Rodrick Wallace · Deborah Wallace Gene Expression and Its Discontents The Social Production of Chronic Disease Second Edition Gene Expression and Its Discontents Rodrick Wallace • Deborah Wallace Gene Expression and Its Discontents The Social Production of Chronic Disease Second Edition 123 RodrickWallace DeborahWallace DivisionofEpidemiology NewYork,NY,USA TheNewYorkStatePsychiatricInstitute atColumbiaUniversity NewYork,NY,USA ISBN978-3-319-48077-0 ISBN978-3-319-48078-7 (eBook) DOI10.1007/978-3-319-48078-7 LibraryofCongressControlNumber:2016955556 ©SpringerInternationalPublishingSwitzerland2010,2016 Thisworkissubjecttocopyright.AllrightsarereservedbythePublisher,whetherthewholeorpartof thematerialisconcerned,specificallytherightsoftranslation,reprinting,reuseofillustrations,recitation, broadcasting,reproductiononmicrofilmsorinanyotherphysicalway,andtransmissionorinformation storageandretrieval,electronicadaptation,computersoftware,orbysimilarordissimilarmethodology nowknownorhereafterdeveloped. Theuseofgeneraldescriptivenames,registerednames,trademarks,servicemarks,etc.inthispublication doesnotimply,evenintheabsenceofaspecificstatement,thatsuchnamesareexemptfromtherelevant protectivelawsandregulationsandthereforefreeforgeneraluse. Thepublisher,theauthorsandtheeditorsaresafetoassumethattheadviceandinformationinthisbook arebelievedtobetrueandaccurateatthedateofpublication.Neitherthepublishernortheauthorsor theeditorsgiveawarranty,expressorimplied,withrespecttothematerialcontainedhereinorforany errorsoromissionsthatmayhavebeenmade. Printedonacid-freepaper ThisSpringerimprintispublishedbySpringerNature TheregisteredcompanyisSpringerInternationalPublishingAG Theregisteredcompanyaddressis:Gewerbestrasse11,6330Cham,Switzerland Preface Within the United States, beginning in the late 1980s, several chronic conditions began epidemic increases of both incidence and prevalence. These conditions includedasthma,obesity,obesity-relateddiseasessuchasdiabetes,certaincancers, andAlzheimer’sdisease(AD).Scientificpapersdulyreportedtheexistenceofgenes that putatively made their carriers more vulnerable to these conditions than the generalpublic.However,thegeneticcompositionofUSpopulationsdidnotchange so rapidly as to be a basis for these rapid epidemics. HIV/AIDs and tuberculosis, although infectious, are classed as chronic diseases and also became epidemic in the United States during these years. Mental disorders also form an important set ofpersistentchronicconditionshaving“environmental”correlationsthatchallenge simplegeneticetiologies. Furthermore, many of these epidemics had geographic foci at multiple levels of organization: neighborhood, municipality, county, state, and country. Many conditions formed “syndemics”—multiple epidemics with the same geography. Poor neighborhoods of color showed heightened incidence and prevalence within citiesandformedthecentersfromwhichtheepidemicsspread.Poorneighborhoods thathadexperiencedresidentialupheavalsandinstabilitiesparticularlyshowedgreat vulnerability. Cities with residential and economic instability showed higher inci- dence/prevalence than others and formed the foci of spread between metropolitan regionsofthecountry.ThestatesoftheSoutheast,characterizedbyextremesocial andeconomicinequality,rigidsocioeconomichierarchyovertime,loweducational attainment, and a culture-based ideology of individualism, showed the highest incidence/prevalenceofobesity,obesity-relateddiseasesandmortalities,AIDS,and ADmortality. Maps of prevalence and incidence reflect complex cognitive processes. Socioe- conomic and environmental signals impinge on populations and their individual constituents,havingvaryingsensitivityandvulnerability.Sensitivityandvulnerabil- ityaredeterminedbytheinterlinkedfactorsofculture,historicaltrajectory,material resources,socialstructureandstability,and,mostcentrally,publicpoliciesthatcan mitigateorexacerbatethesefactors. v vi Preface Individualsandpopulationsarecognitive—abletochooseoneorafewresponses fromalargersetofthosepossible—andactinamultilevellinkedprocessagainst, or consonant with, these signals. Within individuals, the signals and responses involve internal cognitive processes, for example, the “fight or flight” response to a perceived threat, a response involving the brain, pituitary gland, adrenal gland, circulatory system, and energy regulatory mechanisms. Epigenetic changes triggered by the signals or the initial recognition of the signals induce cognitive geneticprocessesaswell. The strong influence of cognitive processes at levels of organization from the nationdowntothemolecularbiologyofindividualsimpliesthatinformationtheory, controltheory,andmathematicalmodelingbasedonthemcandescribeandpredict patterns of chronic disease in cultural and socioeconomic contexts. In this book, we develop statistical models of such processes that are akin in spirit to—but differentfrom—ordinaryregressionmodelsandreportempiricaldataandanalyses toillustratethisparadigm. The first six chapters use the asymptotic limit theorems of information theory tounderstandhowepigeneticcontextaffectsorganismaldevelopmentbyinvokinga cognitiveparadigmforgeneexpression.Asimpleargumentsuggeststhatepigenetic information sources act as analogs to a tunable catalyst, directing development to differentcharacteristicpathwaysinamannersimilartoecosystemresilienceshifts. Theresultshavesignificantimplicationsforepigeneticepidemiology,showinghow environmentalstressors,inalargesense,caninduceaspectrumofchronicdisorders. Chapter 7 examines the US obesity epidemic from this viewpoint. Chapters 8 and9applytheperspectivetoheartdiseaseandcancerand,intheirlatersections, introduce tools from control theory that illuminate the central role of “environ- mental” context. Chapters 10–12 apply the general model to a number of diseases broadly associated with obesity that are becoming pandemic, using US data at different scales of observation. Chapters 13 and 14 study how “culture” and “environment”affecttheonsetandprogressionofmentaldisorders.Chapters15–18 provide case histories involving low weight births, “Right-to-work” laws and AD, diabetesandthyroidcancerinManhattan’sChinatown,andtheetiologyofviolence andobesity.Chapter19exploresacompositemodelofpsychopathology,sleep,and cultureinthecontextofenvironmentalinsult. Thetheoryappears toworkverywellatindividual andsimpleaggregate levels for anumber of chronic conditions instressedpopulations. Environments thatcan be characterized as having regularities of “grammar” and “syntax” can interact with organismal development via epigenetic catalysis to literally write distorted images of themselves onto the human life course in a highly pleiotropic and oftenpunctuatedmanner,producingtrajectoriestoarangeofseriousdysfunctions. Communities, in which individuals respond collectively, however, display more complicated patterns of chronic disease that may represent another example of a “mesoscale resonance” in which the dynamics of ecological keystone structures entrainphenomenaatotherscales. One implication of this work is that pandemic chronic diseases at both the individual, via pleiotropy, and the population scales, via collective modalities Preface vii of gene expression, are unlikely to respond to individual-level—i.e., medical— interventionsinthefaceofserious,persistentindividualandcommunitystressand may require large-scale changes in public policy and resource allocation for their amelioration.Drugspowerfulenoughtoaffectdeleteriousepigeneticprogramming are likely to trigger profound iatrogenic “side effects” that, over the life course, wouldnotonlyobviatetheinterventionbutmostlikelyleadtoshortenedlifespans. The book, a synthesis across a number of peer-reviewed publications and additionalmaterialwrittenforthisvolume,canbereadatseverallevels.Chapters1 and 6–20 form a natural introductory unit that can be followed by the more mathematicalsectionsasdesired.Mathematicaldetailsarecollectedinanappendix. However,thecontroltheorymethodsintroducedinthelatterpartsofChaps.8and9 areusedextensivelyinChaps.14and19. In sum, we provide something of a badly needed corrective to simplistic “genetic”explanationsofchronicdiseasethat,politically,areinherentlyusefulfor blamingthevictimandundercuttinginterventionstrategiesseenasdisruptivetothe interestsofrulingelites.Wefocusinsteadonthegenerationofdiseasephenotypes bysocialforcesthatcanbemitigatedoramplifiedbypublicpolicy. NewYork,NY,USA RodrickWallace DeborahWallace Contents 1 Introduction ................................................................ 1 1.1 TowardNewTools.................................................. 1 1.2 EpigeneticEpidemiology........................................... 2 1.3 EcosystemResilience............................................... 6 1.3.1 ComorbidDisorders....................................... 7 1.3.2 SomeCognitiveModulesofHumanBiology............ 8 1.3.3 Cognitionas“Language”:anIntroduction............... 11 1.3.4 AMultiplicityofResilienceTopologies ................. 12 1.3.5 InSummary................................................ 14 1.4 AFirstSurveyoftheObesityPandemicintheUSA.............. 15 2 ModelsofDevelopment .................................................... 27 2.1 TheSpinglassModel ............................................... 27 2.2 ShiftingPerspective:CognitionasanInformationSource........ 30 3 GroupoidSymmetries...................................................... 35 3.1 TheFirstLevel...................................................... 36 3.2 TheSecondLevel................................................... 36 3.3 SpontaneousSymmetryBreaking.................................. 37 3.4 ABiologicalExample .............................................. 38 4 EpigeneticCatalysis........................................................ 43 4.1 TheBasicIdea ...................................................... 43 4.2 RateDistortionDynamics.......................................... 44 4.3 MoreTopology...................................................... 47 4.4 InheritedEpigeneticMemory ...................................... 48 4.5 MultipleProcesses.................................................. 49 4.6 “Coevolutionary”Development.................................... 50 4.7 MultipleModels .................................................... 51 4.8 EpigeneticFocus.................................................... 52 ix x Contents 5 DevelopmentalDisorders.................................................. 55 5.1 NetworkInformationTheory....................................... 55 5.2 EmbeddingEcosystemsasInformationSources.................. 56 5.3 EcosystemsFarmDevelopment.................................... 56 5.4 ASimpleProbabilityArgument.................................... 59 5.5 DevelopmentalShadows............................................ 60 5.6 EpigeneticProgrammingofArtificialSystems forBiotechnology................................................... 62 6 AnInterimPerspective..................................................... 63 7 TheObesityPandemicintheUSA........................................ 67 7.1 Introduction ......................................................... 67 7.2 StressandtheHPAAxis............................................ 68 7.3 HPAAxisCognition................................................ 69 7.4 InteractingInformationSources.................................... 69 7.5 AHPAAxisModel................................................. 71 7.6 PsychosocialStress,OccupationalControl,andWeightGain.... 74 7.7 ObesityasaDevelopmentalDisorder.............................. 74 7.8 RecentTrajectoriesofStructuredStressintheUSA.............. 75 7.9 ConfrontingtheObesityEpidemic................................. 82 8 HeartDisease................................................................ 87 8.1 CoronaryHeartDiseaseintheUSA ............................... 87 8.1.1 Cognition,ImmuneCognition,andCulture ............. 90 8.1.2 PunctuatedInterpenetration:Adaptingto PathogenicHierarchy ..................................... 93 8.1.3 ImplicationsforIntervention ............................. 94 8.2 Thrombogenesis..................................................... 97 8.2.1 ControlTheory:TheDataRateTheorem................ 98 8.2.2 TheInformationCostofHemostaticRegulation........ 99 8.2.3 ControlFailureDynamics ................................ 101 8.2.4 CognitiveSymmetryBreaking ........................... 102 8.2.5 Onsetof“Turbulent”ClotGrowth ....................... 103 8.2.6 ImplicationsforIntervention ............................. 104 9 Cancer ....................................................................... 107 9.1 ADevelopmentalModel............................................ 107 9.2 EnvironmentalInsultandRegulatoryFailure ..................... 114 10 AutoimmuneDisorders .................................................... 121 10.1 Introduction ......................................................... 121 10.2 NonorthogonalEigenmodesofImmuneCognition............... 124 10.3 CircadianandOtherCycles ........................................ 126 10.4 TheRetinaoftheImmuneResponse .............................. 129 10.5 Circadian-HormonalCycleSynergism ............................ 130 10.6 TheCognitiveHPAAxis ........................................... 131 Contents xi 10.7 PhaseTransitionsofInteractingInformationSystems............ 132 10.8 AutoimmuneDisease............................................... 133 10.9 AnApplicationtoAsthma.......................................... 135 10.10 ImagesofPathogenicSocialHierarchy............................ 136 11 DemoralizationandObesityinUpperManhattan...................... 141 11.1 Introduction ......................................................... 141 11.2 Methods ............................................................. 142 11.2.1 RecruitmentoftheMothers............................... 142 11.2.2 PrenatalQuestionnaire.................................... 142 11.2.3 SocioeconomicData ...................................... 144 11.2.4 ChronicCommunityStressIndex........................ 144 11.3 DataAnalysis ....................................................... 147 11.4 ModelingDemoralizationandChronicStress..................... 147 11.5 Results............................................................... 148 11.5.1 DemoralizationandChronicStress ...................... 148 11.5.2 SignalTransductionModeling............................ 150 11.5.3 BodyMassIndex.......................................... 151 11.5.4 HouseholdDeprivation ................................... 152 11.6 Discussion........................................................... 154 11.6.1 TheAsymmetricInverted“U”Curve .................... 154 11.6.2 TheBodymassIndex..................................... 155 11.7 Conclusion .......................................................... 157 12 Death at an Early Age: AIDS and Related Mortality inNewYorkCity ........................................................... 161 12.1 Introduction ......................................................... 161 12.2 DataandAnalysis................................................... 163 12.3 Results............................................................... 165 12.4 Discussion........................................................... 170 13 WesternAtomismandItsCulture-BoundSyndromes ................. 181 13.1 Introduction ......................................................... 181 13.2 WesternAtomisticEconomics ..................................... 183 13.3 CognitionasanInformationSource ............................... 185 13.4 EnvironmentasanInformationSource............................ 187 13.5 InteractingInformationSources.................................... 188 13.6 CrosstalkTopologies................................................ 189 13.7 PunctuatedCriticalPhenomena.................................... 190 13.8 Implications......................................................... 192 14 EnvironmentalInductionofNeurodevelopmentalDisorders.......... 195 14.1 Introduction ......................................................... 195 14.2 StabilizingGeneExpression ....................................... 197 14.3 TheCostofRegulation............................................. 198 14.4 Parsing(cid:2)............................................................. 198 14.5 TheDynamicsofControlFailure.................................. 199