József Haller Neurobiological Bases of Abnormal Aggression and Violent Behaviour Neurobiological Bases of Abnormal Aggression and Violent Behaviour . Jo´zsef Haller Neurobiological Bases of Abnormal Aggression and Violent Behaviour Jo´zsefHaller DepartmentofBehavioralNeurobiology InstituteofExperimentalMedicine Budapest,Hungary ISBN978-3-7091-1267-0 ISBN978-3-7091-1268-7(eBook) DOI10.1007/978-3-7091-1268-7 SpringerWienHeidelbergNewYorkDordrechtLondon LibraryofCongressControlNumber:2014934422 ©Springer-VerlagWien2014 Thisworkissubjecttocopyright.AllrightsarereservedbythePublisher,whetherthewholeorpart of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation,broadcasting,reproductiononmicrofilmsorinanyotherphysicalway,andtransmissionor informationstorageandretrieval,electronicadaptation,computersoftware,orbysimilarordissimilar methodologynowknownorhereafterdeveloped.Exemptedfromthislegalreservationarebriefexcerpts inconnectionwithreviewsorscholarlyanalysisormaterialsuppliedspecificallyforthepurposeofbeing enteredandexecutedonacomputersystem,forexclusiveusebythepurchaserofthework.Duplication ofthispublicationorpartsthereofispermittedonlyundertheprovisionsoftheCopyrightLawofthe Publisher’s location, in its current version, and permission for use must always be obtained from Springer.PermissionsforusemaybeobtainedthroughRightsLinkattheCopyrightClearanceCenter. 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Printedonacid-freepaper SpringerispartofSpringerScience+BusinessMedia(www.springer.com) Preface Understanding the brain control of aggression was greatly enhanced over the last decade.Outofthemultitudeofnewdevelopments,thisbookwillprimarily focus on two: the emergence of abnormal aggression models in animals and the intro- ductionandexpansionofbrainimagingtechniquesinhumans.Althoughapparently unrelated, these developments bridged an important gap between animal and humanaggressionresearch. In sharp contrast with human research where aggression-related psychopathol- ogiesare ofmajorinterest,animal research wasforlong dominatedbylaboratory models of natural aggressiveness. Newly developed models detached from this classical approach by mimicking etiological factors of aggression-related psycho- pathologies and by identifying deviant forms of aggression that arise as a conse- quenceofthesetreatments.Thus,animalresearchgraduallyshiftedfromstudying aggression as a natural phenomenon to studying models of abnormal aggression. Recently developed models made clear that laboratory equivalents of etiological factorsinduceprofoundchangesinbrainfunctionandalterqualitativelytheneural circuits that are activated by social conflict and that regulate aggressive behavior underthesecircumstances. Beforetheadventofbrainimagingtechniques,humanresearchlackedadequate toolstostudybrainfunction.Thisisinsharpcontrastwithanimalresearchwherea widerangeofadvancedtechnologiesweredevelopedoverthelastdecades.Inlack ofappropriateresearchtools,assumptionsonhumanbrainmechanismswerebased onanimalstudiesthatwereoccasionallycross-checkedbystudiesinvolvingpeople with accidental brain lesions and by brain stimulation techniques that were rather infrequentlyemployed.Brainimagingtechniquesprovidepowerfultoolsofinves- tigation,whichshowedspectacularadvancementsoverthelastdecade.Newtech- nologies not only allow the study of structural features but also reveal brain connectivity, neurotransmitter receptor profiles, and other important aspects of brainfunction. Inbrief,modelsofabnormalaggressionmadeanimalstudiesmorerelevantfor human research, while brain imaging techniques made human research more relevant for understanding brain mechanisms. These newly acquired features of v vi Preface the two main sides of aggression research have the potential to make them closer partnersandtostartaprocessofintegrationthatisbeneficialforbothsidesandfor aggressionresearchingeneral.Themainaimofthisbookistocreateaplatformfor interactive thinking. We strongly believe that the control of aggression in general and of abnormal aggressiveness in particular cannot be understood without inte- grating animal findings of translational value and human findings. Close interac- tionsbetweenthetwosidesofferhumanresearchthechancetotakeadvantageof thedepthofanalysisallowedbytheadvancedneuroanatomicalandneurofunctional methodologiescurrentlyusedinanimalresearch,whileresearchonanimalaggres- sion will greatly benefit from incorporating information on the phenomenon it models.Thetwodevelopmentsdiscussedhereopenednewchannelsofinformation exchange and created the possibility of jointly addressing the triple linkage of etiological factors, brain changes, and behavior and to unravel novel treatment opportunitiesthattakeintoaccountallthree.Thisbookintendstobethefirststep towardstheintegrationofconceptsandfindingsthatmakesthispossible. Budapest,Hungary Jo´zsefHaller Contents 1 NormalandAbnormalAggressions:DefinitionsandOperational Approaches. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.1 DemarcatingandCharacterizingAggression:Theoretical Definitions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 1.1.1 BasicDefinitions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 1.1.2 DefinitionsforSubtypes. . . . . . . . . . . . . . . . . . . . . . . . . 4 1.1.3 NormalandAbnormalAggressions:BasicPrinciples. .. . 5 1.1.4 ATheoreticalClassificationofAggressiveBehaviors. . . 7 1.2 QuantifyingAggression:OperationalApproaches. . .. . . .. . . .. 9 1.2.1 ModelsofNormalAggressioninAnimals. . . . . . . . .. . . 9 1.2.2 ModelsofAbnormalAggressioninAnimals. . . . . . . . . . 13 1.2.3 ClassificationofAbnormalAggressionModels. . . . . . . . 19 1.2.4 NormalandAbnormalAggressionsinHumans. . . . . . . . 20 1.2.5 ClassificationsofOperationalApproachesinHumans. . . 27 1.3 Definitions,Approaches,andtheValidityofConclusions. . . . . . 29 2 HormonalDeterminants. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 2.1 HormonesandBrainFunction. . . . . . . . . . . . . . . . . . . . . . . . . . 33 2.2 Testosterone. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 2.2.1 MechanismsofAction. . . . . . . . . . . . . . . . . . . . . . . . . . 36 2.2.2 DevelopmentalEffectsonAggressioninAnimals andHumans. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 2.2.3 PostpubertalEffectsinAnimals:NormalandAbnormal Aggressions. . .. . . . .. . . . .. . . . .. . . . .. . . . .. . . . .. 41 2.2.4 DoesTestosteroneAffectAggressioninHumans?. . . . . . 46 2.2.5 TestosteroneandAbnormalAggressioninHumans. . . . . 50 2.2.6 Overview. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 2.3 Glucocorticoids. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 2.3.1 MechanismsofAction. . . . . . . . . . . . . . . . . . . . . . . . . . 53 2.3.2 NormalAggressioninAnimals. . . . . .. . . . . . .. . . . . .. 55 2.3.3 AbnormalAggressioninAnimals. . . . . . . . . . . . . . . . . . 58 vii viii Contents 2.3.4 HealthyHumanControls. . . . . . . . . . . . . . . . . . . . . . . . 59 2.3.5 AbnormalAggressioninHumans. . . . . . . . . . . . . . . . . . 61 2.3.6 Overview. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 2.4 OverallEvaluationofHormonalDeterminants. . . . . . . . . . . . . . 68 3 NeuralCircuitsSubservingAggression:GeneralModels. . . . . . . . 69 3.1 Animals. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 3.1.1 Cats. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 3.1.2 Rats. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 3.2 Humans. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 3.3 Outlook. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76 4 FocalPointsofAggressionControl. . . . . . . . . . . . . . . . . . . . . . . . . 79 4.1 TheHypothalamus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 4.1.1 HypothalamicallyControlledBehaviors. . . . . . . . . . . . . 79 4.1.2 HypothalamicControlofAggressioninAnimals andHumans. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82 4.1.3 HypothalamicMechanismsofAbnormalAggressionin Animals. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88 4.1.4 TheHumanCase. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94 4.1.5 Overview:EtiologicalFactor-DependentAlterationsinthe Hypothalamus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95 4.2 ThePrefrontalCortex. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96 4.2.1 PrefrontalAnatomyofViolence:APrelude. . . . . . . . . . 96 4.2.2 AnOverallSummaryoftheGeneralView. . . . . . . . . . . 97 4.2.3 ProblemswiththeGeneralView. . . . . . . . . . . . . . . . . . 99 4.2.4 The“PsychologicalLandscape”Hypothesis. . . . . . . . . . 112 4.2.5 The“NeuralNetwork”Hypothesis. . . . . . . . . . . . . . . . . 117 4.3 TheAmygdala. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120 4.3.1 StructureandGeneralRolesinBehavior. . . . . . . . . . . . . 121 4.3.2 NormalAggressioninAnimals. . . . . .. . . . . . .. . . . . .. 124 4.3.3 AbnormalAggressioninAnimals. . . . . . . . . . . . . . . . . . 127 4.3.4 NormalandAbnormalAggressionsinHumans. . . . . . . . 129 4.3.5 Overview. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134 4.4 ThePeriaqueductalGray. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135 4.4.1 TheRoleofthePeriaqueductalGray(PAG)inBehavioral Control. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135 4.4.2 TheRoleofthePAGinAnimalAggression. . . . . . . . . . 138 4.4.3 TheRoleofthePAGinHumanAggression. . . . . . . . . . 143 4.4.4 Overview. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144 5 TheRoleofEmergingTechniquesinUnderstandingAggression. . . 145 5.1 Optogenetics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145 5.2 Epigenetics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146 5.3 FunctionalPharmacology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148 5.4 GeneticsandPharmacogenetics. . . . . . . . . . . . . . . . . . . . . . . . . 149 5.5 Overview. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150 Contents ix 6 SummaryandSynthesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151 6.1 Who’sFlyingthePlaneandWhatKindofPlane?. . . . . . . . . . . . 151 6.2 BehaviorandBrainFunctioninAnimalAggression. . . . . . . . . . 152 6.2.1 NormalAggression. . . . . . . . . . . . . . . . . . . . . . . . . . . . 152 6.2.2 AbnormalAggression. . . . . . . . . . . . . . . . . . . . . . . . . . 154 6.2.3 TheRoleofthePrefrontalCortex. . . . . . . . . . . . . . . . . . 157 6.3 BehaviorandBrainFunctioninHumanAggression. . . . . . . . . . 158 6.3.1 TheDualTheoryofAggression. . . . . . . . . . . . . . . . . . . 159 6.3.2 TypesofAggressionandBrainFunction. . . . . .. . . . . . . 162 6.4 Hormones. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 164 Postscript. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167 Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215