Psychiatric Symptoms of Patients With Anti-NMDA Receptor ...

As anti–NMDAR encephalitis is an IgG antibody mediated autoimmune disorder, the severity of the disease is closely related to the titers of the ... Articles JoseF.Tellez-Zenteno UniversityofSaskatchewan,Canada VictorR.Santos FederalUniversityofMinasGerais,Brazil SeyedMirsattari WesternUniversity(Canada),Canada ManabuTakaki GraduateSchoolofMedicineDentistryandPharmaceuticalSciences,OkayamaUniversity,Japan Theeditorandreviewers'affiliationsarethelatestprovidedontheirLoopresearchprofilesandmaynotreflecttheirsituationatthetimeofreview. Abstract Methods Results Discussion DataAvailabilityStatement EthicsStatement AuthorContributions Funding ConflictofInterest Acknowledgments References SuggestaResearchTopic> DownloadArticle DownloadPDF ReadCube EPUB XML(NLM) Supplementary Material Exportcitation EndNote ReferenceManager SimpleTEXTfile BibTex totalviews ViewArticleImpact SuggestaResearchTopic> SHAREON OpenSupplementalData ORIGINALRESEARCHarticle Front.Neurol.,24January2020 |https://doi.org/10.3389/fneur.2019.01330 PsychiatricSymptomsofPatientsWithAnti-NMDAReceptorEncephalitis WeiWang1,2†,LeZhang1†,Xiao-SaChi1,LiHe1,DongZhou1*andJin-MeiLi1* 1DepartmentofNeurology,WestChinaHospital,SichuanUniversity,Chengdu,China 2DepartmentofNeurology,XuanwuHospital,CapitalMedicalUniversity,Beijing,China Objective:Weconductedthisstudytoanalyzetheclinicalcharacteristicsofthepsychiatricsymptomsofpatientswithanti-NMDARencephalitis. Methods:Aretrospectivestudyofanti-NMDARencephalitisinChinawasperformed.Theclinicalcharacteristicsofthepsychiatricsymptoms,therelationshipbetweentheantibodiestitersandclinicalcharacteristicsofpatientswithanti-NMDARencephalitisweredetermined. Results:Atotalof108patientswithadefinitivediagnosisofanti-NMDARencephalitiswereincludedinthisstudy.103patients(95%)developedoneorseveralpsychiatricsymptoms.Thecomparisonofthehightitergroupandthelowtitergroupshowedthatmorepatientspresentedpsychiatricsymptomsastheinitialsymptominthehightitergroup(P=0.020),theprevalenceofthesymptomssuchasdepressive,catatonic,andcentralhypoventilationwerealsohigherinthehightitergroupthanthelowtitergroup(P=0.033,0.031and0.006,respectively).Meanwhile,morepatientsreceivedacombinationtreatmentofIVIgandcorticosteroidsinthehightitergroupthanthelowtitergroupandpatientsinhightitergroupwereprescriptwithanti-psychiatricdrugsmoreoftenthanthepatientsinlowtitergroup(P=0.026and0.003,respectively). Conclusions:Psychiatricsymptomsarethemostcommonclinicalcharacteristicsofpatientswithanti-NMDARencephalitis.Patientswithhigherantibodiestitersmoreoftenpresentedwithpsychiatricsymptomsastheinitialsymptom,andshowedamoresevereclinicalfeature.Screeningfortheanti-NMDARantibodiesisessentiallyimportantinpatientswhopresentpsychiatricsymptomswithorwithoutotherneurologicalsymptoms. Anti–N-methyl-D-aspartatereceptor(NMDAR)encephalitisisanautoimmunedisorderinwhichIgGantibodiesaredirectedagainsttheNR1subunitoftheNMDAR.Thedisorderincludesarangeofpsychiatricsymptomsearlyinthecourseofthedisease,followedbyneurologicalsymptoms,suchasmemoryproblems,seizure,decreasedconsciousness,dyskinesia,autonomicinstabilityandhypoventilation(1,2).Thepsychiatricsymptomsofthisdisordercouldpresentaspsychosis,anxiety,insomnia,mania,andcatatonicsymptoms(3,4),andmanypatientswereinitiallyseenbypsychiatristsoradmittedtopsychiatriccenters.Asanti–NMDARencephalitisisanIgGantibodymediatedautoimmunedisorder,theseverityofthediseaseiscloselyrelatedtothetitersoftheantibodies.Previousstudieshaveshownthatpatientswhoimprovedhadaparalleldecreaseofserumtiters,whereasthosewhodidnotimprovemaintainedhightitersinserumandcerebrospinalfluid(CSF)(2).Althoughimmunotherapieshavebeensuggestedtobethefirst-linetreatmentstrategyofpatientswithanti-NMDARencephalitis,and79%patientscanreachagoodoutcome(3),anti-psychotictherapiesmaystillbeimplantedduetotheprominentpsychiatricsymptoms.Manyofthestudiestodatethathavelookedattreatmentalgorithmsforanti-NMDRencephalitishavefocusedonimmunotherapy,withonlyafewreportslookingattreatmentofthepsychiatricmanifestationsofthedisease.Therefore,weconductedthisstudytofurtheranalysistheclinicalcharacteristicsofthepsychiatricsymptomsofpatientswithanti-NMDARencephalitis,aswellastherelationshipbetweentheantibodiestitersandclinicalcharacteristics,especiallypsychiatricsymptoms,andthetreatmentstrategyofpatientswithanti-NMDARencephalitis. Methods Patients Patientswhopresentedwithpsychiatricsymptoms,seizuresorfocalneurologicalsignsweretestedforthepresenceofNMDARantibodiesinserumorCSFsampleattheWestChinaHospitalofSichuanUniversitybetweenJune2011andApril2016.Allpatientwhotestedpositiveforanti-NMDARantibodiesinCSFor/andserumwereincludedinthisstudyandpatientslackingkeyclinicaldataorsuspectingofvirusencephalitisorotherinfectiousencephalitiswereexcluded.Thediagnosisofanti-NMDARencephalitisisconsistentwithpreviousstudies(5,6).Clinicalinformationwasobtainedbytheauthorsorreferringphysiciansatsymptomonsetandatregularintervalsduringthecourseofthedisease.Fifty-onepatientshavebeenpartlyreported(5).Wesystemicallyreviewedthepsychiatricsymptomsofeachpatientinthefollowingcategory:aggression,depressive,catatonic,disorganized,anxious,psychotic(hallucinationordelusions),manic,suicidal,andinsomnia.ThediagnosisofeachcategorymeettheDiagnosticandStatisticalManualofMentalDisorders,FifthEdition(DSM-5)(7,8). TheoutcomewasassessedusingthemodifiedRankinScale(mRS)atthelastvisit(9,10).Adiagnosisofanti-NMDARencephalitiswasconsideredtobedefinitivewhen(1)encephaliticsignssuchaspsychiatricsymptoms,seizures,orfocalneurologicalsignswereshown;(2)anti-NMDARantibodiesweredetectedinCSFor/andserum.Centralhypoventilationwasconsideredifthepatientneedsrespiratorysupportsuchasmechanicalventilation.Relapsewasdefinedastheonsetorworseningofsymptomsatleast2monthsafterimprovement. SubgroupAnalysis BasedonthetiteroftheantibodiesintheserumandCSF,wedividedallthepatientsintotwogroups:lowtitergroupandhightitergroup.Thepsychiatricsymptomswerecomparedbetweenthesetwogroups.Theantibodytiters≧1:32inCSF/≧1:100inserumwereconsideredhightiter,andtheantibodytiter<1:32inCSF/<1:100inserumwereconsideredlowtiter. AntibodiesStudy ThisstudywasapprovedbytheResearchEthicsCommitteeofSichuanUniversity.Writteninformedconsentwasobtainedfromeachsubject.Theserumand/orCSFsamplesofallpatientsweresenttotwoinstitutions(OumengBiotechnologyCorporation,orPekingUnionMedicalCollegeHospital,Beijing,China)todetectantibodiesagainstNMDAR,contactin-associatedprotein2(CASPR2),GABARB1/B2,AMPAreceptors1/2andleucine-richglioma-inactivatedprotein1(LGI1).Thedatathatsupportthefindingsofthisstudyareavailablefromthecorrespondingauthoruponreasonablerequest.SampleswereclassifiedaspositiveornegativebyindirectimmunofluorescenceusingEU90cellsaccordingtopreviousstudy(5). StatisticalAnalyses StatisticalanalyseswereperformedusingSPSSversion20.0.Weperformedaunivariateanalysisincontinuousvariablessuchasage.Genderanddifferentclinicalsymptomswereanalyzedascategoricalvariables.Theindependentt-testorone-wayanalysisofvariance(ANOVA)wasusedforcontinuousvariables,andtheChi-squaretestorFisher'sexacttestwasusedforcategoricalvariables.Whencountsofzerocellswererecorded,oddsratios(ORs)werecalculatedusingHaldane'smodification,whichadds0.5toallcountstoaccommodatepossiblezerocounts(11).P-values<0.05(two-sided)wereconsideredtobesignificant. Results Atotalof108patientswithadefinitivediagnosisofanti-NMDARencephalitiswereincludedinthisstudy.Seventy-eightpatientshadpositiveantibodyresultsinbothCSFandserum,and30patientsonlyhadCSFpositiveantibodyresults.Thetestforotherautoimmuneantibodies,suchasantibodiesagainstAMPAreceptors1/2,CASPR2,LGI1,andGABARB1/B2werenegative.ThedemographicandgeneralclinicalcharacteristicsaresummarizedinTable1.Sixty-threepatientswerefemale(58%),andthemeanagewas27.1years(range:9–71). TABLE1 Table1.Clinicalcharacteristicsofpatientswithanti-NMDARencephalitis. ClinicalSymptoms Sixty-twopatients(57%)presentedwithpsychiatricsymptomsastheinitialsymptom,includingmoodalteration(anxiousordepressive),aggression,manic,delusion,andvisualorauditoryhallucinations.Forty-twopatients(39%)presentedwithneurologicalsymptoms,suchasseizure,movementdisorder,andspeechdisturbances,astheinitialsymptom. Duringthediseasecourse,103patients(95%)developedoneorseveralpsychiatricsymptoms,includingaggression(43patients,40%),depressive(28patients,26%),catatonic(15patients,14%),disorganized(76patients,70%),anxious(26patients,24%),psychotic(54patients,50%),manic(67patients,62%),suicidal(11patients,10%)andinsomnia(28patients,26%).Hundredandtwopatients(94%)inthiscohorthadneurologicalsymptoms,includingseizuresin89patients(82%),memorydeficitsin56patients(52%),speechdisturbancesin68patients(63%),dyskinesiasandmovementdisordersin47patients(44%),autonomicinstabilityin45patients(42%),decreasedconsciousnessin70patients(65%)andcentralhypoventilationin27patients(25%). SubgroupAnalysis—LowTiterGroupVersesHighTiterGroup TheresultsofthecomparisonbetweenthelowtitergroupandhightitergroupshowninTable2andFigure1.Intotal,58patientswereincludedinthelowtitergroupand50patientswereincludedinthehightitergroup.Twenty-sevenpatientspresentedpsychiatricsymptomsastheinitialsymptominthelowtitergroupwhile35patientsinthehightitergrouppresentedpsychiatricsymptomsastheinitialsymptom(P=0.020,OR=0.373,95%CI:0.169–0.827).Fourpatientshadcatatonicsymptomsinthelowtitergroupwhile11patientshadcatatonicsymptomsinthehightitergroup(P=0.031,OR=0.263,95%CI:0.078–0.886).Tenpatientsexperienceddepressiveinthelowtitergroupwhereas18patientsexperienceddepressiveinthehightitergroup(P=0.033,OR=0.370,95%CI:0.152–0.905).Eightpatientsinthelowtitergroupwhereas19patientsinthehightitergroupsufferedfromcentralhypoventilation(P=0.006,OR=0.261,95%CI:0.102–0.668),andeightpatientsinthelowtitergroupand18patientsinthehightitergrouphadmechanicalventilationduringtheperiodofhospitalization(P=0.011,OR=0.284,95%CI:0.111–0.731).Thefrequencyofotherpsychiatricsymptomsandclinicalfeatures,suchasaggression,disorganized,anxious,psychotic,manic,suicidal,insomnia,prodromalsymptoms,seizure,memorydeficits,speechdisturbances,dyskinesiaandmovementdisorders,autonomicinstability,decreaseconsciousness,tracheotomy,abnormalMRIfindings,abnormalEEGfindings,abnormalCSFfindings,andthetumorpresentationratewerenotsignificantlydifferentbetweenthetwogroups.Wealsocomparedthetreatmentstrategiesbetweenthehightitergroupandlowtitergroup.Andwefoundthatpatientsinhightitergroupwereprescriptwithanti-psychiatricdrugsmoreoftenthanthepatientsinlowtitergroup(P=0.003,OR=0.168,95%CI:0.046–0.616),butthefrequenciesofdifferenttypesofanti-psychiatricdrugswerenotsignificantlydifferent.Meanwhile,morepatientsreceivedacombinationtreatmentofIVIgandcorticosteroidsinthehightitergroupthanthelowtitergroup(P=0.026,OR=0.415,95%CI:0.190-0.906).Inaddition,therelapserate,themeanmRSandthefrequencyoftheresidualsymptomsatthelastvisitwerenotshownsignificantdifferencebetweenthetwogroups. TABLE2 Table2.Comparisonbetweenpatientswithlowantibodytiterandhighantibodytiter. FIGURE1 Figure1.Tendencyofthefrequencyofdifferentpsychiatricsymptomsbetweenthelowtitergroupandhightitergroupduringthehospitalizationandatlastvisit. TreatmentStrategies Asforthetreatmentstrategies,105outof108patients(97%)receivedimmunotherapy,including49patientstreatedwithintravenousimmunoglobulin(IVIg,0.4g/kgperdayfor5days)onceorseveraltimes,sevenpatientsweretreatedwithintravenousmethylprednisolone(1g/dayfor5days)alone,46patientsreceivedacombinationtreatmentofIVIgandintravenousmethylprednisolone,onepatientreceivedacombinationtreatmentofIVIg,intravenousmethylprednisoloneandplasmaexchange,andtwopatientsreceivedIVIg,intravenousmethylprednisoloneandasecond-linetherapy(onewithcyclophosphamide,onewithrituximab).Eighty-ninepatients(82%)wereprescriptdrugstocontrolthepsychiatricsymptoms,including37patientswithanti-psychoticdrugsalone,fourpatientswithanti-anxietydrugsalone,38patientswithacombinationofanti-psychoticdrugsandanti-anxietydrugs,onepatientwithacombinationofanti-psychoticandanti-depressivedrugs,9patientswithacombinationofanti-psychotic,anti-anxietyandanti-depressivedrugs.Theantipsychoticdrugsincludetypical(haloperidolandtiapride)andatypical(risperidone,olanzapine,quetiapine,andclozapine).Threepatientshadelectroconvulsivetherapy(ECT)isolatedorcombinedwithotheranti-psychoticdrugs.Twelvepatientsunderwenttumorresection. Asforthesideeffectoftheantipsychotics,threepatientshadextrapyramidalsymptoms,onepatienthadtardivedyskinesia,twopatientshaddecreasedconsciousness(somnolence)andonepatienthadliverfunctiondamageafterusingantipsychotics.However,asallpatientswereprescriptwithotherdrugsatthesametime,thesideeffectsmayalsoduetotheuseofotherdrugsandmayalsoreflectthenaturalprogressionofanti-NMDAreceptorencephalitis. Follow-Up Themedianfollow-updurationwas17months(1–47months).Atthelastvisit,themeanmRSwas1.33±1.83.Forty-fourpatients(46%)reachedfullyrecovery(mRS=0),33patients(34%)hadmilddeficits(mRS1-2),10patients(11%)hadseveredeficits(mRS3-5),andninepatients(9%)died.Duringthefollow-upperiod,17patientsstillhadmemorydeficits,sevenhadspeechdisturbance,andtwohadoneorseveralepisodesofseizures.Theremainingpsychiatricsymptomsincludedaggression(23patients),depressive(fivepatients),catatonic(threepatients),disorganized(fourpatients),anxious(fourpatients),psychoticsymptoms(threepatients),manic(threepatients),suicidal(twopatients)andinsomnia(fivepatients).Sevenpatientsrelapsedduringthecourseofthisstudy.Twelvepatientswerelosttofollow-up. Discussion ThepresentstudynotonlyfurtherprovedthatChinesepatientswithanti-NMDARencephalitismighthavealowerincidenceoftumorandarelativelybetteroutcomecomparedwithstudiesfromothercountriesandregions,whichisconsistentwithourpreviousstudy(5),butalsorevealseveralfeaturesmainlyfocusonthecharacteristicandtreatmentofthepsychiatricsymptomsofpatientswithanti-NMDARencephalitis. Psychiatricsymptomsarethemostcommonclinicalcharacteristicofpatientswithanti-NMDARencephalitis;theincidenceisaround65–80%(2,9,12).AntibodiesagainstNMDARmaybeassociatedwithpsychiatricsymptomsforseveralreasons.StudieshaveshownthatdysfunctionofNMDARandtheglutamatergicsystemmaybeassociatedwiththepathogenesisofschizophrenia,asantagonistsofNMDAR,includingphencyclidineandketamine,havebeenshowntoinducepsychoticsymptoms(positiveandnegative)andbehavioralandcognitiveimpairmentssimilartothoseobservedinpatientswithschizophrenia,afindingwhichsuggeststhatNMDARhypofunctionmayleadtosecondarydopaminergicdysregulation(13–15).Isolatedpsychiatricepisodescanalsobefoundinpatientswithpositiveanti-NMDARantibodies,inaprevalenceof~4%,eitheratdiseaseonsetorrelapse(16,17).Andpatientswithisolatedpsychiatricsymptomsormilderpresentationsdonotnecessarilyprogresstomoreseveremulti-symptomstage,despiteprolongedperiodswithouttreatment(17). Recently,severalstudiesexploredtherelationshipbetweenanti-NMDARantibodiesandwell-definedpsychiatricdisorders,suchasschizophrenia,majordepressivedisorder,andborderlinepersonalitydisorder(18–21).AlthoughitisreportedthatseveraltypesofserumNMDARantibodieswerepresentin9.9%ofacutelyillpatientswhowereinitiallydiagnosedwithschizophrenia(21),theantibodysubtypeprofileofthesepatientsdifferedfromthoseofnon-schizophrenicanti-NMDARencephalitispatients,andthefrequencyofantibodypositivityinthesepatientswassimilartothatobservedinthecontrols(22–24).Kawaietal.reviewedagroupofpatientswithmooddisorderandfoundthatfouroutof13patientswhoseCSFwasobtainedhadpositiveanti-NMDARantibodies.Andallofthefourpatientsdevelopedsomeneurologicalsymptomsduringtheclinicalcourse(25).Thisstudypresentedtherelationshipbetweenpsychiatricdisorders(mooddisorder)andanti-NMDAreceptorantibodiesfromadifferentperspective.Positiveanti-NMDAreceptorantibodiesinpatientswithpsychiatricsymptomsusuallyindicateneurologicaldiseaseratherthanpurelypsychiatricdisorders,andthetreatmentstrategyalsoneedtobechangedaccordingtotheunderlineetiology. Inthepresentstudy,wedividedthepatientsintotwogroupsaccordingtotheantibodiestitersandfoundthepatientswithhigherantibodiestitersmoreoftenpresentedpsychiatricsymptomsastheinitialsymptomandshowedamoresevereclinicalfeature.Morepatientsinthehightitergrouppresenteddepressiveandcatatonicsymptoms,andmorepatientshadcentralhypoventilationwhichmayneedmechanicalventilationortracheotomy.Previousstudieshaveshownthatdepressiveandcatatoniaarethemostcommonpsychiatricsymptomsinpatientswithanti-NMDARencephalitis(26).Asanti–NMDARencephalitisisanIgGantibodymediatedautoimmunedisorder,theseverityofthediseaseiscloselyrelatedtothetitersoftheantibodies.Patientswhoimprovedhadaparalleldecreaseofserumtiters,whereasthosewhodidnotimprovemaintainedhightitersinCSFandserum(2). Fromclinicalpracticewenoticedthatpatientswithahighertitermighthaveamoresevereclinicalimpression,especiallyinpatientswhopresentedcatatonic/stuporandpatientswhoneedmechanicalventilation.Althoughcatatoniahascommonlybeenascribedtoschizophrenia,itismorecommonlyseeninaffectivedisordersandmedicalandneurologicaldisorders,andanti-NMDARencephalitisisconsideredtobeanautoimmunetypeofcatatonia.(27).Theprevalenceofcatatoniaisestimatedtobe10–25%inthemixedinpatientpopulationsofpsychiatricinstitutions,however,thereisalackofsystematicinvestigationsonthepresentationofcatatoniaindifferentpatientgroups(28,29).Ithasbeenproposedthatcatatoniaresultsfromdysregulationintheglutamate,GABA-A,anddopaminepathways(30),andtheNMDAreceptorantagonistketamineelicitedcatatonia-likesignswhenadministeredinhealthysubjects(31,32).AndhypoventilationcanbearesultsofthedisruptionofNR1subunitoftheNMDAreceptor(33). Previousstudiesshowedthatanti-NMDARencephalitisoftenhasagoodoutcomeifappropriatetreatmentsuchasimmunotherapyortumorremovalarecarriedoutintime(3),however,ashighas45%ofourpatientshadresidualsymptomssuchasmemorydeficits,speechdisturbancesandespeciallypsychiatricsymptoms,whichmaystillaffectthequalityoflifeofthesepatients.Itissuggestedthataround25%ofthepatientswithanti-NMDARencephalitisareleftwithmemory,cognitive,andmotordeficits(34).Themilddeficitssymptomssuchaspoorattention,behavioraldisinhibition,andsleepdysfunctionduringtherecoveryperiodmaybeduetothefrontal-lobedysfunction(2).Notably,althoughthefrequencyofthedepressiveandcatatonicsymptomsweresignificantlydifferentduetothedifferentantibodiestitersintheearlystageofthediseasecourse,thefrequencyoftheresidualsymptomswasnosignificantdifferencebetweenthelowtitergroupandhightitergroup,whichsuggestsarelativegoodtreatmentresultsdespitetheformerseveresymptomspresentedinthehightitergroup. Althoughimmunotherapieshavebeensuggestedtobethefirst-linetreatmentstrategyofpatientswithanti-NMDARencephalitis,and79%patientscanreachagoodoutcome(3),anti-psychotictherapiesmaystillbeimplantedduetotheprominentpsychiatricsymptoms,andasmallportionofthepatientsonlyhadpsychiatricsymptoms(17).Manyofthestudiestodatethathavelookedattreatmentalgorithmsforanti-NMDRencephalitishavefocusedonimmunotherapy,withonlyafewreportslookingattreatmentofthepsychiatricmanifestationsofthedisease(27,35).Nospecificguidelinesexistfortreatmentofpsychiatricsymptomsinthissetting.Ourresultsshowedthateighty-ninepatients(82%)wereprescriptdrugsinordertocontroltheprominentpsychiatricsymptoms.PreviousreportssuggestedthatECTmayhelpstabilizingthepsychiatricsymptomsofpatientswithanti-NMDARencephalitis(27).Butsomesuggestedthatuseofhighlysedatingmedicationssuchasquetiapine,chlorpromazine,valproicacid,andbenzodiazepines;high-potencyantipsychoticslikehaloperidolmayexacerbatemotorsymptomsinpatientswithanti-NMDARencephalitis(36).Asallofourpatientswereprescriptwithanti-psychiatricdrugsasanadditionaltherapytotheimmunotherapy,andthecategoriesandthedosagesofthedrugsaretoovarious,itisdifficulttofurtherconfirmwhethertheseanti-psychiatricdrugsistrulyeffectiveornot.Furtherstudiesareneededtoanalyzetheunderlyingmechanismsandeffectivenessoftheanti-psychiatricdrugsinthesettingofpatientswithanti-NMDARencephalitis,andifeffective,astandardtreatmentalgorithmisalsorequired. Therearesomelimitationsinthepresentstudy.Giventheretrospectivenatureofthisstudy,theremayhavepossibleselectionbias.Allpatientswererecruitedfromthedepartmentofneurology,therefore,someofthepatientswhoonlypresentedwithpsychiatricsymptomsmaybeunderestimatedandtheevaluationofsomepsychiatricsymptomsmaybeinsufficient.Andtheprevalenceofmemorydeficitsmayalsobeunderestimatedbecausepatientswithseverepsychosisorcognitivedisordersattheearlystageofthediseasecannotbeevaluated.Meanwhile,thepsychiatricsymptomswereevaluatedatthefirstadmissionandduringtheclinicalcourse(whenpatientscancooperate)inthepresentstudy,sotheevaluationtimepointofeachpatientmaybedifferent. Inconclusion,psychiatricsymptomsarethemostcommonclinicalcharacteristicsofpatientswithanti-NMDARencephalitis.Patientswithhigherantibodiestitersmoreoftenpresentedwithpsychiatricsymptomsastheinitialsymptom,andshowedamoresevereclinicalfeature.Screeningfortheanti-NMDARantibodiesisessentiallyimportantinpatientswhopresentpsychiatricsymptomswithorwithoutotherneurologicalsymptoms. DataAvailabilityStatement Alldatasetsgeneratedforthisstudyareincludedinthearticle/supplementarymaterial. EthicsStatement ThestudiesinvolvinghumanparticipantswerereviewedandapprovedbyThisstudywasapprovedbytheResearchEthicsCommitteeofSichuanUniversity.Writteninformedconsenttoparticipateinthisstudywasprovidedbytheparticipants'legalguardian/nextofkin. AuthorContributions WWwrotethemainmanuscript,analyzedthedata,madetheTables1,2,andFigure1.WW,LZ,X-SC,andLHcollectedthedata.DZandJ-MLcameupwiththemainideas,leadtheresearchgroup,andarrangedtheworkofallauthors.Allauthorsreviewedthemanuscript. Funding ThisstudywassupportedbytheNationalNaturalScienceFoundationofChina(GrantNos.81571272and81801285).Thistwofundssupportedstudiesrelatedtoencephalitisandepilepsy.Thefunds(GrantNo.81571272)willpayfortheopenaccesspublicationfee. ConflictofInterest Theauthorsdeclarethattheresearchwasconductedintheabsenceofanycommercialorfinancialrelationshipsthatcouldbeconstruedasapotentialconflictofinterest. Acknowledgments Wethankallofthesubjectswhoparticipatedinthisstudy. 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Keywords:anti-NMDAreceptorencephalitis,psychiatricsymptoms,antibodytiter,treatmentstrategy,neurologicalsymptoms Citation:WangW,ZhangL,ChiX-S,HeL,ZhouDandLiJ-M(2020)PsychiatricSymptomsofPatientsWithAnti-NMDAReceptorEncephalitis.Front.Neurol.10:1330.doi:10.3389/fneur.2019.01330 Received:30June2019;Accepted:02December2019;Published:24January2020. Editedby:JoseF.Tellez-Zenteno,UniversityofSaskatchewan,Canada Reviewedby:ManabuTakaki,OkayamaUniversity,JapanVictorRodriguesSantos,FederalUniversityofMinasGerais,BrazilSeyedMirsattari,UniversityofWesternOntario,Canada Copyright©2020Wang,Zhang,Chi,He,ZhouandLi.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense(CCBY).Theuse,distributionorreproductioninotherforumsispermitted,providedtheoriginalauthor(s)andthecopyrightowner(s)arecreditedandthattheoriginalpublicationinthisjournaliscited,inaccordancewithacceptedacademicpractice.Nouse,distributionorreproductionispermittedwhichdoesnotcomplywiththeseterms. *Correspondence:Jin-MeiLi,[email protected];DongZhou,[email protected] †Theseauthorshavecontributedequallytothiswork COMMENTARY ORIGINALARTICLE Peoplealsolookedat SuggestaResearchTopic>