Schizofrenie

SCHIZOPHRENIAResearchAn ofcial journal of the Schizophrenia International Research SocietyVolume 153 Supplement 1April 2014 ISSN 0920-9964 Abstracts of the4th Biennial Schizophrenia International Research ConferenceFlorence, Italy, 59 April 2014Volume 153 (2014)SCHIZOPHRENIARESEARCHAN OFFICIAL JOURNAL OF THE SCHIZOPHRENIA INTERNATIONAL RESEARCH SOCIETYSchizophrenia Research has no page charges.SCHIZOPHRENIARESEARCHAN OFFICIAL JOURNAL OF THE SCHIZOPHRENIA INTERNATIONAL RESEARCH SOCIETYJ. Addington, CanadaD. Barch, U.S.A.D.L. Braff, U.S.A.P. Buckley, U.S.A.K. Cadenhead, U.S.A.E. Cantor-Graae, SwedenA. Carlsson, SwedenE.Y. Chen, ChinaJ.G. Csernansky, U.S.A.M. Davidson, IsraelP. Dazzan, U.K.M. De Hert, BelgiumR. Emsley, South AfricaW.W. Fleischhacker, AustriaR. Freedman, U.S.A.J. Ford, U.S.A.D. Goff, U.S.A.A.A. Grace, U.S.A.M.F. Green, U.S.A.R.E. Gur, U.S.A.P.J. Harrison, U.K.P.D. Harvey, U.S.A.S. Heckers, U.S.A.D.C. Javitt, U.S.A.R.S. Kahn, The NetherlandsJ.M. Kane, U.S.A.S. Kapur, U.K.R. Keefe, U.S.A.M. Keshavan, U.S.A.S. Leucht, GermanyD.A. Lewis, U.S.A.J.A. Lieberman, U.S.A.D. Malaspina, U.S.A.S.R. Marder, U.S.A.D. Mathalon, U.S.A.P. McGorry, AustraliaJ.J. McGrath, AustraliaP. McGuire, U.K.J. Meador-Woodruff, U.S.A.K. Mueser, U.S.A.R.M. Murray, U.K.C.B. Nemeroff, U.S.A.K. Nuechterlein, U.S.A.J.J. van Os, The NetherlandsC. Pantelis, AustraliaS. Park, U.S.A.A. Sawa, U.S.A.S.C. Schulz, U.S.A.S.G. Schwab, AustraliaM.E. Shenton, U.S.A.M. Takeda, JapanC.A. Tamminga, U.S.A.R. Tandon, U.S.A.S. Tianmei, P.R. ChinaH. Verdoux, FranceJ.L. Waddington, U.K.C.S. Weickert, AustraliaD.R. Weinberger, U.S.A.T. Wykes, U.K.A. Yung, AustraliaR.B. 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Souers Professor and Chair Department of Neurology and Psychiatry St. Louis UniversitySchool of Medicine 1438 S. Grand Blvd, St. Louis, MO 63104, USA,Tel: +1 314 977 4824, Fax: +1 314 977 4876 E-mail: [email protected]. E. DELISI, M.D.Professor of Psychiatry Harvard Medical SchoolVA Boston Healthcare System940 Belmont AveBrockton, Mass 02301E-mail: [email protected] 153, 2014Amsterdam Boston London New York Oxford Paris Philadelphia San Diego St. LouisSCHIZOPHRENIARESEARCHAN OFFICIAL JOURNAL OF THE SCHIZOPHRENIA INTERNATIONAL RESEARCH SOCIETY 2014 Elsevier B.V. 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Because of rapid advances in the medical sciences, in particular, independent verification of diagnoses and drug dosages should be made.Although all advertising material is expected to conform to ethical (medical) standards, inclusion in this publication does not constitute a guarantee or endorsement of the quality or value of such product or of the claims made of it by its manufacturer.Available online at www.sciencedirect.comSchizophrenia Research 153, Supplement 1 (2014) S1S384Abstracts of the 4th Biennial Schizophrenia International Research ConferenceFlorence, Italy, 59 April 2014PLENARY & SYMPOSIA SESSIONS, ORAL PRESENTATIONS AND WORKSHOPSSpecial SessionITALIAN RESEARCH DAYSaturday, 5 April 2014 10:00 AM 5:15 PMThissatellitemeetingbuildsonaverysuccessful similardayatthelastSIRS meeting. It provides the opportunity to all attendees, and to allthose interested in mental illness, to hear the best of Italian Research intoSchizophrenia, both from those Italian research scientists now working inother countries and those carrying out research in major Italian Centres.Wewill hearofhowtheincidenceofschizophreniaappearssurprisinglylowindifferent centresinItaly, of therelativeimportanceinItalyandelsewhere of risk factors for schizophrenia such as child abuse, immigrationanddrugabuse(includingnovel internetdrugs). Wewill alsohearhowimaging canpredict outcome of psychosis andhowit reects geneticpredisposition.Theafternoonwill includesessions ontheways inwhichrelatives areinvolved in care of people with psychosis in Italy. The day will close with apanel of very distinguished clinicians from across the globe discussing themeritsanddemeritsof thecareofferedtopeoplewithschizophreniaintheir respective countries.The day will be in English and is open and free to all attendees at the SIRSmeeting and indeed the general public (Italian and non-Italian alike). Thosewith experience of psychosis and their relatives are very welcome.THE ROAD FROM DAMASCUS: A SCIENTIFIC JOURNEYHuda AkilUniversity of Michigan, United States of AmericaInthistalk, Dr. Akil will shareher transitionfromSyriatotheUSAtobecomeascientist, witnessingthediscoveryof Endorphins, her currentinterests in neuroscience, and lessons she learned along the way about howto keep her love of science alive.Plenary SessionIMPACT OF GENOMICS AND CONNECTOMICS APPROACHES ONSCHIZOPHRENIA RESEARCHChairpersons: Lynn DeLisi and Ren KahnSunday, 6 April 2014 8:30 AM 12:00 PMWikepedia denes Omics as an informal sux that implies the collectivecharacterizationandquanticationof pools of biological molecules thattranslateintothestructure, function, anddynamics of anorganismororganisms. Thus, genomics describes all that is known about the multi-pleaspectsofthegeneticarchitectureofanorganismoritsdisordersand0920-9964/$ see front matter 2014 Elsevier B.V. All rights reserved.connectomics describes the complex cerebral architecture that is uniquelyhumanandcandevelopindeviantwaysinschizophrenia. Inthissessionwe thus aim to review the most up-to-date knowledge in the elds of bothgenomics and connectomics as they relate to improving our understandingabout schizophrenia. Researchndingsareaccumulatingsorapidlynowthateventhelatestpublishedliteraturecannotkeepupwiththepaceofprogress in these elds.In the genomics session, Dr. Patrick Sullivan will cover the latest Genome-Wide Association Study (GWAS) ndings of common alleles with increasedrisk for schizophrenia fromthe large international collaborative effort,ThePsychiatricGenomicsConsortium(PGC). Hewill befollowedbyDr.JonathanSebatwhowill discusshowraregeneticvariants, suchasCopyNumber Variants (CNVs) can play a role in risk for schizophrenia. This willbefollowedbyadiscussionof environmental-geneinteractionasledbyDr. Tiina Paunio. All panelists will then discuss the eld of Next-GenerationSequencing and how it will be effective in nding genes for schizophrenia.Wewill endthissessionwithadiscussionofcontroversial ethical issuesthat theeldof psychiatricgeneticsisnowfacedwith, includingcom-mercial direct-to-consumer genome testing availability.This will be led byDr. Francis McMahon, president of The International Society of PsychiatricGenetics. General audience participation will be encouraged.The secondhalf of this plenary will be devotedto Connectomics inthehumanbrainandhowconnectivityisinuencedbygenetics. It willincludeDrs. EdBullmore, Jeff LichtmanandDeannaBarch. All of theseresearchers have developed innovative methods for viewing how the braincommunicatesandfunctionsthroughitsconnectivityandhowgenesin-uence the variation that exists in human brain connections. Some of thelatter variation may be relevant to neurodevelopmental disorders, such asschizophrenia. They will then lead a panel discussion session with audienceparticipation to conclude this session.SymposiumDEVELOPMENTAL STRESS IN SCHIZOPHRENIA: EPIDEMIOLOGYAND POSSIBLE MECHANISMSChairpersons: Preben Bo Mortensen and James KoenigDiscussant: James KoenigSunday, 6 April 2014 2:00 PM 4:00 PMOverall Abstract: Thedevelopingandmaturingbrainishighlysensitiveto the detrimental effects induced by environmental adversities. Early-lifeexposuretoenvironmental stressorssuchasprenatal maternal stressorchildhood psychological trauma have been identied as possible risk factorsof schizophreniaandrelateddisorders. Despiteepidemiological evidencefor such associations, several controversial issues still exist in the eld thatwarrant close examination, including the role of developmental timing andthespecicityofdevelopmentalstressors. Moreover, theextenttowhichearly-life exposure to stress interacts with other genetic or environmentalS2 Abstracts of the 4th Biennial Schizophrenia International Research Conference/ Schizophrenia Research 153, Supplement 1 (2014)S1S384riskfactors of schizophreniais currentlybeinginvestigatedextensively,and so are the potential mechanisms mediating increased disease risk fol-lowing developmental stress exposure. This symposium will bring togetherleading epidemiologists and basic researchers who use distinct scientic ap-proaches to address some of these burning questions. Preben B. Mortensen(National Centre for Register-based Research, Aarhus University, Denmark)will present ndings from register-based psychiatric epidemiology address-ingthe role of developmental stress inschizophrenia andwill discussepidemiological associationslinkingearly-lifestressandschizophreniainrelation to their conceptual and methodological strengths and limitations.Urs Meyer (Swiss Federal Institute of Technology, ETH Zurich, Switzerland)will discussanimal workshowingthat prenatal adversities intheformof in-uteroimmunechallengecanfunctionasadiseaseprimerthat in-creasestheoffspringsvulnerabilitytothedetrimental neuropathologicalstressinpuberty. Furthermore, hewillpresentnovelndingsobtainedinthis two-hit model suggesting that developmental neuroinammation maybeoneofthecritical mechanismsmediatingthepathological interactionbetweenprenatal infectionandpubertal stressexposure. MarcoA. Riva(CenterofNeuropharmacology, UniversityofMilan, Italy)willfocusonawell-establishedanimal model of prenatal stresstohighlight itsimpacton neuronal plasticity across distinct time windows of brain developmentandmaturation. Hewill alsoshowhowepigeneticsignaturesinspecicbrainregionsmayallowtheidenticationof novel genesandpathwaysthat are affected as a consequence of antenatal stress exposure. Akira Sawa(Departmentsof PsychiatryandNeuroscience, JohnsHopkinsUniversity,USA) will discuss novel epigenetic mechanisms that can compromise adultneuronal networksfollowingexposuretoadolescentstress. Inparticular,hewill presentndingsdemonstratingalteredDNAhypermethylationofdopaminergic systems andassociatedbehavioral dysfunctions followingadolescent stressexposureinamousemodel withadominant-negativeDISC1 (disrupted-in-schizophrenia-1) expression. Collectively, the epidemi-ological and experimental work described in this symposium corroboratestherelevanceof thedevelopmental stressinschizophreniaandsuggestsseveral molecular mechanisms involved in this association. The latter mayopennewavenues toattenuate or evenprevent long-termpsychiatricoutcomes following developmental stress exposures.EPIDEMIOLOGICAL EVIDENCE FOR A ROLE OF DEVELOPMENTAL STRESSIN SCHIZOPHRENIAPreben Bo MortensenNational Centre for Register-based Research, Aarhus UniversityEpidemiological studiesandotherevidencehavesuggestedawiderangeof factors affecting fetal development to be associated with schizophreniarisk. Factors as maternal infections, dietary deciencies, and pregnancy andbirth complications have been repeatedly implicated, and also more generalenvironmental factors as diverse as urban place of birth, stressful life eventsand war or natural disasters have been found to increase the risk of devel-opingschizophrenia. Stressorsduringinfancy, childhoodandadolescencehavebeenlesswell studied, but, again, awiderangeofexposures, fromfrequent moves to severe injury or adversity, have been implicated in thiscontext. This presentation will review some of the available evidence andpresent more recent and ongoing large scale register-based Danish studiesthat exploretheepidemiological relevanceof stress exposures over theearly life course, from conception through adolescence.TRANSIENT NEUROINFLAMMATION IS A KEY MECHANISM MEDIATINGTHE NEUROPATHOLOGICAL INTERACTIONS BETWEEN PRENATALIMMUNE CHALLENGE AND PERIPUBERTAL STRESSUrs Meyer1, Sandra Giovanoli21Swiss Federal Institute of Technology (ETH), Zurich, Switzerland;2Physiologyand Behavior Laboratory, Swiss Federal Institute of Technology (ETH), Zurich,SwitzerlandPrenatal infection and exposure to traumatizing experiences in peripuber-tal life have each been associated with increased risk for neuropsychiatricdisease, especially schizophrenia and related psychotic illnesses. Our labora-tory has recently developed a translational mouse model of combined expo-sure to prenatal immune challenge and peripubertal stress to study possibleneuropathological synergismsbetweenthesetwoadverseenvironmentalfactors. Inthis two-hit model, therst environmental hit is composedof prenatal viral-like immune activationinducedbymaternal adminis-trationof thesyntheticdouble-strandedRNApoly(I:C) (polyriboinosinic-polyribocytidilic acid) during mid-gestation. The resulting offspring arethen either left undisturbed or exposed to subchronic unpredictable stressduring peripuberty. Using this two-hit environmental model, we reveal thatprenatal immune activation and pubertal stress synergistically interact witheach other to facilitate the emergence of schizophrenia-relevant behavioraland neurochemical abnormalities, including sensorimotor gating deciency,hypersensitivitytopsychotomimeticdrugs, anddopaminergicimbalancesin striatal and hippocampal areas. We further nd that the prenatal insultmarkedlyincreasesthevulnerabilityof thepubescent offspringtobrainimmunechangesinresponsetostress. Inparticular, offspringsubjectedto combinedprenatal immune challenge andperipubertal stress showmarkedsigns of neuroinammationthat arecharacterizedbymicrogliaoveractivationandhypersecretionofbraininammatorycytokines. Basedon these latter ndings, we have recently begun to test whether normaliz-ingacuteneuroinammationintheeventofperipubertalstressexposuremay prevent the subsequent emergence of schizophrenia-relevant decitsinprenatally primedoffspring. As a rst proof-of principle supportingthishypothesis, wereveal that theadult onset of behavioral abnormal-itiesinducedbycombinedprenatal immunechallengeandperipubertalstress can be prevented by administration of the broad-spectrum antibioticminocyclineduringthecourseofperi-pubertalstressexposure. Thisanti-inammatorydrugregimenalsopreventsoveractivationofmicrogliaandaltered pro-inammatory cytokine secretion in prenatally primed offspringexperiencing additional stress in puberty. Our experimental data highlightthat stress exposure in puberty can unmask latent neuropathological conse-quences of early prenatal environmental insults such as prenatal maternalinfection. Furthermore, anti-inammatory strategies targeting microgliaoveractivation may represent a valid pharmacological approach to preventfull-blownbrainabnormalitiesemerginginsubjectsexposedtomultipleenvironmental hits such as prenatal infection and pubertal stress.EPIGENETIC PROFILING OF PRENATAL STRESS AND LONG-TERMPSYCHOPATHOLOGICAL IMPLICATIONSMarco A. Riva1, Alessia Luoni2, Alessandra Berry3, Renaud Massart4,Francesca Cirulli3, Moshe Szyf41Dept. of Pharmacological and Biomolecular Sciences, University of Milan,Milan, Italy;2Department of Pharmacological and Biomolecular Sciences,University of Milan, Italy;3Department of Cell Biology and Neurosciences,Istituto Superiore di Sanita, Rome, Italy;4Department of Pharmacology andTherapeutics, McGill University, Montreal, Quebec, CanadaPerinatal life is a period of high plasticity and vulnerability to adverse lifeconditions, whichmayprogramchronicdiseasesinadulthood, includingpsychiatric disorders. Inparticular, exposure tostress during gestationproducesanarrayof behavioral alterations, includingmooddisturbanceand cognitive decits. We used the rat prenatal stress (PNS) model to inves-tigate attentional impairment (object Recognition Test -ORT), as behavioralreadout of cognitivefunction, andtocharacterizelong-lastingmolecularalterations that may contribute to late psychopathology susceptibility. WefoundthatmaleandfemaleratsexposedtoPNSshowasignicantim-pairment intheORT. At molecular level, PNSrats showaregion- andtime-specic reductioninthe expressionof the neurotrophinBDNF, amarker of neuronal plasticity that has an important role in mood and cog-nitivefunction. BDNFchangeswereparticularlyevidentintheprefrontalcortexandwere sustainedbythe modulationof specic neurotrophintranscripts withthe contributionof epigenetic mechanism. Inorder tofurthercharacterizetheepigeneticchangesproducedinresponsetoPNS,weperformedanepigenome-wideanalysisinmaleprefrontal cortexus-inga400Kpromoter tilingarray. About 5%of genesweredifferentiallymethylatedinPNSratswhencomparedtocontrolanimals, withahighlysignicantassociationforneuronalfunctionsandpsychiatricdisorders, inparticularschizophrenia. Finally, someof themodicationsatepigeneticlevel displayahighcorrelationwithmRNAlevels, indicatingonceagainthat the effects observed at adulthood are the consequence of a latent epi-geneticsystem-wideregulation. WenextemployedacrossspeciesstudyAbstracts of the 4th Biennial Schizophrenia International Research Conference/ Schizophrenia Research 153, Supplement 1 (2014)S1S384 S3comparing the list of genes differentially methylated in the PFC of PNS ratswithsimilarresultsobtainedinmonkeysexposedtomaternalseparationas well as with a human cohort characterized by early life stress (ELS). Suchanalyses allowed us to prioritize the list of genes that may be affected byELSandthatmaythereforeplayarelevantroleforpsychopathologyanddisease susceptibility. Collectively, our data provide further support to thenotion that in-utero exposure to stress leads to permanent functional andmolecularchangesintheoffspring. Moreover, theseresultshighlighttheimportance of the identication of methylation signatures in a convergentapproachthatcouldserveaspredictiveanddiagnosticmarkers. Thiswilleventually lead to the identication of novel genes and pathways that areaffectedasaconsequenceof ELSandthat maycontributetolong-termsusceptibility for mental illness.ADOLESCENT STRESS-INDUCED EPIGENETIC CONTROL OF NEURONALNETWORKSAkira Sawa1, Minae Niwa2,3, Richard Lee31Johns Hopkins University School of Medicine;2Department of ChemicalPharmacology, Meijo University Graduate School of Pharmaceutical Sciences,Nagoya, Japan;3Department of Psychiatry and Behavioral Sciences, JohnsHopkins University School of Medicine, Baltimore, MDEnvironmental stressors during childhood and adolescence inuence post-natal brainmaturationandhumanbehavioral patternsinadulthood. Ac-cordingly, excess stressors result in adult-onset neuropsychiatric disorders.Here we present an underlying mechanism by linking adolescent stressorsto epigenetic controls in neurons via glucocorticoids. A mild isolation stressin adolescence (for 3 weeks) affects mesocortical projection of dopaminer-gicneuronsinwhichDNAhypermethylationofthetyrosinehydroxylasegene is elicited, only when combined with a relevant genetic risk for neu-ropsychiatricdisorders(DISC1). Associatedwiththesemolecularchangesseveralneurochemicalandbehavioraldecitsoccurinthismousemodel,allofwhichareblockedbyaglucocorticoidreceptorantagonist. Thefaceand predictive validities of the mice offer a model for psychotic depression,acommonanddebilitatingpsychiatricdisease. Althoughpreliminary, wewill includetwopublishednewdataasfollowsinourpresentation: wehave narrowed down the most critical term of isolation in adolescence forjustoneweek. Wehavealsoextendedourstudyonepigeneticimpactofthe gene-environmental interactions (e.g.,adolescent isolation and DISC1)at the whole genome levels beyond the tyrosine hydroxylase gene.SymposiumNEGATIVE SYMPTOMS AND SOCIAL COGNITION INSCHIZOPHRENIA: NEURAL CIRCUITRY, FUNCTIONAL OUTCOMES,AND TREATMENT INNOVATIONChairperson: Aristotle VoineskosDiscussant: Celso ArangoSunday, 6 April 2014 2:00 PM 4:00 PMOverall Abstract: Individuals with schizophrenia spectrum disorders (SSDs;i.e., schizophrenia, schizoaffective disorder, schizophreniform disorder) ex-hibit a continuum of impairment in social functioning. This symposium willexplore the neural correlates of lower-level and higher-level social cognitiveprocessingimpairmentamongpeoplewithSSDs. Effortwillalsobemadetoshowhowschizophreniapatientswithprominentnegativesymptomsdemonstrate impairments in similar brain systems that may be responsiblefor social cognitive performance. Finally, a novel interventionthat canimprovesocial functionbytargetingmotivationandemotionrecognitionusing an innovative neuroplasticity-based cognitive training approach willbedescribed. First, Dr. Michael Greenwill present results from3fMRIstudiesandoneEEGstudythatattemptedtoexplorehigher-andlower-level systemsinschizophrenia. Thehigher-level mentalizingsystemwasstudiedwithselectivebeliefattributionoremotionattributiontasks. Thelower-level mirroring system was studied with a mirror neuron task in thescanner, and an EEG mu suppression task. The integration of these systemswasalsoexaminedwithanempathicaccuracytask. Resultssuggest themirroringsystemislargelyintactinschizophrenia. However, individualswithschizophrenia showimpairment inother aspects of social cogni-tion, includingmentalizing. Dr. AristotleVoineskoswillthenpresentdatademonstrating heterogeneous ndings in patients with schizophrenia in cir-cuits that may underlie these two systems. He will show that schizophreniapatients with prominent negative symptoms, or decit schizophrenia haveimpairment in right fronto-parietal circuit structure, which predicts impair-ment in social function. Such impairment was not found in other subjectswith a major psychotic disorder, or healthy controls. Dr. Voineskos will alsopresentpreliminaryresultsusingacontinuum-basedapproachthatmayilluminateapparentdiscrepanciesregardingimpairmentofthemirroringsysteminschizophrenia. Dr. Anil Malhotrawill thenpresent datausingresting state fMRI which shows that schizophrenia patients with the decitsubtypedemonstratealterations inthecortical midlinenetwork, whichis considered important for mentalization,introducing the possibility thatthese more impaired patients may also have impairment in the higher-levelmentalizing network. Dr. Robert Buchanan will then put the previous talksintocontextbyutilizingthenewResearchDomainCriteriaframeworktointegrate ndings from patients with prominent enduring negative symp-toms, withnewer researchonsocial cognitiveimpairment, bothcriticaldeterminantsofsocialfunction. Dr. Buchananwilldescribetheimpactofsocial cognitive impairment on long-term functioning in SSDs and presentdata implicating right fronto-parietal white matter microstructural abnor-malitiesinpeoplewithprominent negativesymptoms, whoaresociallyimpaired. Finally, Dr. SophiaVinogradovwill present dataoncognitivetraining approaches relevant to schizophrenia patients with negative symp-toms, social cognitiveimpairment orboth. Thetreatment approachthatshe will present uses a bottom-up approach to include behaviorally salientandecologicallymeaningfulsocialandemotionalstimuliwiththegoalofrestoring function in the neural correlates of reward anticipation and emo-tion recognition in people with schizophrenia. She will present preliminarydata indicating that re-engaging the dopaminergic reward system throughtrainingfacilitatestheuseof positiveincentivestomotivatebehaviorinsocial and nonsocial domains.NETWORK TOPOLOGY IN DEFICIT SCHIZOPHRENIA, NONDEFICITSCHIZOPHRENIA, AND BIPOLAR DISORDER: FROM CIRCUITS TOFUNCTIONAL OUTCOMEAristotle Voineskos1, Anne Wheeler2, Jason Lerch3, Mallar Chakravarty2,Anthony Jun2, Philip R. Szeszko4, Anil K. Malhotra4, Julia Linke5,Michele Wessa51Centre for Addiction and Mental Health, University of Toronto;2Centre forAddiction and Mental Health;3Hospital for Sick Children;4Zucker HillsideHospital;5University of MainzPurpose: Recent datasuggestssubstantial sharedetiologyforthemajorpsychoses(schizophreniaandbipolardisorder). However, asubsetofpa-tients with schizophrenia (with the decit form of illness) may representoneendofacontinuumofneurobiologicalandsocialimpairmentamongpatients with major psychoses. We sought to compare patients character-izedbystrongnegativesymptomburdenandpoorsocial function, whohave beenclassiedas decit syndrome, to nondecit patients withminimalnegativesymptomburdenandbipolardisorderpatients, usingabrainnetworkconnectivityapproach, andrelateabnormalbraincircuitryto impairment in social function.Methods: Followinghighresolutionstructural magneticresonanceimag-ing, and diffusion tensor imaging, brain-wide inter-regional correlations incorticalthicknesswereexaminedinschizophreniasubjectsrankedinthetop(n=18decitsubjects)andbottom(n=18nondecitsubjects)quartileof decit scores. Then, n=32decit, n=32nondecit subjects, andn=32healthy controls were combined from the Hillside and Toronto samples. Inaddition, n=32 bipolar subjects were compared to n=32 controls using thesame network topology methods to investigate cortical thickness networksacross the major psychoses. Asubset of schizophrenia patients (n=22)completedthequalityof lifescale(QLS). Correlationswithalteredbrainnetworkstructureinrelationtosocial andfunctional outcomemeasureswere examined.Results: Decit schizophreniasubjectsdemonstratedalargernumberofstrong positive correlations among cortical regions compared to individualswith nondecit schizophrenia, bipolar disorder, or healthy controls subjectsresulting in a network with increased density of connections. The networkS4 Abstracts of the 4th Biennial Schizophrenia International Research Conference/ Schizophrenia Research 153, Supplement 1 (2014)S1S384inthedecit subjects containedanincreasednumber of highlycentralnodessuchasthesupramarginal, superiortemporal andinferiorfrontalgyri (i.e., fronto-parietal)thatwerelessprominentinthenondecitandcontrol networks. In addition, highly central nodes were also found in cor-tical midline regions, specically cingulate and parahippocampal gyrus. Nonetworkdifferencesweredetectedbetweenbipolarandmatchedhealthycontrolgroups. Meandiffusivityoftherightarcuatefasciculus, thewhitematter tract connecting the fronto-parietal circuit was inversely correlatedwith the QLS interpersonal subscale (r=0.49, p=0.02).Discussion: Decit syndrome subjects demonstrated an increased networkdensity compared to nondecit subjects, bipolar subjects, and healthy con-trols, whoall demonstratedsimilar networkdensity. Increasednetworkdensityindecit subjects was particularlyprominent infronto-parietalandcortical midlinecircuitry. Fronto-parietal circuitryinparticular hasbeen related to social impairment in autismspectrumdisorders. Ourndings clearly demonstrate differences in cortical regions comprisingfronto-parietal circuitryindecit patients, whohave severe social im-pairmentcomparedtootherpatientswithmajorpsychoses, whoarelesssocially impaired. We directly related impairment in this circuit to impair-mentinsocialfunctionusingtheQLS. Theseinterregionalfronto-parietaland cortical midline alterations may serve as neurobiological correlates of asubgroup of especially socially impaired (decit) people with schizophrenia.The fronto-parietal circuit should be considered as a useful biomarker andtreatment target of impaired social function in people with schizophreniaspectrum disorders.NEUROSCIENTIFIC EXPLORATIONS OF TWO LEVELS OF SOCIALCOGNITION IN SCHIZOPHRENIAMichael Green1,2, Junghee Lee, William P. Horan, Philippe-Olivier Harvey31UCLA Semel Institute for Neuroscience and Human Behavior; VA VISN 22MIRECC;2VA Greater Los Angeles;3McGill UniversitySocial cognition has become an important focus of study in schizophrenia.The terminology and concepts in this area are still being rened. One usefuldistinction is to separate social cognition into two levels: higher and lower.Anexampleof higher-level social cognitionisthementalizingsystem,which is involved in making inferences about people and their mental states(e.g., theory of mind), and the ability to take someone elses point of view(e.g., perspective taking). Key regions for the mentalizing system include thetemporoparietal junction and the ventral prefrontal region. An example of alower-level social cognition is the relatively automatic mirroring system,which is involved in experience sharing, emotional contagion, and commonneuralcodingofactionexecutionandobservation. Keymirroringregionsinclude the inferior parietal and premotor cortex. In this presentation, wewill present results from 4 neuroscientic studies (3 fMRI studies and oneEEGstudy)thatexploredhigher-levelandlower-levelsystemsassociatedwithempathyinschizophrenia. Forthehigher-level mentalizingsystemweconductedanfMRI studyusingtasksthat selectivelyrequiredbeliefattribution or emotion attribution. For the lower-level mirroring system weconducted a validated mirroring paradigm (imitation, execution, and obser-vationtasks)inthescanner. WealsoconductedanEEGtaskofmirroring(mu suppression). Lastly, we examined the integration of mentalizing andmirroring systems by assessing empathic accuracy in the scanner. For thistask, subjectscontinuouslyratedchangesinthemoodofasocialtargetshowninavideoclip. Weobtainedavariedpatternof results. Patientsshowedafailuretoactivatekeyregionsassociatedwithmentalizing. Incontrast, the fMRI andEEGresults indicate that the mirroring systemislargelyintact inschizophreniafortheparadigmsthat wereused. Forempathicaccuracy, patientsshoweddifferencesfromcontrolsinabroadrange of both higher and lower-level regions. In particular, patients showedmuch fewer brain regions that modulated their activity with changes in theemotionalexpressionofthesocialtarget. Thepatternofresultsindicatescleargroupdifferencesinmentalizing, butnotmirroring, neural systemsin schizophrenia. Group differences were also seen on the integrative taskofempathicaccuracy. Thereasonforthedifferentbetween-groupresultsat higher versus lower levels may involve selective higher-level decits, orreduced ability to connect lower and higher-level social cognitive systemsin schizophrenia.BEHAVIORAL AND NEURAL SYSTEM EFFECTS OF COMPUTERIZED SOCIALCOGNITIVE TRAINING EXERCISES IN SCHIZOPHRENIASophia Vinogradov1,2, Mor Nahum3, Karuna Subramaniam, Melissa Fisher,Christine Hooker1University of California, San Francisco;2Associate Chief of Staff for MentalHealth, SFVA MEdical Center;3Brain Plasticity InstituteRecentresearchsuggeststhatunderlyingdecitsinbothneurocognitionand social cognition contribute to motivational impairments in schizophre-nia, which in turn, affect functional outcome. Accurate processing ofsocio-emotive stimuli is intimately integrated with neural systems relatedtoreward, learning, andmotivation. Forexample, positivesocial stimuli,suchashappyfaces, arehighlyrewardingandcanserveasprimaryrein-forcement, activating reward-related neural structures such as the ventralstriatumandventromedialprefrontalcortex. Thesedataindicatethatim-provement intheaccuracyanddelityof social cognitiveprocessinginschizophrenia could have benecial effects in the neurobehavioral systemsthatunderpinmotivatedbehavior. Wewill reportonpreliminaryresultsfrom intensive computerized neuroplasticity-based cognitive training stud-ies that focus on improving incentive salience via the creation of strong andpredictableassociationsbetweensuccessful learningeventsandrewards.Bottomuptrainingthatemphasizesimprovedperceptual processingisexpanded to include behaviorally salient and ecologically meaningful socialandemotional stimuli withthegoal of restoringfunctionintheneuralcorrelatesof rewardanticipationandemotionrecognitioninindividualswithschizophrenia. Wewill presentpreliminarydataindicatingthatre-engaging this dopaminergic reward system through training facilitates theuse of positive incentives to improve motivated behavior in both social andnon-social domains.THE NEURAL CIRCUITRY OF SOCIAL IMPAIRMENTS IN SCHIZOPHRENIASPECTRUM DISORDERSRobert W. Buchanan1, Laura M. Rowland, Philip R. Szeszko2,Aristotle Voineskos31University of Maryland School of Medicine;2Zucker Hillside Hospital;3Centrefor Addiction and Mental Health, University of TorontoBackground: People withschizophrenia spectrumdisorders (SSDs) arecharacterizedbymarkedimpairments insocial function. Theseimpair-ments severelyimpact qualityof life, andpredict relapse, poor illnesscourse, andunemployment. Overthepast decade, considerableprogresshasbeenmadeindelineatingthesocialcognitiveprocessesthatunderlietheseimpairments. However, muchlessisknownabout theneural cir-cuitrythatsupportstheseprocesses. TheNIMHRDoCinitiativeprovidesaframeworkfor evaluatingtheneural basis of social cognition. InthecontextoftheRDoCSystemsforSocialProcessesDomain:thePerceptionandUnderstandingof Others, therightfronto-parietal networkhasbeenhypothesized to subserve lower-level social cognitive processes necessaryfor understanding the actions and basic emotions of others, and the corticalmidline circuit, has been hypothesized to subserve higher-level processesnecessary for understanding the perspective of others (theory of mind). Inorder to evaluate the hypothesized involvement of the fronto-parietal net-workinsocialfunctionimpairments, wehaveconducteddiffusiontensorimaging (DTI) studies in three independent samples to examine this circuitinpeoplewiththedecitformofschizophrenia, aformofschizophreniacharacterized by impaired social function.Methods: Study 1: Twenty participants withDSM-IVschizophrenia orschizoaffective disorder (decit: n=10 and nondecit: n=10) and 11 healthysubjectsparticipatedinthisstudy. Study2: Thirty-sixparticipantswithDSM-IV schizophrenia (decit: n=18 and nondecit: n=18) and 18 healthysubjects participatedinthis study. Study3: Fifty-oneparticipants withDSM-IVschizophrenia(decit:n=14andnondecit:n=37)participatedinthis study. DTI was used to assess the integrity of the superior longitudinalfasciculus(SLF), themajorwhitemattertractconnectingthefrontal andparietal lobes.Results: Study 1: There was a signicant FAgroupdifference for theright hemisphere SLF (F=3.6 df=2,27; p=0.04). The decit group had lowerFAthanthehealthycontrol group(p