The contributions of early adverse experiences and trajectories of respiratory sinus arrhythmia on

16 Pages·2014·0.34 MB·English

DevelopmentandPsychopathology26(2014),901–916
#CambridgeUniversityPress2014
doi:10.1017/S095457941400056X
The contributions of early adverse experiences and trajectories
of respiratory sinus arrhythmia on the development of
neurobehavioral disinhibition among children with prenatal
substance exposure
ELISABETHCONRADT,a,bDAVIDDEGARMO,c,dPHILFISHER,c,dBEAUABAR,aBARRYM.LESTER,a,b,d
LINDAL.LAGASSE,a,b,dSEETHASHANKARAN,eHENRIETTABADA,fCHARLESR.BAUER,g
TONIM.WHITAKER,hANDJANEA.HAMMONDi
aWomen&InfantsHospitalofRhodeIsland;bWarrenAlpertMedicalSchoolofBrownUniversity;cOregonSocialLearningCenter;
dUniversityofOregon;eWayneStateUniversitySchoolofMedicine;fUniversityofKentuckyCollegeofMedicine;gUniversityof
Miami;hUniversityofTennessee;andiResearchTriangleInstitute
Abstract
Neurobehavioraldisinhibition(ND)isacomplexconditionreflectingawiderangeofproblemsinvolvingdifficultieswithemotionregulationand
behaviorcontrol.Respiratorysinusarrhythmia(RSA)isaphysiologicalcorrelateofemotionregulationthathasbeenstudiedinavarietyofat-riskpopulations;
however,therearenostudiesofRSAinchildrenwithND.Dataweredrawnfromaprospectivelongitudinalstudyofprenatalsubstanceexposurethat
included1,073participants.BaselineRSAandRSAreactivitytoanattention-demandingtaskwereassessedat3,4,5,and6years.NDwasassessedatages
8/9,11,and13/14yearsviabehavioraldysregulationandexecutivedysfunctioncompositemeasures.Greaterexposuretoearlyadversitywasrelatedto
lessRSAreactivityat3years,increasesinRSAreactivityfromages3to6years,andincreasedbehavioraldysregulationfromages8/9to13/14.RSAreactivity
wasexaminedasamoderatoroftheassociationbetweenearlyadversityandchangesinND.AsignificantEarlyAdversity(cid:2)RSAReactivityquadratic
interactionrevealedthatchildrenwithdecelerationsinRSAreactivityexhibitedincreasesinbehavioraldysregulation,regardlessoftheirexposuretoearly
adversity.However,greaterexposuretoearlyadversitywasrelatedtogreaterincreasesinbehavioraldysregulation,butonlyifchildrenexhibited
accelerationsinRSAreactivityfromages3to6years.Theresultscontributetoourunderstandingofhowinteractionsacrossmultiplelevelsofanalysis
contributetothedevelopmentofND.
The identification of factors that contribute to the develop- example that holds promise is neurobehavioral disinhibition
ment of psychological disorders across behavioral, environ- (ND), a complex condition of emotional and behavioral
mental,andbiologicallevelsofanalysisisofcentralimpor- dysregulation reflecting awide range of problems including
tance to the field of developmental psychopathology. One oppositionaldefiantdisorder(ODD),conductdisorder,atten-
tion-deficit/hyperactivity disorder (ADHD), major depres-
sive disorder, and the initiation of substance use (Habeych,
ThisstudywassupportedbytheEuniceKennedyShriverNationalInstitute
ofChildHealthandHumanDevelopment(NICHD)NeonatalResearchNet-
work and an interinstitute agreement with the National Institute on Drug ditiontothoselistedasauthors,thefollowingindividualsandfederalfunding
Abuse (NIDA) through cooperative agreements U10-DA-024117-01 and grantscontributedtothisstudy:BrownUniversity,WarrenAlpertMedical
U10-HD-21385 (to S.S.), I10-DA-024128-06 and U10-HD-2786 (to SchoolWomen&InfantsHospitalofRhodeIsland(U10HD27904,N01
H.S.B.), U10-DA-024119-01 and U10-HD-27904 (to B.M.L.), and U10- HD23159)toCynthiaMiller-Loncar,JeanTwomey,LauraDietz,andMe-
DA-024118-01 and U10-HD-21397 (to C.R.B.); NICHD contract N01- lissaKupchak;NIDAtoVincentL.SmeriglioandNicoletteBorek;RTIIn-
HD-2-3159 (to B.M.L.); a National Research Service Award from the ternational(U10HD36790)toW.KennethPoole,AbhikDas,andDebra
NIDA, F32DA032175 (to E.C.); and partial support from NIDA Grants Fleischmann;UniversityofMiamiHoltzChildren’sHospital(GCRCM01
P20DA17952andP50DA035763(toD.D.).Thecontentissolelythere- RR16587,U10HD21397)toAnnL.Graziotti,TonyaBarriere-Perez,Janine
sponsibility of the authors and does not necessarily represent the official Closius,DiedreGallop,EdgarGarcia,SusanGauthier,WendyGriffin,Eliza-
viewsoftheNIDA,theEuniceKennedyShriverNICHD,ortheNationalIn- bethJacque,JenniferLewis,DanielA.Messinger,andYamilleValdez;Uni-
stitutesofHealth.SupportfortheMaternalLifestyleStudywasprovidedby versityofTennessee(U10HD42638)toCharlotteBursi,DelorisLee,and
theNationalInstitutesofHealththroughtheNIDAandtheEuniceKennedy LillieHughey;andWayneStateUniversityHutzelWomen’sHospitaland
ShriverNICHD,withsupplementalfundingfromtheNationalInstituteof Children’s Hospital of Michigan (U10 HD21385) to Eunice Woldt, Jay
MentalHealth,theAdministrationonChildren,Youth,andFamilies,and AnnNelson,CatherineBartholomay,LisaSulkowski,andNicoleWalker.
theCenterforSubstanceAbuseandTreatment,USDepartmentofHealth Address correspondence and reprint requests to: Elisabeth Conradt,
andHumanServices.Weareindebtedtoourmedicalandnursingcolleagues BrownCenterfortheStudyofChildrenAtRisk,50HoldenStreet,Provi-
andtheinfantsandtheirparentswhoagreedtotakepartinthisstudy.Inad- dence,RI02908;E-mail:[email protected].
901
902 E.Conradtetal.
Charles, Sclabassi, Kirisci, & Tarter, 2005; Lester et al., to challenge and increases once the challenge has resolved
2012; McNamee et al., 2008; Tarter et al., 2003). Children (Beauchaine, 2001). Moderate RSAwithdrawal in response
withNDappeartofollowfairlyconsistentnegativelongitu- to attention-demanding tasks is functional and may reflect
dinal trajectoriesthat include peer rejection, academic diffi- “optimal” engagement with the environment (Beauchaine,
culties,delinquency,andhighratesofmentalhealth,special 2001;Marcovitchetal.,2010).Incontrast,greaterRSAwith-
education, residential care, and juvenile justice system in- drawalmayinsteadbeaformofemotionallabilitysuggestive
volvement (Clausen, Landsverk, Ganger, Chadwick, & Lit- offight/flightresponding(Beauchaine,2001).
rownik,1998;Harden,2004).KeyfeaturesofNDincludedif- ItmaybeparticularlyimportanttostudychangesinRSA
ficulties with emotion regulation, impulse control (Iacono, during early childhood. Alterations in RSA associated with
Carlson, Taylor, Elkins, & McGue, 1999), and executive laterexternalizingpsychopathology,akeycomponentofthe
functioning(Tarteretal.,2003).Emotionregulationiscritical NDconstruct,appeartodevelopsometimebetweenpreschool
foradaptiverespondinginsocialsituationsandsocialaffilia- and middle childhood (Beauchaine et al., 2007). Given the
tion,keyconstructsthatareimpairedamongyouthswithex- presumed plasticity of the parasympathetic nervous system
ternalizingbehavior(Hill,Degnan,Calkins,&Keane,2006; duringearlychildhood,changesinRSAacrossthistimepe-
Vasilev,Crowell,Beauchaine,Mead,&Gatzke-Kopp,2009), riodbecauseofearlyadverseexperiencesand/orprenatalsub-
conduct disorder and ODD (Beauchaine, Gartner, & Hagen, stanceexposure maybeprognosticof laterexternalizingbe-
2000;Beauchaine,Gatzke-Kopp,&Mead,2007;Beauchaine, haviorandbehaviordysregulation(Beauchaine,2001).
Hinshaw,&Pang,2010;Beauchaine,Hong,&Marsh,2008), Previous work has focused on the parasympathetic ner-
major depressive disorder (Rottenberg, Gross, & Gotlib, vous system and the behavior dysregulation component of
2005),andADHD(Musseretal.,2011),mostofwhicharein- ND. Although there are exceptions (Musser et al., 2011),
cludedonthespectrumofND(Iaconoetal.,1999). youths prone to ND, including preschoolers with ADHD
Children exposed to substances prenatally and who have andODD(Crowelletal.,2006)andadolescents(Beauchaine
faced significant early life adversity may be particularly et al., 2000), and boys with conduct problems (Beauchaine,
likelytodevelopND(Chapman,Tarter,Kirisci,&Cornelius, Hong, et al., 2008) exhibit lower baseline RSA. Children
2007;Fisheretal.,2011),perhapsinpartbecausesuchearly (Beauchaine et al., 2007) and adolescents (Beauchaine
life stress is known to affect neural systems associated with et al., 2000) with clinical levels of externalizing behavior,
behavior regulation and modulation (Kishiyama, Boyce, Ji- and boys with conduct problems (Beauchaine, Hong, et al.,
menez,Perry,&Knight,2009).Respiratorysinusarrhythmia 2008) also exhibit attenuated baseline RSA. In addition,
(RSA)isaphysiologicalcorrelateofemotionregulationthat boys (but not girls) with lower initial levels of baseline
hasbeenstudiedinavarietyoftypicallydeveloping andat- RSAhadexternalizingbehaviorthatincreasedacrossadoles-
riskpopulations;however,therearenostudiesofRSAinchil- cence(El-Sheikh&Hinnant,2011).
dren with ND. RSA is a phenomenon whereby heart rate Some studies have found no significant association be-
shows high frequency variability in time with respiration tween RSA reactivity and externalizing behavior in clinical
(Beauchaine, 2001; Porges, 2007). There is likely consider- samples(Beauchaineetal.,2000,2007),bitothersfoundsig-
ableequifinality,ortheprocessbywhichdifferentetiological nificantrelationsincommunitysamples(Keller&El-Sheikh,
pathwaysleadtothesamedisorder,tothedevelopmentofND 2009)andinchildrenwithADHD(Musseretal.,2011).For
that includes transactions across genetic, physiologic, and instance,childrenwithreducedautonomicfunctioninginthe
contextuallevels(Fisheretal.,2011).Incorporatingmeasures formoflowerRSAreactivity(Keller&El-Sheikh,2009)and
ofRSAintolongitudinalstudiesofNDmayhelpustoiden- thecombinationofbothlowbaselineRSAandlowerRSAre-
tifychildrenwhoaremostsusceptibletothedevelopmentof activity (Hinnant & El-Sheikh, 2009) exhibited the greatest
ND by virtue of their profile of RSA reactivity across early levelsofexternalizingbehavior.Incontrast,others(Calkins,
childhoodandtheirexposuretoadverseeventsearlyinlife. Graziano, & Keane, 2007) found no differences in baseline
RSA among 5-year-old children at risk for behavior prob-
lems.However,childrenatriskforbothexternalizingandin-
RSAandND
ternalizing problems exhibited the greatest RSA reactivity
RSAistypicallymeasuredintwoways:duringbaselineand compared to children with low behavior problems and chil-
in response to task demands, termed RSA reactivity. High drenatriskforexternalizingproblemsonly.
baseline RSA reflects the functional relationship between Althoughyouthsatriskforthedevelopmentofexternaliz-
the central nervous system and the heart as mediated by the ingdisordermayexhibitaprofileofreducedautonomicfunc-
vagus (Berntson et al., 1997; Porges, 2007). High baseline tioning, a second plausible pathway to the development of
RSA is thought to reflect a baseline of neural integrity and ND exists. The theory of diathesis stress suggests that a
a readiness to respond to environmental stressors (Beau- “risk”factorincombinationwithanadverseorstressfulenvi-
chaine,2001).Change inRSAin response toacute stressis ronmentleadstogreaterriskforthedevelopmentofproblem
termedRSAreactivity.WeusethetermRSAreactivitytore- behavior(Monroe&Simons,1991).Childrenwhoaremore
flectdecreasesinRSAinresponsetotaskdemands.Intypi- physiologicallyreactivemaybemorelikelytoexhibitNDif
callydevelopingchildren,RSAreliablydecreasesinresponse theyarealsoraisedinadverseenvironments.Forinstance,in
Prenatalexposure,RSA,andND 903
acommunitysampleofchildren,Obradovic´,Bush,Stamper- substances prenatally typically use other substances; there-
dahl, Adler, and Boyce (2010) found that children with fore, polydrug use could be conceptualized as a cumulative
greaterRSAreactivityexhibited lessprosocial behaviorand prenatal stressor (Lester & Padbury, 2009). Support for this
schoolengagement,butonlyiftheywereexposedtogreater viewcomesfromtheworkofFisheretal.(2011),whofound
environmentaladversity(operationalizedasacumulativein- that a summative index of prenatal substance exposure pre-
dex of six measures of family stress). Thus, RSA reactivity dicted blunted hypothalamus–pituitary–adrenal axis reactiv-
may moderate the effect of early adversity and/or prenatal ityamongchildreninfostercare.Theliteraturelinkingprena-
substanceexposuresuchthatchildrenwhoaremorereactive talsubstanceexposuretoRSAissmall,andnostudythatwe
willbemorelikelytoexhibitgrowthinNDifexposedtomore knowofhasexaminedtheeffectsofpolysubstanceexposure.
substances in utero or if reared in particularly adverse envi- Thus,wefocusedonpolysubstanceexposure,withthecaveat
ronments. that different substances may impact RSA via different
ThereiscomparativelylessinformationaboutRSAandex- mechanismsthatareunknownthusfar.
ecutive dysfunction, a second component of ND. Children Studiesexaminingtheeffectsofprenatalsubstanceexpo-
withhigherbaselineRSAperformbetterontasksofattention sureonRSAaremixed,andtheyarelargelylimitedtoinfants.
and working memory (Hansen, Johnsen, & Thayer, 2003; Infantswithprenatalsubstanceexposurehavelowerlevelsof
Marcovitch et al., 2010; Staton, El-Sheikh, & Buckhalt, baselineRSAat1and7monthsthandononexposedinfants
2009),perhapsbecausethesechildrenarebetterabletoengage (Schuetze & Eiden, 2006; Schuetze, Eiden, & Edwards,
with environmental demands and also self-regulate during 2009), and an absence of RSA reactivity at 7 months
bothcognitiveandemotionalchallenges.Moderatedecreases (Schuetze,Eiden,&Coles,2007).Othergroupsfoundnosig-
inRSAappeartoberelatedtoimprovedexecutivefunctioning, nificant associations with either baseline RSA (DiPietro,
includinggreateron-taskbehavior,behavioralinhibition,and Suess,Wheeler,Smouse,&Newlin,1995)orRSAreactivity
set shifting (Blair, 2003; Marcovitch et al., 2010), though (DiPietroetal.,1995;Sheinkopfetal.,2007)comparedtonon-
null findings with RSA reactivity and executive functions exposedchildren.IncreasedbaselineRSA(Mehtaetal.,1993)
havealsobeenfound(Statonetal.,2009).Thus,highbaseline has alsobeenreported ininfantswithprenatal cocaine expo-
RSAandmoderatedecreasesinRSAinresponsetochallenge sure,whichmaybeduetotheneedtoutilizegreaterneurobi-
maybeprognosticofbetterexecutivefunctioningcomparedto ologicalresourcesinordertomeetenvironmentaldemands.
lowbaselineRSAandanabsenceofRSAreactivity. The development of children with prenatal substance ex-
posureisalsocomplicatedbyahostofadditionalriskfactors.
Earlyadverseexperiencesamongchildrenwithprenatalsub-
PrenatalSubstanceExposure,EarlyAdversity,
stanceexposuretendtoco-occurandincludeexposuretopa-
andRSA
rental psychopathology, neighborhood violence, chaotic
Thepurposeofmanyprenataldrugexposurestudiesistoex- home environments, and lack of monetary resources (Dong
amine the effects of a single substance (such as cocaine), et al., 2004; Propper, 2012), making it extremely difficult
while controlling for the effects of all other substances to separate the effect of one adverse experience from the
(suchasalcohol,tobacco,andmarijuana).Acomplementary other. Manyresearchersthereforetakeacumulative riskap-
approachistotakeintoaccountrecent worksuggestingthat proach to studying the impact of co-occurring risk factors
prenatalsubstance exposureisastressor (Lester&Padbury, on physiological functioning (Eiden, Granger, Schuetze, &
2009), and as such, cumulative prenatal stress models may Veira, 2011; Fisher et al., 2011; Sameroff, Seifer, Baldwin,
provide an alternative way of modeling the contribution of & Baldwin, 1993). Cumulative risk models have also been
prenatal substance exposure to relevant developmental pro- shown to be a more powerful predictorof externalizing and
cesses. Specifically,in additionto itsteratogenic properties, internalizing behavior among children with prenatal sub-
prenatalsubstanceexposurecanaltertheinfant’sphysiolog- stanceexposurethanrisksexaminedinisolation(Yumoto,Ja-
ical response to the postnatal environment (Lester, Marsit, cobson,&Jacobson,2008).
Conradt, Bromer, & Padbury, in press; Lester & Padbury, Earlyadverseexperienceshavebeenrelatedtothesympa-
2009). That is, exposure to substances prenatally acts as a thetic and hypothalamus–pituitary–adrenal systems (Blair
stressorthatmayaltertheexpressionofspecificgenesimpor- etal., 2011;Gunnar&Fisher,2006;Heimetal., 2004;Lu-
tanttoplacentalfunctioninlategestation(Lester&Padbury, pien, King, Meaney, & McEwen, 2001; Saridjan et al.,
2009),whichmayleadtofetalexposureofhighlevelsofma- 2010),thoughevidenceofhowtheseadverseexperiencesim-
ternalcortisol(Lester&Padbury,2009).Theeffectsofprena- pact the parasympathetic system is scarce (Propper, 2012),
tal substance exposure as an intrauterine stressor that alters despiteknownassociationsbetweenearlyadversityandemo-
physiological response systems (Lester & Padbury, 2009) tionregulation(Pechtel&Pizzagalli,2011;Tottenhametal.,
couldresultindisruptedparasympatheticresponding,leading 2011). Though there are exceptions, low income (Propper,
tothedevelopmentofND.Asimilarprocessisthoughttooc- 2012), exposure to domestic violence (Rigterink, Fainsilber
cur in response to prenatal alcohol (Hellemans, Sliwowska, Katz, & Hessler, 2010), and marital conflict (El-Sheikh &
Verma, & Weinberg, 2010) and tobacco (Heim, Plotsky, & Hinnant,2011)havebeenassociatedwithalteredRSAeither
Nemeroff, 2004) exposure. Furthermore, women who use intheformoflowerbaselineRSA(Field,Pickens,Fox,Na-
904 E.Conradtetal.
wrocki,&Gonzalez,1995;Pickens&Field,1995;Schuetze function components of ND. We employed longitudinal
&Eiden,2006;Schuetzeetal.,2009)orlessgrowthinbase- growth modeling to better understand both normative and
line RSA (Rigterink et al., 2010). El-Sheikh and Hinnant problematicgrowthtrajectoriesofND,aswellastheimpact
(2011)found thatboyswith greater RSAreactivity whoex- of prenatal substance exposure, early adversity, RSA, and
periencedhighermaritalconflictatage8orincreasingmar- theirinteractiononthisgrowth.
italconflictfromages8to11exhibiteddecreasesinbaseline Ourfirstgoalwastodescribetheunconditionalgrowthtra-
RSAacrossearlyadolescence,suggesting“wearandtear”on jectoriesofbaselineRSAandRSAreactivityatages3,4,5,and
the parasympathetic system. Exposureto adverse conditions 6years.Onthebasisofpriorevidence,weexpectedthatbase-
among children with prenatal substance exposure could ex- line RSA would increase with age (Schuetze et al., 2009),
acerbateanalreadysensitivephysiologicalstresssystem(Les- whereas the magnitude of RSA reactivity would decrease
ter & Padbury,2009), contributingto difficulties with emo- (Blandon, Calkins, Keane, & O’Brien, 2010; Propper et al.,
tion regulation and risk for the development of ND. In 2008).Oursecondgoalwastoexaminethemaineffectsofpre-
other words, children with prenatalsubstance exposure may natalsubstanceexposure,earlyadversity,andRSAonthede-
beatmoreofadisadvantagebyvirtueoftheincreasedlike- velopment of the behavior dysregulation and executive dys-
lihoodofexposuretoadverseconditionspostnatally. function components of ND. We hypothesized that decreases
inbaselineRSAandincreasesinRSAreactivitywouldbeas-
sociated with increases in behavior dysregulation. Following
StudyAimsandHypotheses
prior research, we expected that greater increases in baseline
Datafromthisstudycomefromaprospectivelongitudinalin- RSA and moderate decreases in RSA reactivity over time
vestigationofchildrenwithprenatalsubstanceexposureand wouldbeassociatedwithlowerlevelsofexecutivedysfunction.
from whom extensive measures of early adversity and ND Based on prior evidence with this sample, we expected that
wereassessed.Acrossearlychildhood,assessmentsofRSA greaterlevelsofprenatalsubstanceexposureandearlyadversity
at baseline and in response to challenge were conducted. (Fisheretal.,2011)wouldberelatedtoincreasesinbothbehav-
Wethus have the uniqueopportunitytoexamine theeffects ior dysregulation and executive dysfunction over time, even
ofprenatalsubstanceexposureandearlyadversityongrowth when including measures of RSA in our models. Motivated
inbaselineRSAandRSAreactivitywhenthesephysiological by theories suggesting that interactions across multiple levels
systemsareintheprocessofmaturingandarearguablyquite ofanalysiscontributetothedevelopmentofpsychopathology,
vulnerable to environmental influence (Beauchaine, Neu- ourthirdgoalwastotestinteractionsbetweenourstressvari-
haus, Brenner, & Gatzke-Kopp, 2008). We focused on ables (prenatal substance exposure and early adversity) and
RSA as a possible physiological correlate of ND owing to RSAongrowthinND.Basedonthetheoryofdiathesisstress,
itsassociationwithemotionregulation. weexpectedthatgreaterearlyadversityandprenatalsubstance
There are inconsistencies regarding which disorders are exposure,combinedwithincreasedRSAreactivityordecreased
included as components of ND. Tarteret al. (2003) include baseline RSA (in separate models), would be related to in-
both internalizing and externalizing problems because both creasesinND(boththebehaviordysregulationandexecutive
arerelatedtoproblemswithemotionalandbehavioraldysreg- dysfunctionconstructs)inadolescence.
ulation and frequently co-occur, whereas others (Krueger
etal.,2002;Krueger&South,2009)includeonlyexternaliz-
Method
ing symptoms. Tarter et al. also include executive function
deficits in their model of ND while others do not (Iacono,
Participants
Malone,&McGue,2008;Krueger&South,2009).Further-
more, adolescents whose parents have substance use disor- Weuseddatacollectedfrom1,387participantsintheMater-
ders are frequently included in studies by Tarter. Based on nal Lifestyle Study (MLS), a multisite (Detroit, MI; Mem-
carefulconsiderationoftheseinconsistenciesintheliterature, phis, TN; Miami, FL; and Providence, RI) investigation of
and because of the similarities in our two samples, we de- the effects of prenatal substance exposure in a longitudinal
cided to follow Tarter et al.’s approach to modeling ND, follow-upfromages1monthto16years.Detailsontheen-
which includes both internalizing and externalizing symp- rollmentandexclusioncriteriaaredescribedelsewhere(Les-
toms as well as executive dysfunction. We focused on the teret al., 2002). In brief, families were selected to be in the
constructofND,ratherthanitscomponentparts,basedonob- exposedgroup(i.e.,maternalreportofcocaineoropiateuse
servationsthatpsychiatricdisordersrarelyoccurinisolation duringpregnancyandgaschromatography–massspectrome-
butoftenoccurinclusters(Lilienfeld,2003). try confirmation of presumptive positive meconium screens
WeexaminedgrowthinNDusingameasureofNDvali- for cocaine or opiate metabolites) or the comparison group
datedwiththecurrentsamplefrommiddlechildhoodtoado- (i.e.,maternaldenialofcocaineoropiateuseduringthepreg-
lescence(Fisheretal.,2011;Lesteretal.,2012).NDwasas- nancyandanegativeenzymemultipliedimmunoassaymeco-
sessed during the transition to adolescence because it is niumscreenforcocaineandopiatemetabolites).Theexposed
during this time that extensive development in prefrontal andcomparisonyouthsweregroupmatchedonrace,sex,and
areas are associated with the self-regulatory and executive gestationalagewithineachstudysite.Othersubstancesasso-
Prenatalexposure,RSA,andND 905
ciated with cocaine use (e.g., alcohol, tobacco, and mari- byPorges(1985)andisoneofseveralacceptableapproaches
juana)werepresentinbothgroupssothatgroupdifferences forcalculatingRSA(Berntsonetal.,1997).RSAdatawerecal-
couldbe attributed to cocaine. Thus, most participants were culatedin30-soverlappingwindowsandthenaveragedwithin
polysubstanceexposed. eachepisode(baselineandattentiontask).TheRSAdataforan
Thestudywasapprovedbytheinstitutionalreviewboardat individualwasusedaslongastherewasa30-ssegment,with
eachstudysite,andwritteninformedconsent(caregivers)was less than 20% of segments identified with artifact (Jennings
obtainedfromallparticipants.Eachsitehadacertificateofcon- et al., 1981), which is the shortest duration recommended
fidentialityfromtheNationalInstituteonDrugAbuse.Forthis when calculating RSA with children. Thirty-second epochs
study,weuseddatafromvisitstothehospitalclinicatages3,4, arefrequentlysampledinstudiesofyoungchildren(Blandon
5,6,9,11,and13years.TheMLSsampleincludeschildrenin et al., 2010; Buss, Goldsmith, & Davidson, 2005; Huffman,
the following racial and ethnic categories: African American 1998; Moore & Calkins, 2004). In addition, small amounts
(77%), Caucasian (16%),Hispanic (6%),and children whose of artifact can be expected to have a minimal effect on mea-
parentsidentifiedotherracialorethnicbackgrounds(1%). sures of heart rate variability such as RSA (Berntson, Ca-
cioppo,&Quigley,1993).
BaselineRSAwasassessedwhilethechildrenwerewait-
Measures
ingforamasterymotivationprocedure(describedbelow)to
RSA.BaselineRSAandRSAreactivityweremeasuredat3, begin.BecauseRSAcanbeactivatedbypsychomotoractiv-
4,5,and6years.RSAwasderivedfromtheR-Rtimeseries ity(Bazhenova&Porges,1997),likeothers(Obradovicetal.,
collectedfromdigitizedelectrocardiogram(ECG)recordings 2010), we assessed baseline RSA during a nonchallenge
usingthe Porgesalgorithm from MXEdit (Delta-Biometrics “control”taskthatparalleledthemotordemandsofourchal-
Inc., 1988–1993). ECGs were recorded via three electrodes lenge task. Specifically, children played with a toyalone or
placed on the child’s chest and abdomen. The ECG signal with an experimenter for an average of 164.8 s (range ¼
wassampledat1kHzandstoredonacomputerforlaterscor- 135.6–199.3s)whilesittingatatable.Althoughthisbaseline
ing.InterbeatintervalsweredefinedbydetectionofR-waves requiredsomeattention,whichmayevokevagalwithdrawal
tothenearestmillisecond. (Suess,Porges,&Plude,1994),thetoywithwhichthechild
Postprocessingofthedatatookplaceoff-linebyusingaser- playedwassimple,andnotaskdemandswereplacedonthe
iesofautomatedalgorithms.R-Rintervalsoutsideofexpected childduringthistime.OurestimatesofbaselineRSAaresim-
valueswereidentified.MissedorspuriousR-waveswereflag- ilar(within1SD)tootherstudiesofyoungchildrenofsimilar
gedandcorrectedbylinearinterpolation.A21-pointmoving ages (Alkon et al., 2003; Buss et al., 2005; Calkins et al.,
polynomialwasthenappliedtoremovelowfrequencytrends 2007; Calkins & Keane, 2004; Doussard-Roosevelt, Mont-
intheheartratesignal.Next,abandpassfilterextractedthevar- gomery, & Porges, 2003), who have also calculated RSA
ianceinheartperiodwithinthefrequencybandofspontaneous based on the Porges technique. Furthermore, the sample as
respirationinyoungchildren(0.24–1.04Hz).Thisprocessre- awholehadRSAlevelsthatdecreasedfromthisbaselineto
movesperiodicitiesintheECGsignalthatareoutsidethefre- theattentiondemandingtaskateachageassessed(Table1),
quencyrangeoftherespiratorycycle.Theresultingmeasureof indicating that our baseline measure was perceived as less
RSAisinthefrequencyrangeofrespiration.RSAwascompu- stressfulthantheattention-demandingtask.
tedasthenaturallogarithmofheartperiodvarianceinmillise- RSAreactivitywasassessedinresponsetoamasterymoti-
condssquared[ln(ms)2].Thismethodwas describedinitially vationprocedure(Dwek,1991).Theattention-demandingtask
Table 1.Meansand standard deviations for RSA andneurobehavioral disinhibition over time
Age M SD DataPresent M SD DataPresent
BaselineRSA RSAReactivity
3years 5.64 1.29 53.4% 0.60 0.56 51.6%
4years 5.78 1.26 51.6% 0.29 0.55 50.6%
5years 6.06 1.23 48.1% 0.27 0.55 47.6%
6years 6.27 1.23 51.9% 0.57 0.58 51.4%
BehavioralDysregulation ExecutiveDsyfunction
Age8/9 0.24 0.12 77.4% 0.48 0.10 68.4%
Age11 0.23 0.13 69.8% 0.40 0.12 67.6%
Age13/14 0.24 0.13 71.0% 0.33 0.12 66.4%
Note:RSA,respiratorysinusarrhythmia.Neurobehavioraldisinhibitionindicators(behavioraldysregulationandexecutivefunction
difficulties)wererescaledonacontinuous0–1metricandaveragedtocomputethebehavioraldysregulationandexecutivedysfunc-
tionconstructs.
906 E.Conradtetal.
comprisedthefirst3minoftheprocedure.Childrentransitioned construct scores and have labeled the assessment periods as
fromsupportiveplaywithanexperimentertoplaywithamod- years8/9,11,and13/14throughoutthetext.
eratelychallengingtoyjustabovethedevelopmentallevelofthe To evaluate comparable means over time, the composite
childwithout the aidofthe experimenterorcaregiver, though growthscorenecessitatesrescalingtheoriginalrangeofindica-
theexperimenterwaspresentduringthetask.Toysincludeda torstoacommonmetricrangingfrom0to1asacontinuouslevel
pathfinder (3 years), tinker toys (4 and 5 years), and a puzzle scale.Thecompositeiscomputedastheaverageofthethreein-
(6years).Performanceduringmasterymotivationtasksisposi- dicators.Cronbachavalueswere0.73,0.80,and0.80,respec-
tively related to emotion regulation (Heckhausen & Dweck, tively,overtimeforthecompositescoreofbehavioraldysregu-
1998); therefore, it was expected that this challenge should lation.Usingprincipalcomponentsfactoranalyses,weobtained
alsotaxemotionsystems.RSAreactivitywascalculatedusing asingle-factorsolutionateachtimepoint:eigenvaluesof2.98,
adifferencescore(RSA –RSA ).Positivevaluesreflect 3.27,and3.25,respectively,explainedover50%ofthevariance.
baseline task
greaterRSAreactivity(i.e.greaterdecreaseofRSA).Ouresti- Executive dysfunction was measuredwith two computer-
matesofRSAreactivityaresimilar(within1SD)tootherstud- izedtestsfromtheCambridgeNeuropsychologicalTestAu-
iesofyoungchildrenofsimilaragesusingattention-demanding tomatedBatteries(Luciana,2003)atages9,11,and13.There
tasksandthePorgestechnique(Alkonetal.,2003;Bussetal., isvariabilityintheindicatorsresearchersusetomeasureex-
2005;Calkinsetal.,2007;Calkins&Keane,2004). ecutive dysfunction as acomponent of ND. We chose tasks
thatassessspatialworkingmemory,thinkingtime,andplan-
ND.Twolongitudinalconstructscoreswereemployedtoas- ning,allofwhichhavebeenshowntoberelatedtobrainareas
sessgrowthinNDoverthreeassessmentperiodsduringearly relatedtodeficienciesamongchildrenexposedprenatallyto
adolescenceusingastrategypreviouslyemployedinstudies drugs(Sheinkopfetal.,2009).Thespatialworking-memory
involvingthesamesample(Fisheretal.,2011;Lesteretal., taskisself-orderedandrequirestherespondenttofinda“to-
2012). The construct scores for behavioral dysregulation ken”inanarrayofcoloredboxes;wemeasuredthetotalnum-
andexecutivedysfunctionwerecomputedfrommultimethod, beroferrorsonthetask.TheStockingsofCambridgetaskin-
multiagent, validated, well-established measures. The ND volvesspatialplanning,andtherespondentsmustuse“balls”
constructhasgoodpredictivevalidity,particularlyitsability inonedisplaytocopythepatternshowninanotherdisplay.
topredictsubstance-useonset,andgoodconstruct,discrimi- Thinkingtimeincludestwotrialsmeasuringthetimetoselect
native,andconcurrentvalidity,aswellasgoodtest–retestand theinitialstimulus.Shortertimeshavebeenrelatedtoimpul-
internalreliability(Mezzichetal.,2007). sivity.Wemeasuredthetotalnumberofcorrectsolutionsin
The behavioral dysregulation construct was a composite theminimalnumberofmoves(reversescoredtoindicateex-
scoreofsixmeasuresofinternalizingandexternalizingprob- ecutive dysfunction). The composite growth score was the
lems: (a) problem behaviors reported by caregivers on the averageofthetwoindicatorsrescaledto0–1.
ChildBehaviorChecklist(Achenbach,1992)usingthestan-
dardized T scores for total problem behaviors at ages 9, 11, Keypredictors.Prenatalsubstanceexposurewasmeasuredas
and13(weusedTscoresratherthanrawscoresbecausewe a summative index ranging from 0 to 5 for mother-reported
were interested in comparing children’s behavior relative to (or gas chromatography–mass spectrometry confirmation of
same-aged peersandnormed bysex;incontrast,rawscores presumptivepositivemeconiumscreensforcocaineoropiate
cannotbeusedtocomparechildren’sbehavioragainstpopu- metabolites)useofcocaine,opiates,marijuana,alcohol,and
lation norms of otherchildren of the same age and sex, and tobaccoduringpregnancy.Maternalreport/meconiumscreen
theuseofChildBehaviorChecklistTscoresisthereforecom- ofdruguse(1¼yes,0¼no)prenatallywascomputed.One
mon in longitudinal research in which trajectories of symp- point was assigned for each substance used. Dichotomous
toms are assessed; e.g., see Milan & Pinderhughes, 2006); measuresarefrequentlyusedintestingprenatalsubstanceex-
(b)ODD,(c)conductdisorder,(d)ADHD,(e)andmajorde- posure effects (Fisher et al., 2011; Smith, Johnson, Pears,
pressionsymptomcountsreportedbytheparentfromtheDi- Fisher,&DeGarmo,2007).
agnostic Interview Schedule for Children—IV (Shaffer, Earlyadversitywasasummativeriskindexfrombirthto
Fisher, Lucas, Dulcan, & Schwab-Stone, 2000) at ages 8, the age 3 assessments and included nine risk factors. Each
11,and14;and(f)delinquencysummaryscoresforthenum- risk factor was either a continuous scale or a count score
berofself-reportedcrimesagainstpeopleandactsofgeneral and was dichotomized to create an overall risk index (0 ¼
delinquency and school delinquency from the Things That no/none, 1 ¼ yes/one or more): (a) annual assessments of
You Have Done measure (Elliott, Huizinga, & Ageton, postnatalsubstanceuseofcocaine,opiates,tobacco,alcohol,
1985; Ingoldsby, Kohl, McMahon, Lengua, & Group, ormarijuanauptotheYear3assessment;(b)chronicpoverty
2006) at ages 9, 11, and 13. This measure is commonly statuscalculatedasincomebelow$10,000overannualvisits;
usedasanoutcomevariableinstudiesexaminingpredictors (c) low social status scored from the Hollingshead Index of
of delinquent behavior (Bierman et al., 2004; Kaplow, Cur- SocialPosition(Hollingshead,1975)usingeducationandoc-
ran,&Dodge,2002;Lamis,Malone,Lansford,&Lochman, cupation averaged over annual visits and scored as 1 SD or
2012).BecausetheDiagnosticInterviewScheduleforChil- morebelowthemean;(d)primarycaretakerchanges;(e)sex-
dren—IVwasadministeredatyears8and14,wecomputed ual or physical abuse of the child as reported by caregivers;
Prenatalexposure,RSA,andND 907
(f)caregiverdepressionof1SDorgreaterabovethemeanfor tionandexecutivedysfunction,weremodeledseparately.We
averaged depressive symptoms on the caregiver reported tested two overarching models. In the first, latent growth
Beck Depression Inventory (Beck, Steer, & Brown, 1996); curves were used to test a series of models examining the
(g)caretakerpsychologicaldistressof1SDorgreaterabove levelandshapeofchildren’sbaselineRSAfrom3to6years
themeanforaveragedpsychologicalsymptomsaboveclini- of age and ND (behavior dysregulation and executive dys-
cal cutoff on the Brief Symptom Inventory (Derogatis & function modeled separately) from ages 8/9 to 13/14. The
Coons, 1993); (h) poor quality home environment of 1 SD fourchronometrictimeweightsforbaselineRSAwerespeci-
ormorebelowthemeanontheHomeObservationMeasure- fiedat0,1,2,and3.Inthesecond,weexaminedtheleveland
mentoftheEnvironment(Caldwell&Bradley,1984);and(i) shapeofchildren’sRSAreactivityfrom3to6yearsandND
any history of Child Protective Services Involvement as- (behavior dysregulation and executive dysfunction modeled
sessedannuallyuntiltheYear3assessment. separately)fromages8/9to13/14.RSAreactivitywasthere-
foremodeledasadevelopmentalprocessusingaflexibleap-
proach to the structure of the SEMmodel. We specified the
Missingdata
fourchronometrictimeweightsfortheRSAreactivitylinear
Participantsfromthecurrentstudycomefromthesampleused slopefactorat0,1,2,and3,andthequadraticslopeas0,1,4,
inFisheretal.(2011),whichincluded1,073MLSfamiliesin and 9.Wespecifiedthreechronometrictimeweightsforthe
whichthemothershadprenatalsubstanceexposurescoresand NDslopefactorat0,1,and2.Thismodelallowedustotest
theyouthshadoutcomedatabytheadolescentfollow-uppe- thehypothesisthatgrowthinRSApredictsgrowthinND.
riod.TheMLSstudyoriginallyenrolled1,388motherswith WeusedanSEMapproachtotesttheinteractionbetween
prenatal substance exposure scores. By the age 8/9 assess- growthinRSAandprenatalsubstanceexposure/earlyadversity
ment,81%ofmothershaddataontheyouthsenrolledinthe on growth in ND (Klein & Moosbrugger, 2000). SEM uses
study. Attrition analyses are described in detail in Fisher maximum likelihood estimation of model parameters, and
etal(2011).Inbrief,therewerenodifferencesonprenatalsub- whenlatentvariableinteractionsareincludedinthemodel,it
stanceexposurewhencomparingmotherswithyouthdataat does not yield chi-square and related model fit statistics be-
follow-upandthosewithout.Significantdifferenceswereob- cause means, variances, and covariances are not sufficient
servedforearlyadversity,withmothersandyouthsinfollow- for model estimation. Instead, nested models were compared
upexhibitingmoreriskcomparedtomotherswhosechildren usingthesample-sizeadjustedBayesianinformationcriterion
werelosttofollow-up(M¼1.80,SD¼1.14,andM¼1.56, (Sclove, 1987) and the Akaike information criterion (AIC;
SD¼1.07,respectively,p,.01).Therewerenosignificant Akaike,1987)todeterminewhethertheinteractionmodelre-
differencesinprenatalsubstanceexposureorearlyadversity sultedinbettermodelfitcomparedtothemaineffectsmodel.
betweenchildrenwithandwithoutbaselineRSAandRSAre- Lower sample-size adjusted Bayesian information criterion
activity data within each age (all ps . .14). Children with and AIC values indicated better model fit. All analyses were
missingRSAdataat3and4yearshadsignificantlyhigherbe- conductedusingMplus5.1(Muthe´n&Muthe´n,2007).
haviordysregulationandexecutivedysfunctionscoresatage
8/9comparedtochildrenwithoutmissingRSAdataat3and
Results
4years(ps,.02).ChildrenwithmissingRSAdataat4years
alsohadlessgrowthinbehaviordysregulation(b¼–0.24,p¼
Preliminaryanalyses
.02).TherewerenootherdifferencesinND(assessedviathe
behaviordysregulationandexecutivedysfunctiongrowthfac- The meanof the prenatalsubstance exposure indexwas 1.89
tors) between children with and without baseline RSA and substances (SD ¼ 1.38,range¼ 0–5).Forty-three percent of
RSAreactivitydatawithineachage(allps..19). the sample was cocaine exposed, 8.3% opiate exposed,
58.5% alcohol exposed, 53.0% tobacco exposed, and 23.0%
marijuanaexposed.Themeannumberofearlyadversityfactors
Analyticstrategy
was2.35(SD¼1.43,range¼0–8).Asexpected,therewasa
Weemployedstructuralequationmodeling(SEM)tounder- steadyincreaseinbaselineRSAfrom3to6years(seeTable1).
stand whether prenatal substance exposure and early adver- RSAreactivityshowedacurvilineartrend,withgreaterRSAre-
sity were related to the level and change over time in RSA activityat3years,decreasingRSAreactivityat4and5years,
andND.WithinthisSEMframework,weusedlatentvariable andincreasingRSAreactivityagainat6years.Themeancom-
growthmodelingtotestthehypothesisthatchangeinRSAis positegrowthconstructscoreforbehavioraldysregulationwas
relatedtochangeinND.ChangeinRSAandchangeinND largely stable over time (see Table 1). The mean composite
were characterized by scale-specific intercepts and slopes scoreforexecutivefunctiondifficultiesdecreasedovertime.
thatwereallowedtorandomlyvaryacrosspeople.
Within-person variation in RSA and ND over time was
Correlations
modeledwithindividual-specificgrowthparameters(i.e.,in-
tercept,linearslope,and,whenappropriate,quadraticslope). CorrelationsbetweenbaselineRSA,RSAreactivity,prenatal
ThetwocomponentsthatcompriseND,behaviordysregula- substance exposure, early adversity, behavioral dysregula-
908 E.Conradtetal.
tion,andexecutivedysfunctionarepresentedinTable2.The *
*
intercorrelationsbetweenbaselineRSAat3,4,5,and6years 15 —9*
5
were positively and strongly correlated. Intercorrelations .
among RSA reactivity measures were less strong, though **
**
4 —**
alsopositive.Greaterexposuretoearlyadversity,andlessex- 1 94
44
posuretosubstancesprenatally,wasrelatedtolessRSAreac- ..
tivity at 3 years, but greater exposure to early adversity and ***** y.
drugs prenatally was associated with greater RSA reactivity 13 —.11*.20*.20* activit
at6years.Prenatalsubstanceexposurewasalsosignificantly e
andpositivelyassociatedwithearlyadversity.Greaterlevels 2 —************ SAr
1 2199 R
of behavioral dysregulation at all ages were associated with .6.1.1.1 er
greaterlevelsofprenatalsubstanceexposureandearlyadver- ********** great
switeyr,ewonhleyresaigsngirfeicaatenrtllyevaeslssocoifateexdecwuittihvegrfeuantecrtiolenvedlisffoicfuelatirelys 11 —.58*.49*.17*.26*.25* eflect
r
adversity. Behavioral dysregulation and executive function *** R
difficulties were positively and moderately correlated (rs ¼ 10 —1**6**0**465 SA-
112000 R
.11–.26, ps , .001). In addition, behavioral dysregulation ...... of
c(srtorsnu¼sctt.rs4u9(cr–tss.6¼a2t)a.,4lal4sa–wg.5ee9sr)ew.theereepxoecsiuttiivveelyfuanncdtiostnrodnigffliycuclotirerselcaotend- 9 —.40***.22***.25***.24***.12***.15***.12*** herlevels
*** ** Hig
8 —1008020407040311 n.
..2.2.2.2.2.2. ctio
Unconditionalgrowthmodels n
u
Bshaaspeelinoef cRhSilAd.reMn’osdRelSsAwterraejetcetsotreidesedxuarmininginthgetbhaeselelivneeleapnid- 7 —.25***.08*.04.03.06.052.072.042.02 utivedysf
sode. Individual, within-person variation in RSA over time ec
was allowed to vary across persons. On average, children 6 —9***1*21125126 EF,ex
stihmoew.eCdhaildsriegnn’isficbaansetlilnineeaRrSiAncareta3seyeinarsbawsaeslin5e.6R3SlnA(mosv)e2r, .1.12.02.0.02.0.02.0.0.0 ation;
and the average rate of change in baseline RSA was 0.19 ***** * gul
ln(ms)2.Significantvariabilitywasfoundforchildren’sinter- 5 —.07.04.132.09.092.082.012.052.042.092.08 dysre
cepts(s2 ¼0.79,p,.001),butnotslopes(s2 ¼0.003,p¼ al
.86).ThissuggeststhattheinitiallevelforbaselineRSAvaried ** ****** * vior
acrosschildren,buttherateofchangewasrelativelyconstant. 4 —17*0811*23*11*13*0402040613*06 beha
Themodelfitthedatawell,x2(4)¼4.40,p¼.35;comparative ........2.... D,
fitindex(CFI;Bentler,1990)¼1.00,rootmeansquareerrorof B
* * y;
approximation(RMSEA;Browne&Cudeck,1993)¼0.01. 3 —49**030527**0908*09*09*0205030504 ctivit
.2......2.2....2. ea
r
A
RSAreactivity.IdenticalmodelsalsotestedRSAreactivityin **** ** * RS
response to the attention-demanding task. A model that in- s 2 —6*9*44*61048*155011*6 R,
cludedacurvilineargrowthterm(quadratic)providedexcel- ure .4.4.0.3.0.02.0.0.0.0.0,.0.1.0 SA-
RleMntSfEitAto¼th0e.0d1at(aB,exn2tle(r4,)1¼9904;.4B5r,owpn¼e &.35C;uCdeFcIk¼, 1909.939),, meas ******** mia;R
withreactivityhighestat3years,decreasingat4and5years, dy 1 —49*43*51*26*0040100400308*0303020300202 yth
andthenincreasingagainat6years.Children’saveragelinear stu .....2..2..2..2.2..2. arrh
0slbfi5saecelin.iogsa1raliesnpnin4tndyteid,rfteqaeiwpitacncurhcaac¼raettosnehdipstvide.rns0teasevcte3cocaiorhr)cfrepve.iia2aaetalCsrdrb.rseea1hriintmen2liiaidnlmgttdely,n(ratreseese(gsuprmn(u2iesnMgr,gtsede6gog)lrseiec2nnee(emseMnpsataattirttoinviq¼snnanulegogaggsrpd0ttaeerhrdt.agah0¼ta3iietfce8te,fyc,d¼e–daehpr1eltaeishc0.l,rno2dasr.ce14tr.eee.a5t,S0xshns,pi0heegwap1iss,ncbe;e,ariirsofttpe.eis02laac.disb0ntga0tee0naee1cacr1strh)sosn,)vil4iomlsgfawdpranderoiriinneii¼mtaffhngd--- ble2.Correlationsamong RSA36monthsRSA48monthsRSA60monthsRSA72monthsRSA-R36monthsRSA-R48monthsRSA-R60monthsRSA-R72monthsEarlyadversityPrenatalsubstanceexposureBDage8/9BDage11BDage13/14EFage8/9EFage11EFage13/14 e:RSA,baselinerespiratorysinus,,,pp.05.**.01.***.001.
inthispatternovertime(s2quadratic ¼.001,p¼.05). Ta 1.2.3.4.5.6.7.8.9.10.11.12.13.14.15.16. Notp*
Prenatalexposure,RSA,andND 909
ND.DetailsregardingtheunconditionalmodelofNDcanbe growth in the behavioral dysregulation and executive dys-
foundinFisheretal(2011).Inbrief,thereweresignificantin- function components of ND. The main effect model for be-
dividual differences in the trajectories of adolescent behav- havioral dysregulation showed acceptable fit (CFI ¼ 0.98,
ioraldysregulationandexecutivefunctiondifficulties.There RMSEA¼0.03),x2(20)¼40.28,p¼.05.Greaterexposure
wasnonsignificantmeangrowthinbehavioraldysregulation, toearlyadversitywasrelatedtolessRSAreactivityat3years
whereasexecutivefunctiondifficultiesdecreasedovertime. (b¼–0.32,p,.001),increasedlineargrowthinRSAreac-
tivityfrom3to6years(b¼0.29,p¼.01),butnotquadratic
growth(b¼–18,p¼.10).Incontrast,greaterprenatalsub-
Effectsofprenatalsubstanceexposureandearlyadversity
stanceexposurewasassociatedwithgreaterRSAreactivityat
ongrowthinbaselineRSAandND
3years(b¼0.30,p,.001),lesslineargrowthinRSAreac-
Wenextenteredthemaineffectsofprenatalsubstanceexposure tivity(b¼–0.27,p¼.01),andgreaterquadraticgrowth(e.g.,
andearlyadversityongrowthinbaselineRSAonthebehav- greateraccelerations)ofRSAreactivityfrom3to6years(b¼
ioral dysregulation and executive dysfunction components of 0.25,p¼.03).Higherdrugexposurewasassociatedwithless
ND.Childsexwasenteredasacovariateinallmodels.Thefac- RSAreactivityat4and5years,followedbyasteeperincrease
torvarianceforthebaselineRSAslopewasfixedat0owingto inRSAreactivityatage6.Malesexhibitedmorebehavioral
itsverylowandnonsignificantvalue.Wethereforedidnotin- dysregulationatage8/9(b¼–0.16,p,.001).Higherlevels
cludeanypredictorsofgrowthinbaselineRSAnorwasgrowth of early adversity were associated with greater behavioral
inbaselineRSAincludedasapredictorofbehavioraldysregu- dysregulation at age 8/9 (b ¼ 0.24, p ¼ .002). There were
lation or executive dysfunction. This constraint did not affect nomaineffectsofRSAreactivityoninitiallevelsorgrowth
modelfitandimprovedtheestimationoftheoverallmodel. inbehavioraldysregulation.
Themaineffectmodelforbehavioraldysregulationshowed Themaineffectmodelforexecutivedysfunctionshowed
acceptablefit(CFI¼0.98,RMSEA¼0.03),x2(33)¼70.98, good fit (CFI ¼ 0.99, RMSEA ¼ 0.02), x2 (20) ¼ 27.22,
p,.001.Thefindingsindicatethatgreaterprenatalsubstance p . .05. Greater exposure to early adversity was related to
exposurewasassociatedwithgreaterbaselineRSAatage3(b lessRSAreactivityat3years(b¼–0.32,p,.001),increased
¼0.14,p,.001)andgreaterincreasesinbehavioraldysreg- lineargrowthinRSAreactivityfrom3to6years(b¼0.28,
ulationovertime(b¼0.15,p¼.01).Greaterlevelsofearly p¼ .01), but not quadratic growth (b¼ –0.18,p¼.09). In
adversitywererelatedtohigherinitiallevelsofbehavioraldyr- contrast, greater prenatal substance exposurewas associated
egulationatage8/9(b¼0.27,p,.001).Maleshadgreater withgreaterRSAreactivityat3years(b¼0.30,p,.001),
levelsofbehavioraldysregulationatage8/9thandidfemales less linear growth in RSA reactivity (b ¼ –0.26, p ¼ .01),
(b ¼ –0.15, p , .001). There were no significant effects of and greater quadratic growth (e.g., greater accelerations) of
RSAoninitialstatusorgrowthinbehavioraldysregulation. RSAreactivityfrom3to6years,b¼0.24,p¼.03.Higher
The main effect model for the executive dysfunction out- drug exposure was associated with less RSA reactivity at 4
comealsodemonstratedacceptablefit (CFI¼0.98,RMSEA and5yearsfollowedbyasteeperincreaseinRSAreactivity
¼0.02),x2 (33)¼54.37,p¼.01.Greaterlevelsofprenatal atage6.Therewasonlyonesignificantassociationbetween
substanceexposurewere relatedtogreater baseline RSAat 3 thesubstantivecovariatesandtheexecutivefunctiondifficul-
years(b¼0.14,p,.001).Therewasonlyonesignificantas- ties construct. Greater levels of early adversity were associ-
sociationbetweenthesubstantivecovariatesandtheexecutive ated with greater executive function difficulties at age 8/9
functiondifficultiesconstruct.Greaterlevelsofearlyadversity (b¼0.18,p¼.02).
were associatedwithgreaterexecutive function difficulties at Inseparatemodels,wethenexaminedtheinteractionbe-
age8/9(b¼0.18,p,.001).Therewerenosignificanteffects tweengrowthinRSAreactivityandprenatalsubstanceexpo-
ofRSAoninitiallevelsorgrowthinexecutivedysfunction. sureandearlyadversityoninitialstatusandgrowthinbehav-
We then examined interactions between cumulative sub- ioral dysregulation. There were no significant interactions
stance and baseline RSA at 3 years on initial status and between prenatal substance exposure and linear growth, or
growth in behavioral dysregulation, and the interaction be- prenatalsubstanceexposureandquadraticgrowthinRSAre-
tweenearlyadversityandbaseline RSAat3years oninitial activity,onbehavioraldysregulationinterceptorlinearslope.
status and growth in behavioral dysregulation (in separate We next examined interactions between early adversity and
models). No significant interaction effects emerged. We linearandquadraticgrowthinRSAreactivityoninitialstatus
alsoexaminedtheseinteractionsoninitialstatusandgrowth andgrowthinbehavioraldysregulation.Therewasasignifi-
in executive dysfunction. As with behavioral dysregulation, cantinteractionbetweenearlyadversityandquadraticgrowth
therewerenosignificantinteractioneffects. inRSAreactivity(butnotwithinitialstatusorlineargrowth;
see Figure 1). The inclusion of this interaction resulted in a
significantlybettermodelfit(Table3).Weprobedthisinter-
Effectsofprenatalsubstanceexposureandearlyadversity
actionbyplottingRSAreactivityscoresonestandarddevia-
ongrowthinRSAreactivityandND
tionaboveandbelowthemean(Figure2).Theeffectofearly
WerepeatedtheaboveanalyseswithRSAreactivity,prenatal adversityongrowthinbehavioraldysregulationdependedon
substance exposure, and early adversity as predictors of quadratic growth in RSA reactivity. Children with decelera-
910 E.Conradtetal.
Figure1.Theeffectsofprenatalsubstanceexposure,earlyadversity,growthinrespiratorysinusarrhythmia(RSA)reactivity,andtheirinterac-
tionongrowthinbehavioraldysregulationacrosschildhoodandadolescence.Pathsarebetacoefficients.Allassociationsbetweencovariatesand
growthfactorsweremodeled.Weonlyincludethesignificantpathwaysforeaseofpresentation.RSA-R,RSAreactivity;BD,behavioraldys-
regulation;EA,earlyadversity.*p,.05,**p,.001.
tions in RSA reactivity exhibited growth in behavioral dys- havioral dysregulation. We calculated the effect size as the
regulation regardless of whether they were exposed to early proportionofexplainedvarianceusingthefollowingformula
adversity.ChildrenwhoexhibitedaccelerationsinRSAreac- (Feingold,2009):
tivity, however, showed increases in behavioral dysregula-
tion, but only if they were also raised in environments of R2 ¼ðresidual variance for growth in BD without the
high early life adversity. Children who exhibited accelera-
interaction(cid:3)residual variance for BD with theÞ=
tionsinRSAreactivityandwhowereraisedinenvironments
interaction residual variance for growth in BD
oflessearlyadversityexhibitednosignificantgrowthinbe-
without the interaction:
Table 3.Model fit indices for latent factor main and
interaction effects Theeffectsize(R2)was.40,indicatingthattheinteraction
explainedapproximately40%ofthevarianceingrowthinbe-
RSA-R haviordysregulation.
Next,weexaminedwhethertherewereinteractioneffects
Model SSABIC AIC
on executive function difficulties. The first model included
Maineffectofbehavioraldysregulation 9577.36 9497.09 the interaction between prenatal substance exposure and
Mainandinteractioneffects:EA×RSA-R 9094.38 9014.35 change in RSA reactivityon initial status and change in ex-
ecutivefunctiondifficulties.Thesecondincludedtheinterac-
Note:Onlythemainandinteractioneffectsaspredictorsofgrowthinbehav- tionbetweenearlyadversityandchangeinRSAreactivityon
ioraldysregulationarereported.RSA-R,respiratorysinusarrhythmiareactiv-
initial status and change in executive function difficulties.
ity; SSABIC, sample size adjusted Bayesian information criterion; AIC,
Akaikeinformationcriterion;EA,earlyadversity. Neitheroftheinteractioneffectswassignificant.