Journal of Neurology

, Volume 264, Issue 12, pp 2378–2386 | Cite as

Suicidality is a common and serious feature of anti-N-methyl-D-aspartate receptor encephalitis

  • Le Zhang
  • Josemir W. Sander
  • Lan Zhang
  • Xin-Yue Jiang
  • Wei Wang
  • Kun Shuang
  • Ammar Taha Abdullah Abdulaziz
  • Meng-Qian Wu
  • Xiao-Sa Chi
  • Jin-Mei LiEmail author
  • Dong ZhouEmail author
Original Communication


We aimed to assess suicidality risk amongst people who had had anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. All people with a definitive diagnosis of anti-NMDAR encephalitis in West China Hospital between June 2012 and February 2017 were identified and their notes were retrospectively reviewed. Demographic and clinical characteristics and risk predictors for suicidality were summarized; those with suicidality were compared to those without. 17 of 133 people (13%) presented with suicidality symptoms: 7 (5%) with suicidal ideation; 8 (6%) who attempted suicide; and 2 (1.5%) who completed suicide. Median age was 27 (16–78) years, most were female [13 (76%)]. Compared with those with no suicidality, psychiatric symptoms as the initial symptoms were more frequent in those who reported suicidality (p = 0.039); insomnia, aggression, mania, depression and delusion were also more common (p < 0.05). The use of antidepressants (p < 0.001) and recurrence of encephalitis (p = 0.020) were higher in people with suicidality than in those without. Other characteristics were not significantly different in those who had suicidality and those who did not. Suicidality is a common and potentially lethal risk for people with anti-NMDAR encephalitis. Those presenting with psychiatric symptoms as the initial symptom and with insomnia, aggression, mania, depression and delusion should be carefully screened for suicidality. Closely monitoring people who have been treated with antidepressants is necessary.


Anti-NMDAR encephalitis Suicidal rate Psychiatric symptom Predictors 



We are grateful to Dr. Hai-tao Ren from the Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, China, for testing for anti-NMDAR antibodies and for technical support. We also grateful to Dr. Gail S Bell for reviewing the manuscript. JWS is based at UCLH/UCL Comprehensive Biomedical Research Centre, which receives a proportion of funding from the UK Department of Health’s National Institute for Health Research Biomedical Research Centres funding scheme. He receives support from the Dr. Marvin Weil Epilepsy Research Fund and the UK Epilepsy Society endows his current position. We thank all the subjects who participated in this study.

Compliance with ethical standards

Conflicts of interest

No author has any conflict of interest in respect to this work. LZ, LZ, XYJ, WW, KS, ATA, MQW, XSC, DZ, and JML have no disclosures to make. JWS has received research grants and honoraria from UCB, Eisai, and Janssen.


  1. 1.
    Gleichman AJ, Spruce LA, Dalmau J, Seeholzer SH, Lynch DR (2012) Anti-NMDA receptor encephalitis antibody binding is dependent on amino acid identity of a small region within the GluN1 amino terminal domain. J Neurosci 32(32):11082–11094. doi: 10.1523/jneurosci.0064-12.2012 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Dalmau J, Tuzun E, Wu HY, Masjuan J, Rossi JE, Voloschin A, Baehring JM, Shimazaki H, Koide R, King D, Mason W, Sansing LH, Dichter MA, Rosenfeld MR, Lynch DR (2007) Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol 61(1):25–36. doi: 10.1002/ana.21050 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Zhang L, Wu MQ, Hao ZL, Chiang SM, Shuang K, Lin MT, Chi XS, Fang JJ, Zhou D, Li JM (2017) Clinical characteristics, treatments, and outcomes of patients with anti-N-methyl-D-aspartate receptor encephalitis: a systematic review of reported cases. Epilepsy Behav 68:57–65. doi: 10.1016/j.yebeh.2016.12.019 CrossRefPubMedGoogle Scholar
  4. 4.
    Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, Cortese I, Dale RC, Gelfand JM, Geschwind M, Glaser CA, Honnorat J, Hoftberger R, Iizuka T, Irani SR, Lancaster E, Leypoldt F, Pruss H, Rae-Grant A, Reindl M, Rosenfeld MR, Rostasy K, Saiz A, Venkatesan A, Vincent A, Wandinger KP, Waters P, Dalmau J (2016) A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 15(4):391–404. doi: 10.1016/s1474-4422(15)00401-9 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Titulaer MJ, McCracken L, Gabilondo I, Armangue T, Glaser C, Iizuka T, Honig LS, Benseler SM, Kawachi I, Martinez-Hernandez E, Aguilar E, Gresa-Arribas N, Ryan-Florance N, Torrents A, Saiz A, Rosenfeld MR, Balice-Gordon R, Graus F, Dalmau J (2013) Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol 12(2):157–165. doi: 10.1016/s1474-4422(12)70310-1 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Wang W, Li JM, Hu FY, Wang R, Hong Z, He L, Zhou D (2016) Anti-NMDA receptor encephalitis: clinical characteristics, predictors of outcome and the knowledge gap in southwest China. Eur J Neurol 23(3):621–629. doi: 10.1111/ene.12911 CrossRefPubMedGoogle Scholar
  7. 7.
    Dalmau J, Lancaster E, Martinez-Hernandez E, Rosenfeld MR, Balice-Gordon R (2011) Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol 10(1):63–74. doi: 10.1016/s1474-4422(10)70253-2 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Inskip HM, Harris EC, Barraclough B (1998) Lifetime risk of suicide for affective disorder, alcoholism and schizophrenia. Br J Psychiatry 172:35–37CrossRefPubMedGoogle Scholar
  9. 9.
    Palmer BA, Pankratz VS, Bostwick JM (2005) The lifetime risk of suicide in schizophrenia: a reexamination. Arch Gen Psychiatry 62(3):247–253. doi: 10.1001/archpsyc.62.3.247 CrossRefPubMedGoogle Scholar
  10. 10.
    Pompili M, Amador XF, Girardi P, Harkavy-Friedman J, Harrow M, Kaplan K, Krausz M, Lester D, Meltzer HY, Modestin J, Montross LP, Mortensen PB, Munk-Jorgensen P, Nielsen J, Nordentoft M, Saarinen PI, Zisook S, Wilson ST, Tatarelli R (2007) Suicide risk in schizophrenia: learning from the past to change the future. Ann Gen Psychiatry 6:10. doi: 10.1186/1744-859x-6-10 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Viaccoz A, Desestret V, Ducray F, Picard G, Cavillon G, Rogemond V, Antoine JC, Delattre JY, Honnorat J (2014) Clinical specificities of adult male patients with NMDA receptor antibodies encephalitis. Neurology 82(7):556–563. doi: 10.1212/wnl.0000000000000126 CrossRefPubMedGoogle Scholar
  12. 12.
    Sakamoto H, Hirano M, Samukawa M, Ueno S, Maekura S, Fujimura H, Kuwahara M, Hamada Y, Isono C, Tanaka K, Kusunoki S, Nakamura Y (2013) Details of treatment-related difficulties in men with anti-N-methyl-D-aspartate receptor encephalitis. Eur Neurol 69(1):21–26. doi: 10.1159/000342023 CrossRefPubMedGoogle Scholar
  13. 13.
    Kuppuswamy PS, Takala CR, Sola CL (2014) Management of psychiatric symptoms in anti-NMDAR encephalitis: a case series, literature review and future directions. Gen Hosp Psychiatry 36(4):388–391. doi: 10.1016/j.genhosppsych.2014.02.010 CrossRefPubMedGoogle Scholar
  14. 14.
    Pruss H, Dalmau J, Harms L, Holtje M, Ahnert-Hilger G, Borowski K, Stoecker W, Wandinger KP (2010) Retrospective analysis of NMDA receptor antibodies in encephalitis of unknown origin. Neurology 75(19):1735–1739. doi: 10.1212/WNL.0b013e3181fc2a06 CrossRefPubMedGoogle Scholar
  15. 15.
    Tanyi JL, Marsh EB, Dalmau J, Chu CS (2012) Reversible paraneoplastic encephalitis in three patients with ovarian neoplasms. Acta Obstet Gynecol Scand 91(5):630–634. doi: 10.1111/j.1600-0412.2011.01365.x CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Day GS, High SM, Cot B, Tang-Wai DF (2011) Anti-NMDA-receptor encephalitis: case report and literature review of an under-recognized condition. J Gen Intern Med 26(7):811–816. doi: 10.1007/s11606-011-1641-9 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Finke C, Kopp UA, Pruss H, Dalmau J, Wandinger KP, Ploner CJ (2012) Cognitive deficits following anti-NMDA receptor encephalitis. J Neurol Neurosurg Psychiatry 83(2):195–198. doi: 10.1136/jnnp-2011-300411 CrossRefPubMedGoogle Scholar
  18. 18.
    Wang R, Guan HZ, Ren HT, Wang W, Hong Z, Zhou D (2015) CSF findings in patients with anti-N-methyl-D-aspartate receptor-encephalitis. Seizure 29:137–142. doi: 10.1016/j.seizure.2015.04.005 CrossRefPubMedGoogle Scholar
  19. 19.
    Zung WW (1965) A SELF-RATING DEPRESSION SCALE. Arch Gen Psychiatry 12:63–70CrossRefPubMedGoogle Scholar
  20. 20.
    Zung WW (1971) A rating instrument for anxiety disorders. Psychosomatics 12(6):371–379. doi: 10.1016/s0033-3182(71)71479-0 CrossRefPubMedGoogle Scholar
  21. 21.
    Beghi E (2004) Efficacy and tolerability of the new antiepileptic drugs: comparison of two recent guidelines. Lancet Neurol 3(10):618–621. doi: 10.1016/s1474-4422(04)00882-8 CrossRefPubMedGoogle Scholar
  22. 22.
    Harden C (2001) Safety profile of levetiracetam. Epilepsia 42(Suppl 4):36–39CrossRefPubMedGoogle Scholar
  23. 23.
    Braun C, Bschor T, Franklin J, Baethge C (2016) Suicides and suicide attempts during long-term treatment with antidepressants: a meta-analysis of 29 placebo-controlled studies including 6,934 patients with major depressive disorder. Psychother Psychosom 85(3):171–179. doi: 10.1159/000442293 CrossRefPubMedGoogle Scholar
  24. 24.
    Friedman RA, Leon AC (2007) Expanding the black box—depression, antidepressants, and the risk of suicide. N Engl J Med 356(23):2343–2346. doi: 10.1056/NEJMp078015 CrossRefPubMedGoogle Scholar
  25. 25.
    Erhardt S, Lim CK, Linderholm KR, Janelidze S, Lindqvist D, Samuelsson M, Lundberg K, Postolache TT, Traskman-Bendz L, Guillemin GJ, Brundin L (2013) Connecting inflammation with glutamate agonism in suicidality. Neuropsychopharmacology 38(5):743–752. doi: 10.1038/npp.2012.248 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Yin H, Xu L, Shao Y, Li L, Wan C (2016) Relationship between suicide rate and economic growth and stock market in the People’s Republic of China: 2004–2013. Neuropsychiatr Disease Treat 12:3119–3128. doi: 10.2147/ndt.s116148 CrossRefGoogle Scholar
  27. 27.
    Kruse JL, Lapid MI, Lennon VA, Klein CJ, Toole OO, Pittock SJ, Strand EA, Frye MA, McKeon A (2015) Psychiatric autoimmunity: N-methyl-D-aspartate receptor IgG and beyond. Psychosomatics 56(3):227–241. doi: 10.1016/j.psym.2015.01.003 CrossRefPubMedGoogle Scholar
  28. 28.
    Dean B, Gibbons AS, Boer S, Uezato A, Meador-Woodruff J, Scarr E, McCullumsmith RE (2016) Changes in cortical N-methyl-D-aspartate receptors and post-synaptic density protein 95 in schizophrenia, mood disorders and suicide. Austr N Z J Psychiatry 50(3):275–283. doi: 10.1177/0004867415586601 CrossRefGoogle Scholar
  29. 29.
    Kjelby E, Sinkeviciute I, Gjestad R, Kroken RA, Loberg EM, Jorgensen HA, Hugdahl K, Johnsen E (2015) Suicidality in schizophrenia spectrum disorders: the relationship to hallucinations and persecutory delusions. Eur Psychiatry 30(7):830–836. doi: 10.1016/j.eurpsy.2015.07.003 CrossRefPubMedGoogle Scholar
  30. 30.
    Allan NP, Conner KR, Pigeon WR, Gros DF, Salami TK, Stecker T (2017) Insomnia and suicidal ideation and behaviors in former and current U.S. service members: does depression mediate the relations? Psychiatry Res 252:296–302. doi: 10.1016/j.psychres.2017.03.009 CrossRefPubMedGoogle Scholar
  31. 31.
    Sher L, Fisher AM, Kelliher CH, Penner JD, Goodman M, Koenigsberg HW, New AS, Siever LJ, Hazlett EA (2016) Clinical features and psychiatric comorbidities of borderline personality disorder patients with versus without a history of suicide attempt. Psychiatry Res 246:261–266. doi: 10.1016/j.psychres.2016.10.003 CrossRefPubMedGoogle Scholar
  32. 32.
    Witt K, Hawton K, Fazel S (2014) The relationship between suicide and violence in schizophrenia: analysis of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) dataset. Schizophr Res 154(1–3):61–67. doi: 10.1016/j.schres.2014.02.001 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Hor K, Taylor M (2010) Suicide and schizophrenia: a systematic review of rates and risk factors. J Psychopharmacol (Oxf Engl) 24:81–90. doi: 10.1177/1359786810385490 CrossRefGoogle Scholar
  34. 34.
    Gresa-Arribas N, Titulaer MJ, Torrents A, Aguilar E, McCracken L, Leypoldt F, Gleichman AJ, Balice-Gordon R, Rosenfeld MR, Lynch D, Graus F, Dalmau J (2014) Antibody titres at diagnosis and during follow-up of anti-NMDA receptor encephalitis: a retrospective study. Lancet Neurol 13(2):167–177. doi: 10.1016/s1474-4422(13)70282-5 CrossRefPubMedGoogle Scholar
  35. 35.
    Dalmau J, Gleichman AJ, Hughes EG, Rossi JE, Peng X, Lai M, Dessain SK, Rosenfeld MR, Balice-Gordon R, Lynch DR (2008) Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 7(12):1091–1098. doi: 10.1016/s1474-4422(08)70224-2 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Martin PC, Zimmer TJ, Pan LA (2015) Magnetic resonance imaging markers of suicide attempt and suicide risk in adolescents. CNS Spectr 20(4):355–358. doi: 10.1017/s1092852915000048 CrossRefPubMedGoogle Scholar
  37. 37.
    Angst J, Angst F, Gerber-Werder R, Gamma A (2005) Suicide in 406 mood-disorder patients with and without long-term medication: a 40 to 44 years’ follow-up. Arch Suicide Res 9(3):279–300. doi: 10.1080/13811110590929488 CrossRefPubMedGoogle Scholar
  38. 38.
    Sharma T, Guski LS, Freund N, Gotzsche PC (2016) Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports. BMJ 352:i65. doi: 10.1136/bmj.i65 CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Coupland C, Hill T, Morriss R, Arthur A, Moore M, Hippisley-Cox J (2015) Antidepressant use and risk of suicide and attempted suicide or self harm in people aged 20 to 64: cohort study using a primary care database. BMJ 350:h517. doi: 10.1136/bmj.h517 CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Stone M, Laughren T, Jones ML, Levenson M, Holland PC, Hughes A, Hammad TA, Temple R, Rochester G (2009) Risk of suicidality in clinical trials of antidepressants in adults: analysis of proprietary data submitted to US Food and Drug Administration. BMJ 339:2880. doi: 10.1136/bmj.b2880 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Department of Neurology, West China HospitalSichuan UniversityChengduChina
  2. 2.NIHR University College London Hospitals Biomedical Research CentreUCL Institute of Neurology, Queen SquareLondonUK
  3. 3.Chalfont Centre for EpilepsyChalfont St PeterUK
  4. 4.Stichting Epilepsie Instellingen Nederland (SEIN)HeemstedeThe Netherlands
  5. 5.Mental Health Center, West China HospitalSichuan UniversityChengduChina
  6. 6.West China College of MedicineSichuan UniversityChengduChina

Personalised recommendations