Drugs

, Volume 77, Issue 8, pp 829–842 | Cite as

Psychiatric Symptoms in Patients with Cushing’s Syndrome: Prevalence, Diagnosis and Management

  • Alicia Santos
  • Eugenia Resmini
  • Juan Carlos Pascual
  • Iris Crespo
  • Susan M. Webb
Therapy in Practice

Abstract

Cushing’s syndrome (CS) results from chronic exposure to cortisol excess, produced by the adrenal cortex. Hypercortisolism predisposes to psychiatric and neurocognitive disorders, mainly to depression and anxiety disorders. Screening tools to identify psychiatric symptoms are available for clinicians in their daily practice, although a specific diagnosis should be performed by specialists. Even if psychiatric symptoms improve after remission of hypercortisolism, complete recovery may not be achieved. Given the burden of these symptoms, psychiatric or psychological monitoring and treatment should be offered through all phases of CS, with a multidisciplinary approach. The aim of this article is to review data on the prevalence, diagnosis and management of psychiatric symptoms seen in patients with CS and to propose therapeutic approaches that may be followed in clinical practice. The prevalence of different psychiatric disorders has been described in both the active phase and after CS remission. Patients may not talk spontaneously about psychiatric symptoms they present, thus clinicians should ask directly about them. We recommend the use of screening tools in clinical practice to detect and treat these symptoms promptly. Even if reference endocrinologists cannot perform a definite psychiatric diagnosis, it will be important to ask patients directly about the presence of symptoms and refer if necessary to a psychiatrist. Additionally, patient information and educational programmes could be useful to manage psychiatric symptoms and to improve quality of life in patients with CS.

References

  1. 1.
    Heim C, Nemeroff CB. The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies. Biol Psychiatry. 2001;50:200–4.CrossRefGoogle Scholar
  2. 2.
    Carpenter L, Carvalho JP, Tyrka AR, et al. Decreased adrenocorticotropic hormone and cortisol responses to stress in healthy adults reporting significant childhood maltreatment. Biol Psychiatry. 2007;62:1080–7.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Joëls M, Karst H, Krugers HJ, Lucassen PJ. Chronic stress: implications for neuronal morphology, function and neurogenesis. Front Neuroendocrinol. 2007;28:72–96.CrossRefPubMedGoogle Scholar
  4. 4.
    Resmini E, Santos A, Gómez-Anson B, et al. Verbal and visual memory performance and hippocampal volumes, measured by 3-Tesla magnetic resonance imaging, in patients with Cushing’s syndrome. J Clin Endocrinol Metab. 2012;97:663–71.CrossRefPubMedGoogle Scholar
  5. 5.
    Wang J, Barak LS, Mook RA Jr, Chen W. Glucocorticoid hedgehog agonists in neurogenesis. Vitam Horm. 2011;87:207–15.CrossRefPubMedGoogle Scholar
  6. 6.
    Tata DA, Marciano VA, Anderson BJ. Synapse loss from chronically elevated glucocorticoids: relationship to neuropil volume and cell number in hippocampal area CA3. J Comp Neurol. 2006;498:363–74.CrossRefPubMedGoogle Scholar
  7. 7.
    Gold PW, Drevets WC, Charney DS. New insights into the role of cortisol and the glucocorticoid receptor in severe depression. Biol Psychiatry. 2002;52:381–5.CrossRefPubMedGoogle Scholar
  8. 8.
    de Kloet ER, Joëls M, Holsboer F. Stress and the brain: from adaptation to disease. Nat Rev Neurosci. 2005;6:463–75.CrossRefPubMedGoogle Scholar
  9. 9.
    Goodwin G. Neurobiological aetiology of mood disorders. In: Gelder MG, Lopez-Ibor JJ, Andreasen N, editors. New Oxford textbook of psychiatry. Oxford: Oxford University Press; 2000. p. 711–9.Google Scholar
  10. 10.
    Sheline YI, Sanghavi M, Mintun MA, Gado MH. Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression. J Neurosci. 1999;19:5034–43.PubMedGoogle Scholar
  11. 11.
    Resmini E, Santos A, Aulinas A, et al. Reduced DNA methylation of FKBP5 in Cushing’s syndrome. Endocrine. 2016;54:768–77.CrossRefPubMedGoogle Scholar
  12. 12.
    De Leo M, Pivonello R, Auriemma RS, et al. Cardiovascular disease in Cushing’s syndrome: heart versus vasculature. Neuroendocrinology. 2010;92:50–4.CrossRefPubMedGoogle Scholar
  13. 13.
    Jacoby RC, Owings JT, Ortega T, et al. Biochemical basis for the hypercoagulable state seen in Cushing syndrome. Arch Surg. 2001;136:1003–6.CrossRefPubMedGoogle Scholar
  14. 14.
    Kaltsas G, Makras P. Skeletal diseases in Cushing’s syndrome: osteoporosis versus arthropathy. Neuroendocrinology. 2010;92:60–4.CrossRefPubMedGoogle Scholar
  15. 15.
    Sonino N, Fava GA. Psychosomatic aspects of Cushing’s disease. Psychother Psychosom. 1998;67:140–6.CrossRefPubMedGoogle Scholar
  16. 16.
    Pereira AM, Tiemensma J, Romijn JA. Neuropsychiatric disorders in Cushing’s syndrome. Neuroendocrinology. 2010;92:65–70.CrossRefPubMedGoogle Scholar
  17. 17.
    Bolland MJ, Holdaway IM, Berkeley JE, et al. Mortality and morbidity in Cushing’s syndrome in New Zealand. Clin Endocrinol (Oxf). 2011;75:436–42.CrossRefGoogle Scholar
  18. 18.
    Santos A, Resmini E, Gómez-Ansón B, et al. Cardiovascular risk and white matter lesions after endocrine control of Cushing’s syndrome. Eur J Endocrinol. 2015;173:765–75.CrossRefPubMedGoogle Scholar
  19. 19.
    Forget H, Lacroix A, Somma M, Cohen H. Cognitive decline in patients with Cushing’s syndrome. J Int Neuropsychol Soc. 2000;6:20–9.PubMedGoogle Scholar
  20. 20.
    Sonino N, Fava GA. Psychiatric disorders associated with Cushing’s syndrome: epidemiology, pathophysiology and treatment. CNS Drugs. 2001;15:361–73.CrossRefPubMedGoogle Scholar
  21. 21.
    Starkman MN, Schteingart DE, Schork MA. Depressed mood and other psychiatric manifestations of Cushing’s syndrome: relationship to hormone levels. Psychosom Med. 1981;43:3–18.CrossRefPubMedGoogle Scholar
  22. 22.
    Bourdeau I, Bard C, Forget H, et al. Cognitive function and cerebral asessment in patients who have Cushing’s syndrome. Endocrinol Metab Clin N Am. 2005;34:357–69.CrossRefGoogle Scholar
  23. 23.
    Sonino N, Bonnini S, Fallo F, et al. Personality characteristics and quality of life in patients treated for Cushing’s syndrome. Clin Endocrinol (Oxf). 2006;64:314–8.CrossRefGoogle Scholar
  24. 24.
    Tiemensma J, Biermasz NR, Middelkoop HA, et al. Increased prevalence of psychopathology and maladaptive personality traits, after long-term cure of Cushing’s disease. J Clin Endocrinol Metab. 2010;95:129–41.CrossRefGoogle Scholar
  25. 25.
    Dimopoulou C, Ising M, Pfister H, et al. Increased prevalence of anxiety-associated personality traits in patients with Cushing’s disease: a cross-sectional study. Neuroendocrinology. 2013;97:139–45.CrossRefPubMedGoogle Scholar
  26. 26.
    Michaud K, Forget H, Cohen H. Chronic glucocorticoid hypersecretion in Cushing’s syndrome exacerbates cognitive aging. Brain Cogn. 2009;71:1–8.CrossRefPubMedGoogle Scholar
  27. 27.
    Webb SM, Badia X, Barahona MJ, et al. Evaluation of health-related quality of life in patients with Cushing’s syndrome with a new questionnaire. Eur J Endocrinol. 2008;158:623–30.CrossRefPubMedGoogle Scholar
  28. 28.
    Lindsay JR, Nansel T, Baid S, et al. Long-term impaired quality of life in Cushing’s syndrome despite initial improvement after surgical remission. J Clin Endocrinol Metab. 2006;91:447–53.CrossRefPubMedGoogle Scholar
  29. 29.
    Hawn MT, Cook D, Deveney C, Sheppard BC. Quality of life after laparoscopic bilateral adrenalectomy for Cushing’s disease. Surger. 2002;132:1064–8.CrossRefGoogle Scholar
  30. 30.
    Dorn LD, Burgess ES, Dubbert B, et al. Psychopathology in patients with endogenous Cushing’s syndrome: atypical or melancholic features. Clin Endocrinol. 1995;43:433–42.CrossRefGoogle Scholar
  31. 31.
    Kelly WF. Psychiatric aspects of Cushing’s syndrome. Q J Med. 1996;89:543–51.CrossRefGoogle Scholar
  32. 32.
    Santos A, Resmini E, Crespo I, et al. Small cerebellar cortex volume in patients with active Cushing’s syndrome. Eur J Endocrinol. 2014;171:461–9.CrossRefPubMedGoogle Scholar
  33. 33.
    Cosci F, Fava GA, Sonino N. Mood and anxiety disorders as early manifestations of medical illness: a systematic review. Psychother Psychosom. 2015;84:22–9.CrossRefPubMedGoogle Scholar
  34. 34.
    Rasmussen SA, Rosebush PI, Smyth HS, Mazurek MF. Cushing disease presenting as primary psychiatric illness: a case report and literature review. J Psychiatr Pract. 2015;21:449–57.CrossRefPubMedGoogle Scholar
  35. 35.
    Tang A, O’Sullivan AJ, Diamond T, et al. Psychiatric symptoms as a clinical presentation of Cushing’s syndrome. Ann Gen Psychiatry. 2013;12:23.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Loosen PT, Chambliss B, de Bold CR, et al. Psychiatric phenomenology in Cushing’s disease. Pharmacopsychiatry. 1992;25:192–8.CrossRefPubMedGoogle Scholar
  37. 37.
    Sonino N, Fava GA, Belluardo P, et al. Course of depression in Cushing’s syndrome: response to treatment and comparison with Graves’ disease. Horm Res. 1993;39:202–6.CrossRefPubMedGoogle Scholar
  38. 38.
    Sonino N, Fava GA, Raffi AR, et al. Clinical correlates of major depression in Cushing’s disease. Psychopathology. 1998;31:302–6.CrossRefPubMedGoogle Scholar
  39. 39.
    Sonino N, Zielezny M, Fava GA, et al. Risk factors and long-term outcome in pituitary-dependent Cushing’s disease. J Clin Endocrinol Metab. 1996;81:2647–52.PubMedGoogle Scholar
  40. 40.
    Haskett RF. Diagnostic categorization of psychiatric disturbance in Cushing’s syndrome. Am J Psychiatry. 1985;142:911–6.CrossRefPubMedGoogle Scholar
  41. 41.
    Hudson JI, Hudson MS, Griffing GT, et al. Phenomenology and family history of affective disorder in Cushing’s disease. Am J Psychiatry. 1987;144:951–3.CrossRefPubMedGoogle Scholar
  42. 42.
    Sablowski N, Pawlik K, Lüdecke DK, Herrmann HD. Aspects of personality in patients with pituitary adenomas. Acta Neurochir (Wien). 1986;83:8–11.CrossRefGoogle Scholar
  43. 43.
    Valassi E, Santos A, Yaneva M, ERCUSYN Study Group, et al. The European Registry on Cushing’s syndrome: 2-year experience: baseline demographic and clinical characteristics. Eur J Endocrinol. 2011;165:383–92.CrossRefPubMedGoogle Scholar
  44. 44.
    Dorn LD, Burgess ES, Friedman TC, et al. The longitudinal course of psychopathology in Cushing’s syndrome after correction of hypercortisolism. J Clin Endocrinol Metab. 1997;82:912–9.PubMedGoogle Scholar
  45. 45.
    Starkman MN, Giordani B, Gebarski SS, Schteingart DE. Improvement in mood and ideation associated with increase in right caudate volume. J Affect Disord. 2007;101:139–47.CrossRefPubMedGoogle Scholar
  46. 46.
    Kelly WF, Kelly MJ, Faragher B. A prospective study of psychiatric and psychological aspects of Cushing’s syndrome. Clin Endocrinol (Oxf). 1996;45:715–20.CrossRefGoogle Scholar
  47. 47.
    Cohen SI. Cushing’s syndrome: a psychiatric study of 29 patients. Br J Psychiatry. 1980;136:120–4.CrossRefPubMedGoogle Scholar
  48. 48.
    Jeffcoate WJ, Silverstone JT, Edwards CR, Besser GM. Psychiatric manifestations of Cushing’s syndrome: response to lowering of plasma cortisol. Q J Med. 1979;48:465–72.PubMedGoogle Scholar
  49. 49.
    Valassi E, Crespo I, Keevil BJ, et al. Affective alterations in patients with Cushing’s syndrome in remission are associated with decreased BDNF and cortisone levels. Eur J Endocrinol. 2017;176:221–31.CrossRefPubMedGoogle Scholar
  50. 50.
    Ziegelstein RC, Fauerbach JA, Stevens SS, et al. Patients with depression are less likely to follow recommendations to reduce cardiac risk during recovery from a myocardial infarction. Arch Intern Med. 2000;160:1818–23.CrossRefPubMedGoogle Scholar
  51. 51.
    Katon WJ. Epidemiology and treatment of depresssion in patients with chronic medical illness. Dialog Clin Neurosci. 2011;13:7–23.Google Scholar
  52. 52.
    Ragnarsson O, Berglund P, Eder DN, Johannsson G. Long-term cognitive impairments and attentional deficits in patients with Cushing’s disease and cortisol-producing adrenal adenoma in remission. J Clin Endocrinol Metab. 2012;97:1640–8.CrossRefGoogle Scholar
  53. 53.
    Andela CD, van der Werff SJ, Pannekoek JN, et al. Smaller grey matter volumes in the anterior cingulate cortex and greater cerebellar volumes in patients with long-term remission of Cushing’s disease: a case–control study. Eur J Endocrinol. 2013;169:811–9.CrossRefPubMedGoogle Scholar
  54. 54.
    Martin SB, Covell DJ, Joseph JE, et al. Human experience seeking correlates with hippocampus volume: convergent evidence from manual tracing and voxel-based morphometry. Neuropsychologia. 2007;45:2874–82.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Martín-Blanco A, Ferrer M, Soler J, et al. The role of hypothalamus-pituitary-adrenal genes and childhood trauma in borderline personality disorder. Eur Arch Psychiatry Clin Neurosci. 2016;266:307–16.CrossRefPubMedGoogle Scholar
  56. 56.
    Martínez-Momblán MA, Gómez C, Santos A, et al. A specific nursing educational program in patients with Cushing’s syndrome. Endocrine. 2016;53:199–209.CrossRefPubMedGoogle Scholar
  57. 57.
    Gotch PM. Cushing’s syndrome from the patient perspective. Endocrinol Metab Clin N Am. 1994;23:607–17.Google Scholar
  58. 58.
    van Aken MO, Pereira AM, Biermasz NR, et al. Quality of life in patients after long-term biochemical cure of Cushing’s disease. J Clin Endocrinol Metab. 2005;90:3279–86.CrossRefPubMedGoogle Scholar
  59. 59.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington: American Psychiatric Association; 2014.Google Scholar
  60. 60.
    Pivonello R, Simeoli C, De Martino MC, et al. Neuropsychiatric disorders in Cushing’s syndrome. Front Neurosci. 2015;9:129.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Ritzel K, Beuschlein F, Mickisch A, Osswald A, et al. Clinical review: outcome of bilateral adrenalectomy in Cushing’s syndrome: a systematic review. J Clin Endocrinol Metab. 2013;98:3939–48.CrossRefPubMedGoogle Scholar
  62. 62.
    Sonino N, Fallo F, Fava GA. Psychosomatic aspects of Cushing’s syndrome. Rev Endocr Metab Disord. 2010;11:95–104.CrossRefPubMedGoogle Scholar
  63. 63.
    Santos A, Crespo I, Aulinas A, et al. Quality of life in Cushing’s syndrome. Pituitary. 2015;18:195–200.CrossRefPubMedGoogle Scholar
  64. 64.
    Starkman MN. Neuropsychiatric findings in Cushing’s syndrome and exogenous glucocorticoid administration. Endocrinol Metab Clin N Am. 2013;42:477–88.CrossRefGoogle Scholar
  65. 65.
    Nieman LK, Biller BM, Findling JW, et al. Treatment of Cushing’s syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2015;100:2807–31.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Lau D, Rutledge C, Aghi MK. Cushing’s disease: current medical therapies and molecular insights guiding future therapies. Neurosurg Focus. 2015;38:E11.CrossRefPubMedGoogle Scholar
  67. 67.
    Bratek A, Kozmin-Burzynska A, Gorniak E, Krysta K. Psychatric disorders associated with Cushing’s syndrome. Psychiatr Danub. 2015;27:S339–43.PubMedGoogle Scholar
  68. 68.
    Saad MF, Adams F, Mackay B, et al. Occult Cushing’s disease presenting with acute psychosis. Am J Med. 1984;76:759–66.CrossRefPubMedGoogle Scholar
  69. 69.
    Zielasek J, Bender G, Schlesinger S, et al. A woman who gained weight and became schizophrenic. Lancet. 2002;360:1392.CrossRefPubMedGoogle Scholar
  70. 70.
    Baba M, Ray D. Severe psychosis due to Cushing’s syndrome in a patient with a carcinoid tumour in the lung: a case report and review of the current management. World J Surg Oncol. 2015;13:165.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Górniak M, Rybakowski J. Paranoid syndrome in the course of Cushing’s disease. Post Psychiatr Neurol. 2005;14:18–20.Google Scholar
  72. 72.
    Johanssen S, Allolio B. Mifepristone (RU 486) in Cushing’s syndrome. Eur J Endocrinol. 2007;157:561–9.CrossRefPubMedGoogle Scholar
  73. 73.
    Castinetti F, Fassnacht M, Johanssen S, et al. Merits and pitfalls of mifepristone in Cushing’s syndrome. Eur J Endocrinol. 2009;160:1003–10.CrossRefPubMedGoogle Scholar
  74. 74.
    van der Lely AJ, Foeken K, Van Der Mast RC, Lamberts SW. Rapid reversal of acute psychosis in the Cushing syndrome with the cortisol-receptor antagonist mifepristone (RU 486). Ann Intern Med. 1991;114:143–4.CrossRefPubMedGoogle Scholar
  75. 75.
    Chu JW, Matthias DF, Belanoff J, et al. Successful long-term treatment of refractory Cushing’s disease with high-dose mifepristone (RU 486). J Clin Endocrinol Metab. 2001;86:3568–73.PubMedGoogle Scholar
  76. 76.
    Bilgin YM, van der Wiel HE, Fischer HR, De Herder WW. Treatment of severe psychosis due to ectopic Cushing’s syndrome. J Endocrinol Investig. 2007;30:776–9.CrossRefGoogle Scholar
  77. 77.
    Beaufrere B, de Parscau L, Chatelain P, et al. RU 486 administration in a child with Cushing’s syndrome. Lancet. 1987;2:217.CrossRefPubMedGoogle Scholar
  78. 78.
    Bertagna X, Bertagna C, Laudat MH, et al. Pituitary-adrenal response to the antiglucocorticoid action of RU 486 in Cushing’s syndrome. J Clin Endocrinol Metab. 1986;63:639–43.CrossRefPubMedGoogle Scholar
  79. 79.
    Chrousos GP, Laue L, Nieman LK, et al. Clinical applications of RU 486, a prototype glucocorticoid and progestin antagonist. In: Mantero F, Takeda R, Scoggins BA, et al., editors. The adrenal and hypertension: from cloning to clinic. New York: Raven Press; 1989. p. 273–84.Google Scholar
  80. 80.
    Cassier PA, Abou-Amara-Olivieri S, Artru P, et al. Mifepristone for ectopic ACTH secretion in metastatic endocrine carcinomas: report of two cases. Eur J Endocrinol. 2008;158:935–8.CrossRefPubMedGoogle Scholar
  81. 81.
    Mutter GL, Bergeron C, Deligdisch L, et al. The spectrum of endometrial pathology induced by progesterone receptor modulators. Mod Pathol. 2008;21:591–8.CrossRefPubMedGoogle Scholar
  82. 82.
    Fleseriu M, Biller BM, Findling JW, SEISMIC Study Investigators, et al. Mifepristone, a glucocorticoid receptor antagonist, produces clinical and metabolic benefits in patients with Cushing’s syndrome. J Clin Endocrinol Metab. 2012;97:2039–49.CrossRefPubMedGoogle Scholar
  83. 83.
    National Collaborating Centre for Mental Health (UK). Depression: the treatment and management of depression in adults (updated edition). National Institute for Health and Clinical Excellence: guidance. Leicester: British Psychological Society; 2010.Google Scholar
  84. 84.
    Gallagher P, Malik N, Newham J, et al. Antiglucocorticoid treatments for mood disorders. Cochrane Database Syst Rev. 2008;1:CD005168.Google Scholar
  85. 85.
    Brykalski J, Papierska L, Załuska M. Acute psychosis in the course of treatment of acute adrenal crisis with hydrocortisone in the patient with secondary adrenal insufficiency: a case study. Psychiatr Pol. 2015;49:673–81.CrossRefPubMedGoogle Scholar
  86. 86.
    Løvas K, Husebye ES. High prevalence and increasing incidence of Addison’s disease in western Norway. Clin Endocrinol (Oxf). 2002;56:787–91.CrossRefGoogle Scholar
  87. 87.
    Erichsen MM, Løvås K, Skinningsrud B, et al. Clinical, immunological, and genetic features of autoimmune primary adrenal insufficiency: observations from a Norwegian registry. J Clin Endocrinol Metab. 2009;94:4882–90.CrossRefPubMedGoogle Scholar
  88. 88.
    Anglin RE, Rosebush PI, Mazurek MF. The neuropsychiatric profile of Addison’s disease: revisiting a forgotten phenomenon. J Neuropsychiatry Clin Neurosci. 2006;18:450–9.CrossRefPubMedGoogle Scholar
  89. 89.
    Schultebraucks K, Wingenfeld K, Heimes J, et al. Cognitive function in patients with primary adrenal insufficiency (Addison’s disease). Psychoneuroendocrinology. 2015;55:1–7.CrossRefPubMedGoogle Scholar
  90. 90.
    Thomsen AF, Kvist TK, Andersen PK, Kessing LV. The risk of affective disorders in patients with adrenocortical insufficiency. Psychoneuroendocrinology. 2006;31:614–22.CrossRefPubMedGoogle Scholar
  91. 91.
    Holtzman CW, Trotman HD, Goulding SM, et al. Stress and neurodevelopmental processes in the emergence of psychosis. Neuroscience. 2013;249:172–91.CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Farah Jde L, Lauand CV, Chequi L, et al. Severe psychotic disorder as the main manifestation of adrenal insufficiency. Case Rep Psychiatry. 2015;2015:512430.PubMedGoogle Scholar
  93. 93.
    Tatsuzawa Y, Ono Y, Takahashi T, et al. Case of isolated adrenocorticotropic hormone deficiency mimicking major depressive disorder. Psychiatry Clin Neurosci. 2011;65(3):302.CrossRefPubMedGoogle Scholar
  94. 94.
    Martínez MA, Gómez C, Santos A, et al. Quina informació van rebre els malalts amb síndrome de Cushing i risc cardiovascular? Ag Inf. 2012;16:17–22.Google Scholar
  95. 95.
    Kreitschmann-Andermahr I, Psaras T, Tsiogka M, et al. From first symptoms to final diagnosis of Cushing’s disease: experiences of 176 patients. Eur J Endocrinol. 2015;172:285–9.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  1. 1.Department of Endocrinology/Medicine, Hospital Sant Pau, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER 747)Institut d’Investigació Biomèdica-Sant Pau (IIB-SANT PAU)BarcelonaSpain
  2. 2.Department of Psychiatry, Hospital Sant Pau, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)Institut d’Investigació Biomèdica-Sant Pau (IIB-SANT PAU)BarcelonaSpain
  3. 3.Universitat Autònoma de BarcelonaBarcelonaSpain

Personalised recommendations