招标采购招标公告（首都医科大学2024）
王刚/周佳等（安定医院）BrainStimulation--Effectofadd-ontranscranialalternatingcurrentstimulation(tACS)inmajordepressivedisorder:Arandomizedcontrolledtrial
文件下载
ContentslistsavailableatScienceDirectBrainStimulationjournalhomepage:www.journals.elsevier.com/brain-stimulationEffectofadd-ontranscranialalternatingcurrentstimulation(tACS)inmajordepressivedisorder:ArandomizedcontrolledtrialJingjingZhoua,b,1,DanLia,b,1,FukangYea,b,1,RuiLiua,b,YuanFenga,b,ZizhaoFenga,b,RuinanLia,b,XiaoyaLia,b,JingLiua,b,XueshanZhanga,b,JiaZhoua,b,*,GangWanga,b,**aBeijingKeyLaboratoryofMentalDisorders,NationalClinicalResearchCenterforMentalDisorders&NationalCenterforMentalDisorders,BeijingAndingHospital,CapitalMedicalUniversity,Beijing,ChinabAdvancedInnovationCenterforHumanBrainProtection,CapitalMedicalUniversity,Beijing,ChinaARTICLEINFO，ABSTRACTKeywords:，Background:Theeffectoftranscranialalternatingcurrentstimulation(tACS)onmajordepressivedisorder(MDD)Transcranialalternatingcurrentstimulationwasnotconfirmed.Majordepressivedisorder，Objective:Toevaluatethefeasibility,safety,andefficacyoftACSasanadd-ontreatmentforthesymptomsofAntidepressanttreatment，depressionandtounderstandhowtACSaffectsbrainactivity.Leftfrontalalphaoscillations，Methods:The4-week,double-blind,randomized,sham-controlledtrialwasperformedfromJanuary29,2023toDecember22,2023.Sixty-sixparticipantswererecruitedandrandomlyassignedtoreceive2040-minsessionsofeitheractive(77.5Hz,15mA)orshamstimulation,withoneelectrodeontheforeheadandtwoonthemastoid,eachday(n=33foreachgroup)forfourweeks(tillWeek4).Theparticipantswerefollowedfor4moreweeks(tillWeek8)withoutstimulationforefficacy/safetyassessment.Duringthe4-weektrial,allparticipantswererequiredtotake10–20mgofescitalopramdaily.TheprimaryefficacyendpointwasthechangeinHAMD-17scoresfrombaselinetoWeek4(with20treatmentsessionscompleted).Resting-stateelectroencephalography(EEG)wascollectedwitha64-channelEEGsystem(BrainProducts,Germany)atbaselineandtheWeek4follow-up.Thechi-squaretest,Fisher’sexacttest,independent-samplet-test,orWilcoxonrank-sumtestwereused,asappropriate,tocomparethedifferencesinvariablesbetweengroups.TheeffectoftheinterventionontheHAMD-17scorewasalsoevaluatedwithlinearmixedmodeling(LMM)assensitivityanalysis.ThecorrelationbetweenthemeanreductioninEEGandthemeanreductionintheHAMD-17totalscorewasevaluatedusingSpearmancorrelationanalysis.Results:Atotalof66patients(mean[SD]age,28.4[8.18]years;52[78.8%]female)wererandomized,and57patientscompletedthestudy.SignificantdifferenceswerefoundinthereductionsintheHAMD-17scoresatWeek4(t=3.44,P=0.001).ResponseratesatWeek4weresignificantlyhigherintheactivetACSgroupthanintheshamtACSgroup(22outof33patients[66.7%]versus11outof33[33.3%],P=0.007).IntheactivetACSgroup,acorrelationbetweenthemeanchangeinalphapowerandHAMD-17scoresatWeek4wasfound(r=2.38,P=0.024),andthemeanchangeinalphapowerwassignificantlybiggerforresponders(Z=2.46,P=0.014).Noseriousadverseeventswereobservedinthistrial.Conclusion:TheadditionalantidepressanteffectoftACSissignificant,andthecombinationoftACSwithanti-depressantsisafeasibleandeffectiveapproachforthetreatmentofMDD.TheantidepressantmechanismoftACSmaybethereductioninalphapowerintheleftfrontallobe.FutureresearchdirectionsmayincludeexploringmoreappropriatetreatmentparametersoftACS.*Correspondingauthor.JiaZhou.TheNationalClinicalResearchCenterforMentalDisorders&BeijingKeyLaboratoryofMentalDisorders,BeijingAndingHospital,CapitalMedicalUniversity,5AnkangLane,DewaiAvenue,XichengDistrict,Beijing,100088,China.**Correspondingauthor.GangWang.TheNationalClinicalResearchCenterforMentalDisorders&BeijingKeyLaboratoryofMentalDisorders,BeijingAndingHospital,CapitalMedicalUniversity,5AnkangLane,DewaiAvenue,XichengDistrict,Beijing,100088,China.E-mailaddresses:sophie_2020@ccmu.edu.cn(J.Zhou),gangwangdoc@ccmu.edu.cn(G.Wang).1Theseauthorscontributedequallytothiswork.https://doi.org/10.1016/j.brs.2024.06.004Received15April2024;Receivedinrevisedform7June2024;Accepted10June20241.Introduction2.MethodsMajordepressivedisorder(MDD)isacommondiseaseaffecting2.1.StudyDesignandparticipantsmorethan300millionpeople.Itisaleadingcauseofdisabilityworld-wideandamajorcontributortotheoverallglobalburdenofdiseaseThe4-week,double-blind,randomized,sham-controlledtrialwas(WorldHealthOrganization,2018).Therefore,thedevelopmentofperformedatBeijingAndingHospital,CapitalMedicalUniversity,fromeffective,accessibleinterventionsforMDDisahighpriorityfortheJanuary29,2023toDecember22,2023.Thetrialreceivedinstitutionalimprovementofpublichealth.First-line,evidence-basedtreatmentop-reviewboardapproval,wasperformedinaccordancewithethicaltionsforMDDincludepsychopharmacologyandpsychotherapeuticprinciplesoriginatingintheDeclarationofHelsinki[26],andwasre-approaches.However,30–50%ofpatientsdonotadequatelyrespondtoportedinaccordancewithCONSORTguidelines[27].Thestudywasfirst-linetreatments.whichgenerallyinvolveacombinationofantide-registeredontheChictr.org.cnwebsitebeforeenrollmentpressantsandcognitive-behavioraltherapy[1],sothereisanurgent(ChiCTR2300067443,https://www.chictr.org.cn/index.html).Thereneedfornewtreatmentoptions.，wasnochangeintheprotocolduringthestudy.AllpatientsprovidedTranscranialalternatingcurrentstimulation(tACS)isaneuro-writteninformedconsentpriortoenrollment.Thetrialwascompletedmodulationtechniquethatapplieselectricalcurrentswithchangingonreachingpredeterminedtargetenrollmentnumbers.Afterthe4-weekintensitytothescalptoregulatecorticalexcitabilityandspontaneoustrial,allpatientsenteredthedepressioncohortandwerefollowedupforbrainactivity.Ithasbeenusedforoveradecadeindifferentfields(for8weeks.instance,cognitiveneuroscience)[2,3].However,ithasonlybeenappliedinpsychiatricclinicalresearchinrecentyears[4,5].Atpresent,2.2.SamplesizecalculationmostclinicalstudiesondepressionusedtACSwithfrequenciesof10Hz[6],40Hz[7],or77.5Hz[8]andstimulationsitesselectedinthefrontalPreviously,thereisonlyonerandomizedcontrolledtrialinvesti-lobe.OnestudyhasprovedthattACSwithacurrentof15mAandagatingtheeffectivenessoftACSasanadd-ontoantidepressantsinfrequencyof77.5Hzcandeliverelectricalcurrentstodeepbraintissuestreatingdepression[14].However,wefoundthattheeffectsizederived[9].ItwasalsofoundthattACS(frequency77.5Hz)enhancedthelevelsfromthisstudywasextremelylarge.Thesamplesizecalculatedbasedonofendorphinsandneurotransmitters(includingserotonin)intheCSF,thiseffectsizewas3,whichwouldbetoosmalltoverifytheeffectbrainstem,hypothalamus,andcortexβ[10,11].Someofendorphinsandstatistically.Therefore,weusedaconservativeestimateof0.8,whichneurotransmitterschangesarebelievedtobetheneurobiologicalwasconsideredthecriteriaforlargeeffects,tocalculateoursamplesizemechanismsforimprovingdepressivesymptoms[12,13].，instead.PASS2021wasappliedtocalculatethesamplesize.WesetAstudyexaminingtACS’sroleintreatingMDDrevealedthattACSeffectsize=0.8,α(two-sided)=0.05,power=0.8,andβ=0.2andwith15mAand77.5Hzwaseffectiveinalleviatingdepressivesymp-foundaftercalculationthateachgroupwouldrequire33participants,tomsinMDD[8].However,becauseonlyfirst-episodedrug-naivepa-witha20%dropoutrate.Therefore,theexperimentalandcontroltientswithMDDwereincludedinthestudy,thegeneralizabilityofitsgroupswouldneed33participantseach,makingatotalsamplesizeoffindingswaslimited.AnotherstudyexaminedtheefficacyoftACS66.combinedwithSSRIs,butitdidnotlimitthetypeanddoseofthean-tidepressantsusedinthestudy[14].Astheantidepressantefficacyof2.3.Inclusion/exclusioncriteriadifferentSSRIsvaried[15],itisstillunknownwhetherthecombinationofantidepressantsandtACScouldenhancetheefficacyofantidepres-Participantswererecruitedthroughphysicianreferralsandposters.santsandbridgethegapinthefirstfewweekswhenantidepressantsTheinclusioncriteriawere:(1)being18–55yearsold;(2)beingdiag-havenottakeneffect.Inaddition,theantidepressantmechanismoftACSnosedwithMDDbyapsychiatristusingtheStructuredClinicalInter-iscomplexandcurrentlyunclear.，viewforDiagnosticandStatisticalManualofMentalDisorders,FifthDepressionisrelatedtoacomplexpictureofalteredbrainoscilla-Edition(DSM-5);(3)havingatotalscoreof17ormoreonthe17-itemtions[16].Theresting-statelow-frequencybands(delta,beta,andHamiltonRatingScaleforDepression(HAMD-17)andaHAMD-17alpha)inelectroencephalography(EEG),especiallythealphaband,Item1(Depression)scoreof2ormore;(4)havingnotreceivedanywereenhancedinpatientswithdepressionintermsofeitherpowerorantidepressantmedicationsforthecurrentdepressiveepisode;(5)beingcoherence.Moreover,theenhancementpersistedevenafteranindi-abletounderstandandsigntheinformedconsent.Someoftheexclusionvidualchangedfromaneye-closedtoaneye-openstate[17–20].Pa-criteriawere:(1)havingacurrentorhistoryofseizures,epilepsy,hy-tientswithMDDexhibitelevatedoscillatoryactivity,specificallyinthedrocephalus,centralnervoussystemtumors,oracutebraininjuryandalphafrequencyband(8–12Hz)[21].Althoughalphaoscillationsserveinfection;(2)havingasignificantriskofsuicideindicatedbyascoreof3importantfunctionsinthehealthybrain[22,23],increasedalphaor4ontheHAMD-17Item3orwithahistoryofsuicidalbehavior;(3)oscillationinpatientswithdepressionrepresentsastateofneuronalhavingbeenexposedtoelectroconvulsivetherapy(ECT),modifiedhypoactivityleadingtodisruptedaffectiveprocessing.Researcherselectroconvulsivetherapy(MECT),transcranialmagneticstimulationfoundthattheleftprefrontalcortexwasinhibited,indexedbyincreased(TMS),transcranialdirectcurrentstimulation(tDCS),tACS,orotheralphafrequencypower,duringtheprocessingofpositiveemotionsinneurostimulationtreatmentsinonemonthbeforeenrollment;(4)beingindividualswithdepression[24].Sincetheelevatedamplitudeofleftpregnantorbreastfeeding;(5)patientswithanysevereorganicdiseasesfrontalalphaoscillationsistheorizedtocorrespondtoareductioninorwereinanunstableconditionbecauseofanorganicdisease.Thetrialapproachingpositiveexperiences[24,25],wehypothesizedthataprotocol,whichcontainsadditionalinclusionandallexclusioncriteria,stimulationmayproduceaselectivedecreaseinleftfrontalalphaos-isavailableinSupplement1.cillationstowardsimagesratedaspositive.Therefore,weconductedadouble-blindstudytoevaluatethe2.4.Randomization,concealment,andblindingfeasibility,safety,andefficacyoftACSasatreatmentforthesymptomsofdepression.TounderstandhowtACSaffectsbrainactivity,weAcomputer-generatedrandomizationscheduleusingrandomlymeasuredalphapowerchangesasoursecondaryoutcomeusinghigh-permutedblocksrandomlyassignedeligiblepatientstotheactiveanddensityEEG.，shamtACSgroupsina1:1ratio.First,arandomnumbertablecon-tainingrandomizationsequenceswasgeneratedwiththePLANstepintheSAS9.4softwarebyastatisticiannotinvolvedinconductingthistrial.Second,anurse(alsonotinvolvedinconductingthistrial)putgroupassignmentresultsgeneratedfromtherandomnumbertableinalphafrequencyband(8–12Hz)wascalculatedtocompareidentical,sequentiallynumbered,opaque,sealedenvelopes.Third,eachchangesinEEG.Channelsofleftfrontallobewereselectedandpatientreceivedasealedenvelopeatenrollment.Finally,onthepa-averagedtorepresentthealphapowerintheleftfrontallobe.tient’sfirstdayofenrollment,orthedaythepatientreceivedthefirststimulationsession,theenvelopewithgroupassignmentinformationwouldbeopenedbyaresearcher.，2.7.OutcomemeasuresInthewholerandomizationprocessandthroughouttrial,activeorshamgroups,aswellastheactiveorshamstimulationdevices,TheprimaryefficacyendpointwaschangeinHAMD-17[29]wererepresentedwiththelettersAorB(onlythedeviceoperatorsgotscoresfrombaselinetoWeek4(with20treatmentsessionscompleted).informationonletterassignedtoapatient),sothatallin-Secondaryefficacyendpointsincluded:ClinicalGlobalImpressionofdividualsinvolvedinthetrialwereblindedtothetypeofstimulationImprovement(CGI-I)atWeeks2and4;thechangesfrombaselineto(activeorsham)theygaveorreceived.Also,therewasnodifferenceWeek4(with20treatmentsessionscompleted)inscoresonbetweentheactiveandshamstimulationdevicesintermsofappearanceHAMD-17reflectingdepression(Items1,2,3,7,8),anxiety(Items9,10,andthewaytheyinfluencethepatient’ssenses,sothepatientandthe11,15,17),insomnia(Items4,5,6),andsomaticsymptoms(Items12,operatorcouldnotdistinguishwhichinstrumentwastheactivestimu-13,14,16)[30],GeneralizedAnxietyDisorder-7(GAD-7)[31],16-itemlationdevicebasedontheappearanceofthedeviceorthesubjectiveQuickInventoryofDepressiveSymptomatologySelf-Reportfeelingsofpatients.Afterstatisticalanalysesinthisstudywere(QIDS-SR16)[32],PittsburghSleepQualityIndex(PSQI)[33],Clin-completed,unblindingwasperformed.，icalGlobalImpressions-SeverityofIllnessScale(CGI-S)[34];thepro-portionsofresponders(definedwithareductionof50%ormorefrom2.5.ProceduresbaselineintheHAMD-17totalscore)ateachvisits;andepileptiformactivitiesrevealedbyEEGrecordings.ParticipantswereaskedtositcomfortablyinrecliningchairswhileSafetyandtolerabilitywereevaluatedwithadverseevents(AEs),receivingFDA/NMPA(NationalMedicalProductsAdministration)vitalsigns,clinicallaboratoryevaluations,andelectrocardiogrampa-approvedtACS(NexalinTechnology,Inc.)administeredbytrainedrameters.SeriousAEsweredefinedasanyuntowardmedicaloccurrencenursesinaccordancewithstandardizedinstructions.A4.45×9.53cmthatresultedindeath,waslifethreatening(atthetimeoftheevent),electrodewasplacedontheforeheadatFpz,Fp1,andFp2inthe10/20requiredinpatienthospitalization,resultedinpersistentorsignificantinternationalplacementsystem.Two3.18×3.81cmelectrodesweredisability.placedoneachsideofthemastoid.ThetACSstimulationwaveformsincluderamp-upandramp-downperiodsof180and12s,respectively.Thewaveformsweresquarewaveswithanaverageamplitudeof15mA2.8.Statisticalanalysisandweredistributedequallyfromthefrontalregiontothemastoidareas(amplitudeswerereportedaszero-to-peak).，Themainanalyseswerecompletedonanintent-to-treatbasis,Allparticipantsreceived20sessionsofstimulationat77.5Hzand15meaningallrandomizedpatientswereincluded.MissingdataformA,whiletheshamtACShadnoactivestimulation.FromMondaytoHAMD-17scoreswereimputedusingthelastobservationcarriedfor-Friday,one40-minsessionwasadministeredatafixedtimeeachday.ward.Descriptivedataatbaselinewerereportedwithmean(standardDuringthe4-weektrial,allparticipantswerealsoaskedtotake10–20deviation)ormedianandinterquartilerange(IQR)forcontinuousvar-mgofescitaloprameachday.，iablesandcount(percentage)forcategoricalvariables.ThisstudyinvolvedthecombineduseofescitalopramthroughouttheTheprimaryendpointwasassessedwithanindependent-samplet-4-weekperiod.Allmedicationsweretakenorallyafterbreakfast(oncetestbasedondatawithlastobservationcarriedforward(LOCF)daily).Themedicationusedinthisstudywas10-mgescitalopramtab-imputation.Weperformedthreesensitivityanalysesfortheprimarylets.Dosetitrationwasperformedbytheresearchersbasedonsideef-outcometoassesstherobustnessoftheresults.InSensitivityAnalysis1,fectsand/orclinicalcourse.Theinitialdoseofescitalopramwas5mg/multipleimputationformonotonemissingdata,wefittedaregressionday,whichcouldbeincreasedto10mg/dayafter2weeksbasedonthemodelfromobserveddataandpotentialpredictors(i.e.,age,sex,patient’scondition.Thedosecouldbefurtherincreasedto20mg/dayifbaselinescore,firstepisode)togenerateimputedvalues.WeusedSASnecessary.Eachincreaseindoseshouldbespacedabout2weeksapartmultipleimputations(PROCMI)toimpute25valuesforeachmissingandnotlessthan4daysapart.，observationandcombinedestimatesusingPROCMIANALYZEinSAS.SensitivityAnalysis2,aper-protocolanalysis,wasalsoperformedto2.6.EEGexaminewhetherthereductionsinthescoresontheHAMD-17andtheresponseratesdifferedbetweenthetwogroups.SensitivityAnalysis3Resting-stateEEGdatawerecollectedatbaselineandtheWeek-4evaluatedtheeffectofinterventionontheHAMD-17scoreswithfollow-upusinga64-channelEEGsystem(BrainProducts,Germany).linearmixedmodeling(LMM)basedonallavailabledatawithoutTheelectrodeswerepositionedaccordingtothestandardinternationalimputation,withthetreatmentgroup,visit,andtheirinteraction(group10/20system.Thesamplingfrequencywas5000Hz,andelectrode×visit)asfixedeffectsandtheparticipantasarandomeffect.impedancewaskeptbelow10KΩ.Participantshadtheireyesopenfor5Asecondaryoutcome,theresponserate,wascomparedusingthechi-min,thenhadtheireyesclosedfor5min.Duringtheeyes-opencondi-squaretest.ThereductionsinthescoresofeachfactoroftheHAMD-17tion,participantswereinstructedtofixateonacross-hair.ParticipantsandscoresofCGIandCGI-SwerecomparedusingtheWilcoxonalsocompletedaface-wordStrooptask,resultsofwhicharenotrank-sumtest.Anindependent-samplet-testwasusedtocomparethepresentedhere.，differencesbetweenreductionsinscoresontheQIDS-SR16,TheEEGLAB[28]toolboxinMatlabwasusedtopreprocesstheEEGGAD-7,andPSQIintheactiveandshamtACSgroups.Thecorrelationdata.ThestepsofEEGdatapreprocessingwere:(1)channelselectionbetweenthemeanreductioninEEGandthemeanreductionin(removedIOchannel);(2)FIRbandpassfilter(0.1–50Hz);(3)seg-HAMD-17totalscorefrombaselinetoWeek4wasevaluatedwithmentationofepochsinto2-ssegments;(4)badchannelsrejection;(5)Spearmancorrelationanalysis.resamplingto500Hz;(6)re-referencetobilateralmastoid;(7)Inde-AlldatawereanalyzedusingSASforWindows,version9.4(SASpendentComponentAnalysis(ICA)andICA-basedmanualartifactInstitute,Cary,NC)andR4.3.2(RFoundationforStatisticalComputing,removal.Afterpreprocessing,thepowerspectraldensity(PSD)ofEEGVienna,Austria).AllPvaluesweretwo-sided,andthedifferenceswerewasestimatedwiththefastFouriertransformmethod,andthePSDofconsideredstatisticallysignificantwhenthePvaluewas<0.05.3.ResultsTable1Basicinformation.3.1.ParticipantsVariablesActivetACSShamtACSAtotalof152patientswithMDDwereassessedforeligibility,and66Male，8(24.24)6(18.18)SexpatientsmettheinclusioncriteriaandwererandomlyallocatedtotheFemale，25(75.76)27(81.82)activetACSgroup(n=33)orshamtACSgroup(n=33).AfterEducationallevelrandomization,sevenparticipantsintheshamtACSgroupwerelostatGraduate，24(72.73)23(69.70)week2,andtwoparticipantsintheactivetACSgroupdidnotcompleteMaster/Doctor，5(15.15)6(18.18)Highschool，4(12.12)4(12.12)thestudy(Fig.1).Theparticipants’demographicandclinicalcharac-ResidenceteristicsaresummarizedinTable1.MorethanhalfoftheparticipantsCity，32(96.97)32(96.97)werefemale(78.8%);meanvaluesforotherdemographicsincludedCountry，1(3.03)1(3.03)28.42±8.18yearsforage,22.25±4.44kg/m2forBMI,and3(1–12)Marriagestatusmonthsforthedurationoftherecentepisode.Ofallparticipants,50%Married，8(24.24)6(18.18)Unmarried，25(75.76)27(81.82)werefirstepisode,and9.1%hadafamilyhistoryofmentaldisorders.Monthlyincome(ChineseYuan)Ofthe66patients,64startedatadoseof5mg/dayofescitalopramMorethan1000013(39.39)13(39.39)andincreasedto10mg/dayafter4days,withtwopatientsineachgroup1001-5000，2(6.06)3(9.09)increasingto15mg/dayafter2weeks.Inaddition,onepatientintheWorkstatus5001-10000，18(54.55)17(51.52)activetACSgroupdidnottakeescitalopram,andonepatientintheshamUnemployed/other9(27.27)5(15.15)tACSgroupmaintainedadoseof5mg/day.，Employed，12(36.36)15(45.45)Student，12(36.36)13(39.39)Smokinghistory，5(15.15)5(15.15)3.2.PrimaryoutcomesAlcoholhistory8(24.24)11(33.33)Firstepisode，15(45.45)18(54.55)Intheintention-to-treatanalysis,significantdifferenceswerefoundFamilyhistoryofmentaldisorder4(12.12)2(6.06)inthemeanreductionoftheHAMD-17scoresatWeek4(t=3.44,P=Age(Year)，29.36(8.76)27.48(7.58)Bodymassindex，23.29(5.32)21.21(3.08)0.001).TherewerealsostatisticallysignificantdifferencesintheTotalcourseofMDD(months)49.0030.00(6.00–79.00)reductionoftheHAMD-17scoresbetweenthetwogroupsatbothweeks，(10.00–104.00)2and8(week2:t=3.48,P<0.001;week8:t=3.19,P=0.002)Durationofcurrentepisode3.00(1.00–19.00)3.00(1.00–10.00)(Fig.2).Therawandreductionmeanscoresofalloutcomesatalltime(months)pointsareshowninSupplementaryMaterialsTableS1.，(18.00–22.00)TotalscoreofHAMD-17atbaseline20.00(18.00–22.00)20.00Frequencyofepisode2.00(1.00–3.00)1.00(1.00–3.00)3.3.SecondaryoutcomesNote:n(%)ormean(standarddeviation)ormedian(interquartilerange).SignificantlymoreparticipantsintheactivetACSgroup(n=22/33,66.7%)responded(definedwithareductionof50%ormorefromFig.1.FlowChart.J.ZhouetalBrainStimulation12（2024）760-768GroupActivetACsShamedtAcs日1工-15Bascline2weck4week8weekVisitFig.2.TheMeanReductionsofthe17-itemHamiltonRatingScaleforDepression（HAMD-17）ScoresfromBaselinetoWeeks2,4,and8intheActivetACSandShamtACSGroupsNote:HAMD-17（the17-itemHamiltonRatingScaleforDepression；range:0-51；higherscoresindicatemoreseveredepressivesymptoms）.TheerrorbarsindicateSEs.ThemissingdataoftheHAMD-17scoresfor1patientinWeek4and8patientsinWeek8wereimputedusingthelastobserationcarriedforwardarepresentsP<0.05.baselineintheHAMD-17totalscore）atWeek4comparedwiththoseinnotstatisticallysignificantP>0.05）（SupplementaryMaterialstheshamtACSgroup（n=11/33,33.3%；x2=7.33,P=0.007).ThisTableS4）.differencewasalsoobservedatWeek2（activetACS:n=14/33,42.4%;shamtACS:n=6/33,18.2%;x2=4.59,P=0.032）andWeek8（active3.4SensitivityanalysistACS:n=22/33,66.7%;shamtACS:n=11/33,33.3%;x²=7.33,P=0.007）（Fig.3）.ComparedwiththoseintheshamtACSgroup，there-TheresultsofthemultipleimputationwereconsistentwiththoseofductionsinthescoresonthedepressionandinsomniasubscalesofthetheprimaryanalysisTheresultsshowedthattheestimatedmeanHAMD-17intheactivetACSgroupatWeek2weresignificantlylargerHAMD-17reductionintheactivetACSgroupwaslargerthaninthe（P<0.05）.AtWeek4,thereductionsinthescoresonthedepressionshamtACSgroup（t=2.19,P=0.031）atweek4.Theper-protocolinsomnia，andsomaticsubscalesoftheHAMD-17intheactivetACSanalysisalsosupportedthisresult(SupplementaryMaterialsTableS5）.groupweresignificantlylarger（SupplementarymaterialsTableS2）.AtInaddition,amixed-effectsmodelanalysiswiththetreatmentgroupWeek4,theCGI-SscorereductionintheactivetACSgroupwassignif-visit，andtheirinteraction（groupxvisit）asfixedeffectsandtheicantlyhigher（Z=-2.37P=0.018）（Supplementarymaterialsparticipantasarandomeffectrevealedasignificanttreatmentgroup-by-TableS3).ThedifferencesbetweenthereductionsintheQIDS-SR16,timeinteraction（F=5.75.P=0.004）.TheimprovementovervisitsinGAD-7,andPSQIscoresintheactiveandshamedtACSgroupswerethestudy（baseline,Week2,andWeek4）wassignificantlygreaterintheactivetACSgroup.Theleast-squaresmeanreductionintheHAMD-17scorefrombaselinetoWeek4was12.70（se0.75）intheactivetACsgroupand8.77(se0.81）intheshamtACSgroup（between-groupdif-80Groupference3.93[se1.11],95%CI1.94to6.12;p=0.001）.（SupplementaryAotivetACSaShamedtACsmaterialsTableS6）66.67a66.6718.1833.33603.5.Blindingintegrity52.52Totestthequalityoftheblindinginourstudy.wepaidreturnvisitstoallpatients.Intheactivestimulationgroup,25patientsthoughtthey33.33receivedactivestimulation,6thoughttheyreceivedshamstimulationand2werelosttofollow-up;intheshamstimulationgroup,21thought20theyreceivedactivestimulation,9thoughttheyreceivedshamstimu-lation,and3werelosttofollow-up.Inboththeactiveandshamstim-ulationgroups，mostpatients（80.6%and70%，respectively）believedtheyreceivedactivetACS.Also,therewasnostatisticaldifferencebe-02wock4wcck8wecktweenthetwogroupsinthenumberofpatientswhobelievedtheyVisitreceivedactiveorshamstimulations.p=0.563）.Fig.3.TheResponseRatesatDifferentVisitsintheActivetACSandShamtACSGroups3.6.MechanismexplorationNote:Responsewasdefinedasa50%reductioninthe17-itemHamiltonRatingScaleforDepression（HAMD-17,range:0-51；higherscoresindicatingmoreToverifywhethertACSwaseffectiveinchangingalphaoscillationsseveredepressivesymptoms）.MissingdataoftheHAMD-17scoresfor1patientinWeek4and8inWeek8wereimputedusingthelastobservationcarriedweassessedthechangesinresting-statealphapowerattheWeek-4forwardfollow-upinthePPsample.BaselinealphapowerwasnotdifferentarepresentsP<0.05.betweenthetwogroups.Wecomparedthechangesinalphapower764DownloadedforAnonymousUser（n/a）atCapitalMedicalUniversityfromClinicalKey.combyElsevieronJune25.2024.Forpersonaluseonly.Nootheruseswithoutpermission.Copyright2024.ElsevierInc.Allrightsreservedbetweenthetreatmentgroupsbutfoundnosignificantdifference4.Discussion(SupplementarymaterialsFig.S1).Then,weconductedanin-depthexploratoryanalysis.IntheactivetACSgroup,wefoundacorrelationInthisrandomized,double-blind,controlledtrialstrictlyrestrictingbetweenthemeanreductionofPSDineye-closedstateEEGandthethetypeanddoseofantidepressantinvolved,weconfirmedtheeffectofmeanreductionintheHAMD-17totalscorefrombaselinetoWeek4(rtACSusedasanadjuncttotreatmentsofpatientswithMDDtoimprove=2.38,P=0.024).Also,intheactivetACSgroup,themeanreductionoftheefficacyofantidepressants.ComparedwiththoseofpatientsPSDfrombaselinetoWeek4ineye-closedstateEEGwassignificantlyreceivingtheshamadd-ontreatment,almostalldomainsofdepressivelargerintherespondersthaninthenon-responders(Z=2.46,P=symptomsofthepatientsreceivingtheactiveadd-ontreatmentsignifi-0.014).Ontheotherhand,intheshamtACSgroup,noconsistentresultscantlyimproved.Self-reportedandseriousadverseeventsdidnotwerefound(Fig.4).Asimilaranalysisoftheeye-openstatedidnotsignificantlydifferbetweenthegroups.Thesefindingsindicatethatrevealanysignificanteffectofthestimulationonchangingalphapower.comparedtoantidepressantmonotherapy,theadd-ontACScanenhanceTakentogether,ourresultsindicatethattACSwaseffectiveintargetingtheefficacyinacutetreatment.alphaoscillationsintheleftfrontalregions,andthischangehadaRegardingtheprimaryoutcome,ourstudyfoundthattACScom-relationshipwithclinicalsymptoms.，binedwithescitalopramwassignificantlymoreeffectivethanescitalo-pramalone,indicatingthattACShadapromisingantidepressant3.7.Safetyefficacy.Wealsofoundasignificantadd-onantidepressanteffectafter4weeksoftreatment,andthementionedeffectspersistedfor4weeksafterNoseriousadverseeventswereobservedinthistrial.ThereportedtheendofthetACStreatment.ClinicalstudiesontACSinthefieldofgeneralsideeffectsintheactivetACSgroup(comparedwiththeshamMDDinvolvedfrequenciesof10Hz,40Hz,and77.5Hz,andallthreetACSgroup)includedheadache(3/33comparedwith0/33),drowsinessfrequencieshadshownantidepressanteffects.StudiesontACSat40Hz(3/33comparedwith0/33),anddizziness(0/33comparedwith2/33).includeacasereport[35]andaclinicaltrialin6patientswithMDD[7];participantsinbothstudiesimprovedafter2weeksoftreatmentandhadimprovedcognitivefunction.After2weeksof40-HztACScombinedFig.4.RelationshipbetweenchangesinEEGalphapowerandHAMD-17Note:A:IntheactivetACSgroup,thecorrelationbetweenthemeanreductioninEEGandthemeanreductionintheHAMD-17totalscorefrombaselinetoWeek4,evaluatedwithSpearman(r=2.38,P=0.024)B:IntheactivetACSgroup,thedifferenceinthemeanreductionsfrombaselinetoWeek4inEEGbetweenrespondersandnon-respondersatWeek4,evaluatedusingtheWilcoxonRankSumTest(Z=2.46,P=0.014)C:IntheactivetACSgroup,thecorrelationbetweenthemeanreductioninEEGandthemeanreductionintheHAMD-17totalscorefrombaselinetoWeek4,evaluatedwithSpearman(r=2.16,P=0.203)D:IntheactivetACSgroup,thedifferenceinthemeanreductionsfrombaselinetoWeek4inEEGbetweenrespondersandnon-respondersatWeek4,evaluatedusingtheWilcoxonRankSumTest(Z=0.62,P=0.533)arepresentsP<0.05.withantidepressants,theaveragereductionrateoftheHAMDscoresTheCGIwasalsousedtoassessseverityofpatient’sreached73.5%.Alexanderetal.[6]randomized32patientswithMDDdepressivesymptomsandthedegreeofimprovement.TheCGI-Sscoresintothreestudygroupsof10-HztACS,40-HztACS,andshamstimula-atWeek2suggestedthatthetACSgrouphadmoreimprovementthantionandadministeredone40-mininterventionsessioneachdayfor5theshamgroup.TheresultsoftheCGI-Srevealedthepositiveimpactofconsecutivedaysalongwithantidepressants.TheresponserateofthetACSontheoverallclinicalimpressionofpatientswithMDD.Although10-HztACSgroupatWeek2wassignificantlyhigherthanthe40-HzandCGIisaninstrumentrelyingonsubjectivejudgmentofshamstimulationgroups,suggestingthat10-HztACShadabetteran-evaluators,itprovidesimportantinformationoneffectivenessoftidepressantefficacy.ThemostreliableevidenceinMDDisfortACStreatment,especiallyfortheevaluationofpracticalclinicalsignificance.with15mA,77.5Hz:AnRCToftACSin100drug-naïvepatientswithThesafetyofusinghighcurrentsisaconcern.Inthisstudy,86.4%MDD[8]showedaresponserateof70%andaremissionrateof62%(57/66)oftheparticipantscompletedthe4-weekstudy.Thedropoutafter4weeksoftACStreatment,whichweresignificantlyhigherthanratewaslowerthantheestimationof20%,suggestingthatthetACStheresponseandremissionratesaftershamstimulation(42%and26usedinthisstudywassafeandwelltolerated.Allpatientswerefollowed%).However,thisstudyonlyincludedfirst-episodedrug-naïvepatients,upforadverseevents,andmostsideeffectsinthisstudyweremildandmoresignificanttreatmenteffectmaybebecauseofthat.(somepatientsexperienceddizziness,headache,anddaytimesleepi-AnotherRCTstudiedtACScombinedwithantidepressantsin62patientsness).Moreimportantly,therewasadifferencebetweentheadverse[14]andfoundapromisingclinicalefficacy,withareductionof74.29%eventsinthetwogroups.PreviousstudiesdidnotreportsideeffectsofintheHAMDscoresintheactivegroupand32.54%intheshamgroupdaytimesleepiness[8,14].However,weobservedprolongeddaytimeattheendofWeek4.Althoughthisstudyhadlimitationsandtheuseofsleepinessthatwasclearlyrelatedtotreatment,withsleepinessantidepressantswasnotlimited,tACSasanadd-ontoantidepressantsbeingthemostpronouncedattheendoftACS(althoughitshouldbemaybeagoodoptionforpatientswhoneedafasteffect.Alongwithnotedthatthisfindingstillneedstobevalidatedinfuturestudies).otherneuromodulations,rTMSalsoenhancestheclinicalresponsetoTherefore,itmaybenecessarytonotifypatientswhodrivevehicles.Inantidepressants[36]andsignificantlyacceleratesalleviationofaddition,nomanicorhypomanicsymptoms,seizures,neurologiccom-depressivesymptoms[37]inpatientswithMDD.Astudyof2-weekplications,opticalillusions,deaths,orotherseriousadverseeventswererTMScombinedwithcitalopramfoundthattheresponseratesinobservedinourstudy.Overall,thesafetyoftACSincombinationwithactivegroupversustheshamgroupwere39%versus29%atWeek2antidepressantsfortreatmentofMDDwasconfirmed,suggestingand46%versus36%atWeek4[38].Astudyof4-weekrTMSinthatfutureclinicaltrialswithtACSarefeasible.combinationwithparoxetinefoundaresponserateof95.5%andaThephysiologicaltargetofthecurrentstudywasleftfrontalalpharemissionrateof68.2%intheactivegroup,whichweresignificantlyoscillations.EEGalphaactivityismorepronouncedwitheyesclosedhigherthanthoseintheshamgroup(71.4%and38.1%)atWeek4,[44],andalphapowerasymmetryhasbeenfoundtobemorereliablealthoughtherewasnosignificantdifferenceatWeek8[39].Studiesofwitheyesclosedthanwitheyesopen[45].ThealterationofalphapowertDCSasanadd-ontreatmenttoantidepressantsalsodemonstratedtheinourstudyalsooccurredonlyintheeye-closedstate.Thisalterationsynergisticeffectofcombinationtherapy.Onestudyfoundthatpartic-wasthoughttoreflectreducedneuronalactivityintheleftfrontallobe,ipantsreceiving4weeksoftDCScombinedwithsertralinehadaoneofseveralkeyregionswhereabnormalitieshavebeenfoundinbrainresponserateof53.3%andaremissionrateof23.3%,significantlyimagingstudiesofdepression[46].OnearticlehasexaminedEEGhigherthanthoseinthesertraline-onlygroup(26.7%and13.3%)[40].changesafterreceivingtACSinpatientswithMDD;itfoundthat10-HzInanotherstudy,patientswithMDDweredividedintothreegroups:tACSresultedinasignificantreductioninalphaoscillationsintheleft30-min,20-min,andshamtDCS,combinedwithsertraline.Aftertenfrontalregionwitheyesclosed,whereasnochangeswerefoundwithdaysoftDCSstimulation,the30-min,20-min,andshamgroupsshowed40-HztACS.Inaddition,10-HztACSshowedbetterantidepressantef-responseratesof89%,68%,and50%andremissionratesof70%,27fects[6].AnotherstudyfoundthattACSwithindividualizedalphafre-%,and35%,respectively.Theimprovementindepressivesymptomsquency(IAF)couldreduceresting-stateleftfrontalalphapowerinwasmoresubstantialinactivestimulationgroups,andpatientswithMDD.Furthermore,reductionofleftfrontalalphaimprovementinthe30-mingroupwassignificantlylargerthanintheoscillationbytACSwasspecificforstimuliwithpositivevalence[47].20-mingroup[41].Insummary,tACSisexpectedtobeaneffectiveOurstudyalsofoundadecreaseinleftfrontalalphafrequencyinpa-add-onantidepressanttreatmentcomparabletorTMSandtDCS.How-tientswhorespondedtothetACStreatmentbutnotinpatientswithnoever,consideringthatrTMSandtDCShavebeenevaluatedinlarge-scaleresponse.WehypothesizethattheantidepressanteffectoftACSmaybemulti-centertrials,whereastACShasonlybeenstudiedinsmall-scalerelatedtothedecreaseinleftfrontalalphapower.Theexactmechanismtrials,itshouldbenotedthatthereisariskoffalse-positivefindingsoftACShasnotbeendetermined;studieshaveshownthattACSinducesandourfindingsneedtobeconfirmedbylargertrialsinthefuture.corticaloscillationsbyentrainmentandspike-timingdependentplas-TheQIDS-SR16scoresdidnotrevealanysignificanttreatmentticity[48].StudieshaveconsistentlydemonstratedthelocalizedpoweradvantageintheactivetACSstimulationgroupovertheshamstimula-enhancementaftertACSandhavefoundthatimmediatetACStiongroup.Somestudieshavefoundthatpatientsscoredthemselvesafter-effectsledtoanincreaseinresting-statealphapower[49].Thehigheronself-reportmeasuresthanthecliniciansratedthem.Expla-transientalphapowerenhancementafterasingletACStreatmentmaynationsforthisphenomenonincludethedifferencesinthefocusofthebeduetoastimulusdosethatisnotsufficientlypersistenttoinduceclinicianandpatient,overestimationofsymptomseveritybythepa-long-termplasticity[50].Theincreaseintransientalphapowermaytients,highlevelsofanxiety,needforapproval(especiallysocialreflectneuralinductionoftime-synchronizedcorticaloscillationsbydesirability),andhighlevelsofself-transcendence(especiallyself-exogenousstimuli[51,52],butevidenceforlong-termeffectsremainsforgetfulness)[42].Furthermore,aftercomparingeachfactorinlimited.Wefoundadecreaseinalphapowerafter20sessionsoftACS,HAMD-17,wefoundthatfactorsdepressedmood,insomnia,andwhichisoppositetoimmediateeffect,suggestingthatrepeatedsomatizationshowedmorepronouncedimprovements,whereastheseapplicationoftACSmayleadtooscillatorresetting,whichinturnleadssymptomswerelighterweightedintheQIDS-SR16;thisdifferencemaytoadecreaseinalphapowerthroughahomeostaticmechanism[53],bepartofthereasonswhythechangesinthetotalscorewerenotsig-producinganantidepressanteffect.Therefore,theresultsofthisstudynificant.Previousstudiesexaminingconcordancebetweenonceagainsuggestedthattheintrinsicregulationofalphaoscillationsself-reportandclinician-ratedmeasureswereinconsistent,andthisismaybeanimportantmechanismfortheantidepressanteffectoftACS.themainreasonwhymostclinicaltrialswouldusebothself-reportandThisstudyhassomelimitations.First,weonlyobservedtheefficacyclinician-ratedmeasuresasoutcomeinstruments,withthelatterservingintheacutephase,andweonlyincludeda4-weekfollow-up,whichisasthemeasurementtoolfortheprimaryoutcome[42,43].rathershortcomparedtocurrentbest-practiceRCTsinMDD.Therefore,J.ZhouetalBrainStimation12（2024）760-768themaintenanceeffectstillneedstobefurtherinvestigated.SecondweReferencesusedonlytACSwith77.5Hz,15mA，andafixedstimulationposition.Theantidepressantefficacyofdifferentfrequenciescurrents.andelec-[1]RushAJ,TrivediMH.WisniewskiSRNierenbergAA,StewartJW.WardenD,etalAcuteandlonger-termoutcomesindepressedoutpatientsrequiringoneorseveraltrodecombinationsisunknown.Thirdweonlycomparedthechangesintreatmentsteps:aSTAR*Dreport.AmJPsychiatr2006;163（11）:1905-17.leftfrontalalphapower，anditisunclearwhethertheEEGatotherlo-[2]AntalA,BorosK,PoreiszC,ChaiebL,TerneyD,PaulusW.Comparativelyweakcationsandfrequencieschanged.Also,allpatientsusedantidepressantsafter-effectsoftranscranialalternatingcurrentstimulation（tACS）oncorticalwhichmayhaveaffectedtheEEG.Thegrowingrecognitionoftheexcitabilityinhumans.BrainStimul2008;12）:97-105.[3]MarshallL,Helgad6ttirH,MolleM,BornJ.BoostingslowoscillationsduringsleeppresenceofabnormaloscillatorydynamicsinthepathologyofMDDhaspotentiatesmemory.Nature2006;444(7119):610-3.generatedstronginterestinthedirectmodulationofendogenousos-[4]WangHX.WangL.ZhangWR.XueO.PengM.SunZC.etal.Effectoftranscranialcillations.FuturestudiesonvariousformsofneuromodulationandEEGalternatingcurrentstimulationforthetreatmentofchronicinsomnia:arandomized.double-blind,parallel-group，placebo-controlledclinicaltrialalterationsinunmedicatedpatientsareneeded.Finally，thedropoutPsvchotherPsychosom2020:89(1）:38-47.rateswerehigherintheshamgroup，whichmightberelatedtothelack[5]ElyamanyO,LeichtGHerrmannCS,MulertC.Transcranialalternatingcurrentofantidepressanteffectinthatgroup.Futurestudiesshouldmakeeffortsstimulation(tACS):frombasicmechanismstowardsfirstapplicationsinpsychiatry.EurArchPsychiatrClinNeurosci2021:271(1:135-56.toreducethedropoutrateintheshamgroup.Insummary,althoughour[6]AlexanderML,AlagapanS,LugoCEMellinJM,LustenbergerC,RubinowDR,etaltrialprovidedpreliminaryevidencefortheantidepressanteffectsofDouble-blindrandomizedpilotclinicaltrialtargetingalphaoscillationswithtACS,largerlong-termtrialsareneededtoderivemorereliabletranscranialalternatingcurrentstimulation（tACS)forthetreatmentofmajordepressivedisorder（MDD).TranslPsychiatry2019;9（1）：106.conclusions[7]HallerN,SennerF,BrunoniAR,PadbergF,PalmU.GammatranscranialOurresultssuggestthattheadditionalantidepressanteffectoftACsalternatingcurrentstimulationimprovesmoodandcognitioninpatientswithwassignificantandlastedforatleast4weeks.andcombiningtACSwithmajordepression.JPsychiatrRes2020;130:31-4.[8]WangH.WangK,XueQ,PengM,YinL,GuX,etal.Transcranialalternatingantidepressantsisafeasibleandeffectiveapproachforthetreatmentofcurrentstimulationfortreatingdepression:arandomizedcontrolledtrial.BrainMDD.TheantidepressantmechanismoftACSmaybethereductionof2022:1451:83-91thealphapowerintheleftfrontallobe.Futureresearchdirectionsmay[9]ShanY,WangH,YangY,WangJ,ZhaoW,HuangY,etal.EvidenceofalargecurrentoftranscranialalternatingcurrentstimulationdirectlytodeepbrainincludeexploringmoreappropriatetreatmentparametersoftACS.regions.MolPsychiatr2023:1-9.[10]LebedevVPMalyginAV,KovalevskiAV,RychkovaSV,SisoevVNKropotovSPFundingetal.Devicesfornoninvasivetranscranialelectrostimulationofthebrainendorphinergicsystem:applicationforimprovementofhumanpsycho-physiologicalstatus.ArtifOrgans2002;26（3):248-51.ThisstudywasfundedbySTI2030-MajorProjectsWhiteNE,RichardsLM.Nexalinandrelatedformsofsubcorticalelectrical[11]WhiteNE,RichardsLM.Nexalinandrelatedformsofsubcorticalelectrical（2021ZD0200600），TrainingPlanforHighLevelPublicHealthTech-stimulation.In:Rhythmicstimulationproceduresinneuromodulation.Elsevier;2017.p.131-57.nicalTalentsConstructionProject（DisciplineBackbones-02-39），and[12]HegadorenK,O'donnellT,LaniusR,CouplandN,Lacaze-MasmonteilN.TheroleCapitalHealthResearchDevelopmentSpecialProject（2024-2-2125）.ofβ-endorphininthepathophysiologyofmaiordepression.Neuropeptides2009:43(5）:341-53.CRediTauthorshipcontributionstatement[13]MaybergHS,BrannanSKTekellJL,SilvaJA,MahurinRK,McGinnisS,etalRegionalmetaboliceffectsoffluoxetineinmajordepression:serialchangesandrelationshiptoclinicalresponse.BiolPsychiatr2000:48(8):830-43JingjingZhou:Writing-review&editing,Supervision,Methodol-[14]JiongLuoCS,PanWeigang，etal.Efficacyandsafetyoftranscranialalternatingogy，Formalanalysis,Conceptualization.DanLi:Writing-originalcurrentstimulationcombinedwithantidepressantsindepressiveepisodes.Journaldraft，Formalanalysis,Datacuration.FukangYe:Investigation,DataofCapitalMedicalUniversity2022:43（2）:244-8.[15]CiprianiA，FurukawaTA,SalantiG,ChaimaniA,AtkinsonLZ,OgawaY,etalcuration.RuiLiu:Methodology，Datacuration.YuanFeng:ProjectComparativeefficacyandacceptabilityof2lantidepressantdrugsfortheacuteadministration，Investigation，Fundingacquisition.ZizhaoFeng:treatmentofadultswithmajordepressivedisorder:asystematicreviewandInvestigationDatacuration.RuinanLi:Datacuration.XiaoyaLi:Datanetworkmeta-analysis.Lancet2018:391010128:1357-66.[16]FingelkurtsAA，FingelkurtsAA.Alteredstructureofdynamiccuration.JingLiu:Datacuration.XueshanZhang:Datacuration.Jiaelectroencephalogramoscillatorypatterninmajordepression.BiolPsychiatr2015;Zhou:Writing-review&editing,Visualization，Formalanalysis.Gang77（12):1050-60.[17]SmartOL,TiruvadiVR,MaybergHS.MultimodalapproachestodefinenetworkWang:Supervision,Software,Resources,Fundingacquisitionoscillationsindepression.BiolPsychiatr2015;77（12):1061-70.[18]OlbrichS,ArnsM.EEGbiomarkersinmajordepressivedisorder:discriminativeDeclarationofcompetinginterestpowerandpredictionoftreatmentresponse.IntRevPsychiatr2013;25(5):604-18.[19]NorthoffG.Howdorestingstatechangesindepressiontranslateintopsychopathologicalsymptoms?FromSpatiotemporalcorrespondencetoTheauthorsdeclarenocompetinginterestsSpatiotemporalPsychopathology'.CurrOpinPsychiatr2016:29（1）:18-24[20]NewsonJJ,ThiagarajanTC.EEGfrequencybandsinpsychiatricdisorders:aAcknowledgementsreviewofrestingstatestudies.FrontHumNeurosci2018;12:521.[21]LeuchterAF,CookIA,HunterAM,CaiC,HorvathS.Resting-statequantitativeelectroencephalographyrevealsincreasedneurophysiologicconnectivityinWewouldliketothankthedoctorsandnursesfortheirgenerousdepression.PLoSOne2012;7（2):e32508.supportduringtheconductofthestudy,andallthepatientsandtheir[22]JensenO,MazaheriA.Shapingfunctionalarchitecturebyoscillatoryalphaactivity:gatingbyinhibition.FrontHumNeurosci2010;4:186.familiesforparticipatinginthistrial.WealsothankNexalinTechnol-[23]Klimeschw.x-bandoscillations,attention,andcontrolledaccesstostoredogy,Inc.,Houston,TX,USA,forprovidingthetranscranialalternatinginformation.TrendsCognitSci2012;16（12):606-17.currentstimulationdevicesfreeofcharge.Neitherofthementioned[24]Harmon-JonesE,GablePA.Ontheroleofasymmetricfrontalcorticalactivityinfundersorcompanywasinvolvedintheconceptionandperformanceofapproachandwithdrawalmotivation:anupdatedreviewoftheevidencePsychophysiology2018:55（1）.thestudy.[25]]DavidsonRJ.Anteriorcerebralasymmetryandthenatureofemotion.BrainCognit1992:2001):125-51.[26]WorldMedicalAssociationDeclarationofHelsinki.EthicalprinciplesformedicalAppendixA.Supplementarydataresearchinvolvinghumansubjects.BullWorldHealthOrgan2001;79（4):373-4.[27]BoutronI,MoherD,AltmanDG,SchulzKF,RavaudP.ExtendingtheCONSORTSupplementarydatatothisarticlecanbefoundonlineathttps://doi.statementtorandomizedtrialsofnonpharmacologictreatment:explanationandorg/10.1016/j.brs.2024.06.004.elaboration.AnnInternMed2008;148（4):295-309.[28]DelormeA，MakeigS.EEGLAB:anopensourcetoolboxforanalysisofsingle-trialEEGdynamicsincludingindependentcomponentanalysis.JNeurosciMethods2004:134（1）:9-21.[29]ZhengYP,ZhaoJPPhillipsM.LiuJB,CaiMF,SunSO.etal.ValidityandreliabilityoftheChineseHamiltondepressionratingscale.BrJPsychiatry1988;152:660-4767DownloadedforAnonymousUser（n/a）atCapitalMedicalUniversityfromClinicalKey.combyElsevieronJune252024.Forpersonaluseonly.Nootheruseswithoutpermission.Copyright2024.ElsevierInc.Allrightsreserved[30]LinJ,WangX,DongF,DuY,ShenJ,DingS,etal.ValidationoftheChineseversioncombinedwithsertralineforthetreatmentofdepression.ProgNeuro-oftheHamiltonratingscalefordepressioninadultswithepilepsy.EpilepsyBehavPsychopharmacolBiolPsychiatry2018;82:31–8.2018;89:148–52.，[42]CorrubleE,LegrandJM,ZvenigorowskiH,DuretC,GuelfiJD.Concordance[31]ShihYC,ChouCC,LuYJ,YuHY.ReliabilityandvalidityofthetraditionalChinesebetweenself-reportandclinician’sassessmentofdepression.JPsychiatrRes1999;versionoftheGAD-7inTaiwanesepatientswithepilepsy.JFormosMedAssoc33(5):457–65.2022;121(11):2324–30.，[43]SousaS,RobinsonL,FranklinM,WatsonS.Patient-reportedandclinician-rated[32]LiuJ,XiangYT,WangG,ZhuXZ,UngvariGS,KilbourneAM,etal.Psychometricoutcomemeasures:complementaryevidencefromtwodifferentperspectives.propertiesoftheChineseversionsoftheQuickinventoryofdepressive，JAffectDisord2020;276:848–9.Symptomatology-clinicianrating(C-QIDS-C)andself-report(C-QIDS-SR).JAffect[44]BarryRJ,ClarkeAR,JohnstoneSJ,MageeCA,RushbyJA.EEGdifferencesbetweenDisord2013;147(1–3):421–4.，eyes-closedandeyes-openrestingconditions.ClinNeurophysiol2007;118(12):[33]LiuX.ReliabilityandvalidityofthePittsburghsleepqualityindex.Chinesejournal2765–73.ofpsychiatry1996;29:103.，[45]MetzenD,GençE,GetzmannS,LarraMF,WascherE,OcklenburgS.Frontaland[34]BerkM,NgF,DoddS,CallalyT,CampbellS,BernardoM,etal.ThevalidityoftheparietalEEGalphaasymmetry:alarge-scaleinvestigationofshort-termreliabilityCGIseverityandimprovementscalesasmeasuresofclinicaleffectivenesssuitableondistinctEEGsystems.BrainStructFunct2022;227(2):725–40.forroutineclinicaluse.JEvalClinPract2008;14(6):979–83.，[46]KoenigsM,GrafmanJ.Thefunctionalneuroanatomyofdepression:distinctroles[35]WilkeningA,KurzeckA,DechantsreiterE,PadbergF,PalmU.Transcranialforventromedialanddorsolateralprefrontalcortex.BehavBrainRes2009;201(2):alternatingcurrentstimulationforthetreatmentofmajordepressionduring239–43.pregnancy.PsychiatrRes2019;279:399–400.，[47]RiddleJ,AlexanderML,SchillerCE,RubinowDR,FrohlichF.Reductioninleft[36]BerlimMT,VandenEyndeF,DaskalakisZJ.High-frequencyrepetitivetranscranialfrontalalphaoscillationsbytranscranialalternatingcurrentstimulationinmajormagneticstimulationacceleratesandenhancestheclinicalresponseto，depressivedisorderiscontextdependentinarandomizedclinicaltrial.Biolantidepressantsinmajordepression:ameta-analysisofrandomized,double-blind,Psychiatr:CognitiveNeuroscienceandNeuroimaging2022;7(3):302–11.andsham-controlledtrials.JClinPsychiatry2013;74(2):e122–9.，[48]VogetiS,BoetzelC,HerrmannCS.Entrainmentandspike-timingdependent[37]RumiDO,GattazWF,RigonattiSP,RosaMA,FregniF,RosaMO,etal.Transcranialplasticity–areviewofproposedmechanismsoftranscranialalternatingcurrentmagneticstimulationacceleratestheantidepressanteffectofamitriptylineinstimulation.FrontSystNeurosci2022;16:827353.severedepression:adouble-blindplacebo-controlledstudy.BiolPsychiatr2005;57[49]ClancyKJ,BaisleySK,AlbizuA,KartvelishviliN,DingM,LiW.Lasting(2):162–6.，connectivityincreaseandanxietyreductionviatranscranialalternatingcurrent[38]HuangML,LuoBY,HuJB,WangSS,ZhouWH,WeiN,etal.Repetitivetranscranialstimulation.SocCognitAffectNeurosci2018;13(12):1305–16.magneticstimulationincombinationwithcitalopraminyoungpatientswithfirst-[50]KastenFH,DowsettJ,HerrmannCS.Sustainedaftereffectofα-tACSlastsupto70episodemajordepressivedisorder:adouble-blind,randomized,sham-controlledminafterstimulation.FrontHumNeurosci2016;10:245.trial.AustNZJPsychiatr2012;46(3):257–64.，[51]ReatoD,RahmanA,BiksonM,ParraLC.Effectsofweaktranscranialalternating[39]WangYM,LiN,YangLL,SongM,ShiL,ChenWH,etal.Randomizedcontrolledcurrentstimulationonbrainactivity-areviewofknownmechanismsfromanimaltrialofrepetitivetranscranialmagneticstimulationcombinedwithparoxetineforstudies.FrontHumNeurosci2013;7:687.thetreatmentofpatientswithfirst-episodemajordepressivedisorder.Psychiatr[52]HelfrichRF,SchneiderTR,RachS,Trautmann-LengsfeldSA,EngelAK,Res2017;254:18–23.，HerrmannCS.Entrainmentofbrainoscillationsbytranscranialalternatingcurrent[40]BrunoniAR,ValiengoL,BaccaroA,Zan˜aoTA,deOliveiraJF,GoulartA,etal.Thestimulation.CurrBiol2014;24(3):333–9.sertralinevs.electricalcurrenttherapyfortreatingdepressionclinicalstudy:[53]LeuchterAF,CookIA,JinY,PhillipsB.Therelationshipbetweenbrainoscillatoryresultsfromafactorial,randomized,controlledtrial.JAMAPsychiatr2013;70(4):activityandtherapeuticeffectivenessoftranscranialmagneticstimulationinthe383–91.，treatmentofmajordepressivedisorder.FrontHumNeurosci2013;7:37.[41]PavlovaEL,MenshikovaAA,SemenovRV,BocharnikovaEN,GotovtsevaGN,DruzhkovaTA,etal.Transcranialdirectcurrentstimulationof20-and30-minutes
投标 / 标书制作要点（原创）
本涉及「招标公告」，投标方需重点关注：① 营业执照经营范围须含招标公告或对应服务类目；② 提供同类项目业绩证明；③ 报价方案与售后响应须明确；④ 紧盯投标截止与开标节点，建议提前完成标书制作与盖章。当地项目常要求本地化服务能力与快速响应，务必在投标文件中凸显。
标书制作联系冯经理：17551026086
