder (OR 9.68). Muscle pain (OR 2.79), abdominal pain (OR 5.78), neuropathic pain (OR 3.91), migraines (OR 2.63) and fatigue (OR 3.78) were significantly associated with having an anxiety or mood disorder. Joint hypermobility and the classic dermatological features of EDS showed no significant association with having a psychiatric disorder. Our findings demonstrate a high frequency of psychiatric disorders and an association with pain symptoms in EDS.
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Hakim AJ, Sahota A (2006) Joint hypermobility and skin elasticity: the hereditary disorders of connective tissue. Clin Dermatol 24:521–533
Beighton P, De Paepe A, Steinmann B, Tsipouras P, Wenstrup RJ (1998) Ehlers–Danlos syndromes: revised nosology, Villefranche, 1997. Ehlers–Danlos National Foundation (USA) and Ehlers–Danlos Support Group (UK). Am J Med Genet 1998(77):31–37
Malfait F, Wenstrup R, De Paepe A (2007) Ehlers–Danlos syndrome, classic type [Updated 2011]. GeneReviews® [Internet]. University of Washington, Seattle, WA, 1993–2015. http://www.ncbi.nlm.nih.gov/books/NBK1244/
Levy HP (2004) Ehlers–Danlos syndrome, Hypermobility type. [Updated 2012]. GeneReviews® [Internet]. University of Washington, Seattle, WA, 1993–2015. http://www.ncbi.nlm.nih.gov/books/NBK1279/
Tinkle BT, Bird HA, Grahame R, Lavallee M, Levy HP, Sillence D (2009) The lack of clinical distinction between the hypermobility type of Ehlers–Danlos syndrome and the Joint Hypermobility Syndrome (a.k.a. Hypermobility Syndrome). Am J Med Genet A 149A:2368–2370
Bulbena A, Duró JC, Porta M, Martín-Santos R, Mateo A, Molina L et al (1993) Anxiety disorder in the joint hypermobility syndrome. Psychiatry Res 46:59–68
Bulbena A, Gago J, Pailhez G, Sperry L, Fullana MA, Vilarroya O (2011) Joint hypermobility syndrome is a risk factor trait for anxiety disorders: a 15-year follow-up cohort study. Gen Hosp Psychiatry 33:363–370
Hagberg C, Berglund B, Korpe L, Andersson-Norinder J (2004) Ehlers–Danlos syndrome (EDS) focusing on oral symptoms: a questionnaire study. Orthod Craniofac Res 7:178–185
Lumley MA, Jordan M, Rubenstein R, Tsipouras P, Evans MI (1994) Psychosocial functioning in the Ehlers–Danlos syndrome. Am J Med Genet 53:149–152
Pasquini M, Celletti C, Berardelli I, Roselli V, Mastroeni S, Castori M et al (2014) Unexpected association between joint hypermobility syndrome/Ehlers–Danlos syndrome hypermobility type and obsessive–compulsive personality disorder. Rheumatol Int 34:631–636
Baeza-Velasco C, Pailhez G, Bulbena A, Baghdadli A (2015) Joint hypermobility and the heritable disorders of connective tissue: clinical and empirical evidence of links with psychiatry. Gen Hosp Psychiatry 37:24–30
Sinibaldi L, Ursini G, Castori M (2015) Psychopathological manifestations of joint hypermobility and joint hypermobility syndrome/Ehlers–Danlos syndrome, hypermobility type: the link between connective tissue and psychological distress revised. Am J Med Genet C Semin Med Genet 169C:97–106
Ghibellini G, Brancati F, Castori M (2015) Neurodevelopmental attributes of joint hypermobility syndrome/Ehlers–Danlos syndrome, hypermobility type: update and perspectives. Am J Med Genet C Semin Med Genet 169C:107–116
Atkinson JH, Slater MA, Patterson TL, Grant I, Garfin SR (1991) Prevalence, onset, and risk of psychiatric disorders in men with chronic low back pain: a controlled study. Pain 45:111–121
Katon W, Egan K, Miller D (1985) Chronic pain: lifetime psychiatric diagnoses and family history. Am J Psychiatry 142:1156–1160
McWilliams LA, Cox BJ, Enns MW (2003) Mood and anxiety disorders associated with chronic pain: an examination in a nationally representative sample. Pain 106:127–133
Tunks ER, Crook J, Weir R (2008) Epidemiology of chronic pain with psychological comorbidity: prevalence, risk, course, and prognosis. Can J Psychiatry 53:224–234
Eccles JA, Owens AP, Mathias CJ, Umeda S, Critchley HD (2015) Neurovisceral phenotypes in the expression of psychiatric symptoms. Front Neurosci 9:4
Bulbena A, Pailhez G, Bulbena-Cabré A, Mallorqui-Bagué N, Baeza-Velasco C (2015) Joint hypermobility, anxiety and psychosomatics: two and a half decades of progress toward a new phenotype. Adv Psychosom Med 34:143–157
World Health Organization (1992) International Statistical Classification of Diseases and Related Health Problems 10th Revision, Geneva
Smetanin P, Stiff D, Briante C, Adair CE, Ahmad S, Khan M (2011) The life and economic impact of major mental illnesses in Canada: 2011 to 2041. Risk Analytica, on behalf of the Mental Health Commission of Canada 2011
Statistics Canada (2013) Canadian Community Health Survey, 2012: Mental Health component [public-use microdata file]. Statistics Canada. Health Statistics Division, Data Liberation Initiative, Ottawa, ON [producer and distributor]
Baeza-Velasco C, Gely-Nargeot MC, Vilarrasa AB, Fenetrier C, Bravo JF (2011) Association between psychopathological factors and joint hypermobility syndrome in a group of undergraduates from a French university. Int J Psychiatry Med 41:187–201
Bulbena A, Agulló A, Pailhez G, Martín-Santos R, Porta M, Guitart J et al (2004) Is joint hypermobility related to anxiety in a nonclinical population also? Psychosomatics 45:432–437
Bendik EM, Tinkle BT, Al-shuik E, Levin L, Martin A, Thaler R et al (2011) Joint hypermobility syndrome: a common clinical disorder associated with migraine in women. Cephalalgia 31:603–613
Berglund B, Anne-Cathrine M, Randers I (2010) Dignity not fully upheld when seeking health care: experiences expressed by individuals suffering from Ehlers–Danlos syndrome. Disabil Rehabil 32:1–7
Gratacòs M, Nadal M, Martín-Santos R, Pujana MA, Gago J, Peral B et al (2001) A polymorphic genomic duplication on human chromosome 15 is a susceptibility factor for panic and phobic disorders. Cell 106:367–379
Simon V, Czobor P, Bálint S, Mészáros A, Bitter I (2009) Prevalence and correlates of adult attention-deficit hyperactivity disorder: meta-analysis. Br J Psychiatry 194:204–211
Koldaş Doğan S, Taner Y, Evcik D (2011) Benign joint hypermobility syndrome in patients with attention deficit/hyperactivity disorders. Arch Rheumatol 26:187–192
Shiari R, Saeidifard F, Zahed G (2013) Evaluation of the prevalence of joint laxity in children with attention deficit/hyperactivity disorder. Ann Paediatr Rheumatol 2:78–80
Castori M, Dordoni C, Valiante M, Sperduti I, Ritelli M, Morlino S et al (2014) Nosology and inheritance pattern(s) of joint hypermobility syndrome and Ehlers–Danlos syndrome, hypermobility type: a study of intrafamilial and interfamilial variability in 23 Italian pedigrees. Am J Med Genet A 164A:3010–3020
Sacheti A, Szemere J, Bernstein B, Tafas T, Schechter N, Tsipouras P (1997) Chronic pain is a manifestation of the Ehlers–Danlos syndrome. J Pain Symptom Manag 14:88–93
Voermans NC, Knoop H, Bleijenberg G, van Engelen BG (2010) Pain in Ehlers–Danlos syndrome is common, severe, and associated with functional impairment. J Pain Symptom Manag 40:370–378
Demyttenaere K, Bruffaerts R, Lee S, Posada-Villa J, Kovess V, Angermeyer MC et al (2007) Mental disorders among persons with chronic back or neck pain: results from the world mental health surveys. Pain 129:332–342
Von Korff M, Crane P, Lane M, Miglioretti DL, Simon G, Saunders K et al (2005) Chronic spinal pain and physical–mental comorbidity in the United States: results from the national comorbidity survey replication. Pain 113:331–339
Currie SR, Wang J (2004) Chronic back pain and major depression in the general Canadian population. Pain 107:54–60
Clark C, Khattab A, Carr E (2014) Chronic widespread pain and neurophysiological symptoms in joint hypermobility syndrome (JHS). Int J Ther Rehabil 21:60–68
Acasuso-Diaz M, Collantes-Estévez E (1998) Joint hypermobility in patients with fibromyalgia syndrome. Arthritis Care Res 11:39–42
Gedalia A, Press J, Klein M, Buskila D (1993) Joint hypermobility and fibromyalgia in schoolchildren. Ann Rheum Dis 52:494–496
Buskila D, Cohen H (2007) Comorbidity of fibromyalgia and psychiatric disorders. Curr Pain Headache Rep 11:333–338
Uçar M, Sarp Ü, Karaaslan Ö, Gül AI, Tanik N, Arik HO (2015) Health anxiety and depression in patients with fibromyalgia syndrome. J Int Med Res 43(5):679–685
Janssens KA, Zijlema WL, Joustra ML, Rosmalen JG (2015) Mood and anxiety disorders in chronic fatigue syndrome, fibromyalgia, and irritable bowel syndrome: results from the lifelines cohort study. Psychosom Med 77:449–457
Bernik M, Sampaio TP, Gandarela L (2013) Fibromyalgia comorbid with anxiety disorders and depression: combined medical and psychological treatment. Curr Pain Headache Rep 17:358
Alciati A, Sgiarovello P, Atzeni F, Sarzi-Puttini P (2012) Psychiatric problems in fibromyalgia: clinical and neurobiological links between mood disorders and fibromyalgia. Reumatismo 28(64):268–274
Chang MH, Hsu JW, Huang KL, Su TP, Bai YM, Li CT et al (2015) Bidirectional association between depression and fibromyalgia syndrome: a nationwide longitudinal study. J Pain 16:895–902
Rombaut L, Malfait F, De Paepe A, Rimbaut S, Verbruggen G, De Wandele I et al (2011) Impairment and impact of pain in female patients with Ehlers–Danlos syndrome: a comparative study with fibromyalgia and rheumatoid arthritis. Arthritis Rheumatol 63:1979–1987
Sherman JJ, Turk DC, Okifuji A (2000) Prevalence and impact of posttraumatic stress disorder-like symptoms on patients with fibromyalgia syndrome. Clin J Pain 16:127–134
Eccles JA, Beacher FDC, Gray MA, Jones CL, Minati L, Harrison NA et al (2012) Brain structure and joint hypermobility: relevance to the expression of psychiatric symptoms. Br J Psychiatry 200:508–509
Gazit Y, Nahir AM, Grahame R, Jacob G (2003) Dysautonomia in the joint hypermobility syndrome. Am J Med 115:33–40
Radat F, Swendsen J (2005) Psychiatric comorbidity in migraine: a review. Cephalalgia 25:165–178
Breslau N, Davis GC (1992) Migraine, major depression and panic disorder: a prospective epidemiologic study of young adults. Cephalalgia 12:85–90
Abbey SE, Garfinkel PE (1991) Chronic fatigue syndrome and depression: cause, effect, or covariate. Rev Infect Dis 13:73–83
Gurer G, Sendur F, Gultekin BK, Ozcan ME (2010) The anxiety between individuals with and without joint hypermobility. Eur J Psychiatry 24:205–209
Sanches SB, Osório FL, Louzada-Junior P, Moraes D, Crippa JA, Martín-Santos R (2014) Association between joint hypermobility and anxiety in Brazilian university students: gender-related differences. J Psychosom Res 77:558–561
Zeitoun JD, Lefèvre JH, Parades V, Séjourné C, Sobhani I, Coffin B et al (2013) Functional digestive symptoms and quality of life in patients with Ehlers–Danlos syndromes: results of a national cohort study on 134 patients. PLoS ONE 8:e80321
Levy RL, Olden KW, Naliboff BD, Bradley LA, Francisconi C, Drossman DA et al (2006) Psychosocial aspects of the functional gastrointestinal disorders. Gastroenterology 130:1447–1458
Whitehead WE, Palsson O, Jones KR (2002) Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications? Gastroenterology 122:1140–1156
Acknowledgments
The authors would like to thank all of the EDS patients included in this study. S.H. and V.M. were funded by the Mach-Gaensslen Foundation of Canada.
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Hershenfeld, S.A., Wasim, S., McNiven, V. et al. Psychiatric disorders in Ehlers–Danlos syndrome are frequent, diverse and strongly associated with pain. Rheumatol Int 36, 341–348 (2016). https://doi.org/10.1007/s00296-015-3375-1
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DOI: https://doi.org/10.1007/s00296-015-3375-1