Neuroimaging in Addiction

346 Pages·2011·30.01 MB·English

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Neuroimaging
in Addiction
P1:OTA/XYZ P2:ABC
JWST066-FM JWST066-Adinoff August22,2011 11:50 PrinterName: YettoCome
Neuroimaging
in Addiction
Bryon Adinoff
Department of Psychiatry, UT Southwestern Medical Center and VA
North Texas Health Care System, Dallas, TX, USA
Elliot A. Stein
National Institute on Drug Abuse, National Institutes of Health,
Baltimore, MD, USA
A John Wiley & Sons, Ltd., Publication
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Thiseditionfirstpublished2011(cid:2)c 2011byJohnWiley&Sons,Ltd
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LibraryofCongressCataloging-in-PublicationData
Adinoff,Bryon.
Neuroimaginginaddiction/BryonAdinoffandElliotStein.
p.;cm.
Includesbibliographicalreferencesandindex.
ISBN978-0-470-66014-0(cloth)
1.Compulsivebehavior–MagneticResonanceImaging. 2.Brain–Effectofdrugson.
3.Brain–Radiography. I.Stein,Elliot. II.Title.
[DNLM:1.Behavior,Addictive–radiography. 2.Brain–drugeffects. 3.Brain–
radiography. 4.MagneticResonanceImaging–methods. 5.Substance-Related
Disorders–radiography. 6.Tomography,X-RayComputed–methods. WM176]
RC533.A352011
616.8’047572–dc23
2011021437
AcataloguerecordforthisbookisavailablefromtheBritishLibrary.
Thisbookispublishedinthefollowingelectronicformats:ePDF9781119998464;
WileyOnlineLibrary9781119998938;ePUB9781119972709;MobiPocket9781119972716
Typesetin9/11ptTimesbyAptaraInc.,NewDelhi,India
1 2011
CoverfigurecourtesyofDr.XujuanGengoftheNIDA-IRP,wherethisworkwasdone.Dr.Gengis
nowAssistantProfessor,DepartmentofPsychiatry,UniversityofNorthCarolina,USA.
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To my lovely wife, Trish, and my wonderful children, Zack
and Holly. Their love and support through the years have
calmed my limbic hot spots.
Bryon Adinoff
To Marsha, Lindsay and Matthew: All that I am,
all that I do, is better because of you.
Elliot Stein
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Contents
Foreword xi
EdytheD.London
List of Contributors xv
1 Introduction 3
BryonAdinoffandElliotA.Stein
References 5
2 An Integrated Framework for Human Neuroimaging Studies
of Addiction from a Preclinical Perspective 9
KarenD.ErscheandTrevorW.Robbins
2.1 Introduction 9
2.2 AConceptualFrameworkforUnderstandingDrugAddictionBasedon
PreclinicalObservations 9
2.3 NeuropharmacologicalConsiderations 15
2.4 NeuropathologyofChronicDrugAbuse 15
2.5 Impulsivity:AnEndophenotypeforDrugAddiction 17
2.6 Compulsivity:CravingversusDrug-Seeking 20
2.7 Summary 25
References 26
3 Structural and Functional Neuroimaging Methods:
Applications to Substance Abuse and Addiction 39
YihongYang,SvetlanaChefer,XiujuanGeng,HongGu,XiChen,andElliot
A.Stein
3.1 Introduction 39
3.2 MRIBasedImagingToolsandtheirApplicationtoDrugAbuseResearch 40
3.3 MolecularImagingwithPETandSPECT 59
3.4 SummaryandPeekintotheFuture 69
References 69
4 Functional Neuroimaging of the Acute Effects of
Drugs of Abuse 85
LaurenceJohnReedandDavidJ.Nutt
4.1 Introduction 85
4.2 FundamentalNeuronalSystemsRelatedtoAbuseLiabilityinHumans 86
4.3 Psychostimulants 87
4.4 Alcohol 92
4.5 CannabisandtheCannabinoids 95
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viii Contents
4.6 Opioids 96
4.7 ConclusionsandFutureDirections 98
References 99
5 Reward Processing 107
AnneBeck,AnthonyA.Grace,andAndreasHeinz
5.1 Introduction 107
5.2 NeurotransmitterSystemsImplicatedinRewardProcessing 107
5.3 NeurotransmitterSystemsInvolvedinDrug-RelatedRewardProcessing 110
5.4 AlterationsintheMesostriatalSysteminAddiction 116
5.5 SummaryandOutlook 122
5.6 Acknowledgments 123
References 123
6 A Neuroimaging Approach to the Study of Craving 133
FrancescaM.Filbey,EricD.Claus,andKent.E.Hutchison
6.1 ANeuroimagingApproachtotheStudyofCraving 133
6.2 NeuralResponseDuringCue-ElicitedCraving 134
6.3 AssociationsbetweenNeuralandSubjectiveResponseDuring
Cue-ElicitedCraving 141
6.4 ModulatorsofNeuralResponseDuringCue-ElicitedCraving 142
6.5 EffectsofInterventionontheNeuralResponseDuring
Cue-ElicitedCraving 147
6.6 SummaryandIntegrationofFindings 149
6.7 Conclusions 151
References 151
7 Impulsivity and Addiction 159
HughGaravan
7.1 Introduction 159
7.2 ImpulsivityasRewardversusControl 159
7.3 TheNeurobiologyofImpulsivity 161
7.4 ImpulsivityandRiskforDevelopingaDrugUseDisorder 163
7.5 ImpulsivityinCurrentUsers 165
7.6 Impulsivity,Abstinence,andRelapse 168
7.7 Conclusion 170
References 171
8 Cognitive Disruptions in Drug Addiction: a Focus on the
Prefrontal Cortex 179
RitaZ.Goldstein,ScottJ.Moeller,andNoraD.Volkow
8.1 Introduction 179
8.2 Attention 181
8.3 WorkingMemory 190
8.4 Decision-Making 193
8.5 Pre-MorbidVulnerabilities 198
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Contents ix
8.6 OtherBrainRegions 198
8.7 LimitationsAcrossAllStudies 199
8.8 TreatmentImplications 200
8.9 GeneralSummaryandConclusions 200
8.10 Acknowledgments 201
References 201
9 Neural Mechanisms of Stress and Addiction 211
DongjuSeoandRajitaSinha
9.1 StressandAddiction 211
9.2 NeuralCircuitsofStressRegulation 212
9.3 DysfunctionintheNeuralCircuitsUnderlyingStressandAddiction 218
9.4 InterplayofGene,Stress,andDrugIntake 222
9.5 Acknowledgments 224
References 224
10 Anatomical and Neurochemical Evidence of Neurotoxic
Changes in Psychostimulant Abuse and Dependence 237
YoungHoonSungandPerryF.Renshaw
10.1 Introduction 237
10.2 CharacteristicsofPsychostimulants 238
10.3 QuantitativeMRMorphologyChangesAssociatedwith
PsychostimulantDependence 239
10.4 GrossAnatomicChangesinBrainStructuresandSubtleNeurotoxicity 240
10.5 RelationshipbetweenErrantNeuromodulationbyDrugAbuseand
CognitiveAbnormalities 241
10.6 NeurochemicalAlterationsandPsychostimulantDependence 244
10.7 AbnormalWhiteMatterIntegrityinPsychostimulantDependence 249
10.8 AlcoholandOpiateAddiction 251
10.9 Conclusion 252
References 253
11 Neuroimaging in Behavioral Addictions 263
BryonAdinoffandCythniaR.Harrington
11.1 Introduction 263
11.2 DiagnosticConsiderations 264
11.3 MesostriatalDopaminePathway 265
11.4 Reward 269
11.5 Craving 273
11.6 FutureDirections 277
References 279
12 Imaging Genetics and Addiction 287
VibhutiSrivastavaandDavidGoldman
12.1 Introduction 287
12.2 DomainsofVulnerability 289
12.3 CognitiveFunction 300
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12.4 BrainMorphometricChanges 301
12.5 BridgingGaps 302
12.6 ImagingPharmacogenetics 304
12.7 Conclusion 306
Glossary 308
References 309
13 The Diagnostic and Therapeutic Potential of
Neuroimaging in Addiction Medicine 321
MartinaReskeandMartinP.Paulus
13.1 CanfMRIBecometheECGinAddictionMedicine,orWhatArethe
TreatmentImplicationsofNeuroimagingResearchinDrugAddiction? 321
13.2 FunctionalNeuroimaginginAddiction:RelevantCognitiveConstructs
toAddressduringTreatment 322
13.3 DrugChallengeStudiesEnhanceKnowledgeonPharmacokineticsand
Drug-Experience-Relationships 325
13.4 ImagingSymptomSeverity 325
13.5 Neuroimaging-BasedMonitoringofTreatmentRegimesandthe
PredictionofTreatmentOutcomes 326
13.6 AssessingtheRelapsePotentialUsingfMRI 329
13.7 NeurofeedbackasaTherapeuticApproach? 334
13.8 MethodologicalChallengestoUtilizeFunctionalNeuroimagingasa
ClinicalTest 335
13.9 TheNearFutureofBrainImaginginAddictionMedicine 336
References 338
Index 345
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Foreword
Edythe D. London, PhD
SemelInstituteofNeuroscienceandBiobehavioral
Sciences,DepartmentofMolecularandMedical
Pharmacology,DavidGeffenSchoolofMedicineat
UCLA,USA
Addictivedisordersareamongtheprimarypreventablecausesofmajorhealthproblems.
Theyalsopresenttherapeuticchallenges,andoftenaretreatment-resistantandcharac-
terizedbyrelapse.Thequestforeffectiveaddictiontreatmentshasevolvedinparallelwith
major technical advances in the field of brain imaging, which have yielded convincing
illustrations that addictions are “brain diseases.” With this in mind, it seems appropri-
ate that a thorough understanding of how disturbances in brain circuitry promote and
maintainaddictioncanhelpadvancethedevelopmentofeffectiveaddictiontherapies.
Publication of Neuroimaging in Addiction is timely in view of substantial changes in
technology and approaches since the appearance of a previous volume on the same
subject, almost a decade ago [1]. Relevant advances include the development of new
imaging techniques and their application to clinical problems. For example, although a
patentwasissuedfortheuseofdiffusiontensorimaging(DTI)in1996[2],itwasyears
later,afterthetechniquewasdeemedfeasibleforstudiesofthebrain,thattherewasa
proliferationofstudiesusingDTIforassessmentofwhitematter.Notably,mostarticles
usingDTIinstudiesofsubstanceabusehaveappearedintheliteratureonlywithinthe
past three years. Similarly, while the technique of determining functional connectivity,
using functional MRI in the resting state, was described in the late 1990s [3,4], this
approach has only been applied in addiction research in recent years [5]. Not only has
thelastdecadeseentheapplicationofnewimagingtechniques,buttherehavealsobeen
substantialadvancementsinfunctionalandstructuralimageanalysisprocedures,which
havegreatlyinfluencedtheflexibility,scope,andsensitivityofneuroimagingstudies[6].
With that in mind, the editors of this book, Bryon Adinoff and Elliot Stein, have as-
sembledanoutstandinggroupofinternationalscholarswhocontributedtothepresent
volume.Thebookprovidesalogicalsequenceofchapters,beginningwithapresentation
ofcurrentknowledgeregardingtheneuralcircuitsandneurotransmittersaffectedbythe
acute and chronic administration of drugs of abuse, with a focus on findings gleaned
primarilyfromanimalstudies.Afteradescriptionofvariousimagingmodalitiesandhow
they are used in studies of addiction, the next chapters deal with the acute effects
of drugs of abuse, reward processing and craving, and the progression of changes that
occur as addiction develops. The subsequent chapters discuss impulsive behavior and
neuroimagingstudiesofdisruptionsincognitivefunction,suchaschangesindecision-
making, that contribute to the maintenance of addictions and that can interfere with
behavioraltreatments.Next,thereisachapterexploringtheroleofstressinthedevelop-
mentofaddictionandinrelapsetosubstanceabusefollowedbyachapterthatpresents
anatomicalevidenceforstructuralchangesassociatedwithaddictivedisorders.
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xii Foreword
Inviewofresearchdevelopmentsoverthepastdecade,includingevidencethatvarious
addictions(alcohol,drugs,sugar,etc.)involvethesameneurotransmittersandcircuits,as
well as commonalities in genetic markers of addiction vulnerability, the book generally
considers addictions as a group of disorders that share neural substrates, without a
primaryfocusonanyonesubstanceofabuse.Thisisexemplifiedbyachapterwhichhas
beendevotedtoneuroimagingstudiesofnon-chemicaladdictions.Giventheenormous
contribution of uncontrolled eating to obesity, diabetes, and other highly prevalent
anddebilitatingdiseases,suchascardiovasculardiseaseandstroke,majorattentionto
non-substanceaddictionsiswarranted.Brainimagingstudiespointtocommonalitiesin
theneuralcorrelatesofthesedisorders,suggestingthatapproachesaimedatcorrecting
neural function in common circuitry may be useful in treating the array of addictive
disorders.Such approaches have thepotentialtoreduce theburden ofdiseaseacrossa
varietyofsyndromesthatfeaturelossofself-controlasasymptom.
Withrespecttoaddictionvulnerability,linkageanalyses,candidate-geneanalysesand
genome-wide association studies have yielded findings that have implicated specific
genes.Nonetheless,becauseoftheprofoundinfluencesofepigeneticandenvironmental
factors,intermediatephenotypesatthelevelofneuralsystemscanprovidevaluablecor-
relatesofbehavioralmeasures.Furthermore,assessmentsofneuralmarkersandresponses
can be used in studies of the mechanisms by which genotype can influence behavior.
Considering these issues, a chapter in this volume focuses on the use of brain imaging
studiestodescriberelevantintermediatephenotypesthatarelinkedtoaddiction.
The volume closes with a chapter that integrates the previous chapters and provides
examplesandconsiderationsofhowbrainimagingcanbeusedtopredictriskforaddic-
tion,diagnosisofaddictivedisorders,andpersonalizationoftreatment.Identificationof
individuals with neural phenotypes that confer risk for addiction can help target those
who might maximally benefit from targeted preventive interventions. Such prophylaxes
include educational programs, behavioral approaches, and even vaccines against drug
addictions, which are currently under investigation. Although success in clinical trials
can be predicted from self-reports of drug use and urine screening [7], which are less
costlythanneuroimaging,itispossiblethatidentificationofdysfunctionatthecircuit
levelmaybeusefulinselectinganappropriatetargetedtreatment.
The birth of the field of brain imaging brought with it the hopes of diagnosing
neuropsychiatricdiseasesthataredifficulttodiscernfromoneanother,andidentifying
themostrelevanttherapeutictargets.Althoughtheuseofbrainimagingfordiagnostic
purposes has not been as successful as predicted 30 years ago, the increasingly
progressivedevelopmentofbrainimagingtechnologieshasprovideduswiththemeans
toclarifythelinksbetweenneuralcircuitsandbehavioralstatesthatleadtoandresult
fromaddictivedisorders.
This volume brings us up to date on how imaging technologies are applied in under-
standing addiction and the therapeutic targets that it presents. Research in the next
decade promises equally exciting advances in molecular brain imaging techniques and
theirapplicationindrugabuseresearch.Attheveryleast,positronemissiontomography
research is at the brink of providing new radiotracers that extend our ability to study
the brain of drug-abusing individuals and to evaluate effects of treatments. For exam-
ple,whilecurrentlyavailableradiotracerscanbeusedtoassessstriatalandextrastriatal
D2-likedopaminereceptoravailability,ongoingdevelopmentfocusesontracersforquan-
titativeassayofdopaminedynamicsinlow-receptorareasofbrain,suchasthecerebral
cortex.Furthermore,ongoingresearchisdirectedatovercomingtheradiationdosimetry
limitationsofnuclearmedicineapproaches(PETandSPECTscanning),whichrestricttheir