Executive Functioning in Men with Schizophrenia and Substance Use Disorders. Influence of ...

16 Pages·2016·0.95 MB·English

RESEARCHARTICLE
Executive Functioning in Men with
Schizophrenia and Substance Use Disorders.
Influence of Lifetime Suicide Attempts
AnaAdan1,2*,MariadelMarCapella1,GemmaPrat1,DiegoA.Forero3,SilviaLo´pez-Vera1,
Jose´FranciscoNavarro4
1 DepartmentofClinicalPsychologyandPsychobiology,FacultyofPsychology,UniversityofBarcelona,
Barcelona,Spain,2 InstituteofNeurosciences,UniversityofBarcelona,Barcelona,Spain,3 Laboratoryof
NeuroPsychiatricGenetics,BiomedicalSciencesResearchGroup,SchoolofMedicine,UniversidadAntonio
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Nariño.Bogota´,Colombia,4 DepartmentofPsychobiology,SchoolofPsychology,UniversityofMa´laga,
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Ma´laga,Spain
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a1111111111 *[email protected]
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Abstract
OPENACCESS
Background
Citation:AdanA,CapellaMdM,PratG,ForeroDA,
Lo´pez-VeraS,NavarroJF(2017)Executive LifetimesuicideattemptsinpatientswithcomorbiditybetweenpsychoticdisordersandSub-
FunctioninginMenwithSchizophreniaand
stanceUseDisorder(SUD),knownasdualdiagnosis,wasassociatedwithaworseclinical
SubstanceUseDisorders.InfluenceofLifetime
andcognitivestate,poorprognosisandprematuredeath.However,todatenoprevious
SuicideAttempts.PLoSONE12(1):e0169943.
doi:10.1371/journal.pone.0169943 studyhasexaminedthecognitiveperformanceofthesepatientsconsideringasindepen-
dentthepresenceorabsenceoflifetimesuicideattempts.
Editor:AntonioVerdejo-Garc´ıa,Universityof
Granada,SPAIN
Received:May4,2016 Methods
Accepted:December21,2016 Weexploreexecutivefunctioningdifferencesbetweensuicideattemptersandnon-attemp-
Published:January18,2017 tersindualschizophrenia(DS)patientsandthepossiblerelatedfactorsforbothexecutive
performanceandcurrentsuiciderisk.FiftyDSmalepatientsinremissionofSUDandclini-
Copyright:©2017Adanetal.Thisisanopen
accessarticledistributedunderthetermsofthe callystables,24withand26withoutlifetimesuicideattempts,wereevaluated.Weconsid-
CreativeCommonsAttributionLicense,which eredZscoresforallneuropsychologicaltestsandacompositesummaryscoreforboth
permitsunrestricteduse,distribution,and
premorbidIQandexecutivefunctioning.
reproductioninanymedium,providedtheoriginal
authorandsourcearecredited.
DataAvailabilityStatement:Allrelevantdataare Results
withinthepaper.
DSpatientsshowedlowperformanceinset-shifting,planningandproblemsolvingtasks.
Funding:Thisresearchwassupportedbygrants Thosewithsuicideattemptspresentedlowercompositesummaryscores,togetherwith
fromtheSpanishMinistryofEconomyand
worseproblemsolvingskillsanddecision-making,comparedwithnon-attempters.How-
Competitiveness,PSI2012-32669andPSI2015-
65026(MINECO/FEDER/UE),andbytheUniversity ever,aftercontrollingforalcoholdependence,onlydifferencesindecision-makingre-
ofBarcelona(APIF-2011;ResearcherTraining mained.Executivefunctioningwasrelatedtothepremorbidintelligencequotient,and
ProgramgranttoSLV).Theseinstitutionshadno
severalclinicalvariables(duration,severity,monthsofabstinenceandrelapsesofSUD,
roleinstudydesign,datacollectionandanalysis,
globalfunctioningandnegativesymptoms).Arelationshipbetweencurrentsuiciderisk,and
decisiontopublishorpreparationofthe
manuscript. first-degreerelativeswithSUD,insightandpositivesymptomswasalsofound.
PLOSONE|DOI:10.1371/journal.pone.0169943 January18,2017 1/16
SuicideAttemptsandExecutiveFunctioninginDualSchizophrenia
CompetingInterests:Theauthorshavedeclared Conclusions
thatnocompetinginterestsexist.
Ourresultssuggestthatproblemsolvingand,especially,decision-makingtasksmightbe
sensitivetocognitiveimpairmentofDSpatientsrelatedtopresenceoflifetimesuicide
attempts.Theassessmentoftheseexecutivefunctionsandcognitiveremediationtherapy
whennecessarycouldbebeneficialfortheeffectivenessoftreatmentinpatientswithDS.
However,furtherresearchisneededtoexpandourfindingsandovercomesomelimitations
ofthisstudy.
Introduction
SubstanceUseDisorder(SUD)isbecomingmoreprevalentovertheyearsanditishighlycom-
moninSchizophrenia(SZ),acomorbidityknownasDualSchizophrenia(DS).Thisdualdiagno-
sishasrelevantclinicalimplications,giventhatsubstanceusecouldexacerbatetheSZsymptoms
[1]aswellasthecognitiveimpairment[2,3],italsoworsenstheprognosisofthedisorder[4,5],
andincreasestheriskofsuicide[6].Thus,itisnecessarytostudynewwaystoimprovethe
health-relatedqualityoflifeandreducingmortalityofDSpatients.Giventhatsuicideisoneof
themaincausesofprematuredeathinSZ[7,8],preventingsuicideanddiminishingitsriskfac-
torsdeservegreatconsiderationasmaintargetsofcare,especiallyintheDSpopulation.
Around20–50%ofSZpatientswillattemptsuicideintheirlifetime[9,10].Thesuiciderisk
isgreaterinfirstoracutepsychoticepisodes,duringthefirstsixmonthsafterhospitalization
[11,12]andinSUDcomorbidconditions[6,8,11,13–16].Alcoholisoneofthemoststudied
substancessinceithasbeenshowntohaveasignificantimpactonsuicide[17–19]andcogni-
tion[20,21].Furthermore,DSpatients,comparedtoSUDpatients,arelessmotivatedto
changetheirconsumptionpattern,aremoredifficulttoinvolveintreatment,exhibitslower
progress,tendtogiveuplong-termprograms[22]andremainatriskofrelapseevenyears
afteraperiodoffullremission[23].
InadditiontotheSUD,otherriskfactorsforsuicidedescribedinSZpatientsare:malegen-
der,singlemaritalstatus,livingaloneandsocialisolation,familyorpersonalhistoryoflifetime
suicideattempts,aggressivebehavior,depressionandhopelessness,lowstressresistance,
higherinsightandmetacognitionability.Moreover,otherfactorsarealsolinkedtosuiciderisk
inSZpatients:lowadherencetonon-pharmacologicaltreatment,moretypicalantipsychotic
prescriptions,long-termillnesswithseveralexacerbations,lossoffaithintreatment,fearof
deterioration,higherinsightoftheillness,increasedpositiveandfewernegativesymptoms,
highernicotineconsumptionandgreaterdurationofuntreatedpsychosis[17,24,25].
Ontheotherhand,thestudyoftheclinicalcharacteristicsoftheDSpatientshighlightsthe
importantroleplayedbycognition.Comparedwiththesinglecondition,intheDSithasbeen
observedaworseglobalcognitivestate[26]withamarkeddeteriorationwithage,especiallyin
executiveperformance[2,3,27],anditisconsideredtobeapowerfulpredictorofmaladaptive
functioning[26].Interestingly,higherpremorbidintelligencequotient[17,28],betterexecu-
tive[29,30]andsocialpremorbidfunctioning[18],anddysfunctionalimpulsivity[9,19,28]
havebeenhypothesizedtopredisposeforsuicidalbehaviorandcouldfacilitatetheillegalsub-
stanceacquisition.Inthiscontext,theprimarydrugofdependenceseemsdecisivegiventhat
alcoholisthesubstancethathasshowngreaterneurodegenerativebraineffectsandcognitive
impairment[31].
Takingallthefactorsstatedaboveintoconsideration,DSindividualsareavulnerablepopu-
lationtocommitsuicide,giventhattheymeetmanyofthepreconditionsfortheemergenceof
suicidality.However,fewstudieshaveevaluatedtheexecutivefunctioningoftheDSpatients
PLOSONE|DOI:10.1371/journal.pone.0169943 January18,2017 2/16
SuicideAttemptsandExecutiveFunctioninginDualSchizophrenia
andnonehasaddresseditspossibleinfluenceontheexistenceoflifetimesuicideattemptsand
clinicalvariablesthatmaybemodulatingresults,sonewresearchisneededtoclarifythese
questions.
Theaimofthisstudywastoexplore,firstly,theexecutivefunctioningdifferencesbetween
suicideattemptersandnon-attemptersinDSpatientsandthepossiblepremorbidandclinical
relatedfactors.Todoitanexhaustiveclinicalevaluationandacompleteneuropsychological
batterywasapplied,beingallpatientsinremissionofSUDandclinicallystables.
MaterialsandMethods
Participants
Theparticipantswere50DSmalepatients(36.06±7.79years)fromsevenmedicalcentersin
Barcelona.Theywereassignedtotwogroupsaccordingtotheself-reportedprevioussuicide
attempts:DSattempters(DS+;n=24)andDSnon-attempters(DS-;n=26).Oursamplesize
wasaimedtohaveabalanceddesignintwogroups.Bothgroupswereabstinentforatleast
threemonths,controlledbyurinalysis.
PatientswerederivedbymedicalcentersfromtheirdiagnosesaccordingtotheDSM-IV-
TR(2000)[32]andinclusion/exclusioncriteriarequired.However,eachdiagnosiswascon-
firmedinafirstevaluationsessionbyaresearcherresponsibleforclinicalassessment(Master
inClinicalPsychology)usingtheSCID-Iandastructuredinterviewofsociodemographic
andclinicaldata.Occasionally,somepatientswereruledoutfornotcomplyingwiththedual
diagnosisrequired.Theinclusioncriteriawere:(1)currentdiagnosisofpsychoticspectrum
disorder(schizophreniaandschizoaffective)andcurrentSUDinremissionforatleastthree
months;(2)undertreatment;(3)malegender,consistentwiththesexprevalenceofthe
disorder;(4)agebetween18–55years;(5)clinicallystablepsychiatricsymptomatology.The
exclusioncriteriawere:(1)DSM-IV-TRcriteriaforacurrentsubstanceinduced-psychiatric
disorderorpsychiatricdisorderduetoamedicalcondition;(2)otherseveremedicalillness;
(3)mentalretardation,historyoftraumaticbraininjuryorneurologicalinjury;(4)receiving
electroconvulsivetherapywithin12monthspriortotheirstudyparticipation.Frominitially
derivedsample(n=56)sixpatientswerediscardedforfailingtomeetthediagnosticandclini-
calcriteria.Noneofthepatientsincludedinthestudydroppedoutandtheyallcompleteddata
recordingsessions.
Allpatientswereintreatmentfortheirclinicalconditions(SUDandpsychoticdisorder)
withanintegratedinterventioninwhichaddictionandmentalhealthinterventionareoffered
atthesametimeandbythesameteam[5].Integratedinterventionincludesacombinationof
motivationalinterviewing,contingenceandcasemanagement,cognitivebehavioraltherapy,
socialskillstrainingandrelapseprevention.
TheethiccommitteeoftheUniversityofBarcelonaapprovedthisstudy,whichcomplies
withtheethicalstandardsonhumanexperimentationandwiththeHelsinkideclarationof
1975,asrevisedin2008.Allparticipantsprovidedwritteninformedconsentandwerenot
compensatedfortheirparticipation.Datacollectionwascarriedoutbetween2013and2015.
ClinicalMeasures
InformationwascollectedusingtheStructuralClinicalInterviewforDSM-IV-TRAxisI
Disorders(SCID-I)[33]alongwithastructuredinterviewofsociodemographicandclinical
data.Weconfirmedtheself-reporteddatawiththemedicalhistoryofthemedicalcenters,
withespecialemphasisinourclassificatorycriteriaoflifetimesuicideattempts.Thesuicide
attemptsinDS+grouprangefrom1to5,withthefollowingdistribution:8patientswith
oneattempt,8withtwoattempts,5withthreeattempts,1withfourattemptsand2withfive.
PLOSONE|DOI:10.1371/journal.pone.0169943 January18,2017 3/16
SuicideAttemptsandExecutiveFunctioninginDualSchizophrenia
Chlorpromazineequivalentdoses(CPZ)werecalculatedforantipsychoticmedication[34].
Wealsorecordeddailyconsumptionofcigarettesandcaffeine(milligramsofcoffee,teaor
cola),andtheFagerstro¨mtest[35]wasadministeredtosmokersfornicotinedependence.
Additionally,theClinicalGlobalImpression-Severityscale(CGI-S)[36]wasappliedasa
subjectivemeasureoftheclinicalseverity.Thegenerallevelofsymptomsandfunctioningwas
assessedthroughtheGlobalAssessmentofFunctioning(GAF)[37].ThePositiveandNegative
SyndromeScale(PANSS)[38]wasadministeredasameasureofpsychoticsymptomseverity,
anditem12wasusedforInsightevaluation.SocialadaptationwasmeasuredbytheSocial
AdaptationSelf-EvaluationScale(SASS)[39].Depressivesymptomswereassessedwiththe
BeckDepressionInventory(BDI)[40]andthePlutchikRiskofSuicideScale(RS)[41]was
appliedtoassessthecurrentsuiciderisk,establishingthecut-offof6points[42].Finally,the
severityoftheSUDwasmeasuredwiththeDrugAbuseScreeningTest(DAST-20)[43].
NeuropsychologicalAssessment
WeusedtheVocabularyandBlockDesignsubtests(WAIS-III)asareliableestimateofverbal
andnon-verbalpremorbidIQ[44].Toobtainmeasuresofdorsolateralprefrontalfunctionwe
selectedtheBackwardDigitssubtest(WAIS-III),theTrailMakingTest-trailB-(TMT-B),the
TowerofHanoi(ToH)andthestandardcomputerizedversionoftheWisconsinCardSorting
Test(WCST)asmeasuresofworkingmemory,set-shifting,planningabilitiesandproblem
solving,respectively.TheIowaGamblingTask(IGT)wasadministeredtomeasuredecision-
makingcapacity,asameasureofdysfunctionalimpulsivityrelatedtoorbitofrontalcortex
functioning[45].RawscoresweretransformedtoZscores(mean=0±SD=1)foralltests
(globalscores)anditssubcomponents,basedontheSpanishnormativedatafortheWAIS-III
subtests[46],TMT-B[47,48],WCST[49],onMexicannormativedataforToH[50],andon
AmericannormativedataforIGT[51].AnaverageofZscores(compositesummaryscores)
wereconductedtoyieldageneralmeasureforbothpremorbidIQandexecutivefunctioning.
DataAnalysis
GroupdifferencesindemographicandclinicalvariableswereexploredwiththeMann-Whit-
neyUtest(U)orwiththeChi-Squaretestforcategoricalvariables.Ifthequantitativedataful-
filledthenecessaryconditions,theStudent’st-test(t)wasused;whentheconditionswerenot
met,thenonparametricMann-WhitneyUtestwasusedinstead.DifferencesinZscoresof
neuropsychologicalperformancebetweengroupswereanalyzedwithone-wayanalysisof
covariance(ANCOVA)forVocabulary,BlockDesign,BackwardDigitssubtests,TMT-Band
compositesummaryscoresforbothpremorbidIQandexecutivefunctioning.Multivariate
analysisofcovariance(MANCOVA)wasconductedinthecaseoftheToH,WCSTandIGT.
Repeatedmeasuresmultivariateanalysisofvariance(RMMANCOVA)wasalsousedforthe
fiveblocksoftheIGTdirectscores.Inallcases,weconsideredageascovariatetocontrolfor
possibleeffectsincognitiveperformancebecause,althoughgroupsdidnotshowdifferences,
areknowntheage-relatedeffectsbothingeneralpopulation[50]andDSpatients[2,3].We
repeatedallsignificantanalysesincludingalcoholdependencealsoascovariate.Thepartial
squaredEta(η 2)statisticwasusedtomeasuretheeffectsize,inconjunctionwiththeobserved
p
powerthroughtheoptionavailableintheanalysisofvariance,andthepost-hoccomparisons
wereBonferronicorrected.Finally,weconductedstepwiselinearregressionsconsideringonly
thesignificantvariables(p<0.05)foundinapreviousbivariatecorrelationanalysisforexecu-
tivefunctioningandcurrentsuiciderisk.Inallcasestheconditionsofapplicationandnon-
existenceofcollinearityandmulticollinearitywereverified.DatawereanalyzedusingtheSta-
tisticalPackagefortheSocialSciences(SPSS;version21.0).
PLOSONE|DOI:10.1371/journal.pone.0169943 January18,2017 4/16
SuicideAttemptsandExecutiveFunctioninginDualSchizophrenia
Results
DemographicandClinicalData
Groupsdidnotdifferinsociodemographicdata,medicalcomorbidity,CPZ,CGI,GAF,depressive
symptoms,socialadaptation,dailycaffeineintakeandcurrentsuicideriskscores(seeTable1).
Althoughnosignificantdifferencewerefoundbetweengroupsinthesuiciderisk,consideredas
presentorabsent(χ2 =1.82;p=0.18),wehaveobservedatendencyofhigherproportionsof
(1)
patientswithsuicideriskintheDS+(84.6%)comparedtotheDS-group(58.3%).Dailymedica-
tionwasequivalentbetweengroups,exceptforuseofinterdictors,withhigherconsumptioninthe
DS+group.Moreover,DS+showedahighernumberoffirst-degreerelativesbothwithSUDand
psychiatricdisorders,dailycigaretteconsumptionandnicotinedependencecomparedtoDS-.No
significantdifferenceswerefoundbetweengroupsinpsychoticsymptoms(PANSSscores).
RegardingSUDcharacteristics,polyconsumptionwasthemorefrequentpatterninthe
totalsample(72%)andalsoinbothgroups(DS+:83%andDS-:61%).DS+patientsshowed
greateralcoholconsumptionthanDS-,althoughthepercentageofpatientswiththealcoholas
primarydrugofdependencewasnotdifferentbetweengroups.Moreover,thetwogroupsdid
notshowdifferencesinlengthofabstinence,numberofrelapses,durationofSUDandseverity
ofSUD(DAST-20).
ExecutiveFunctioning
ThetotalsampleshowedalowperformancecomparedtothenormativedataintheTMT-B,
reactiontimeintheToH,andtrialstofirstcategoryinWCST(zscoreslowerto-1SD).Inthe
othertasks,bothintheindividualcomponentsandglobalscores,aswellasinthecomposite
summaryscoreofexecutivefunctioning,performancetendedtobeworsethanaveragebutin
nocaseexceeds-1SD(Table2).
ThegroupsshowedsimilarpremorbidIQ,consideringboththeverbalcomponentasthe
manipulative,andonlyprovideddifferencesintheperformanceofWCSTandIGT.The
WCSTanalysesshowedsignificantworsescoresfortheDS+patientsincategoriescompleted,
trialstofirstcategoryandintheglobalmeasureofWCSTperformance.However,thesediffer-
encesdisappearedwhenthealcoholdependencewasconsideredasacovariateintheanalyses
(F <2.229;p>0.143;η 2<0.049).
(1,46) p
ConsideringtheIGT,weobtainedsignificantdifferencesinthethird,fourthandlastblock
trialsaswellasinthetotalscore(100trials),withtheDS+groupshowingtheworstperfor-
mance.AlthoughtheZscoresforbothgroupsintheIGTwerewithinthemean,whenthetotal
directscoreswereconsideredregardingthetypeofdecision-makingchosen,theDS+group
showedadisadvantageouspatternincomparisontotheDS-(F =11.274;p=0.002;η 2=
(1,47) p
0.193;power=0.907)(seeFig1A).Similarly,theRMMANCOVAforthedirectscoresshowed
asignificantlyworseperformanceoftheDS+group(F =5.203;p=0.027;η 2=0.100;
(1,47) p
power=0.636),withanegativelearningcomparedtotheDS-(seeFig1B).Allsignificantdiffer-
encesbetweengroupsintheIGTremainedwhenalcoholdependencewasconsideredasa
covariateintheanalyses(F >4.64;p<0.037;η 2>0.092;power>0.562).
(1,46) p
Finally,thecompositesummaryscoreofexecutivefunctioningwasworseinDS+groupas
comparedtoDS-anditcontinuedprovidingsignificantdifferenceswhenintheanalysisthealco-
holdependencewasincludedascovariate(F =4.982;p=0.032;η 2=0.096;power=0.603).
(1,46) p
FactorsRelatedtoExecutiveFunctioningandCurrentRiskofSuicide
Inthetotalsample,theregressionanalysisindicatedthatthemodelwassignificantforallcog-
nitivetasksexcepttheIGT,andalsoforthecompositesummaryscoreofexecutivefunctioning
PLOSONE|DOI:10.1371/journal.pone.0169943 January18,2017 5/16
SuicideAttemptsandExecutiveFunctioninginDualSchizophrenia
Table1. SociodemographicandclinicaldataofDualSchizophrenia(DS)patients,andconsideringthepresence(DS+)orabsence(DS-)ofsuicide
attempts. Mean,standarddeviation,frequencywithpercentage,andstatisticalcontrast(Student’st,Mann-WhitneyUorChi-Squaretest).
DS(N=50) DS-(N=26) DS+(N=24) Statisticalcontrast
Sociodemographicdata
Age(yr) 36.06(7.79) 35.92(8.63) 36.21(6.95) t =0.12
(1,48)
Maritalstatus Χ2 =2.48
(2)
Single 41(82.0%) 22(84.6%) 19(79.2%)
Stablepartner 3(6.0%) 2(7.7%) 1(4.2%)
Separated/Divorced 6(12.0%) 2(7.7%) 4(16.6%)
Yearsofeducation 9.84(2.06) 9.38(1.94) 10.33(2.12) t =1.65
(1,48)
Economicsituation χ2 =2.68
(4)
Active 5(10.0%) 2(7.7%) 3(12.5%)
Disabilitypension 35(70.0%) 17(65.4%) 18(75.0%)
Unemployed 5(10.0%) 3(11.5%) 2(8.3%)
Noincome 3(6.0%) 2(7.7%) 1(4.2%)
Offwork(onsickleave) 2(4.0%) 2(7.7%) 0(0%)
Clinicaldata
Numberofmedicalcomorbidities 0.60(0.81) 0.42(0.58) 0.79(0.96) t =1.64
(1,48)
Respiratory-typea 4(8.0%) 3(11.5%) 1(4.2%) χ2 =0.92
(1)
Metabolic-typea 7(14.0%) 3(11.5%) 4(16.7%) χ2 =0.27
(1)
Infectious-typea 6(12.0%) 2(7.7%) 4(16.7%) χ2 =0.95
(1)
Othera 9(18.0%) 4(15.4%) 5(20.8%) χ2 =1.43
(1)
Dailynumberofmedications 3.20(1.78) 2.96(1.93) 3.46(1.61) t =0.98
(1,48)
Typicalantipsychoticsa 13(26.0%) 7(26.9%) 6(25.0%) χ2 =0.02
(1)
Atypicalantipsychoticsa 45(90.0%) 22(84.6%) 23(95.8%) χ2 =1.00
(1)
Antidepressantsa 15(30.0%) 6(23.1%) 9(37.5%) χ2 =2.33
(1)
Moodstabilizersa 12(24.0%) 6(23.1%) 6(25.0%) χ2 =0.07
(1)
Anxiolyticsa 21(42.0%) 9(34.6%) 12(50.0%) χ2 =0.98
(1)
Anticholinergicsa 13(26.0%) 8(30.8%) 5(20.8%) χ2 =0.78
(1)
Interdictora 15(30.0%) 4(15.4%) 11(45.8%) χ2 =5.13*
(1)
Othermedicationa 14(28.0%) 8(30.8%) 6(25.0%) χ2 =0.64
(1)
CPZequivalentdosage(mg) 41.34(90.36) 35.32(97.20) 45.37(83.53) t =1.02
(1,48)
ClinicalGlobalImpression 3.84(1.48) 3.96(1.40) 3.71(1.57) t =0.60
(1,48)
GlobalAssessmentFunctioning 65.78(10.82) 64.46(10.17) 67.21(11.52) t =0.89
(1,48)
Currentsuiciderisk(Plutchikscale) 6.80(2.41) 5.92(1.93) 7.62(2.60) t =1.18
(1,48)
Depressivesymptoms(BDI) 4.53(4.08) 3.80(6.34) 4.83(3.04) t =0.46
(1,48)
Socialadaptation(SASS) 36.55(9.06) 35.33(9.92) 38.38(7.87) t =0.76
(1,48)
Relativeswithpsychiatricdisorder 0.75(0.88) 0.48(0.71) 1.04(0.98) t =2.27*
(1,48)
Ageofpsychoticdisorderonset 24.21(6.70) 23.75(7.36) 24.67(6.10) t =0.47
(1,48)
Durationofillness(yr) 11.88(7.71) 12.20(8.95) 11.54(6.43) t =0.30
(1,48)
Psychiatricdiagnosis χ2 =0.02
(1)
Schizophrenia 42(84.2%) 22(85.0%) 20(83.3%)
Schizoaffective 8(15.8%) 4(15.0%) 4(16.7%)
PANSS-Positivesymptoms 11.37(5.79) 10.79(4.15) 11.83(6.89) t =0.53
(1,48)
PANSS-Negativesymptoms 14.00(7.19) 12.57(6.66) 15.11(7.57) t =0.99
(1,48)
PANSS-Generalpsychopathology 30.09(12.46) 27.43(11.77) 32.16(12.91) t =1.08
(1,48)
Insight 2.10(1.37) 1.62(1.04) 2.44(1.50) t =1.81
(1,48)
FisrtdegreerelativeswithSUD U=180.00**
None 30 23 7
(Continued)
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SuicideAttemptsandExecutiveFunctioninginDualSchizophrenia
Table1. (Continued)
DS(N=50) DS-(N=26) DS+(N=24) Statisticalcontrast
One 6 3 3
Twoormore 14 0 14
Ageofintakeonset(yr) 17.22(5.20) 17.64(5.88) 16.79(4.47) t =0.57
(1,48)
DurationofSUD(yr) 18.39(8.13) 17.97(9.01) 18.83(7.28) t =0.37
(1,48)
Primarydrugofdependence χ2 =1.14
(3)
Alcohol 24(48.0%) 11(42.3%) 13(54.2%)
Cocaine 13(26.0%) 8(30.8%) 5(20.8%)
Cannabis 10(20.0%) 5(19.2%) 5(20.8%)
Other 3(6.0%) 2(7.7%) 1(4.2%)
Numberofsubstancesused 3.80(1.78) 3.31(1.57) 4.26(1.85) t =1.99
(1,48)
Cocainea 47(94.0%) 24(92.3%) 23(95.8%) χ2 =0.27
(1)
Cannabisa 39(78.0%) 20(76.9%) 19(79.2%) χ2 =0.37
(1)
Alcohola 41(82.0%) 17(65.4%) 24(100%) χ2 =10.13**
(1)
Psychodyslepticsa 22(44.0%) 10(38.5%) 12(50.0%) χ2 =0.67
(1)
Opioidsa 12(24.0%) 4(15.4%) 8(33.3%) χ2 =2.20
(1)
Sedativesa 10(20.0%) 4(15.4%) 6(25.0%) χ2 =0.72
(1)
Monthsofabstinence 6.64(4.15) 6.50(4.81) 6.79(3.40) t =0.24
(1,48)
Numberofrelapses U=211.50
None 18 11 7
One 10 7 3
Twoormore 22 8 14
SeverityofSUD(DAST-20) 12.00(2.62) 12.67(2.96) 11.43(2.24) t =1.21
(1,48)
Intermediate 26.9 25.0 28.6
Substantial 69.2 66.7 71.4
Severe 3.8 8.3 0
Dailynumberofcigarettes 20.50(13.49) 16.08(11.52) 25.29(14.04) t =2.54*
(1,48)
Nicotinedependence(Fagerstro¨mtest) 5.82(2.77) 5.00(2.73) 6.71(2.57) t =2.28*
(1,48)
Dailycaffeineintake(mg) 255.51(203.67) 217.69(179.58) 300.00(219.41) t =1.45
(1,48)
CPZ=Chlorpromazine;BDI=BeckDepressionInventory;SASS=SocialAdaptationSelf-EvaluationScale;PANSS=PositiveandNegativeSyndrome
Scale;SUD=SubstanceUseDisorder;DAST-20=DrugAbuseScreeningTest.
aPercentageswillnotequal100aseachparticipantmaytakemorethanonesubstanceormedicationandmayhavemorethanonemedicalcomorbidity.
*p<0.05
**p<0.01.
doi:10.1371/journal.pone.0169943.t001
(seeTable3).Thesignificantindependentvariablesrelatedtothedifferenttaskwerepremor-
bidIQ,GAF,negativesymptoms(PANSS),severity(DAST-20)anddurationofSUD.Premor-
bidIQexplained39%ofthevarianceofworkingmemorytaskand,togetherwithdurationof
SUD,57%ofthevarianceofWCST.ExecutionisbetterashigherOQandshorterdurationof
SUD.Furthermore,GAFexplained13%ofthevarianceintheBackwardDigitssubtest,being
theexecutionhigherasbetterglobalfunctioning.NegativesymptomswithDAST-20described
24%ofthevarianceofToHtest,patientswithlessnegativesymptomsandhigherseverityof
addictionperformedbetter.Consideringtheexecutivefunctioning(compositescore),premor-
bidIQ,DAST-20anddurationofSUDaccountedfor52%oftheirvariance.Thebestcom-
positescoresofexecutivefunctioningarerelatedtohigherIQandseverityofaddictionand
shorterdurationofSUD.
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SuicideAttemptsandExecutiveFunctioninginDualSchizophrenia
Table2. NeuropsychologicaltestsdatainZscoresofDualSchizophrenia(DS)patients,andconsideringthepresence(DS+)orabsence(DS-)of
suicideattempts. Mean,standarderrorandstatisticalcontrastcarriedout(ANCOVAorMANCOVAwithageascovariate).
NeuropsychologicalTests DS(N=50) DS-(N=26) DS+(N=24) F Effectsize Power
(1,47)
PREMORBIDIQ
Vocabulary(WAIS-III) -0.14(0.11) -0.02(0.15) -0.27(0.16) 1.272
BlockDesign(WAIS-III) -0.17(0.15) -0.21(0.20) -0.13(0.22) 0.071
CompositeSummaryScore -0.16(0.12) -0.12(0.16) -0.20(0.17) 0.130
EXECUTIVEFUNCTIONING
WorkingMemory(Backwarddigits,WAIS-III) 0.03(0.19) 0.10(0.26) -0.10(0.28) 0.634
Set-shifting/CognitiveFlexibility(TMT-B) -1.03(0.12) -1.00(0.18) -1.07(0.18) 0.060
Planningabilities(TowerofHanoi)
Numberofmovements 0.32(0.14) 0.36(0.19) 0.28(0.20) 0.092
Reactiontime -1.24(0.20) -1.21(0.28) -1.28(0.30) 0.031
Globalscore -0.46(0.15) -0.42(0.20) -0.50(0.21) 0.065
Abstractreasoning/Problemsolving(WCST)
Trials -0.69(0.16) -0.37(0.22) -1.01(0.24) 3.755
Totalcorrect 0.59(0.16) 0.52(0.22) 0.66(0.23) 0.184
Totalerrors -0.34(0.14) -0.08(0.19) -0.61(0.20) 3.767
Perseverativeerrors 0.41(0.18) 0.66(0.26) 0.16(0.27) 1.777
Non-perseverativeerrors -0.76(0.12) -0.53(0.16) -1.00(0.17) 3.898
Conceptuallevelresponses -0.49(0.15) -0.22(0.21) -0.77(0.21) 3.459
Categoriescompleted -0.74(0.24) -0.05(0.34) -1.42(0.35) 8.013** 0.146 0.792
Trialstofirstcategory -1.12(0.34) -0.36(0.47) -1.88(0.49) 4.969* 0.096 0.598
Failuretomaintainset -0.69(0.20) -0.43(0.28) -0.96(0.29) 1.678
Learntolearn -0.24(0.21) 0.15(0.28) -0.63(0.30) 3.631
Globalscore -0.43(0.13) -0.06(0.18) -0.80(0.19) 7.940** 0.145 0.788
Decision-making(IowaGamblingTask)
Block1(trials1–20) 0.40(0.10) 0.55(0.13) 0.25(0.14) 2.744
Block2(21–40) -0.28(0.08) -0.26(0.11) -0.31(0.12) 0.098
Block3(41–60) -0.59(0.10) -0.32(0.14) -0.87(0.15) 7.790** 0.142 0.781
Block4(61–80) -0.66(0.12) -0.37(0.17) -0.95(0.17) 5.636* 0.103 0.651
Block5(81–100) -0.57(0.11) -0.21(0.15) -0.93(0.16) 10.457** 0.182 0.886
Totalscore(100trials) -0.47(0.09) -0.18(0.12) -0.76(0.13) 11.249** 0.193 0.907
CompositeSummaryScore -0.48(0.07) -0.31(0.10) -0.65(0.10) 5.699* 0.105 0.685
IQ=intelligencequotient;WAIS-III=WechslerAdultIntelligenceScale-RevisedThirdEdition;TMT-B=TrailMakingTest,trailB;WCST=WisconsinCard
SortingTest
*p<0.05
**p<0.01.
doi:10.1371/journal.pone.0169943.t002
IntheDS-group,similarlytothetotalsample,premorbidIQwassignificantforBackward
Digitssubtest,explaining47%ofthevarianceand,togetherwithdurationofSUDdescribed
52%ofthevarianceofWCST.InbothcaseshigherIQwasrelatedtobetterperformance,and
inthesecondcasewiththeshorterdurationofSUD.Ontheotherhand,DAST-20described
48%ofthevarianceofToHtestandmonthsofabstinenceandSUDrelapsesaccountedfor
31%ofthevarianceinTMT-B.Theplanningabilityisbetterashigherseverityofaddiction
andthesuperiorcognitiveflexibilityasmoremonthsofabstinenceandlowerrelapses.Consid-
eringtheDS+group,alsopremorbidIQexplainedthevarianceinBackwardDigitssubtest,
inthiscase26%.AshigherIQ,thebettertheperformanceinworkingmemory.Additionally,
IQtogetherwithdurationofSUDexplained47%ofthevarianceinTMT-Band36%ofthe
PLOSONE|DOI:10.1371/journal.pone.0169943 January18,2017 8/16
SuicideAttemptsandExecutiveFunctioninginDualSchizophrenia
Fig1. Totalscore(100trials)(a)andlearning(b)inIowaGamblingtask(IGT)forDualSchizophrenia
patientswith(DS+)andwithout(DS-)suicideattempts.B1:trials1–20;B2:trials21–40;B3:trials41–60;
B4:trials61–80;B5:trials81–100.
doi:10.1371/journal.pone.0169943.g001
varianceinWCST.Inbothcases,ashigheristheIQbetteristheexecutionandasshorter
durationofSUDbettercognitiveflexibility.Finally,negativesymptomsdescribed38%ofthe
varianceinToHtask,ashigherpresenceofsymptomsworsetheperformance.Fortheexecu-
tivefunctioning(compositescore),intheDS-grouppremorbidIQ,DAST-20anddurationof
SUDexplainedthe87%ofitsvariance,whileintheDS+groupIQtogetherwithdurationof
SUDaccountedforthe52%(seeTable3).Inallcasesthesenseoftherelationshipisestablished
asdescribedinthetotalsample.
Wefoundsignificantcorrelationsbetweencurrentsuicideriskandnumberoffirst-degree
relativeswithSUDandinsight,whichaccountedfor64%ofthevarianceforthetotalsample.
PLOSONE|DOI:10.1371/journal.pone.0169943 January18,2017 9/16
SuicideAttemptsandExecutiveFunctioninginDualSchizophrenia
Table3. Stepwiselinearregressionanalysisofeachindependentvariable,explainingexecutivefunctioningofDualSchizophrenia(DS)patients,
andconsideringthepresence(DS+)orabsence(DS-)ofsuicideattempts.
Executivefunctioning AdjustedR2 F Independentvariablesa βStandardized pvalues Conditionindexb
DS(N=50)
WorkingMemory(Backwarddigits,WAIS-III) 0.393 30.464 PremorbidIQ 0.627 0.001 1.205
Set-shifting/CognitiveFlexibility(TMT-B) 0.127 7.952 GAF 0.380 0.007 12.281
PlanningAbilities(ToH) 0.241 4.813 Negativesymptoms(PANSS) -0.474 0.015 10.800
SeverityofSUD(DAST-20) 0.397 0.049
AbstractReasoning/ProblemSolving(WCST) 0.574 9.092 PremorbidIQ 0.499 0.001 4.880
DurationofSUD(yr) -0.606 0.002
Compositesummaryscore 0.522 6.014 PremorbidIQ 0.592 0.006 10.804
SeverityofSUD(DAST-20) 0.581 0.008
DurationofSUD(yr) -0.505 0.028
DS-(N=26)
WorkingMemory(Backwarddigits,WAIS-III) 0.465 22.758 PremorbidIQ 0.698 0.001 1.550
Set-shifting/CognitiveFlexibility(TMT-B) 0.305 6.274 Monthsofabstinence 0.515 0.006 4.008
SUDrelapses 0.378 0.041
PlanningAbilities(ToH) 0.483 5.532 SeverityofSUD(DAST-20) 0.875 0.008 7.570
AbstractReasoning/ProblemSolving(WCST) 0.522 6.996 PremorbidIQ 0.447 0.014 4.390
DurationofSUD(yr) -0.751 0.006
Compositesummaryscore 0.872 12.311 PremorbidIQ 0.781 0.019 10.168
SeverityofSUD(DAST-20) 0.957 0.005
DurationofSUD(yr) -0.499 0.041
DS+(N=24)
WorkingMemory(Backwarddigits,WAIS-III) 0,260 8.713 PremorbidIQ 0,542 0.008 1.267
Set-Shifting/CognitiveFlexibility(TMT-B) 0.466 10.583 DurationofSUD(yr) -0.741 0.001 6.398
PremorbidIQ 0.682 0.001
PlanningAbilities(ToH) 0.380 4.676 Negativesymptoms(PANSS) -0.760 0.012 4.245
AbstractReasoning/ProblemSolving(WCST) 0.356 7.968 PremorbidIQ 0.524 0.010 6.305
DurationofSUD(yr) -0.436 0.016
Compositesummaryscore 0.517 4.209 PremorbidIQ 0.726 0.014 6.195
DurationofSUD(yr) -0.465 0.029
WAIS-III=WechslerAdultIntelligenceScale-RevisedThirdEdition;IQ=IntelligenceQuotient;TMT-B=TrailMakingTest,trailB;GAF=Global
AssessmentofFunctioning;ToH=TowerofHanoi;PANSS=PositiveandNegativeSyndromeScale;SUD=SubstanceUseDisorder;DAST-20=Drug
AbuseScreeningTest;WCST=WisconsinCardSortingTest;IGT=IowaGamblingTask.
aOnlysignificantvariablesarepresentedthatcompriseeachexplicativemodel.
b.Inmodelswithmorethanonevariableisincludedthesuperior.
Inallcases,theTolerancevalueswerehigherthan0.815andtheVarianceInflationFactorvalueslowerthan1.209.
doi:10.1371/journal.pone.0169943.t003
WhenconsideringthegroupsthisresultcorrespondtotheDS+patients,withfirst-degreerela-
tiveswithSUDandinsighttogetherexplainingthe87%oftheirvarianceforcurrentsuicide
risk.Incontrast,inDS-groupthe47%ofthevarianceofcurrentsuicideriskwasexplainedfor
thepositivesymptoms(PANSS)(Table4).
Discussion
Toourknowledge,thisisthefirststudyaimingtoexploretheexecutivefunctioning,current
suicideriskandclinicalstateinDSpatients,consideringthepresenceorabsenceoflifetime
suicideattemptsandrelatedfactors.
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