Fungal Infections of Central Nervous System and Their Relationship to Neuropsychiatric Disorders

  • Onur Gökçen
  • Nermin Gündüz
  • Mehmet Turgut


Fungal infections involving the central nervous system (CNS) are a worldwide problem, possibly due to increased number of immunosuppressed patients in recent years. Clinically, fungal infections closely mimic neuropsychiatric disorders because some patients with fungal infections have neuropsychiatric symptoms; therefore, early diagnosis and appropriate medical therapy of these cases are of utmost importance. To reduce the mortality and morbidity in these patients, a high index of suspicion is vital for differential diagnosis. In this chapter, relationships between the fungal infections of the CNS and psychiatric disorders are reviewed in terms of neuropsychiatric manifestations of fungal infections, fungal infections in drug abusers, and dermatological fungal infections in neuropsychiatric disorders.


Fungal infection Neuropsychiatric symptoms Differential diagnosis Treatment 



Acquired immunodeficiency syndrome


Cryptococcus neoformans meningitis


Central nervous system


Computed tomography


Extrapyramidal symptoms


Highly active antiretroviral therapy


Human immunodeficiency virus




Magnetic resonance imaging


  1. Aboltins CA, Allen P, Daffy JR. Fungal endophthalmitis in intravenous drug users injecting buprenorphine contaminated with oral Candida species. Med J Aust. 2005;182:427.PubMedGoogle Scholar
  2. Albini TA, Sun RL, Holz ER, Khurana RN, Rao NA. Lemon juice and candida endophthalmitis in crack-cocaine misuse. Br J Ophthalmol. 2007;91:702–3.CrossRefGoogle Scholar
  3. Aylward EH, Henderer JD, McArthur JC, Brettschneider PD, Harris GJ, Barta PE, Pearlson GD. Reduced basal ganglia volume in HIV-1-associated dementia: results from quantitative neuroimaging. Neurology. 1993;43:2099.CrossRefGoogle Scholar
  4. Badiee P, Hashemizadeh Z. Opportunistic invasive fungal infections: diagnosis & clinical management. Indian J Med Res. 2014;139:195–204.PubMedPubMedCentralGoogle Scholar
  5. Bicanic T, Jarvis JN, Muzoora C, Harrison TS. Should antiretroviral therapy be delayed for 10 weeks for patients treated with fluconazole with cryptococcal meningitis? Clin Infect Dis. 2010;51:986–7.CrossRefGoogle Scholar
  6. Bristow IR, Spruce MC. Fungal foot infection, cellulitis and diabetes: a review. Diabet Med. 2009;26:548–51.CrossRefGoogle Scholar
  7. Brown S, Birtwistle J, Roe L, et al. The unhealthy lifestyle of people with schizophrenia. Psychol Med. 1999;29:697–701.CrossRefGoogle Scholar
  8. Bucardo J, Brouwer KC, Magis-Rodríguez C, Ramos R, Fraga M, Perez SG, Patterson TL, Strathdee SA. Historical trends in the production and consumption of illicit drugs in Mexico: implications for the prevention of blood borne infections. Drug Alcohol Depend. 2005;79:281–93.CrossRefGoogle Scholar
  9. Chacon A, Franca K, Fernandez A, Nouri K. Psychosocial impact of onychomycosis: a review. Int J Dermatol. 2013;52:1300–7.CrossRefGoogle Scholar
  10. Chen M, Xu Y, Hong N, Yang Y, Lei W, Du L, Zhao J, Lei X, Xiong L, Cai L, Xu H, Pan W, Liao W. Epidemiology of fungal infections in China. Front Med. 2018;12:58–75.CrossRefGoogle Scholar
  11. Chou PH, Ouyang WC, Lan TH, Chan CH. Secondary mania due to AIDS and cryptococcal meningitis in a 78-year-old patient. Psychogeriatrics. 2016;16:135–8.CrossRefGoogle Scholar
  12. Cohen S, Miller GE, Rabin BS. Psychological stress and antibody response to immunization: a critical review of the human literature. Psychosom Med. 2001;63:7–18.CrossRefGoogle Scholar
  13. Cole C, Jones L, McVeigh J, Kicman A, Syed Q, Bellis M. Adulterants in illicit drugs: a review of empirical evidence. Drug Test Anal. 2011;3:89–96.CrossRefGoogle Scholar
  14. Colville T, Sharma V, Albouaini K. Infective endocarditis in intravenous drug users: a review article. Postgrad Med J. 2016;92:105–11.CrossRefGoogle Scholar
  15. Dalmau AB, Berman BK, Brismar BG. Somatic morbidity among patients diagnosed with affective psychosis and paranoid disorders. Psychosomatics. 1998;39:253–62.CrossRefGoogle Scholar
  16. Deutscher M, Perlman DC. Why some injection drug users lick their needles: a preliminary survey. Int J Drug Policy. 2008;19:342–5.CrossRefGoogle Scholar
  17. Drake LA, Scher RK, Smith EB, Faich GA, Smith SL, Hong JJ, Stiller MJ. Effect of onychomycosis on quality of life. J Am Acad Dermatol. 1998;38:702–4.CrossRefGoogle Scholar
  18. Ellis ME, Al-Abdely H, Sandridge A, Greer W, Ventura W. Fungal endocarditis: evidence in the world literature, 1965–1995. Clin Infect Dis. 2001;32:50–62.CrossRefGoogle Scholar
  19. Friedman H, Pross S, Klein TW. Addictive drugs and their relationship with infectious diseases. FEMS Immunol Med Microbiol. 2006;47:330–42.CrossRefGoogle Scholar
  20. Goeb JL, Leon V, Kechid G. Cryptococcal meningitis with acute psychotic confusion in a sarcoid patient. Prim Care Companion J Clin Psychiatry. 2007;9:393–4.CrossRefGoogle Scholar
  21. Gupta MA, Gupta AK. Psychodermatology: an update. J Am Acad Dermatol. 1996;34:1030–46.CrossRefGoogle Scholar
  22. Hadley C, Mohamed AWH, Singhal A. Central nervous system fungal infection in a young male with a history of intravenous drug abuse and hepatitis C. Radiol Case Rep. 2017;13(12):590–6.CrossRefGoogle Scholar
  23. Henao NA, Vagner B. Infections of the central nervous system by Candida. J Infect Dis Immun. 2011;3:79–81.Google Scholar
  24. Hennekens CH, Hennekens AR, Hollar D, Casey DE. Schizophrenia and increased risks of cardiovascular disease. Am Heart J. 2005;150:1115–21.CrossRefGoogle Scholar
  25. Hirst LW, Thomas JV, Green WR. Endophthalmitis. In: Mandell GL, Bennett JE, Dolin R, editors. Mandell, Douglas, and Bennett’s principles and practice of infectious diseases. Philadelphia, PA: Churchill Livingstone; 2005. p. 760–7.Google Scholar
  26. Holikatti PC, Kar N. Psychiatric manifestations in a patient with HIV-associated neurocognitive symptoms and cryptococcal meningitis. Indian J Psychol Med. 2012;34:381–2.CrossRefGoogle Scholar
  27. Hsueh KL, Lin PY. Treatment-resistant depression prior to the diagnosis of cryptococcal meningitis: a case report. Gen Hosp Psychiatry. 2010;32:560.e9–10.CrossRefGoogle Scholar
  28. Ibanez-Valdes L, Foyaca-Sibat H, Mfenyana K, Chandia J, Gonzalez-Aguilera H. Neuropsychiatry manifestations in patients presenting cryptococcal meningitis. Int J Neurol. 2005;5(1)Google Scholar
  29. Jacob R, Zhimin Z, Rayapureddy S, Isaacs RT. Cryptococcal meningitis presenting as acute psychosis in a HIV positive patient. Asian J Psychiatr. 2013;6:624–5.CrossRefGoogle Scholar
  30. Jeste DV, Gladsjo JA, Lindamer LA, Lacro JP. Medical comorbidity in schizophrenia. Schizophr Bull. 1996;22:413–30.CrossRefGoogle Scholar
  31. Johannessen DJ, Wilson LG. Mania with cryptococcal meningitis in two AIDS patients. J Clin Psychiatry. 1988;49:200–1.PubMedGoogle Scholar
  32. Johnson FY, Naraqi S. Manic episode secondary to cryptococcal meningitis in a previously healthy adult. P N G Med J. 1993;36:59–62.PubMedGoogle Scholar
  33. Kaushik KS, Kapila K, Praharaj AK. Shooting up: the interface of microbial infections and drug abuse. J Med Microbiol. 2011;60:408–22.CrossRefGoogle Scholar
  34. Kawai M, Suzuki T, Hiruma M, Ikeda S. A retrospective cohort study of tinea pedis and tinea unguium in inpatients in a psychiatric hospital. Med Mycol J. 2014;55:E35–41.CrossRefGoogle Scholar
  35. Kernt M, Kampik A. Endophthalmitis: pathogenesis, clinical presentation, management, and perspectives. Clin Ophthalmol. 2010;4:121–35.CrossRefGoogle Scholar
  36. Keyashian K, Malani PN. Endophthalmitis associated with intravenous drug use. South Med J. 2007;100:1219–20.CrossRefGoogle Scholar
  37. Kim DG, Hong SC, Kim HJ, Chi JG, Han MH, Choi KS, Han DH. Cerebral aspergillosis in immunologically competent patients. Surg Neurol. 1993;40:326e31.CrossRefGoogle Scholar
  38. Krause DL, Wagner JK, Wildenauer A, Matz J, Weidinger E, Riedel M, Obermeier M, Gruber R, Schwarz M, Müller N. Intracellular monocytic cytokine levels in schizophrenia show an alteration of IL-6. Eur Arch Psychiatry Clin Neurosci. 2012;262:393–401.CrossRefGoogle Scholar
  39. Kumar A, Gopinath S, Dinesh KR, Karim S. Infectious psychosis: cryptococcal meningitis presenting as a neuropsychiatry disorder. Neurol India. 2011;59:909–11.CrossRefGoogle Scholar
  40. Kuruvila M, Gahalaut P, Zacharia A. A study of skin disorders in patients with primary psychiatric conditions. Indian J Dermatol Venereol Leprol. 2004;70:292–5.PubMedGoogle Scholar
  41. Lee KC, Ladizinski B, Federman DG. Complications associated with use of levamisole-contaminated cocaine: an emerging public health challenge. Mayo Clin Proc. 2012;87:581–6.CrossRefGoogle Scholar
  42. Lubeck DP, Patrick DL, McNulty P, Fifer SK, Birnbaum J. Quality of life of persons with onychomycosis. Qual Life Res. 1993;2:341–3.CrossRefGoogle Scholar
  43. Mantelli F, Lambiase A, Sacchetti M, Orlandi V, Rosa A, Casella P, Bonini S. Cocaine snorting may induce ocular surface damage through corneal sensitivity impairment. Graefes Arch Clin Exp Ophthalmol. 2015;253:765–72.CrossRefGoogle Scholar
  44. Melnychuk EM, Sole DP. A rare central nervous system fungal ınfectıon resultıng from brown heroin. J Emerg Med. 2017;52:314–7.CrossRefGoogle Scholar
  45. Mercan S, Kivac Altunay I. Psychodermatology: collaboration between psychiatry and dermatology. Turk Psikiyatri Derq. 2006;17:305–13.Google Scholar
  46. Moftah NH, Kamel AM, Attia HM, El-Baz MZ, Abd El-Moty HM. Skin diseases in patients with primary psychiatric conditions: a hospital based study. J Epidemiol Glob Health. 2013;3:131–8.CrossRefGoogle Scholar
  47. Mohamed S, Paulsen JS, O’Leary D, Arndt S, Andreasen N. Generalized cognitive deficits in schizophrenia: a study of first-episode patients. Arch Gen Psychiatry. 1999;56:749–54.CrossRefGoogle Scholar
  48. Mookhoek EJ, Van De Kerkhof PC, Hovens JE, Brouwers JR, Loonen AJ. Skin disorders in chronic psychiatric illness. J Eur Acad Dermatol Venereol. 2010;24:1151–6.CrossRefGoogle Scholar
  49. Mookhoek EJ, van de Kerkhof PC, Hovens JE, Brouwers JR, Loonen AJ. Substantial skin disorders in psychiatric illness coincide with diabetes and addiction. J Eur Acad Dermatol Venereol. 2011;25:392–7.CrossRefGoogle Scholar
  50. Morrow R, Wong B, Finkelstein WE, Sternberg SS, Armstrong D. Aspergillosis of the cerebral ventricles in a heroin abuser. Case report and review of the literature. Arch Intern Med. 1983;143:161–4.CrossRefGoogle Scholar
  51. Nakimuli-Mpungu E, Musisi S, Kiwuwa Mpungu S, Katabira E. Early-onset versus late-onset HIV-related secondary mania in Uganda. Psychosomatics. 2008;49:530–4.CrossRefGoogle Scholar
  52. Neves N, Santos L, Reis C, Sarmento A. Candida albicans brain abscesses in an injection drug user patient: a case report. BMC Res Notes. 2014;7:837.CrossRefGoogle Scholar
  53. Prakash PY, Sugandhi RP. Neuropsychiatric manifestation of confusional psychosis due to Cryptococcus neoformans var. grubii in an apparently immunocompetent host: a case report. Cases J. 2009;2:9084.CrossRefGoogle Scholar
  54. Roden MM, Zaoutis TE, Buchanan WL, Knudsen TA, Sarkisova TA, Schaufele RL, Sein M, Sein T, Chiou CC, Chu JH, Kontoyiannis DP, Walsh TJ. Epidemiology and outcome of Zygomycosis: a review of 929 reported cases. CID. 2005;4:634–53.CrossRefGoogle Scholar
  55. Rummel-Kluge C, Komossa K, Schwarz S, Hunger H, Schmid F, Kissling W, Davis JM, Leucht S. Second-generation antipsychotic drugs and extrapyramidal side effects: a systematic review and meta-analysis of head-to-head comparisons. Schizophr Bull. 2012;38:167–77.CrossRefGoogle Scholar
  56. Sa’adah MA, Araj GF, Diab SM, Nazzal M. Cryptococcal meningitis and confusional psychosis: a case report and literature review. Trop Geogr Med. 1995;47:224–6.PubMedGoogle Scholar
  57. Sachs R, Zagelbaum BM, Hersh PS. Corneal complications associated with the use of crack cocaine. Ophthalmology. 1993;100:187–91.CrossRefGoogle Scholar
  58. Sánchez-Portocarrero J, Pérez-Cecilia E, Corral O, Romero-Vivas J, Picazob JJ. The central nervous system and infection by Candida species. Diagn Microbiol Infect Dis. 2000;37:169–79.CrossRefGoogle Scholar
  59. Satishchandra P, Mathew T, Gadre G, Nagarathna S, Chandramukhi A, Mahadevan A, Shankar SK. Cryptococcal meningitis: clinical, diagnostic and therapeutic overviews. Neurol India. 2007;55:226–32.CrossRefGoogle Scholar
  60. Sloan D, Dedicoat MJ, Lalloo DG. Treatment of cryptococcal meningitis in resource limited settings. Curr Opin Infect Dis. 2009;22:455–63.CrossRefGoogle Scholar
  61. Spiegel DR, Bayne CE, Wilcox L, Somova M. A case of mania due to cryptococcal meningitis, successfully treated with adjunctive olanzapine, in a patient with acquired immunodeficiency syndrome. Gen Hosp Psychiatry. 2011;33:301.e3–6.CrossRefGoogle Scholar
  62. Strathdee SA, Case P, Lozada R, Mantsios A, Alvelais J, Pu M, Brouwer KC, Miller CL, Patterson TL. The color of meth: is it related to adverse health outcomes? An exploratory study in Tijuana, Mexico. Am J Addict. 2008;17:111–5.CrossRefGoogle Scholar
  63. Tang WK, Hui M, Ungvari GS, Leung CM. Cryptococcal meningitis mimicking primary mania in a young female. Gen Hosp Psychiatry. 2005;27:301–3.CrossRefGoogle Scholar
  64. Thienhaus OJ, Khosla N. Meningeal cryptococcosis misdiagnosed as a manic episode. Am J Psychiatry. 1984;141:1459–60.CrossRefGoogle Scholar
  65. Weber NS, Cowan DN, Millikan AM, Niebuhr DW. Psychiatric and general medical conditions comorbid with schizophrenia in the National Hospital Discharge Survey. Psychiatr Serv. 2009;60:1059–67.CrossRefGoogle Scholar
  66. Wu BY, Wu BJ, Lee SM, Sun HJ, Chang YT, Lin MW. Prevalence and associated factors of comorbid skin diseases in patients with schizophrenia: a clinical survey and national health database study. Gen Hosp Psychiatry. 2014;36:415–21.CrossRefGoogle Scholar
  67. Wurcel AG, Merchant EA, Clark RP, Stone DR. Emerging and underrecognized complications of illicit drug use. Clin Infect Dis. 2015;15(61):1840–9.Google Scholar
  68. Yuan SM. Right-sided infective endocarditis: recent epidemiologic changes. Int J Clin Exp Med. 2014;7:199–218.PubMedPubMedCentralGoogle Scholar
  69. Zhou M, Farooq AV, Andreoli MT, Ali M, Traish AS. Bilateral Rhizopus keratitis in a cocaine user. Can J Ophthalmol. 2016;51:e21–3.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Onur Gökçen
    • 1
  • Nermin Gündüz
    • 2
  • Mehmet Turgut
    • 3
  1. 1.Psychiatry ClinicKütahya Health Sciences University School of MedicineKütahyaTurkey
  2. 2.Department of PsychiatryKütahya Health Sciences University School of MedicineKütahyaTurkey
  3. 3.Department of NeurosurgeryAydın Adnan Menderes University School of MedicineAydınTurkey

Personalised recommendations