Depression following adult, non-penetrating traumatic brain injury: A meta-analysis examining methodological variables and sample characteristics

ContentslistsavailableatScienceDirect

Neuroscience

and

Biobehavioral

Reviews

j o ur na l ho me p a g e :w w w . e l s e v i e r . c o m / l o c a t e / n e u b i o r e v

Review

Depression

following

adult,

non-penetrating

traumatic

brain

injury:

A

meta-analysis

examining

methodological

variables

and

sample

characteristics

A.J.

Osborn

_,

_J.L.

_Mathias

_,

_A.K.

_{Fairweather-Schmidt}

a_{SchoolofPsychology,UniversityofAdelaide,Adelaide,SouthAustralia,Australia} b_{SchoolofPsychology,FlindersUniversity,BedfordPark,SouthAustralia,Australia}

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received6November2013 Receivedinrevisedform16June2014 Accepted8July2014

Availableonline16July2014 Keywords:

Traumaticbraininjury Majordepression Dysthymia Prevalence Meta-analysis Adult Self-reportmeasures Injuryseverity Post-injuryinterval

a

b

s

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Background:DepressionisoneofthemostfrequentlyreportedpsychologicalproblemsfollowingTBI, howeverprevalenceestimatesvarywidely.Methodologicalandsamplingdifferencesmayexplainsome ofthisvariability,butitisnotknowntowhatextent.

Methods:Datafrom99studiesexaminingtheprevalenceofclinicallydiagnoseddepression(MDD/ dysthymia)andself-reportsofdepression(clinicallysignificantcasesordepressionscalescores) fol-lowingadult,non-penetratingTBIwereanalysed,takingintoconsiderationdiagnosticcriteria,measure, post-injuryinterval,andinjuryseverity.

Results:Overall,27%ofpeoplewerediagnosedwithMDD/dysthymiafollowingTBIand38%reported clini-callysignificantlevelsofdepressionwhenassessedwithself-reportscales.EstimatesofMDD/dysthymia variedaccordingtodiagnosticcriteria(ICD-10:14%;DSM-IV:25%;DSM-III:47%)andinjuryseverity (mild:16%;severe:30%).Whenself-reportmeasureswereused,theprevalenceofclinicallysignificant casesofdepressiondifferedbetweenscales(HADS:32%;CES-D:48%)methodofadministration(phone: 26%;mail46%),post-injuryinterval(range:33–42%),andinjuryseverity(mild:64%;severe:39%). Conclusion:DepressionisverycommonafterTBIandhasthepotentialtoimpactonrecoveryandquality oflife.However,thediagnosticcriteria,measure,timepost-injuryandinjuryseverity,allimpacton prevalenceratesandmustthereforebeconsideredforbenchmarkingpurposes.

CrownCopyright©2014PublishedbyElsevierLtd.ThisisanopenaccessarticleundertheCC BY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/3.0/).

Contents

1. Introduction... 2

2. Methods... 3

2.1. Literaturesearch,inclusionandexclusioncriteria... 3

2.2. Datapreparation... 3

2.3. Datacollectionandeffectsizecalculation... 4

2.4. Statisticalanalyses... 4

3. Results... 5

3.1. Participantdetails... 5

3.2. PrevalenceofformallydiagnoseddepressionfollowingTBI... 5

3.3. Prevalenceofclinicallysignificantlevelsofdepression(‘cases’)followingTBI... 8

3.4. Self-reportedlevelsofdepression:TBIvscontrols... 8

4. Discussion... 8

∗ Correspondingauthorat:SchoolofPsychology,UniversityofAdelaide,Adelaide,SouthAustralia5005,Australia.Tel.:+61883135266;fax:+61883133770. E-mailaddress:[email protected](J.L.Mathias).

http://dx.doi.org/10.1016/j.neubiorev.2014.07.007

0149-7634/CrownCopyright©2014PublishedbyElsevierLtd.ThisisanopenaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/ by-nc-nd/3.0/).

4.1. Limitationsandrecommendationsforfutureresearch... 12

5. Conclusions... 12

AppendixA. Supplementarydata... 13

References... 13

1. Introduction

Traumaticbraininjuries(TBIs)cancauseavarietyofchanges

incognitive,physical andpsychologicalfunctioning,whichmay

impactonallareasofaperson’slife.Cognitivechanges include

problemswithmemoryandattention,poorerexecutive

function-ingandslowedinformationprocessing(Bayetal.,2012;Belmont

etal.,2009;Konradetal.,2011;Rochatetal.,2009),withthe

physi-calconsequencesincludingheadaches,sleepproblemsandfatigue

(Cantoretal.,2012;Chaputetal.,2009;MathiasandAlvaro,2012).

PsychologicalproblemsarealsoverycommonfollowingTBI(fora

reviewseeKimetal.,2007),withthemostwidelyrecognisedand

researchedofthesebeingdepression(Hartetal.,2012;Rapoport,

2012).

Theprevailingbiopsychosocialmodel ofhealthprovidesone

framework for understanding some of the variables that may

contribute to the development of these problems – including

depression – following TBI (Helmchen, 2013). Specifically, this

modelpositsthatillnesses arecausedbya complexinteraction

betweena range of biological, psychological and social factors,

withaperson’svulnerabilitytoillnesschangingovertime(Molina,

1983).InthecontextofTBI,thereareavarietyofneuroanatomical

changesthatmayprovideabiologicalbasisforthedevelopment

of depression. For example, theshear, tensile and compressive

strainsexperiencedduringaTBIcanleadtodiffuseaxonalinjury

inthefrontalandtemporallobes,disruptingtheneuralcircuitry

betweentheprefrontalcortex,amygdala,hippocampus,basal

gan-gliaand thalamus(Jorgeand Robinson,2002;Kumarand Cook,

2002;Morris,2010;Silveretal.,2009).Thisneuronaldamageand

celllosscanoccurforweekstomonthsafteraninjury,andmay

providetheneurologicalsubstrateformanyofthecognitiveand

psychologicalchangesthatoccurafteraTBI(JorgeandStarkstein,

2005;SherinandNemeroff,2011).Neurochemicalchanges,such

ascholinergicandserotonergicdeficits, neuroendocrinal

abnor-malitiesand compromisedhypothalamic–pituitary–adrenal axis

function,alsooccurintheacuteperiodpost-TBI;potentiallyalso

causingdepression(JorgeandStarkstein,2005;Rosenthaletal.,

1998).Psychological variables– suchasa diminishedtolerance

tofrustration,impairedself-awareness,lowself-esteem,andpoor

copingstrategies–mayadditionallyleadtodepressionafteraTBI

(Kelley et al.,2012; Malec etal., 2007;Molina, 1983).Lastly, a

varietyofsocialfactors–includingalackofsocial support,the

lossofpersonalrelationships/friendships,unrealisticexpectations

andinvolvementinlitigation–mayindependentlycontributeto

thedevelopmentofdepressionfollowingTBIorexacerbate

symp-tomsthatarisefromanyoftheaforementionedcauses(Dikmen

et al., 2003; Gunstad and Suhr, 2001; Iverson et al., 2010b; Waljasetal.,2014).Thus, therearealargenumberofvariables

that may explain why depression is a common problem after

TBI.

Estimatesoftheprevalenceofdepressionfollowing TBIvary

considerably–rangingfrom6%to77%(Rutherfordetal.,1977;

Varneyetal.,1987).Thisvariabilitynotonlyseriouslylimitsthe

clinicalutilityofthesefindings, butalsoraises questionsabout

itssource.Differencesinhowdepressionisconceptualised

(diag-noseddisordervsself-reportedsymptoms),thediagnosticcriteria

and/ormeasuresthatareusedtoassessdepressionandanumberof

patientcharacteristics(e.g.,injuryseverity),mayexplaina

signifi-cantamountofthisvariance;however,wedonotcurrentlyknowto

whatextentthesevariablesimpactonestimatesoftheprevalence

ofdepressionfollowingTBI.

Thetwomostcommonlydiagnoseddepressivedisorders

fol-lowingTBIaremajordepressivedisorder(MDD)anddysthymia

(Gomez-Hernandez et al., 1997; Hibbard et al., 1998; Meares etal.,2011;Whelan-Goodinsonet al.,2009a),which are

gener-allydeterminedusingoneoftwocriteria,namelytheDiagnostic

andStatisticalManualofMentalDisorders(DSM-III,DSM-IV,

DSM-5;AmericanPsychiatricAssociation [APA],1987,2001,2013)or

theInternationalClassificationofDiseases(ICD-9,ICD-10;World

HealthOrganisation,1977,1992).Thesedisordershaveoverlapping

symptoms,includingdepressedmood,disturbedsleep,lowenergy

andpoorconcentration.WhereasadiagnosisofMDDrequiresthe

presenceoffiveormoresymptomsduringa2-weekperiod,

dys-thymia(alsoknownaspersistentdepressivedisorder)requiresthe

presenceoftwosymptomsforaminimumof2years(APA,2013).

MDDanddysthymiaarefrequentlydiagnosedusingoneofa

number of structuredclinical interviewstodetermine whether

theirpatientsmeetDSMorICDcriteria(e.g.,StructuredClinical

InterviewforDSM-IVAxisIDisorders[SCID-I];Firstetal.,1997).

However,theseinterviewsexaminesymptomsoverdifferenttime

periods–rangingfromthepreviousweek(e.g.,theClinical

Inter-viewSchedule[CIS]; Lewiset al.,1992)to thepreviousmonth

(e.g., SCID,Schedules for Clinical Assessment in

Neuropsychia-try[SCAN];Wing etal.,1990)orpreceding6months/year (e.g.,

CompositeInternationalDiagnosticInterview[CIDI];Robinsetal.,

1988);whichmayhaveasignificantimpactontheresulting

preva-lencerates.Notonlycanthesymptomsvarybetweenthesetime

frames,butalsomemoryandothercognitiveproblemsfollowing

TBImay affecttheaccuracyof theinformationthat isreported

(Hilsabeck et al.,1998).Therefore, differences inthediagnostic

criteriaand/orinterviewschedulesthatareusedmaybeimpacting

onestimatesoftheprevalenceofMDDanddysthymia.

Prevalence rates may additionally be affected by a number

of sample characteristics, including the time interval between

theinjuryand when depressionis assessed.Somestudieshave

foundthat MDD is more prevalentin theearly stages afteran

injury(Bombardieretal.,2010;Linetal.,2010),possiblyreflecting

neuroanatomicalabnormalitiesorthecascadeofneurochemical

changesthatoccurintheacutepost-TBIperiod(Jorgeetal.,1993a).

Conversely,othershavefoundMDDand/ordysthymiaaremore

commoninthelong-term(Al-Adawietal.,2007;Raoetal.,2010),

whichmaybemoreindicativeofthepsychosocialchallengesfaced

byindividuals astheyadjusttotheiraltered lifecircumstances

(e.g.,lackofsocialsupport,reducedsocialfunctioning)(Jorgeetal.,

1993b).Similarly,theseverityofaninjurycanrangefromminorto

severe,withsomestudiesexaminingmixedsamples(mild,

mod-erateandsevere),otherstargetingspecificinjuries(e.g.,mildor

severe),andstillothersexamininglesscommoncategories,such

as minor (Van DerHorn et al., 2013) or complicated mild TBI

(Bombardieretal.,2010;Fannetal.,2005;Juengstetal.,2013).

Inaddition,controlgroupsareoftenalsorecruitedtoexamine

thebase-ratesofdepressionbecausedepressionisnotuniqueto

TBI,butthesampleschosenforthispurposecanvary.Typically,

medicalpatients(Brownetal.,2004;Jorgeetal.,2004),peoplefrom

thegeneralcommunity(Belmontetal.,2009;Konradetal.,2011;

PonsfordandZiino,2003),orfamilyandfriendsoftheTBIgroup (Perleszetal.,2000;Ponsfordetal.,2003)areusedforthispurpose.

variables(e.g.,illness-relatedstress)ontheprevalenceof

depres-sionand,therefore,thebase-ratesarelikelytodifferbetweenthese

groups.Onceagain,itisnotknownwhetherorhowthechoiceof

controlgroupsimpactsontheconclusionsthataredrawnregarding

post-TBIratesofdepressionwhentheyareusedforcomparative

purposes.

Alsoimportantisthedistinctionbetweenclinicaldiagnosesof

MDD/dysthymiaand assessmentsthat useself-report

question-naires(e.g.,BeckDepressionInventory[BDI];Becketal.,1996)to

assessdepressiononacontinuousscale(minimaltosevere);often

withtheadditionalabilitytoidentifyclinically-significantlevelsof

depression(‘cases’)usingdesignatedcut-offscores(dichotomous

scale).Self-reportscalesarefrequentlyusedinclinicalsettingsto

screenfordepressionandinresearchsettingstoexaminethe

preva-lenceandseverityofdepressionfollowingTBI.However,manyof

thesescaleswerenotspecificallydesignedforusewithTBIgroups

orin medical settings;insteadbeingintended for usewiththe

generalpopulation(e.g.,CenterforEpidemiologicalScale–

Depres-sion[CES-D];Radloff,1977)orpsychiatricpatients(e.g.,Hamilton

DepressionRatingScale[HAM-D];Hamilton,1960).Consequently,

theymaycontainitemsthatcanbeaffectedbythephysical

con-sequencesofaTBI(e.g.,poorsleep,fatigue),whichmayinflatethe

prevalenceofdepression.

Furthermore,thewaythatcliniciansorresearchersadminister

questionnairesmayaffectthedepressionscoresobtainedon

self-reportscales.Variousadministrationmethodshavebeenused,with

someparticipantscompletingthemattheresearchsite (Hudak

etal.,2011;Konradetal.,2011),intheirownhome(Bushniketal., 2008; Kingand Kirwilliam, 2011), over thephone (Bombardier etal.,2010;Hartetal.,2011)orbyusingacombinationofthese

methods(Hawthorneetal.,2009;Smith,1992).Specifically,certain

situationsmayelicit socially-desirableresponses,providefewer

opportunitiestoreflectonandreviseanswers(e.g.,telephone

inter-views),orbesubjecttootherunidentifiedinfluences(e.g.,mailed:

whencompletedandwhethercompletedalone/withothers).These

variablesareknowntohaveanimpactonpeople’sresponses(for

areviewseeRichmanetal.,1999)and,consequently,shouldbe

consideredinthecurrentcontext.

Anyoneormoreofthesevariableshasthecapacitytoinfluence

estimatesoftheprevalenceofdepressionandmayhelptoexplain

whytheaforementionedstatisticsvarysowidely.However,asyet,

theirimpacthasnotbeenassessed.Asystematicanalysisofthe

prevalenceofdepressionfollowingTBIisneededtoevaluatethe

impactofthesevariablesandtoassistcliniciansinselectingthe

mostappropriatebenchmark(s)fortheirparticularcircumstance.

Thecurrentstudythereforemeta-analysedexistingresearchthat

hasexamined:(1)theprevalenceofclinicaldiagnosesofMDDand

dysthymiafollowingTBIor(2)usedself-reportscalestoassessthe

prevalenceofclinicallysignificantsymptomsand/ortheseverityof

depression.Tothisend,theimpactofdiagnosticcriteria,interview

schedule,post-injuryintervalandinjuryseverityontheprevalence

ofMDD/dysthymiawasevaluated,aswasthetypeofcontrolgroup.

Inaddition,theimpactofquestionnaire,methodofadministration,

post-injuryinterval,injuryseverityandtypeofcontrolgroupon

self-reportedmeasuresofdepressionwasexamined.

2. Methods

2.1. Literaturesearch,inclusionandexclusioncriteria

Comprehensive searches of the PsycINFO, Pubmed, Scopus,

and ISI Web of Knowledge electronic databases, from January

1980 to June 2013, were undertaken to identify studies that

examineddepressionfollowingTBIusingsearchtermsthatwere

tailoredforeachdatabase(seeSupplementarydata:TableA).In

addition,thereferencelistsof allstudiesthatwereincludedin

thefinal analysiswereexaminedtoidentifyanyotherrelevant

research.

Forastudytobeincludedinthecurrentmeta-analysis,ithad

tomeetthefollowingcriteria:(1)itexamineddepression

follow-ingnon-penetratingTBI;(2)participantswere18yearsorolder

(whereagerangewasnotprovided:meanageminus1SD≥18);(3)

itreportedtheprevalenceofcurrentMDDordysthymia,whichwas

formallydiagnosedusingDSMorICDcriteria,and/or‘cases’

(clin-icallysignificantlevelsofdepression),ordepressionscalescores

from a common self-report depression scale (excludes general

qualityoflifeandmood-statemeasures,andstudy-specificor

mod-ifiedscales)(seeSupplementarydata:TableBforalistofeligible

measures);(4)datawereprovidedforaTBIsample(single-sample)

orboth aTBIand controlgroup(independent samples);(5) the

data(prevalencerates,casesordepressionscores)werereported

inawaythatenabledthecalculationofaneffectsize;(6)thedata

werepublishedinajournalinEnglishandcontainedoriginaldata

(excludesreviews);and(7)thesamplesizewasgreaterthan15

(excludesverysmallsamplesandcasestudies).

Studieswereexcludedifparticipantsweredrawnexclusively

fromveryspecificorat-riskTBI populations–suchaswar

vet-erans,prisoninmates,victimsoflarge-scaletrauma/terrorism,or

psychiatric populations – as theirexposure to othertraumatic

events/situationsmayhaveincreasedtheirvulnerabilityto

depres-sion,renderingthemlesscomparabletothebroaderTBIpopulation.

Inaddition,controlgroupswereexcludedifthegroupwasvery

specific(e.g.,depressedcontrols),depressionwasnotassessed,or

differentdepressionscaleswereadministeredtotheTBIand

con-trolgroups.Moreover,ifastudyexaminedtheefficacyofsomeform

oftreatment,onlythepre-treatmentdatawereanalysed.

Theliteraturesearchinitiallyidentified8,399potentially

rel-evant articles, 2,217 of which were duplicates. The titles and

abstractsof theremaining 6,182articles werescreened by the

firstauthor(AJO)usingtheaforementionedinclusionand

exclu-sioncriteria,afterwhichthefull-textversionsof459studieswere

retrieved for detailed screening.Re-application of theinclusion

criteriatothesepapersreducedthenumberofeligiblestudiesto

99(seeSupplementarydata:TableCforanoverviewofthestudy

reviewand selectionprocess).Inambiguouscases,papers were

independentlyassessedbyAJOandJLM,andeligibilitydetermined

followingdiscussion.

Datathataremeta-analysedmustbeobtainedfrom

indepen-dent samples (Rosenthal,1995); consequently all studies were

checkedtoestablishindependence.Sixsampleswerefollowed

lon-gitudinally(twoarticleseach);thedatafromthesearticleswere

combined,resultinginsixindependentstudies;furtherreducing

thefinalnumberofeligiblestudiesto93.Moreover,thedatafor

thecontrolgroupsfromfivestudieswereunsuitableforpresent

purposes:only the TBI datafrom thesestudies wereextracted

(Capizzanoetal.,2010;Hawthorneetal.,2009;Rezaetal.,2007; SchnabelandKydd,2012;WoodandWilliams,2008).

2.2. Datapreparation

Somebasicdatapreparationwasneededinordertorenderit

suitableforanalysis.Specifically,wheredemographicdetailswere

reportedforTBIsubgroupsthatwerenotrelevanttothecurrent

analyses(e.g.,fatiguedvsnon-fatiguedTBIpatients),thedatawere

combined.Ifmedianandrangewerereported(e.g.,age),themean

andSDwereestimatedusingthemethodsrecommendedbyHozo

etal.(2005).Inaddition,wherenecessary,standarderrorswere

transformed tostandard deviations and descriptive data

trans-formedtoacommonscaleofmeasurement(e.g.,time-since-injury:

Thepost-injury interval for studies variedwidely – ranging

fromafewdaystoover30years–necessitatingtheclassification

oftheseintervalsintofourbroadgroups:thefirstincludedstudies

thatexaminedmeanpost-injuryintervalsof<6months(acuteto

post-acuteperiod);thesecondincludedintervalsof≥6months

to<2years(shortterm);thethirdspanned≥2yearsto<5years

(mediumterm);and the fourth≥5 years (long-term).

Unfortu-nately,very few studies reportedseparateprevalence rates for

theirmild,moderateandsevereparticipants.Thus,thedatafrom

studiesthatexaminedmild-moderateandmoderate–severe TBI

sampleswerecombinedwiththosethatassessedallthree

cate-gories(mild,moderateandsevere)forpresentpurposes.Further,

wherestudies assesseddepression in a controlgroup,the type

ofcontrolwasclassifiedintooneofthreegroups:‘medical

con-trols’ (spinal cord, orthopaedic or general trauma patients),

‘general community’, or ‘significant other’ (family/friends/

caregivers).

2.3. Datacollectionandeffectsizecalculation

Demographicand injuryinformation (e.g.,age,gender,

time-since-injury,injuryseveritydata),themethodbywhichdepression

wasassessed(e.g.,clinicaldiagnosisofMDD/dysthymia or

self-reportmeasure), thecriteria used to diagnose MDD/dysthymia

(e.g.,DSM-IV,ICD-10),themeasureused(clinicaldiagnoses:SCID-I,

SCAN,etc.,self-report:BDI,HospitalAnxietyandDepressionScale

[HADS],etc.),themethodbywhichself-reportscaleswere

admin-istered(researchcentre,phone,mail,orcombinationofmethods),

sampledetails(i.e.,recruitmentsource,pre-injuryhistoryofmental

healthproblemsandTBIs,currentmedicationuse,typeofcontrol

group[medical,community,significantother]),andstatisticaldata

necessaryforthecalculationofeffectsizeswereextractedfrom

eachstudyforanalysis.Thisinformation wasthen enteredinto

ComprehensiveMeta-AnalysisSoftwareversion2(CMA;©2006,

Biostat,Inc.,Englewood,NJ,USA).

Threetypesofeffectsizewerecalculatedinthecurrentstudy.

Firstly,proportionswereusedtosummarisetheprevalenceof(1)

clinicallydiagnosed cases ofMDD and dysthymia,and (2)

clin-ically significantlevelsof depression, basedon self-reportdata

(‘cases’),instudiesthatusedsingle(TBI)orindependent(TBIand

controls)samplesdesigns.Weightedmeanprevalencerateswere

calculatedusingsamplesizeastheweightingvariable.Secondly,

oddsratioswerecalculatedtomeasureanyincrease(OR>1)or

decrease(OR<1)inthelikelihoodofexperiencingdepression

fol-lowing TBI for those studies that used self-report measuresto

identifyclinically significant levelsof depression (cases) in TBI

andcontrolgroups.Thirdly,weightedstandardisedmean

differ-ences (Hedgesg) were used to estimatethe magnitude of the

differencebetweenthedepressionscalescores(means,SDs)ofTBI

andControlgroups(independentsamplesstudydesign).A

posi-tiveHedgesgindicatesthattheTBIgroupreportedhigherlevels

of depression than thecontrols, witha small effect defined as

≥.2,a moderateeffect as≥.5, anda largeeffectas ≥.8(Cohen,

1992).Asaguide,aHedgesgof.5(mediumeffect)indicatesthat

themeansofthetwogroupsdifferbyhalfofapooledstandard

deviation.

Thecurrent studyuseda conservativerandom-effectsmodel

tocalculateeffectsizes,whichassumesthateffectsizescanvary

duetosamplingerroranddifferencesinstudydesign.Importantly,

whena studyreportedmultiplescoresthat wereeligibletobe

includedin thesame analysis,a mean effectwascalculated to

ensurethateachstudyonlycontributedoneeffectsizetoanygiven

analysis(Lipseyand Wilson,2001).Forestplots weregenerated

toexaminetheeffectsizedistributionsandassistinidentifying

outliers(Boylesetal.,2011),and ninety-fivepercentconfidence

intervals(95%CIs)werecalculatedtoprovidetheupperandlower

boundswithinwhichwecanbe95%confidentthattheactual

pop-ulationprevalenceratefordepressionfollowingTBIlies.Inthecase

ofHedgesg,95%CIsdothatdonotincludezero,indicatethatthere

isasignificantdifferencebetweenthedepressionscoresoftheTBI

andcontrolgroups.

Oneproblemthatmeta-analysesfaceisthattheresearch

lit-erature may be biased towards publishing studies that report

significant findings (publication bias/file-drawer problem) and,

consequently, the resultant analyses tend to exclude

non-significantfindings;therebyinflatingtheeffectsizes(Rosenthal,

1979).Publicationbias wasassessedusing Orwin’s(1983)

Fail-safeNstatistic(Nfs),whichestimatesthenumberofunpublished

studiesthatwouldberequiredtodrawa findingintoquestion.

Orwin’sformularequiresthreevaluestocomputeaNfs:the

num-berofstudiescontributingtoameaneffect,theresultingweighted

meaneffectsize,andanalternativemeaneffectsize,belowwhich

aresultwouldbeconsideredinconsequential/ofminorclinical

sig-nificance.Forcurrentpurposes,TBIprevalenceratesoflessthan

7.5%,oddsratiosof<1.0,andHedgesgvaluesof<0.15weredeemed

tobe of minor clinical significance. These figures were chosen

onthebasis of (a)a population-based surveyof the12-month

prevalenceofdepressioninAustralianadults(AustralianBureauof

Statistics,2008),(b)Hopkin’s(2002)guidelinesforatrivialeffect

whenusingoddsratios,and(c)Cohen’sdefinitionofasmall

stan-dardisedmeandifference.TheresultingNfsindicatesthenumber

ofunpublishedstudies,withnon-significantfindings,thatwould

berequiredtorenderthecurrentfindingsinconsequential.

There-fore,the largertheNfs,the more confidence wecan have in a

finding.

2.4. Statisticalanalyses

ConsistentwithrecommendationsmadebytheMeta-Analysis

ofObservationalStudiesinEpidemiology(MOOSE)groupStroup

etal.(2000),theimpactofavarietyofmethodologicaland

samp-lingvariablesonfindingswereexaminedinordertoaddressthe

factthatfindingsfromdifferentstudieswereheterogeneous.This

approachisalsosuggestedbyBorensteinetal.(2009)whonote

thatarandom-effectsmodelandsubgroupanalysescanbeusedto

identifysourcesofvariabilityinthedata.

TheoverallprevalenceofMDDanddysthymiawascalculated

onthebasis of dataextracted from studiesthat useda

single-sample(TBIgroup)orindependentsamples(TBI+controls)design,

afterwhichtheimpactofanumberofmoderatorvariablesonthe

prevalenceof MDD and dysthymia wasexamined,namelythe:

diagnosticcriteria (DSM-III, DSM-IV, ICD-10);clinical interview

(SCID-I,SCAN,etc.);timepost-injury(<6months,≥6monthsto

<2years,≥2yearsto<5years,≥5years);andinjuryseverity(i.e.,

mild,mild–moderate–severe,severe).Inaddition,theprevalence

ofMDDanddysthymia,relativetocontrols,wasexaminedusing

ORs;bothoverallandbasedonthetypeofcontrolgroup(medical,

community,significantother).

Next,studiesthatusedself-reportscalestoidentifyclinically

significantlevelsofdepressionwereexamined.Theoverall

preva-lenceofdepression(cases)wascalculatedusingdatafromsingle

andindependentsamplesdesigns,andthefollowingmoderator

variables examined: theself-report scale (BDI,HADS, etc.);the

methodofadministration(researchcentre,phone,mail,or

com-binationofmethods);timepost-injury;and injuryseverity.The

prevalenceofclinicallysignificantlevelsofdepression(cases),

rel-ative to controls, wasexamined using ORs – both overall and

bytype ofcontrolgroup.Finally,thedepression scalescoresof

TBIandcontrolgroups(level/severityofdepression)were

com-pared using Hedges g – both overall and by type of control

Table1

Summarydemographicandinjurycharacteristicsforthestudies(N=93).

Variable Nstudies Nparticipants % Mean SD

Samplesize 93 11,926 131 209

Age(years) 93 11,926 37.1 6.8

Gender(males) 93 8,176 68.6

Time-since-injury(months) 92 11,898 33.7 51.7

GlasgowComaScalescore(GCS) 32 4,037 9.7 2.2

Injuryseverity

Mild 12 1,134 9.5

Mild,moderate 8 912 7.6

Mild,moderate,severe 46 6,779 56.8

Moderate,severe 17 2,569 21.5

Severe 8 415 3.8

Detailsnotspecified 2 117 0.9

Recruitmentsource

Outpatients 84 10,815 90.7

Inpatients 6 936 7.8

Both 3 175 1.5

Pre-injuryhistoryofdepressionoranxiety

Participantswithhistoryincluded 38 5,784 48.5

Participantswithhistoryexcluded 15 1,881 15.8

Notspecified 40 4,261 35.7

Pre-injuryhistoryofTBI

HistoryofpriorTBI 12 1,146 9.6

NohistoryofpriorTBI 21 2,051 17.2

Notspecified 60 8,729 73.2

Treatments

Depression/anxietymedication 11 1,180 9.9

Anti-epilepticmedication 2 138 1.2

Medicationorcounselling 1 100 0.8

Participantsexcludedifusingmedication 2 73 0.6

Medicationsused,nofurtherdetail 2 152 1.3

Notspecified 75 10,283 86.2

NStudies NTBI % NControl %

Typeofcontrolgroup

Medical 11 1,077 42.5 1,067 44.6

Generalcommunity 13 809 31.9 691 28.9

Significantothers 7 647 25.5 633 26.5

Total 31 2,533 2,391

Note:NstudiesandNparticipantsrefertothetotalnumberofstudiesandparticipantsforwhichdatawereavailable.Onestudyusedtwodifferentcontrolgroups:communityand

medical(Clarkeetal.,2012).

3. Results

3.1. Participantdetails

The93studiesincludedinthismeta-analysisprovideddatafor

atotalof11,926participants.Thebackgrounddemographicand

injurydataforthesestudiesaresummarisedinTable1,whereit

canbeseenthatthemajorityofparticipantswereyoungto

middle-agedmales.

Moststudiesreportedthemeantimebetweeninjuryand

assess-ment(Nstudies=92),withtheaverageintervalbeingjustunder3

years (seeTable1).In contrast,onlya limitednumber of

stud-iesreportedmeanGlasgowComaScalescores(GCS)(Nstudies=32),

althoughmostprovidedcategoricalinformationrelatingtoinjury

severity.Themajorityofstudiesexaminedmixedsamplesofmild,

moderate and severe TBI (Nstudies=46), however most did not

reportseparateoutcomesforthesesub-groups.

Participants were largely recruited from outpatient settings

(Nstudies=84;seeTable1).Sixstudiesrecruitedfrominpatient

sett-ings,allofwhichexamineddepression1–6monthsaftersevere

TBI.Thirty-eightstudiesincludedparticipantswhohadapre-injury

diagnosisofdepressionoranxiety(779outof5,784participants),

15 excluded participantson this basis, and 40 didnot specify.

Althoughthemajorityofstudiesfailedtoreportwhether

partic-ipantshad previously sustainedaTBI (Nstudies=60)orexcluded

participantswithsuchahistory(Nstudies=21),12studiesreported

that 167of their1,146participants had previouslysustained a

TBI.Similarly,moststudies(Nstudies=75)failedtoreport

medica-tionuse,however11reportedthat314(outof1,180)participants

weretakingmedicationsfordepressionoranxiety.Finally,30

stud-iesrecruitedoneormorecontrolgroups(seeTable1),withthe

majorityusingmedical(Nstudies=11;primarilygeneraltrauma)or

community(Nstudies=13)controls,andafurthersevenrecruiting

significantothers(family,friends,caregiversoftheTBIgroup).

3.2. PrevalenceofformallydiagnoseddepressionfollowingTBI

ThedatafromallstudiesthatreportedtheprevalenceofMDD

and/ordysthymia followingTBI(Nstudies=31,Nparticipants=5,678)

werecombinedinordertocalculateanoverallprevalencerate.

Fig.1a

providesa forestplotoftheprevalenceratesforeach ofthe

individualstudies(rank-orderedbysize),togetherwiththeoverall

weightedmean,whichindicatesthat,onaverage,27%were

diag-nosedwithMDDordysthymiaafteraTBI.TheassociatedNfswas

verylarge(Nfs=81),suggestingthatpublicationbiasisunlikelyto

beaproblem.Importantly,therewassubstantialvariationinthe

prevalenceestimatesofindividualstudies(range:9–67%),

high-lightingtheneedtoundertakeadditionalanalysestoexaminesome

ofthevariablesthatmayhavecontributedtothisvariability.

Studieswerefirstpartitionedaccordingtothediagnostic

Fig.1. PrevalenceofformallydiagnosedMDDanddysthymia:(a)overall,(b)diagnosticcriteria,(c)interviewschedule,(d)timepost-injury,(e)injuryseverity,(f)overall, relativetocontrols,and(g)accordingtothetypeofcontrolgroup.Note:MDD,majordepressivedisorder;CI,confidenceinterval;Nfs,fail-safeN;ICD,InternationalClassification

ofDiseases;DSM,DiagnosticandStatisticalManual;MINI,Mini-InternationalNeuropsychiatricInterview;SCAN,SchedulesClinicalAssessmentinNeuropsychiatry;SCID, StructuredClinicalInterview;PSE,PresentStateExamination;PHQ-9,PatientHealthQuestionnaire-9;CIDI,CompositeInternationalDiagnosticInterview;SADS-L,Schedule forAffectiveDisordersandSchizophrenia(lifetime);DIS,DiagnosticInterviewSchedule;NFI,NeurobehavioralFunctioningInventory;CIS,ClinicalInterviewSchedule.Refer onlineSupplementarydata:TableDfordetailsofstudiescontributingtothesummaryanalysesinthisfigure;Kreutzeretal.,2001usedtheNFItoidentifyandquantify depressivesymptomsofMDDasspecifiedintheDSM-IV.

Fig.1. (Continued)

Thelowestprevalencerate(14%)wasobtainedusingICD-10

crite-riaandthehighest(47%)usingDSM-IIIcriteria.Moreover,theCIs

forICD-10,DSM-IVandDSM-IIIprevalenceratesdidnotoverlap,

indicatingthattheyyieldedsignificantlydifferentrates.

AsseeninFig.1c,atotalof10differentinterviewscheduleswere

usedtodiagnoseMDD/dysthymia, withtheSCID-I(Nstudies=13)

beingthemostcommonlyused,followedbytheSCAN,Mini

Inter-nationalNeuropsychiatricInterview(MINI;Sheehanetal.,1998),

PresentState Examination(PSE;Winget al., 1974)and Patient

HealthQuestionnaire(PHQ-9;Kroenkeetal.,2001),whichwere

eachusedbythreestudies.Theprevalenceratesobtainedusing

thesemeasuresvariedbetween16%and33%;although,withthe

exceptionoftheMINIandPSE,thesedifferenceswerenot

signif-icant.Incontrast,theinterviewsusedbysinglestudies(e.g.,CIDI,

CIS,clinicaldiagnosisbasedontheNeurobehavioralFunctioning

Inventory[NFI];Kreutzeretal.,1999)yieldedsignificantlyhigher

prevalencerates(range:42–54%)thanthemorecommonlyused

measures(i.e.,SCID-I,SCANandMINI).

Next,post-injuryintervalwasexaminedtodeterminewhether

this impactedonprevalencerates (seeFig.1d).The meantime

intervalsfortheacute/post-acute,short,mediumandlong-term

studies were 2.4 months (SD=1.4), 11.5 months (SD=5), 3.1

years (SD=0.8) and 10.5 years (SD=6.5), respectively. Notably,

the mean prevalence of MDD/dysthymia appears to increase

in the first 5 years after a TBI (21–43%), after which it

declinestoacute/post-acutelevels(22%).Moreover,the

medium-term prevalence rate was significantly higher than any other

Although injury severity may impact on the prevalence of

depressionafteraTBI,onlyacoarse-grainedanalysisofthisvariable

waspossiblebecausemanystudiesusedmixedsamples(e.g.,mild,

moderateandsevere)andonlyprovideddataforthewholesample.

AsseeninFig.1e,mildTBIwasassociatedwithasignificantlylower

prevalenceofMDDanddysthymia(16%),comparedwiththemixed

samplecategoryofmild,moderateandsevereTBI(30%).Severe

TBIwasonlyexaminedbyonesmall-scalestudywithawideCI

thatoverlappedwiththeothercategories,indicatingthatitdidnot

differfromthemintermsoftheprevalenceofMDD/dysthymia.

Finally,datafromfivestudiesthat compared theprevalence

of MDD/dysthymia in TBI and control groups were examined

(Nparticipants:TBI=600;controls=712)(seeFig.1f).Overall,there

wasa higherprevalenceofMDD/dysthymiafollowingTBI (23%)

thaninthecontrols(17%),withtheassociatedORindicatingthata

personis1.66timesmorelikelythancontrolstodevelopMDDor

dysthymiaafteraTBI.TherewasconsiderablevariationintheORs

forindividualstudies(.67–7.69),someofwhichmayhaveresulted

fromthechoiceofcontrolgroups.Ofthefivestudies,fourused

med-icalcontrolsandonlyoneusedcommunitycontrols.Importantly,

aftersustainingaTBI,apersonisnearlyeighttimesmorelikely

todevelopMDDordysthymia(OR=7.69)thansomeonefromthe

generalcommunitybutonlyoneandahalftimesmorelikelythan

medicalcontrols(OR=1.55)(seeFig.1g).

3.3. Prevalenceofclinicallysignificantlevelsofdepression

(‘cases’)followingTBI

Whenthedatafromthe57studiesthatusedself-reportscalesto

identifyclinicallysignificantcasesofdepressionfollowingTBIwere

combined,itwasfoundthattheoverallprevalencewas38%(referto

Fig.2a).TheassociatedNfsstatisticwasverylarge(Nfs=232),

indi-catingthatthisisaveryrobustfinding.AswithdiagnosesofMDD

anddysthymia,therewasconsiderablevariabilityinthenumber

ofcasesreportedbyindividualstudies(range:2–74%),again

high-lightingtheimportanceofexaminingsomeofthevariablesthat

mayimpactonthesefindings.

In terms of methodology, the specific self-report scale may

impactontheprevalenceofclinicallysignificantcasesof

depres-sion(seeFig.2b).Indeed,therewasconsiderablevariabilityinthe

meanprevalencerates thatwereobtainedusingthesedifferent

scales,rangingfrom2%fortheMontgomery–AsbergDepression

RatingScale[MADRS](MontgomeryandAsberg,1979)to48%for

theCES-D.However,asisevidentfromtheCIs,theprevalencerates

reportedbystudiesusingthesamemeasurewerealsohighly

vari-able(e.g.,BDI-II;ZungSelf-ratingDepressionScale[ZSDS];Zung,

1965),somuchsothatafterexcludingtheMADRS,whichwasonly

usedbyonesmallstudy,noneoftheothermeasuresdiffered

sig-nificantly;althoughtheHADSandCES-Dapproachedsignificance.

Similarly,whenstudiesweregroupedonthebasisofhowthey

administeredtheself-reportscale–byphone,inperson(research

centre),bymailorusingacombinationofmethods–therewas

sub-stantialvariabilityinthenumberofcasesofdepressionreported

bystudiesusingthesamemethod.Interestingly,althoughonlythe

‘combination’and‘mailed’groupsdifferedsignificantly,therewasa

trendtowardsfewercaseswhenquestionnaireswereadministered

byphone,comparedtomailedquestionnaires(seeFig.2c).

Next,theprevalenceofclinicallysignificantcasesofdepression

wasfoundtosteadilyincrease,albeitnotsignificantly,asthe

post-injuryintervalincreased(seeFig.2d),withestimatesrangingfrom

33%intheacute/post-acuteperiod,35%intheshort-term,41%in

themediumterm,and42%inthelongerterm.Moreover,mildTBIs

wereassociatedwithsignificantlymorecasesofdepression(64%)

thanthemixed(mild/moderate/severe:36%)andsevere(39%)(see

Fig.2e)TBIsamples.

Finally, the data from the 16 studies that used self-report

measurestoidentifycasesofdepressioninTBIandcontrol

sam-pleswereexamined(Nparticipants:TBI=1,055;controls=1,000)(see

Fig.2f).TheoverallmeanprevalenceofdepressionfollowingTBI

(44%)wassubstantiallyhigherthanthatofcontrolgroups(19%),

withtheassociatedORof3.41indicatingthatapersonisnearly

threeandahalftimesmorelikelytoreportclinicallysignificant

depressionafteraTBI,comparedtocontrols.Onceagain,theORs

forindividualstudies variedsubstantially(range: 1–49),raising

thepossibilitythatthetype ofcontrolgroupimpactedonthese

findings.AsseeninFig.2g,controlsfromthegeneralcommunity

reportedthelowestratesofdepression(9%),followedby

signifi-cantothers(23%)andmedicalcontrols(36%).Thiswasreflectedin

theORs,whichindicatedthat,followingaTBI,peoplearenearly

sixtimesmorelikelythanthoseinthegeneralcommunity,three

timesmorelikelythantheirsignificantothers(family,friends),and

overtwiceaslikelyasthosewithothermedicalconditionsto

expe-rienceclinicallysignificantlevelsofdepression.Nevertheless,all

CIsoverlapped,indicatingtheaforementioneddifferenceswerenot

significant.

3.4. Self-reportedlevelsofdepression:TBIvscontrols

Twenty studies provided mean depression scale scores

(continuousdata)forTBIandControlgroups,whichwere

exam-ined (Nparticipants: TBI=1,563; controls=4,017) using Hedges g

(weighted standardised mean difference). Overall, there was a

moderateandsignificantdifferenceinthedepressionscoresofthe

TBIandcontrolgroups(Hedgesg=0.63),togetherwithalargeNfs

statistic(Nfs=43)(seeFig.3a).Whenthesestudiesweregrouped

accordingtotypeofcontrolgroup(medical/community/significant

other),therewasalargeandsignificantdifferencebetweenthe

depressionscoresoftheTBIandcommunitycontrols(seeFig.3b).

Medicaland‘significantother’controlsalsohadsignificantlylower

scoresthantheTBIgroup,butthesedifferencesequatedtosmallto

low-moderateeffects.

4. Discussion

Estimatesof theprevalenceofdepressionfollowing TBIvary

widely,limiting theclinical utilityofthis research.Thepresent

studyanalysedthedatafromresearchthathasexaminedthe

preva-lenceofMDD/dysthymiaorusedself-reportscalestoassessthe

severityofdepressionfollowingTBI.Avarietyofmethodological

(diagnosticcriteria,interviewschedule/self-reportscale,methodof

administeringself-reportscales,controlgroup)andpatient(time

post-injury,injuryseverity)variableswereexaminedtodetermine

whether,andtowhatextent,theyimpactedontheavailable

find-ings.

Overall,thefindingsindicatethatdepressionisextremely

com-monafteraTBI,with27%ofpeoplereceivingaformaldiagnosis

of MDD or dysthymia and 38% reporting clinically significant

symptomsonself-reportscales.Thelowerprevalenceofclinical

diagnosesis not surprising because,in addition to using more

stringentcriteria,theyprovideadetailedassessmentofthe

aeti-ology and chronology of symptoms, and greater opportunities

forclarification(APA,2000).Incontrast,self-reportscales

mea-surethepresenceandseverityofsymptoms,applyingathreshold

to identify clinically significant cases; and do not provide an

opportunitytoclarifywhethersymptomsaretheresult of

pre-existing(e.g.,prior psychiatrichistory)or co-morbidconditions

(e.g.,physical/cognitiveconsequencesofaTBI),whichmayinflate

theprevalencerates(Greenetal.,2001;Schwarzboldetal.,2008).

Moreover, people report more symptoms when prompted

Fig.2. Prevalenceofclinicallysignificantlevelsofdepressionidentifiedusingself-reportscales:(a)overall,(b)self-reportscale,(c)methodofadministration,(d)time post-injury,(e)injuryseverity,(f)overall,relativetocontrols,and(g)accordingtothetypeofcontrolgroup.Note:CI,confidenceinterval;Nfs,fail-safeN;MADRS,

Montgomery–AsbergDepressionRatingScale;HADS,HospitalAnxietyandDepressionScale;GDS,GeriatricDepressionScale;ZSDS,ZungSelf-ratingDepressionScale; BDI,BeckDepressionInventory;Leeds,TheLeedsScalefortheSelf-assessmentofAnxietyandDepression;CES-D,CenterforEpidemiologicalScale–Depression.Referonline Supplementarydata:TableDfordetailsofstudiescontributingtothesummaryanalysesinthisfigure.

Fig.2. (Continued)

(Iverson et al.,2010a), also leading tohigher prevalence rates.

ThecognitivechangesassociatedwithTBIs(e.g.,poorermemory,

impairedinsight)can,however,leadtofewerreportsof

depres-sion(WallaceandBogner,2000);theimpactofwhichmaybeoffset

byusingquestionnaires.Regardlessofthemethodofassessment,

individuals mayexaggeratetheirsymptoms iftheyareseeking

financialcompensation,highlightingtheimportanceofassessing

symptomvaliditywhendisingenuousperformancemaybeanissue

(Whitesideetal.,2012).Oncecompensationclaimshavebeen

set-tled,themotivationtoexaggeratesymptomsislikelytoreduce,

suggestingthatlonger-termprevalenceratesarelesslikelytobe

Fig.3.DifferencesinthedepressionscoresofTBIandControlgroups,asassessedbyself-reportscales:(a)overalland(b)accordingtothetypeofcontrolgroup.Note:CI, confidenceinterval.

EstimatesoftheprevalenceofMDDand/ordysthymiadiffered

whendifferentdiagnosticcriteriawereused,withthehighestrates

notedfortheDSM-III(47%)andDSM-IV(25%)criteria,decreasingto

14%forthetwostudiesthatusedICD-10criteria.Thesedifferences

aresurprising,giventheoverlapbetweenthesecriteriaandthefact

thattheDSM-IVrevisionswererelativelyconservative(First,2010).

However,unliketheDSM,theICD-10categorisessymptomsinto

twogroups,eachofwhichhasadiagnosticthreshold;potentially

resultingincasesthatmeetonecriterion,butnottheotherand

leadingtofewerdiagnoses(First,2009).

Prevalencerateswerealsoaffectedbythespecificinterview

thatwasusedtodiagnoseMDD anddysthymia.Themost

com-monly used schedule– the SCID-I – yielded a prevalencerate

of 23% (Nstudies=13),with the others ranging from 16% (MINI:

Nstudies=3)to54%(CIS;Nstudies=1).Someofthisvariabilitymay

resultfromthedifferenttime framesthatare assessed.Indeed,

theCISand Schedulefor AffectiveDisordersand Schizophrenia

(SADS;Endicottand Spitzer,1978), whichfocusonthe

preced-ing week, had the highest rates (54% and 50%, respectively).

Longertimeframes(previous2weekstomonth)yielded

substan-tiallylowerrates(e.g.,MINI=16%;SCAN=18%;SCID-I=23%).Other

scalesallowclinicianstoselectthetime-frame (e.g.,Diagnostic

InterviewSchedule;Robinset al.,1981),but thiswasoftennot

reported.

Therewas alsoconsiderable variability in the prevalenceof

clinicallysignificantcasesofdepression,identifiedonthebasisof

self-reportscales;withestimatesrangingfrom2%fortheMADRS

(Nstudies=1)to48%fortheCES-D(Nstudies=8).Notably,theCES-D

wasdesignedforuseinthegeneralpopulationandincorporates

itemsthatmaybeindicativeofphysicalorcognitiveTBI

symp-toms(e.g.,sleepdifficulties,fatigue,attentionalproblems),possibly

inflatingthenumberof‘cases’.Interestingly,therateobtainedfrom

themostfrequentlyusedscale–theHADS(Nstudies=19;32%)–was

substantiallylowerthanthefindingfortheCES-D(48%).TheHADS

wasspecificallydesignedforuseinmedicalsettingsand,

conse-quently,doesnotincludeitemsthatmayreflectthephysical,rather

thanpsychological,consequencesofaTBI(ZigmondandSnaith,

1983).Thismeasuremaythereforeprovidethebestestimateof

self-reportedcasesofdepression.

Theprevalenceofself-reported‘cases’ofdepressionalso

dif-feredaccordingtohowthescalewasadministered.Specifically,

morecaseswereidentifiedwhenpeoplecompletedquestionnaires

athomeandreturnedthembymail(46%),thanwhencompleted

byphoneinterview(26%).Phoneadministrationmayencourage

peopletorespondinasocially-desirablemanner,possiblycausing

themtodown-playtheirsymptomsand/orprovidelimited

oppor-tunitytoreflectonandrevisetheiranswers(Azizand Kenford,

2004;Fairweather-SchmidtandAnstey,2012).However,athome,

apersonmaybeinfluencedbyothers,evenwhenthereareexplicit

instructionsstatingthatallresponsesmustbetheirownand/orno

discussionwithothersispermitted(Alfanoetal.,1993;O’Carroll

Inaddition,prevalenceratesvariedaccordingtothepost-injury

interval,withtheprevalenceofMDD/dysthymiasteadilyincreasing

inthefirst5yearspost-TBI(21–27–43%)andsubsequently

declin-ingtoalevelsimilartothatseenintheearlypost-injuryperiod

(22%).Incontrast,thenumberof‘cases’ofdepressionidentified

using questionnaires steadily increased – although not

signifi-cantly–fromtheacute/post-acuteperioduntilthemedium-term

(33–41%),whenit plateaued.These findingshighlight temporal

changestotheriskofdeveloping depression,possiblyreflecting

thechanginginfluenceofanumberofdifferentvariables(e.g.,

neu-ronal/neurochemical,psychological,social).Theyalsounderscore

theimportanceofmonitoringindividualsoveranextendedperiod

oftime andproviding ongoing accesstomental healthsupport

services.

Unfortunately, injury severity could only be examined in a

basicway,duetothelimitedavailabilityofdata.Theseanalyses

revealedthatmildTBIwasassociatedwiththelowestprevalence

ofMDDanddysthymia(16%);aratethatwassignificantlylower

thanthatseeninmixedsamples(30%).Althoughlowerthanthe

rateforsevereTBI(30%),thisdifferencewasnotsignificant,

pos-siblyduetothesmallsamplesize.Thesefindingscontrastedwith

thosefromself-reportmeasures,whichrevealedsignificantlymore

casesofdepressionfollowingmildTBI(64%)(mixedsamples=36%;

severeTBI=39%).There area number of factorsthat may

con-tributetothelatter finding.Forexample, severeTBIsare more

frequentlyassociatedwithmemoryproblemsandimpaired

self-awareness (Evans et al.,2005), which mayreduce the number

ofsymptomsthat areendorsedonquestionnaires(Malec etal.,

2007).Alternatively,personswithmildTBImaybeexaggerating

theirsymptomsfor financialgain(Kurtz etal.,2007).However,

it isalso possiblethat peopledo not receiveadequate

psycho-educationalsupportfollowingamildTBI,whichmayincreasetheir

distressor,intheabsenceofsignificantphysicalinjuries,theymay

focusonotherproblems(Malecetal.,2007).Therefore,even

fol-lowingmildTBI,individualsshouldbemonitoredtoensurethat

thesesymptomsdonotinterferewiththeirrecoveryorqualityof

life.

Relativetoothers,peoplearemorelikelytobediagnosedwith

MDD/dysthymia (OR=1.66), or experience clinically significant

levelsofdepression(OR=3.41)followingaTBI.Evenwhen

con-tributingfactors,suchaspainandhospital/medicalprocedures,are

takenintoaccount,aTBIprovidesanadditional,uniquesourceof

psychologicaldistress.Similarly,TBIgroupswerenearlyeighttimes

morelikelytobediagnosedwithMDD/dysthymia,andoverfive

timesmorelikelytobeclassifiedashavingclinicallysignificant

lev-elsofdepression,thanmembersofthegeneralcommunity.Lastly,

thefamily/friends/caregiversofthose whohavesustaineda TBI

reportedsufferingfromhighlevelsofdepression(23%),indicating

thattheyarealsoatconsiderableriskofdevelopingdepression,and

mayrequiremonitoringandtreatmenttooptimisetheiroutcomes

(Erghetal.,2002;Ponsfordetal.,2010).

Finally, when the full spectrum of self-reported depressive

symptomswasexamined–rangingfromnormaltosevere

depres-sion–itwasfoundthatindividualsexperiencedmoderatelyhigher

levelsofdepressionfollowingaTBIthantheirpeers.Thisfinding

wasimpactedbythesourceofthecontrols,withthelargest

differ-enceassociatedwithpeopleresidinginthecommunity,followed

bysignificantothers and then medicalcontrols.This highlights

theimportance of selectingthe appropriate norms orcontrols,

basedontheclinicalorresearchquestion,toenabledepression

tobeexaminedindependentlyofarangeofconfoundingvariables.

Specifically,medicalcontrolsendeavourtocontrolforpain,other

injuriesandhospitalroutines/procedures(Ponsfordetal.,2011);

significantothers control for the increasedlevels of stress and

emotionaldistressrelatedtoafamilymember’sTBI(Ponsfordand

Schönberger,2010);andcommunitycontrolsenableanassessment

ofdepressionrelativetopeoplewhoareresidinginthegeneral

community(Wacholderetal.,1992).

4.1. Limitationsandrecommendationsforfutureresearch

Thereareanumberoflimitationsthatwarrantconsideration.

First,althoughpriorTBIsandpsychiatrichistorymaycontribute

tothedevelopmentofdepression(Ansteyetal.,2004;Fannetal.,

2002),thesedatawereoftennotreported,orprovidedinaform

thatcouldnotbecompared(e.g.,nomajorpsychiatricillness,no

priorhospitalisation,notcurrentlyusingmedication);precluding

ananalysisofthesevariables.Second,datawereoftencombined

acrossdifferentinjurycategories(mild,moderate,severe),which

meantthat it wasonly possible toundertake a coarse-grained

examinationofTBIseverity.Third,itwasnotpossibletoexamine

theimpactofmedicationsontheprevalenceofdepressionbecause

veryfewstudiesreportedthesedata.Anti-depressantmedications

arelikelytoreducesymptomsandresultinlowerprevalence

esti-mates,makingthis animportantvariabletoconsider.Fourth,it

ispossiblethatgendermayhaveimpactedontheprevalenceof

depression followingTBI becausefemales have a higherrisk of

developingdepression (Kessleretal.,1993),althoughmalesare

morelikelytosustainaTBI(Ansteyetal.,2004).Ofthestudies

thatreportedtheprevalenceofMDD/dysthymia,onlysixprovided

gender-baseddata.Whiletherewasatrendforfemales tohave

higherratesofMDD/dysthymiainthesestudies(47%vs34%),the

differencewasnotsignificant.

Itisrecommendedthatresearchersreportparticipants’history

ofTBIs/psychiatricdiagnosesand,ideally,providesubgroupdata

(mild/moderate/severeTBI;medicatedvsunmedicated;malesvs

females),sothatthesevariablescanbeexaminedingreaterdetail.

Multivariateanalysesofthedatawerenotpossibleduetothe

vari-abilityintheresearchdesignsthathavebeenusedtoexaminethe

prevalenceof depressionfollowing TBI.Alarge-scalestudythat

evaluatestheimpactofthesevariablesisnowneeded.

5. Conclusions

Thereis now asubstantial body of researchthat has

exam-inedtheprevalenceofdepressionfollowingTBI,buttheestimates

from individual studies vary widely. The challenges involved

in interpreting these disparate findings are well-known, with

researchersrepeatedlynotingthatnumerousmethodological

dif-ferences have made it difficult to compare findings and draw

definitiveconclusions(Koponenetal.,2011;Tsaousidesetal.,2013;

Whelan-Goodinsonetal.,2009a).

Overall,theprevalenceofformallydiagnosedMDD and

dys-thymiawas27%,althoughthisvarieddependingonwhetherICD-10

(14%),DSM-IV(25%)orDSM-III(47%)diagnosticcriteriawereused.

Thedifferentinterviewschedulesalsoyieldedvariableprevalence

rates,rangingfrom16%to54%.MDD/dysthymiawasmore

preva-lentbetween2and5yearspost-injury(43%),comparedwiththe

acute/post-acuteperiod(<6months;21%),short-term(≥6months

to<2years;27%),andlong-term(≥5years;22%).Inaddition,the

prevalenceofMDD/dysthymiawassubstantiallyhigherfollowing

severeTBI(30%)thanmildTBI(16%),althoughthisdifferencewas

notsignificant.Moreover,MDD/dysthymiaismorecommon

fol-lowing TBI than it is afterother injuries (OR=1.55) and inthe

generalcommunity(OR=7.69).

Theoverallprevalenceofclinicallysignificant‘cases’of

depres-sion,assessedusingquestionnaires,was38%;althoughthisrate

varied considerably depending on the measure that was used

(2–48%)andthemethodofadministration(phone:26%;mail:46%).

UnlikeMDDanddysthymia,self-reporteddepressioncontinuedto

increaseover time(from 33%to42%)andinjury severityhad a

TBI(64%,severeTBI=39%).Theoddsofdevelopingdepressionafter

aTBIaremorethanfive,threeandtwotimeshigherthanthose

liv-inginthegeneralcommunity,thefamilyandfriendsoftheperson

whosustainedtheTBI,andothermedicalpatients,respectively.

AppendixA. Supplementarydata

Supplementarydataassociatedwiththisarticlecanbefound,

in the online version, at http://dx.doi.org/10.1016/j.neubiorev.

2014.07.007.

References*

*Al-Adawi,S.,Dorvlo,A.S.,Al-Naamani,A.,Glenn,M.B.,Karamouz,N.,Chae,H., Zaidan,Z.A.,Burke,D.T.,2007.TheineffectivenessoftheHospitalAnxietyand DepressionScalefordiagnosisinanOmanitraumaticbraininjuredpopulation. BrainInj.21(4),385–393.

*Al-Adawi,S.,Dorvlo,A.S.S.,Burke,D.T.,Huynh,C.C.,Jacob,L.,Knight,R.,Shah,M.K., Al-Hussaini,A.A.,2004.Apathyanddepressionincross-culturalsurvivorsof traumaticbraininjury.J.NeuropsychiatryClin.Neurosci.16(4),435–442. *Al-Adawi,S.,Powell,J.H.,Greenwood,R.J.,1998.Motivationaldeficitsafterbrain

injury:aneuropsychologicalapproachusingnewassessmenttechniques. Neu-ropsychology12(1),115–124.

*Alexander,M.P.,1992.Neuropsychiatriccorrelatesofpersistentpostconcussive syndrome.J.HeadTraumaRehabil.7(2),60–69.

*Alfano,D.P.,2006.Emotionalandpain-relatedfactorsinneuropsychological assess-mentfollowingmildtraumaticbraininjury.BrainCogn.60(2),194–196. *Alfano,D.P.,Neilson,P.M.,Fink,M.P.,1993.Long-termpsychosocialadjustment

followingheadorspinalcordinjury.NeuropsychiatryNeuropsychol.Behav. Neurol.6(2),117–125.

AmericanPsychiatricAssociation,1987.DiagnosticandStatisticalManualofMental Disorders,3rded.AmericanPsychiatricAssociation,Washington,DC. AmericanPsychiatricAssociation,2000.HandbookofPsychiatricMeasures.

Ameri-canPsychiatricPublishing,Washington,DC.

AmericanPsychiatricAssociation,2001.DiagnosticandStatisticalManualof Men-talDisorders(DSM-IV),4thed.AmericanPsychiatricPublishing,Washington, DC.

AmericanPsychiatricAssociation,2013.DiagnosticandStatisticalManualofMental Disorders,5thed.AmericanPsychiatricPublishing,Arlington,VA.

*Andelic,N.,Hammergren,N.,Bautz-Holter,E.,Sveen,U.,Brunborg,C.,Roe,C.,2009. Functionaloutcomeandhealth-relatedqualityoflife10yearsafter moderate-to-severetraumaticbraininjury.ActaNeurol.Scand.120(1),16–23. *Anson,K.,Ponsford,J.,2006.Copingandemotionaladjustmentfollowingtraumatic

braininjury.J.HeadTraumaRehabil.21(3),248–259.

Anstey,K.J.,Butterworth,P.,Jorm,A.F.,Christensen,H.,Rodgers,B.,Windsor,T.D., 2004.Apopulationsurveyfoundanassociationbetweenself-reportsof trau-maticbraininjuryandincreasedpsychiatricsymptoms.J.Clin.Epidemiol.57 (11),1202–1209.

AustralianBureauofStatistics,2008.4326.0:NationalHealthSurvey:Summaryof Results.ABS,Canberra.

Aziz,M.,Kenford,S.,2004.Comparabilityoftelephoneandface-to-faceinterviews inassessingpatientswithposttraumaticstressdisorder.J.Psychiatr.Pract.10 (5),307–313.

*Baumann,C.R.,Werth,E.,Stocker,R.,Ludwig,S.,Bassetti,C.L.,2007.Sleep–wake disturbances6monthsaftertraumaticbraininjury:aprospectivestudy.Brain 130(7),1873–1883.

*Bay,E.,Hagerty,B.M.,Williams,R.A.,2007.Depressivesymptomatologyafter mild-to-moderatetraumaticbraininjury:acomparisonofthreemeasures.Arch. Psychiatr.Nurs.21(1),2–11.

Bay,E.,Kalpakjian,C.,Giordani,B.,2012.Determinantsofsubjectivememory com-plaintsincommunity-dwellingadultswithmild-to-moderatetraumaticbrain injury.BrainInj.26(7/8),941–949.

*Beaupre,M.,DeGuise,E.,McKerral,M.,2012.TheAssociationbetweenpain-related variables,emotionalfactors,andattentionalfunctioningfollowingmild trau-maticbraininjury.Rehabil.Res.Pract.2012,1–10.

Beck,A.T.,Steer,R.A.,Brown,G.K.,1996.ManualfortheBeckDepressionInventory. ThePsychologicalCorporation,SanAntonio,TX.

*Belmont,A.,Agar,N.,Azouvi,P.,2009.Subjectivefatigue,mentaleffort,and atten-tiondeficitsafterseveretraumaticbraininjury.Neurorehabil.NeuralRepair23 (9),939–944.

*Bombardier,C.H.,Fann,J.R.,Temkin,N.R.,Esselman,P.C.,Barber,J.,Dikmen,S.S., 2010.Ratesofmajordepressivedisorderandclinicaloutcomesfollowing trau-maticbraininjury.J.Am.Med.Assoc.303(19),1938–1945.

Borenstein,M.,Hedges,L.V.,Higgins,J.P.T.,2009.IntroductiontoMeta-analysis. Wiley,Hoboken,NJ,USA.

Boyles,A.L.,Harris,S.F.,Rooney,A.A.,Thayer,K.A.,2011.ForestPlotViewer:anew graphingtool.Epidemiology22(5),746–747.

∗ _{Referencesmarkedwithanasteriskindicatestudiesincludedinthe}

meta-analyses.

*Brown,S.A.,McCauley,S.R.,Levin,H.S.,Contant,C.,Boake,C.,2004.Perceptionof healthandqualityoflifeinminoritiesaftermild-to-moderatetraumaticbrain injury.Appl.Neuropsychol.11(1),54–64.

*Bryant,R.A.,Marosszeky,J.E.,Crooks,J.,Baguley,I.J.,Gurka,J.A.,2001.Posttraumatic stressdisorderandpsychosocialfunctioningafterseveretraumaticbraininjury. J.Nerv.Ment.Dis.189(2),109–113.

*Bryant,R.A.,O’Donnell,M.L.,Creamer,M.,McFarlane,A.C.,Clark,C.R.,Silove,D., 2010.Thepsychiatricsequelaeoftraumaticinjury.Am.J.Psychiatry167(3), 312–320.

*Bush,B.A.,Novack,T.A.,Schneider,J.J.,Madan,A.,2004.Depressionfollowing trau-maticbraininjury:thevalidityoftheCES-Dasabriefscreeningdevice.J.Clin. Psychol.Med.Settings11(3),195–201.

*Bushnik,T.,Englander,J.,Wright,J.,2008.Theexperienceoffatigueinthefirst2 yearsaftermoderate-to-severetraumaticbraininjury:apreliminaryreport.J. HeadTraumaRehabil.23(1),17–24.

Cantor,J.B.,Bushnik,T.A.,Cicerone,K.,Dijkers,M.P.,Gordon,W.,Hammond,F.M., Kolakowsky-Hayner,S.A.,Lequerica,A.,Nguyen,M.,Spielman,L.A.,2012. Insom-nia,fatigue,andsleepinessinthefirst2yearsaftertraumaticbraininjury:an NIDRRTBImodelsystemmodulestudy.J.HeadTraumaRehabil.27(6),E1–E14. *Capizzano,A.A.,Jorge,R.E.,Robinson,R.G.,2010.Limbicmetabolicabnormalitiesin remotetraumaticbraininjuryandcorrelationwithpsychiatricmorbidityand socialfunctioning.J.NeuropsychiatryClin.Neurosci.22(4),370–377. *Carroll,E.,Coetzer,R.,2011.Identity,griefandself-awarenessaftertraumaticbrain

injury.Neuropsychol.Rehabil.21(3),289–305.

*Chalton,L.D.,McMillan,T.M.,2009.Can‘partial’PTSDexplaindifferencesin diagno-sisofPTSDbyquestionnaireself-reportandinterviewafterheadinjury?Brain Inj.23(2),77–82.

*Chamelian,L.,Reis,M.,Feinstein,A., 2004.Six-month recoveryfrommildto moderatetraumaticbraininjury:theroleofAPOE-␧4allele.Brain127(12), 2621–2628.

Chaput,G.,Giguère,J.-F.,Chauny,J.-M.,Denis,R.,Lavigne,G.,2009.Relationship amongsubjectivesleepcomplaints,headaches,andmoodalterationsfollowing amildtraumaticbraininjury.SleepMed.10(7),713–716.

*Chen,J.-K.,Johnston,K.M.,Petrides,M.,Ptito,A.,2008.Neuralsubstratesof symp-tomsof depressionfollowing concussionin maleathleteswith persisting postconcussionsymptoms.Arch.Gen.Psychiatry65(1),81–89.

*Chiu,W.T.,Huang,S.J.,Hwang,H.F.,Tsauo,J.Y.,Chen,C.F.,Tsai,S.H.,Lin,M.R.,2006. UseoftheWHOQOL-BREFforevaluatingpersonswithtraumaticbraininjury.J. Neurotrauma23(11),1609–1620.

*Clarke,L.A.,Genat,R.C.,Anderson,J.F.I.,2012.Long-termcognitivecomplaintand post-concussivesymptomsfollowingmildtraumaticbraininjury:theroleof cognitiveandaffectivefactors.BrainInj.26(3),298–307.

Cohen,J.,1992.Apowerprimer.Psychol.Bull.112(1),155–159.

*Cook,K.F.,Bombardier,C.H.,Bamer,A.M.,Choi,S.W.,Kroenke,K.,Fann,J.R.,2011.Do somaticandcognitivesymptomsoftraumaticbraininjuryconfounddepression screening?Arch.Phys.Med.Rehabil.92,818–823.

*Curran,C.A.,Ponsford,J.,Crowe,S.,2000.Copingstrategiesandemotionaloutcome followingtraumaticbraininjury:acomparisonwithorthopedicpatients.J.Head TraumaRehabil.15(6),1256–1274.

*deAlmeidaLima,D.P.,SimaoFilho,C.,AbibSde,C.,deFigueiredo,L.F.,2008. Qual-ityoflifeandneuropsychologicalchangesinmildheadtrauma.Lateanalysis andcorrelationwithS100BproteinandcranialCTscanperformedathospital admission.Injury39(5),604–611.

*Deb,S.,Lyons,I.,Koutzoukis,C.,Ali,I.,McCarthy,G.,1999.Rateofpsychiatricillness 1yearaftertraumaticbraininjury.Am.J.Psychiatry156(3),374–378. *Diaz,A.P.,Schwarzbold,M.L.,Thais,M.E.,Hohl,A.,Bertotti,M.M.,Schmoeller,R.,

Nunes,J.C.,Prediger,R.,Linhares,M.N.,Guarnieri,R.,Walz,R.,2012.Psychiatric disordersandhealth-relatedqualityoflifeafterseveretraumaticbraininjury: aprospectivestudy.J.Neurotrauma29(6),1029–1037.

*Dikmen,S.S.,Bombardier,C.H.,MacHamer,J.E.,Fann,J.R.,Temkin,N.R.,2004. Natu-ralhistoryofdepressionintraumaticbraininjury.Arch.Phys.Med.Rehabil.85 (9),1457–1464.

Dikmen,S.S.,Machamer,J.E.,Powell,J.M.,Temkin,N.R.,2003.Outcome3to5years aftermoderatetoseveretraumaticbraininjury.Arch.Phys.Med.Rehabil.84 (10),1449–1457.

*Draper,K.,Ponsford,J.,Schönberger,M.,2007.Psychosocialandemotional out-comes10yearsfollowingtraumaticbraininjury.J.HeadTraumaRehabil.22(5), 278–287.

Endicott,J.,Spitzer,R.L.,1978.Adiagnosticinterview:thescheduleforaffective disordersandschizophrenia.Arch.Gen.Psychiatry35(7),837–844.

*Englander,J.,Bushnik,T.,Oggins,J.,Katznelson,L.,2010.Fatigueaftertraumatic braininjury:associationwithneuroendocrine,sleep,depressionandother fac-tors.BrainInj.24(12),1379–1388.

Ergh,T.C.,Rapport,L.J.,Coleman,R.D.,Hanks,R.A.,2002.Predictorsofcaregiverand familyfunctioningfollowingtraumaticbraininjury:socialsupportmoderates caregiverdistress.J.HeadTraumaRehabil.17(2),155–174.

*Evans,C.C.,Sherer,M.,Nick,T.G.,Nakase-Richardson,R.,Yablon,S.A.,2005.Early impairedself-awareness,depression,andsubjectivewell-beingfollowing trau-maticbraininjury.J.HeadTraumaRehabil.20(6),488–500.

*Failla,M.D.,Burkhardt,J.N.,Miller,M.A.,Scanlon,J.M.,Conley,Y.P.,Ferrell,R.E., Wagner,A.K.,2013.VariantsofSLC6A4indepressionriskfollowingsevereTBI. BrainInj.27(6),696–706.

Fairweather-Schmidt,A.K.,Anstey,K.J.,2012.Prevalenceofsuicidalbehaviours intwoAustraliangeneralpopulationsurveys:methodologicalconsiderations when comparing across studies. Soc. PsychiatryPsychiatr. Epidemiol. 47, 515–522.

Fann,J.R.,Leonetti,A.,Jaffe,K.,Katon,W.J.,Cumming,P.,Thompson,R.S.,2002. Psy-chiatricillnessandsubsequenttraumaticbraininjury:acasecontrolstudy.J. Neurol.Neurosurg.Psychiatry72,615–620.

Fann,J.R.,Bombardier,C.H.,Dikmen,S.,Esselman,P.,Warms,C.A.,Pelzer,E.,Rau, H.,Temkin,N.,2005.Validityofthepatienthealthquestionnaire-9inassessing depressionfollowingtraumaticbraininjury.J.HeadTraumaRehabil.20(6), 501–511.

*Fann,J.R.,Katon,W.J.,Uomoto,J.M.,Esselman,P.C.,1995.Psychiatricdisordersand functionaldisabilityinoutpatientswithtraumaticbraininjuries.Am.J. Psychi-atry152(10),1493–1499.

*Fedoroff,J.P.,Starkstein,S.E.,Forrester,A.W.,Geisler,F.H.,1992.Depressionin patientswithacutetraumaticbraininjury.Am.J.Psychiatry149(7),918–923. *Findler,M.,Cantor,J.,Haddad,L.,Gordon,W.,Ashman,T.,2001.Thereliabilityand

validityoftheSF-36healthsurveyquestionnaireforusewithindividualswith traumaticbraininjury.BrainInj.15(8),715–723.

First,M.B.,2010.ParadigmshiftsandthedevelopmentoftheDiagnosticand Statis-ticalManualofMentalDisorder:pastexperienceandfutureaspirations.Can.J. Psychiatry55(11),692–700.

First,M.B.,2009.HarmonisationofICD-11andDSM-V:opportunitiesandchallenges. Br.J.Psychiatry195(5),382–390.

First,M.B.,Spitzer,R.L.,Gibbon,M.,Williams,J.B.,1997.StructuredClinicalInterview forDSM-IVAxisIDisorders,ClinicianVersion(SCID-CV).AmericanPsychiatric Association,Washington,DC.

*Forslund,M.V.,Roe,C.,Sigurdardottir,S.,Andelic,N.,2013.Predictinghealth-related qualityoflife2yearsaftermoderate-to-severetraumaticbraininjury.Acta Neurol.Scand.128,220–227.

*Gagnon,J.,Bouchard,M.-A.,Rainville,C.,Lecours,S.,St-Amand,J.,2006.Inhibition andobjectrelationsinborderlinepersonalitytraitsaftertraumaticbraininjury. BrainInj.20(1),67–81.

*Glenn,M.B.,O’Neil-Pirozzi,T.,Goldstein,R.,Burke,D.,Jacob,L.,2001.Depression amongstoutpatientswithtraumaticbraininjury.BrainInj.15(9),811–818. *Goldstein,F.C.,Levin,H.S.,Goldman,W.P.,Clark,A.N.,Altonen,T.K.,2001.Cognitive

andneurobehavioralfunctioningaftermildversusmoderatetraumaticbrain injuryinolderadults.J.Int.Neuropsychol.Soc.7(3),373–383.

*Gomez-Hernandez,R.,Max,J.E.,Kosier,T.,Paradiso,S.,Robinson,R.G.,1997.Social impairmentanddepressionaftertraumaticbraininjury.Arch.Phys.Med. Reha-bil.78(12),1321–1326.

*Gould,K.R.,Ponsford,J.,Johnston,L.,Schönberger,M.,2011.Thenature,frequency andcourseofpsychiatricdisordersinthefirstyearaftertraumaticbraininjury: aprospectivestudy.Psychol.Med.,1–11.

Green,A.,Felmingham,K.,Baguley,I.J.,Slewa-Younan,S.,Simpson,S.,2001.The clinicalutilityoftheBeckDepressionInventoryaftertraumaticbraininjury. BrainInj.15(12),1021–1028.

Gunstad,J.,Suhr,J.A.,2001.“Expectationasetilogy”Versus“thegoodolddays”: postconcussionsyndromesymptomreportinginathletes,headachesufferers, anddepressedindividuals.J.Int.Neuropsychol.Soc.7(3),323–333.

Hamilton,M.,1960.Aratingscalefordepression.J.Neurol.Neurosurg.Psychiatry 23(1),56.

*Hart,T.,Brenner,L.,Clark,A.N.,Bogner,J.A.,Novack,T.A.,Chervoneva,I., Nakase-Richardson,R.,Arango-Lasprilla,J.C.,2011.Majorandminordepressionafter traumaticbraininjury.Arch.Phys.Med.Rehabil.92(8),1211–1219. *Hart,T.,Hoffman,J.M.,Pretz,C.,Kennedy,R.,Clark,A.N.,Brenner,L.A.,2012.A

longitudinalstudyofmajorandminordepressionfollowingtraumaticbrain injury.Arch.Phys.Med.Rehabil.93(8),1343–1349.

*Hawthorne,G.,Gruen,R.L.,Kaye,A.H.,2009.Traumaticbraininjuryand long-termqualityoflife:findingsfromanAustralianstudy.J.Neurotrauma26(10), 1623–1633.

Helmchen,H.,2013.Differentconceptionsofmentalillness:consequencesforthe associationwithpatients.Front.Psychol.4(269),1–5.

*Henry,J.D.,Phillips,L.H.,Crawford,J.R.,Theodorou,G.,Summers,F.,2006. Cogni-tiveandpsychosocialcorrelatesofalexithymiafollowingtraumaticbraininjury. Neuropsychologia44(1),62–72.

*Herrmann,N.,Rapoport,M.J.,Rajaram, R.D.,Chan,F.,Kiss,A.,Ma,A.K., Fein-stein,A.,McCullagh,S.,Lanctot,K.L.,2009.FactoranalysisoftheRivermead Post-ConcussionSymptomsQuestionnaireinmild-to-moderatetraumaticbrain injurypatients.J.NeuropsychiatryClin.Neurosci.21(2),181–188.

Hibbard,M.R.,Uysal,S.,Kepler,K.,Bogdany,J.,Silver,J.,1998.AxisIpsychopathology inindividualswithtraumaticbraininjury.J.HeadTraumaRehabil.13(4),24–39. Hilsabeck,R.C.,Gouvier,D.Wm.,Bolter,J.F.,1998.Reconstructivememorybiasin recallofneuropsychologicalsymptomatology.J.Clin.Exp.Neuropsychol.20(3), 328–338.

Hopkins,W.,2002.Anewviewofstatistics:ascaleofmagnitudesforeffectstatistics, Retrieved08.03.14.

Hozo,S.P.,Djulbegovic,B.,Hozo,I.,2005.Estimatingthemeanandvariancefrom themedian,range,andthesizeofasample.BMCMed.Res.Methodol.5. *Huang,D.B.,Spiga,R.,Koo,H.,2005.UseoftheZungdepressionscaleinpatients

withtraumaticbraininjury:1yearpost-injury.BrainInj.19(11),903–908. *Hudak,A.,Hynan,L.S.,Harper,C.R.,Diaz-Arrastia,R.,2012.Associationofdepressive

symptomswithfunctionaloutcomeaftertraumaticbraininjury.J.HeadTrauma Rehabil.27(2),87–98.

*Hudak,A.,Warner,M.,MarquezdelaPlata,C.,Moore,C.,Harper,C.,Diaz-Arrastia, R.,2011.Brainmorphometrychangesanddepressivesymptomsaftertraumatic braininjury.PsychiatryRes.191(3),160–165.

Iverson,G.L.,Brooks,B.L.,Ashton,V.L.,Lange,R.T.,2010a.Interviewversus question-nairesymptomreportinginpeoplewiththepostconcussionsyndrome.J.Head TraumaRehabil.25(1),23–30.

Iverson,G.L.,Lange,R.T.,Brooks,B.L.,Rennison,V.L.,2010b.“Goodolddays”bias followingmildtraumaticbraininjury.Clin.Neuropsychol.24(1),17–37. *Jorge,R.E.,Robinson,R.G.,Arndt,S.,1993a.Depressionfollowingtraumaticbrain

injury:a1yearlongitudinalstudy.J.Affect.Disord.27,233–243.

Jorge,R.E.,Robinson,R.G.,Arndt,S.V.,Forrester,A.W.,Geisler,F.,Starkstein,S.E., 1993b.Comparisonbetweenacute-anddelayed-onsetdepressionfollowing traumaticbraininjury.J.NeuropsychiatryClin.Neurosci.5,43–49.

Jorge,R.E.,Robinson,R.G.,2002.Mooddisordersfollowingtraumaticbraininjury. NeuroRehabilitation17,311–324.

*Jorge,R.E.,Robinson,R.G.,Moser,D.,Tateno,A.,Crespo-Facorro,B.,Arndt,S.,2004. Majordepressionfollowingtraumaticbraininjury.Arch.Gen.Psychiatry61(1), 42–50.

Jorge,R.E.,Starkstein,S.E.,2005.Pathophysiologicaspectsofmajordepression fol-lowingtraumaticbraininjury.J.HeadTraumaRehabil.6,475–487.

Juengst,S.,Skidmore,E.,Arenth,P.M.,Niyonkuru,C.,Raina,K.D.,2013.Unique con-tributionoffatiguetodisabilityincommunity-dwellingadultswithtraumatic braininjury.Arch.Phys.Med.Rehabil.94(1),74–79.

Kelley,E.,Sullivan,C.,Loughlin,J.K.,Hutson,L.,Dahdah,M.N.,Long,M.K.,Schwab, K.A.,Poole,J.H.,2012.Self-awarenessandneurobehavioraloutcomes,5years ormore after moderate to severebrain injury. J. HeadTrauma Rehabil., http://dx.doi.org/10.1097/HTR.0b013e31826db6b9(advance online publica-tion).

*Kempf,J.,Werth,E.,Kaiser,P.R.,Bassetti,C.L.,Baumann,C.R.,2010.Sleep–wake dis-turbances3yearsaftertraumaticbraininjury.J.Neurol.Neurosurg.Psychiatry 81(12),1402–1405.

*Kennedy,R.E.,Livingston,L.,Riddick,A.,Marwitz,J.H.,Kreutzer,J.S.,Zasler,N.D., 2005.Evaluationoftheneurobehavioralfunctioninginventoryasa depres-sionscreeningtoolaftertraumaticbraininjury.J.HeadTraumaRehabil.20(6), 512–526.

Kessler,R.C.,McGonagle,K.A.,Swartz,M.,Blazer,D.G.,Nelson,C.B.,1993.Sexand depressionintheNationalComorbiditySurvey.I.Lifetimeprevalence,chronicity andrecurrence.J.Affect.Disord.29(2/3),85–96.

Kim,E.,Lauterbach,E.C.,Reeve,A.,Arciniegas,D.B.,Coburn,K.L.,Mendez,M.F., Rum-mans,T.A.,Coffey,E.C.,2007.Neuropsychiatriccomplicationsoftraumaticbrain injury:acriticalreviewoftheliterature(areportbytheANPAcommitteeon research).J.NeuropsychiatryClin.Neurosci.19(2),106–127.

*King,N.S.,Kirwilliam,S.,2011.Permanentpost-concussionsymptomsaftermild headinjury.BrainInj.25(5),462–470.

*Kinsella,G.,Moran,C.,Ford,B.,Ponsford,J.,1988.Emotionaldisorderandits assess-mentwithinthesevereheadinjuredpopulation.Psychol.Med.18(1),57–63. *Konrad, C., Geburek, A.J., Rist, F., Blumenroth, H., Fischer, B., Husstedt, I.,

Arolt,V.,Schiffbauer,H.,Lohmann,H.,2011.Long-termcognitiveand emo-tional consequencesofmildtraumatic braininjury.Psychol. Med.41(6), 1197–1211.

*Koponen,S.,Taiminen,T.,Hiekkanen,H.,Tenovuo,O.,2011.AxisIandIIpsychiatric disordersinpatientswithtraumaticbraininjury:a12-monthfollow-upstudy. BrainInj.25(11),1029–1034.

*Koponen,S.,Taiminen,T.,Portin,R.,Himanen,L.,Isoniemi,H.,Heinonen,H.,Hinkka, S.,Tenovuo,O.,2002.AxisIandIIpsychiatricdisordersaftertraumaticbrain injury:a30-yearfollow-upstudy.Am.J.Psychiatry159(8),1315–1321. *Kreutzer,J.S.,Seel,R.T.,Gourley,E.,2001.Theprevalenceandsymptomratesof

depressionaftertraumaticbraininjury:acomprehensiveexamination.Brain Inj.15(7),563–576.

Kreutzer,J.S.,Seel,R.T.,Marwitz,J.H.,1999.NeurobehavioralFunctioningInventory: NFI.PsychologicalCorporation,SanAntonio,Texas.

Kroenke,K.,Spitzer,R.L.,Williams,J.B.W.,2001.ThePHQ-9.Validityofabrief depres-sionseveritymeasure.J.Gen.Intern.Med.16,606–613.

Kumar,A.,Cook,I.A.,2002.Whitematterinjury,neuralconnectivityandthe patho-physiologyofpsychiatricdisorders.Dev.Neurosci.24,255–261.

Kurtz,J.E.,Shealy,S.E.,Putnam,S.H.,2007.Anotherlookattheparadoxicalseverity effectsinheadinjurywiththepersonalityassessmentinventory.J.Pers.Assess. 88(1),66–73.

Lewis,G.,Pelosi,A.J.,Araya,R.,Dunn,G.,1992.Measuringpsychiatricdisorderin thecommunity:astandardizedassessmentforusebylayinterviewers.Psychol. Med.22,465–486.

*Lin,M.R.,Chiu,W.T.,Chen,Y.J.,Yu,W.Y.,Huang,S.J.,Tsai,M.D.,2010.Longitudinal changesinthehealth-relatedqualityoflifeduringthefirstyearaftertraumatic braininjury.Arch.Phys.Med.Rehabil.91(3),474–480.

Lipsey,M.W.,Wilson,D.B.,2001.PracticalMetaAnalysis.AppliedSocialResearch MethodsSeries,vol.49.Sage,ThousandOaks,CA.

*Malec,J.F.,Brown,A.W.,Moessner,A.M.,Stump,T.E.,Monahan,P.,2010.A prelimi-narymodelforposttraumaticbraininjurydepression.Arch.Phys.Med.Rehabil. 91(7),1087–1097.

Malec,J.F.,Testa,J.A.,Rush,B.K.,Brown,A.W.,Moessner,A.M.,2007.Self-assessment ofimpairment,impairedself-awareness,anddepressionaftertraumaticbrain injury.J.HeadTraumaRehabil.22(3),156–166.

Mathias,J.L.,Alvaro,P.K.,2012.Prevalenceofsleepdisturbances,disorders,and problemsfollowingtraumaticbraininjury:ameta-analysis.SleepMed.13(7), 898–905.

*McCauley,S.R.,Boake,C.,Pedroza,C.,Brown,S.A.,Levin,H.S.,Goodman,H.S.,Merritt, S.G.,2005.Postconcussionaldisorder:aretheDSM-IVcriteriaanimprovement overtheICD-10?J.Nerv.Ment.Dis.193(8),540–550.

*Meares,S.,Shores,E.A.,Taylor,A.J.,Batchelor,J.,Bryant,R.A.,Baguley,I.J.,Chapman, J.,Gurka,J.,Marosszeky,J.E.,2011.Theprospectivecourseofpostconcussion syndrome:theroleofmildtraumaticbraininjury.Neuropsychology25(4), 454–465.