Abstract
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.
This is a preview of subscription content, access via your institution.
References
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 8.
Inskip HM, Harris EC, Barraclough B (1998) Lifetime risk of suicide for affective disorder, alcoholism and schizophrenia. Br J Psychiatry 172:35–37
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 19.
Zung WW (1965) A SELF-RATING DEPRESSION SCALE. Arch Gen Psychiatry 12:63–70
- 20.
Zung WW (1971) A rating instrument for anxiety disorders. Psychosomatics 12(6):371–379. doi:10.1016/s0033-3182(71)71479-0
- 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
- 22.
Harden C (2001) Safety profile of levetiracetam. Epilepsia 42(Suppl 4):36–39
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
Acknowledgements
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.
Author information
Affiliations
Corresponding authors
Ethics declarations
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.
Rights and permissions
About this article
Cite this article
Zhang, L., Sander, J.W., Zhang, L. et al. Suicidality is a common and serious feature of anti-N-methyl-D-aspartate receptor encephalitis. J Neurol 264, 2378–2386 (2017). https://doi.org/10.1007/s00415-017-8626-5
Received:
Revised:
Accepted:
Published:
Issue Date:
Keywords
- Anti-NMDAR encephalitis
- Suicidal rate
- Psychiatric symptom
- Predictors