CNS Drugs

, Volume 29, Issue 3, pp 189–196 | Cite as

Epidemiology and Management of Neuropsychiatric Disorders in Behçet’s Syndrome

  • Rosaria Talarico
  • Laura Palagini
  • Anna d’Ascanio
  • Elena Elefante
  • Claudia Ferrari
  • Chiara Stagnaro
  • Chiara Tani
  • Angelo Gemignani
  • Mauro Mauri
  • Stefano Bombardieri
  • Marta Mosca
Therapy in Practice


Behçet’s syndrome (BS) is a systemic, chronic, relapsing vasculitis, typically characterized by recurrent orogenital ulcers, ocular inflammation and skin manifestations; articular, vascular, gastroenteric and neurological involvement may also occur. Besides the other clinical features of BS, it seems relatively frequent that patients with BS develop a neurobehavioural syndrome, characterized by euphoria, bipolar disorders and paranoid attitudes, loss of insight/disinhibition, and indifference to their disease, defined as ‘neuro-psycho-BS’. To date, the pathogenetic mechanism underlying neuro-psycho-BS has not been determined. It may be secondary to organic neurological involvement, or it may be related to poor quality of life and the relapsing course of the disease. Another engaging theory suggests that it could be related to the frequent observation of psychiatric symptoms during relapses or, in some cases, in the phases preceding reactivation of the disease; these elements suggest that psychiatric disorders in BS could represent a crucial element, whether a psychiatric subset or a distinct clinical feature of the disease. Moreover, it has been reported that cognitive impairment in BS can be seen with or without central nervous system involvement. Globally, psychiatric symptoms have been described as being multifaceted, ranging from anxiety disorders to depressive–bipolar disorders or to psychotic ones. In addition, some psychological characteristics of BS patients seem to predispose them to maladaptive stress management, which may lead to stress-related disorders, including anxiety and depression. Therefore, the aims of this review are to explore the epidemiology of neuro-psycho-BS by evaluating the relationship between the stress system and the multifaceted psychiatric manifestations in BS, and to summarize the therapeutic strategy used.


Bipolar Disorder Psychiatric Symptom Central Nervous System Involvement Neurological Involvement Harm Avoidance 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



No funding was provided for this study.

Rosaria Talarico, Laura Palagini, Anna d’Ascanio, Elena Elefante, Claudia Ferrari, Chiara Stagnaro, Chiara Tani, Angelo Gemignani, Marta Mosca, Mauro Mauri and Stefano Bombardieri have no conflicts of interest to declare.

The authors would like to thank Ms Wendy Doherty for her invaluable help in revising the manuscript.


  1. 1.
    Hatemi G, Seyahi E, Fresko I, Hamuryudan V. Behçet’s syndrome: a critical digest of the 2012–2013 literature. Clin Exp Rheumatol. 2013;31(3 Suppl 77):108–17.PubMedGoogle Scholar
  2. 2.
    Talarico R, Baldini C, Della Rossa A, et al. Large- and small-vessel vasculitis: a critical digest of the 2010–2011 literature. Clin Exp Rheumatol. 2012;30(Suppl 70):S130–8.PubMedGoogle Scholar
  3. 3.
    Yazici H, Seyahi E, Yurdakul S. Behçet’s syndrome is not so rare: why do we need to know? Arthritis Rheum. 2008;58:3640–3.CrossRefPubMedGoogle Scholar
  4. 4.
    Yazici H. Behçet syndrome: an update. Curr Rheumatol Rep. 2003;5:195–219.CrossRefPubMedGoogle Scholar
  5. 5.
    Wallace GR. HLA-B*51 the primary risk in Behçet disease. Proc Natl Acad Sci USA. 2014;111(24):8706–7.CrossRefPubMedCentralPubMedGoogle Scholar
  6. 6.
    International Study Group for Behçet’s Disease. Criteria for diagnosis of Behçet’s disease. Lancet. 1990;335:1078–80.Google Scholar
  7. 7.
    Davatchi F, Sadeghi Abdollahi B, Shahram F, Nadji A, Chams-Davatchi C, et al. Validation of the International Criteria for Behçet’s Disease (ICBD) in Iran. Int J Rheum Dis. 2010;13(1):55–60.CrossRefPubMedGoogle Scholar
  8. 8.
    Yazici H, Esen F. Mortality in Behçet’s syndrome. Clin Exp Rheumatol. 2008;26(Suppl 51):S138–40.PubMedGoogle Scholar
  9. 9.
    Tursen U, Gurler A, Boyvat A. Evaluation of clinical findings according to sex in 2313 Turkish patients with Behçet’s disease. Int J Dermatol. 2003;42:346–51.CrossRefPubMedGoogle Scholar
  10. 10.
    Serdaroglu P, Yazici H, Ozdemir C, et al. Neurological involvement in Behçet syndrome—a prospective study. Arch Neurol. 1989;46:265–9.CrossRefPubMedGoogle Scholar
  11. 11.
    Talarico R, d’Ascanio A, Figus M, Stagnaro C, Ferrari C, Elefante E, et al. Behçet’s disease: features of neurological involvement in a dedicated centre in Italy. Clin Exp Rheumatol. 2012;30(3 Suppl 72):S69–72.PubMedGoogle Scholar
  12. 12.
    Kidd D, Steuer A, Denman AM, Rudge P. Neurological complications in Behçet’s syndrome. Brain. 1999;122(Pt 11):2183–94.CrossRefPubMedGoogle Scholar
  13. 13.
    Noel N, Bernard R, Wechsler B, Resche-Rigon M, Depaz R, Le Thi Huong Boutin D, et al. Long-term outcome of neuro-Behçet’s disease. Arthritis Rheumatol. 2014;66(5):1306–14.CrossRefPubMedGoogle Scholar
  14. 14.
    Yoon DL, Kim YJ, Koo BS, Kim YG, Lee CK, Yoo B. Neuro-Behçet’s disease in South Korea: clinical characteristics and treatment response. Int J Rheum Dis. 2014;17(4):453–8.CrossRefPubMedGoogle Scholar
  15. 15.
    Hirohata S, Kikuchi H, Sawada T, Nagafuchi H, Kuwana M, Takeno M, Ishigatsubo Y. Clinical characteristics of neuro-Behcet’s disease in Japan: a multicentre retrospective analysis. Mod Rheumatol. 2012;22(3):405–13.CrossRefPubMedCentralPubMedGoogle Scholar
  16. 16.
    Siva A, Hirohata S. Behcet’s syndrome and the nervous system. In: Yazici Y, Yazici H, editors. Behcet’s syndrome. New York: Springer; 2010. p. 95–113.CrossRefGoogle Scholar
  17. 17.
    Akman-Demir G, Serdaroglu P, Tasçi B. Clinical patterns of neurological involvement in Behçet’s disease: evaluation of 200 patients. The Neuro-Behçet Study Group. Brain. 1999;122(Pt 11):2171–82.CrossRefPubMedGoogle Scholar
  18. 18.
    Siva A, Ozdogan H, Yazici H, et al. Headache, neuropsychiatric and computerized tomography findings in Behçet’s syndrome. In: Lehner T, Barnes CG, editors. Recent advances in Behçet’s disease. London: Royal Society of Medicine Services; 2010. pp. 247–54.Google Scholar
  19. 19.
    Monastero R, Camarda C, Pipia C, Lopez G, Camarda LK, Baiamonte V, Ferrante A, Triolo G, Camarda R. Cognitive impairment in Behçet’s disease patients without overt neurological involvement. J Neurol Sci. 2004;220(1–2):99–104.CrossRefPubMedGoogle Scholar
  20. 20.
    Salleh MR. Life event, stress and illness. Malays J Med Sci. 2008;15(4):9–18.PubMedCentralPubMedGoogle Scholar
  21. 21.
    Roth MK, Bingham B, Shah A, Joshi A, Frazer A, Strong R, Morilak DA. Effects of chronic plus acute prolonged stress on measures of coping style, anxiety, and evoked HPA-axis reactivity. Neuropharmacology. 2012;63(6):1118–26.CrossRefPubMedCentralPubMedGoogle Scholar
  22. 22.
    Cohen S, Janicki-Deverts D, Doyle WJ, Miller GE, Frank E, Rabin BS, Turner RB. Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk. Proc Natl Acad Sci USA. 2012;109(16):5995–9.CrossRefPubMedCentralPubMedGoogle Scholar
  23. 23.
    Eriksen HR, Olff M, Murison R, Ursin H. The time dimension in stress responses: relevance for survival and health. Psychiatry Res. 1999;85:39–50.CrossRefPubMedGoogle Scholar
  24. 24.
    Ursin H, Eriksen HR. The cognitive activation theory of stress. Psychoneuroendocrinology. 2004;29(5):567–92.CrossRefPubMedGoogle Scholar
  25. 25.
    Koptagel-Ilal G, Tuncer O, Enbiyaoglu I, Bayramoglu Z. A psychosomatic investigation of Behçet’s disease. Psychother Psychosom. 1983;40:263–71.CrossRefPubMedGoogle Scholar
  26. 26.
    Sim M. Behçet’s syndrome as a psychiatric disorder. Am J Psychiatry. 1983;140(6):816.PubMedGoogle Scholar
  27. 27.
    Karlidag R, Unal S, Evereklioglu C, Sipahi B, Er H, Yologlu S. Stressful life events, anxiety, depression and coping mechanisms in patients with Behçet’s disease. J Eur Acad Dermatol Venereol. 2003;17(6):670–5.CrossRefPubMedGoogle Scholar
  28. 28.
    Epstein RS, Cummings NA, Sherwood EB, et al. Psychiatric aspects of Behçet’s syndrome. J Psychosom Res. 1970;14:161–72.CrossRefPubMedGoogle Scholar
  29. 29.
    Atay IM, Erturan I, Demirdas A, Yaman GB, Yürekli VA. The impact of personality on quality of life and disease activity in patients with Behçet’s disease: a pilot study. Compr Psychiatry. 2014;55(3):511–7.CrossRefPubMedGoogle Scholar
  30. 30.
    Cloninger CR, Svrakic DM, Przybeck TR. A psychobiological model of temperament and character. Arch Gen Psychiatry. 1993;50:975–90.CrossRefPubMedGoogle Scholar
  31. 31.
    Cloninger CR. Completing the psychobiological architecture of human personality development: temperament, character, and coherence. Boston: Kluwer; 2003.Google Scholar
  32. 32.
    Ak M, Haciomeroglu B, Turan Y, Lapsekili N, Doruk A, Bozkurt A, et al. Temperament and character properties of male psoriasis patients. J Health Psychol. 2012;17:774–81.CrossRefPubMedGoogle Scholar
  33. 33.
    Ahrens S, Deffner G. Empirical study of alexithymia: methodology and results. Am J Psychother. 1986;40:430–47.PubMedGoogle Scholar
  34. 34.
    Haviland MG, MacMurray JP, Cummings MA. The relationship between alexithymia and depressive symptoms in a sample of newly abstinent alcoholic inpatients. Psychother Psychosom. 1988;49:37–40.CrossRefPubMedGoogle Scholar
  35. 35.
    Wise TN, Mann LS, Mitchell JD, Hryvniak M, Hill B. Secondary alexithymia: an empirical validation. Compr Psychiatry. 1990;31:284–8.CrossRefPubMedGoogle Scholar
  36. 36.
    Aksoyek S, Aytemir K, Ozer N, Ozcebe O, Oto A. Assessment of autonomic nervous system function in patients with Behcet’ s disease by spectral analysis of heart rate variability. J Auton Nerv Syst. 1999;77(2–3):190–4.CrossRefGoogle Scholar
  37. 37.
    Tellioglu T, Robertson D. Orthostatic intolerance in Behcet’s disease. Auton Neurosci. 2001;89(1–2):96–9.CrossRefPubMedGoogle Scholar
  38. 38.
    Erol T, Tekin A, Tufan M, Altay H, Tekin G, Bilgi M, Özin B, Yücel E, Müderrisoğlu H. Autonomic neural control of the cardiovascular system in patients with Behçet’s disease in the absence of neurological involvement. Clin Rheumatol. 2012;31(10):1499–504.CrossRefPubMedGoogle Scholar
  39. 39.
    Borman P, Tuncay F, Kocaoğlu S, Okumuş M, Güngör E, Ekşioğlu M. The subclinic autonomic dysfunction in patients with Behçet disease: an electrophysiological study. Clin Rheumatol. 2012;31(1):41–7.CrossRefPubMedGoogle Scholar
  40. 40.
    Sepici-Dinçel A, Ozkan Y, Yardim-Akaydin S, Kaymak-Karataş G, Onder M, Simşek B. The association between total antioxidant status and oxidative stress in Behçet’s disease. Rheumatol Int. 2006;26(11):1005–9.CrossRefPubMedGoogle Scholar
  41. 41.
    Sezer ED, Aksu K, Caglayan O, Keser G, Karabulut G, Ercan G. DNA damage and its relationship with other oxidative stress parameters in Behcet’s disease. Rheumatol Int. 2012;32(1):217–22.CrossRefPubMedGoogle Scholar
  42. 42.
    Calikoglu E, Onder M, Cosar B, Candansayar S. Depression, anxiety levels and general psychological profile in Behçet’s disease. Dermatology. 2001;203(3):238–40.CrossRefPubMedGoogle Scholar
  43. 43.
    Gur A, Sarac AJ, Burkan YK, Nas K, Cevik R. Arthropathy, quality of life, depression, and anxiety in Behcet’s disease: relationship between arthritis and these factors. Clin Rheumatol. 2006;25(4):524–31.CrossRefPubMedGoogle Scholar
  44. 44.
    Uğuz F, Dursun R, Kaya N, Cilli AS. Quality of life in patients with Behçet’s disease: the impact of major depression. Gen Hosp Psychiatry. 2007;29(1):21–4.CrossRefPubMedGoogle Scholar
  45. 45.
    Lee SS, Yoon HJ, Chang HK, Park KS. Fibromyalgia in Behçet’s disease is associated with anxiety and depression, and not with disease activity. Clin Exp Rheumatol. 2005;23(4 Suppl 38):S15–9.PubMedGoogle Scholar
  46. 46.
    Taner E, Coşar B, Burhanoğlu S, Calikoglu E, Onder M, Arikan Z. Depression and anxiety in patients with Behçet’s disease compared with that in patients with psoriasis. Int J Dermatol. 2007;46(11):1118–24.CrossRefPubMedGoogle Scholar
  47. 47.
    Melikoglu MA, Melikoglu M. The relationship between disease activity and depression in patients with Behçet disease and rheumatoid arthritis. Rheumatol Int. 2010;30(7):941–6.CrossRefPubMedGoogle Scholar
  48. 48.
    Nakano Y, Hatanaka Y, Ikebuchi E, Shimizu T, Nanko S, Utsumii T. A case of Neuro-Behçet’s disease with early onset of bipolar mood disorder. Seishin Shinkeigaku Zasshi. 2004;106(5):564–73.PubMedGoogle Scholar
  49. 49.
    Alevizos B, Anagnostara C, Christodoulou GN. Resistant bipolar disorder precipitated by Behcet’s syndrome. Bipolar Disord. 2004;6(3):260–3.CrossRefPubMedGoogle Scholar
  50. 50.
    Tascilar NF, Tekin NS, Ankarali H, Sezer T, Atik L, Emre U, Duysak S, Cinar F. Sleep disorders in Behçet’s disease, and their relationship with fatigue and quality of life. J Sleep Res. 2012;21(3):281–8.CrossRefPubMedGoogle Scholar
  51. 51.
    Nkam I, Cottereau MJ. Acute psychosis and Behçet’s disease: a case report. Encephale. 2006;32(3 Pt 1):385–8.CrossRefPubMedGoogle Scholar
  52. 52.
    Deniz O, Cayköylü A, Vural G, Albayrak Y, Temel S, Aydin I, Kuloğlu M. A case study of neuro-psycho-Behçet’s syndrome presenting with psychotic attack. Clin Neurol Neurosurg. 2009;111(10):877–9.CrossRefPubMedGoogle Scholar
  53. 53.
    Patel P, Steinschneider M, Boneparth A, Lantos G. Neuro-Behcet disease presenting with acute psychosis in an adolescent. J Child Neurol. 2014;29(9):NP86–91.Google Scholar
  54. 54.
    Dubovsky AN, Arvikar S, Stern TA, Axelrod L. The neuropsychiatric complications of glucocorticoid use: steroid psychosis revisited. Psychosomatics. 2012;53(2):103–15.CrossRefPubMedGoogle Scholar
  55. 55.
    Aydin N, Aydin MD, Deniz O, Kirpinar I. Neuro-Behçet's disease involving the pons with initial onset of affective symptoms. Eur Arch Psychiatry Clin Neurosci. 2002;252(1):44–6CrossRefPubMedGoogle Scholar
  56. 56.
    Hall RCW, Popkin MK, Stickney SK, Gardner ER. Presentation of the steroid psychoses. J Nerv Ment Dis. 1979;167:229–36.CrossRefPubMedGoogle Scholar
  57. 57.
    Nishimura K, Omori M, Sato E, Katsumata Y, Gono T, Kawaguchi Y, et al. New-onset psychiatric disorders after corticosteroid therapy in systemic lupus erythematosus: an observational case-series study. J Neurol. 2014;261(11):2150–8.CrossRefPubMedGoogle Scholar
  58. 58.
    Kötter I, Günaydin I, Batra M, Vonthein R, Stübiger N, Fierlbeck G, Melms A. CNS involvement occurs more frequently in patients with Behçet’s disease under cyclosporin A (CSA) than under other medications—results of a retrospective analysis of 117 cases. Clin Rheumatol. 2006;25(4):482–6.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Rosaria Talarico
    • 1
  • Laura Palagini
    • 2
  • Anna d’Ascanio
    • 1
  • Elena Elefante
    • 1
  • Claudia Ferrari
    • 1
  • Chiara Stagnaro
    • 1
  • Chiara Tani
    • 1
  • Angelo Gemignani
    • 2
  • Mauro Mauri
    • 2
  • Stefano Bombardieri
    • 1
  • Marta Mosca
    • 1
  1. 1.Rheumatology Unit, Department of Clinical and Experimental MedicineUniversity of PisaPisaItaly
  2. 2.Psychiatry Unit, Department of Clinical and Experimental MedicineUniversity of PisaPisaItaly

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