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Thankyoutooursponsors

TableofContents

Welcome...........................................................................................................................................................7

OpeningAddress:TranslatingBiologicalPsychiatryResearchintotheClinic:ARollerCoasterthatisWorth

theRide.............................................................................................................................................................8

AubreyLewisAwardLecture:DevelopmentofMemoryandMotivation........................................................9

IsaacSchweitzerAwardLecture:FromClinicaltoPre-ClinicalResearch–UsingAnimalModelsto

UnderstandtheNeurobiologyofSchizophrenia............................................................................................10

Symposium1:Therapeuticpotentialofcannabidioltreatmentforpsychiatricillness.................................11

Symposium2:Epigeneticmediatorsofbraindysfunctionandpsychiatricdisorders....................................13

Symposium3:Addictedtoaddiction–isitlackoflove,toomuchstress,orjustyourpersonality(and

genes)?...........................................................................................................................................................15

SpecialSymposium:Highestratedstudentabstracts.....................................................................................17

DataBlitz1......................................................................................................................................................20

DataBlitz2......................................................................................................................................................25

DataBlitz3......................................................................................................................................................30

PosterSession1..............................................................................................................................................35

PosterSession2..............................................................................................................................................60

Maps...............................................................................................................................................................85

PROGRAM

Sunday29October 4

Sunday29thOctoberICAtrium,UniversityofWollongongInnovationCampus

Time Event Speaker PresentationTitle4:00–5:00 Registrationsopen4:30–5:00 Welcomedrinks

5:00–5:40 KeynotepresentationChair:ProfChaoDeng

ProfBrianDean Translatingbiologicalpsychiatryresearchintotheclinic:Arollercoasterthatisworththeride

5:40–7:40

WelcomeMixer/Teamcompetition(Prize:GourmetGiftHamper)HostedbyAlicePettyandJeeKim

Round1NeverHaveIEver..Round2ChineseWhispersCharades

Round3TeamNameInterpretativeDance

Monday30October 5

Monday30OctoberIllawarraRoom,NovotelWollongongNorthbeach

Time Event Speaker PresentationTitle8:00–9:00 Registrationsopen

8:45–9:00 OpeningAddress DrKellyNewell,Chair,LocalOrganisingCommitteeProfDarrylEyles,President,BiologicalPsychiatryAustralia

9:00–10:00 8thAubreyLewisLectureChair:ProfDarrylEyles

DrJeeKim Developmentofmemoryandmotivation

10:00–10:30 DataBlitz1Chair:MaximusBerger

ProfBarbaraMeyer

There'ssomethingfishyabouthisbehaviour:Howdoesomega-3statusinfluenceaggressionand

cognitivefunctionandwhatcanbedonetoensureabetterfuture?

MD.MamunAl-Amin

VitaminDdeficiencyreduceshippocampalsubfieldvolumeanddisruptsright-hippocampalstructuralconnectivity:evidencefrommouseandhumandata

A/ProfOliviaCarter Dosensoryintegrationdeficitsrepresentabiomarkerforschizophrenia?

Ann-KatrinKraeuter

Ketogenicdietnormalizesbehaviouralabnormalitiesinachronicneurodevelopmentalmurinemodelof

schizophrenia

DrLaurenHarmsTheeffectsofmid-lategestationalmaternalimmuneactivationinratsonschizophrenia-relatedbehaviour

10:30–11:00 Morningtea

11:00–12:30

Symposium1:Therapeuticpotentialofcannabidioltreatmentforpsychiatric

illness.Chair:ProfNadiaSolowijDiscussant:A/ProfTimKarl

DrKatrinaWeston-Green

CannabidioltreatmentinapolyI:Cmodelofschizophrenia:cognitivebehaviouralimprovements

andalteredneurotransmission

ProfNadiaSolowijProlongedadministrationofcannabidioltochroniccannabisusers:apragmatictrialanditscognitive

andsymptomaticoutcomes

ProfPaulAmminger

Thecannabidiolyouthanxietypilotstudy(CAPS):a12-weekopen-labelpilotstudyofcannabidiolfor

anxietydisorders

12:30–1:00 DataBlitz2Chair:DrRoseChesworth

DrTertiaPurves-Tyson

Raloxifenemodulatesdopamine-relatedtranscriptsinthemidbraininmalerats

CamillaBeale Effectsofcannabidioltreatmentuponhippocampalsubfieldvolumesincurrentcannabisusers

ShaunHopper

DecreasedhippocampalresponsivenesstomuscarinicM1receptorpositiveallostericmodulationinasub-groupofsubjectswith

schizophrenia

SamuelMillardMaternalfluoxetinetreatmentaltersoffspringbehaviourandNMDAreceptorsubunitprofileat

adolescence

DrRenataPertile EpigeneticregulationofdopaminergicneuronaldifferentiationbyVitaminD

1:00–2:30 Lunchandposters1:30–2:30 Posterpresentations

2:30–4:00

Symposium2:Epigeneticmediatorsofbraindysfunction

andpsychiatricdisorders.Chair/Discussant:ProfAnthony

Hannan

DrTerencePang PaternallifestylefactorswhichalterspermsmallRNAsandoffspringbehaviouralphenotypes

DrIrinaVoineaguTheroleofnon-codingRNAsinautismspectrum

disorder

DrXiangLiDNAmodificationinfear-relatedlearningand

memory4:00–4:30 Afternoontea

4:30–5:30ECRSession

Chairs:DrKatrinaGreenandJeremyLum

StrengtheningthePillarsofBiologicalPsychiatry:AFocusonSupportingtheEarlyCareerResearcher

6:30 Cocktailfunction,LevelOne@harbourfront,2EndeavourDrive,Wollongong

Tuesday31October 6

Tuesday31OctoberIllawarraRoom,NovotelWollongongNorthbeach

Time Event Speaker PresentationTitle

9:00–10:00 5thIsaacSchweitzerLectureChair:ProfNadiaSolowij ProfPatMichie

Fromclinicaltopre-clinicalresearch–usinganimalmodelstounderstandtheneurobiology

ofschizophrenia

10:00–10:30 DataBlitz3Chair:DrLaurenHarms

DrSusanThomasWithdrawalfromthehelpoffriendsandfamilyindepression:Linkstoplasmacortisolandoxytocin

levels

TasnimRahmanDeficitsofsomatostatinandSSTR2mRNAsin

orbitofrontalcortexinschizophrenia

DrWeiLuanMaternalvitaminDtreatmentreversesmaternal

immuneactivationinducedalterationsinmesencepahlicneurogenesis

CassandraWannan Network-basedcorticalthinningintreatmentresistantschizophrenia

HelenCai Changesinperipheralimmunecelltraffickingmoleculesinschizophrenia

10:30–11:00 Morningtea

11:00–12:30

Symposium3:Addictedtoaddiction–isitlackoflove,toomuchstress,orjustyourpersonality(andgenes)?Chair:DrJiameiLianDiscussant:DrJeeKim

ProfIainMcGregor

SerendipityandtheHardSlog:aninsidersaccountofthediscoveryanddevelopmentofanoveltherapeuticfortreatingaddictionand

socialdeficitsProfAndrewLawrence Peptideinteractionsandrelapse

A/ProfChristopherDayas

Thedevilisinthedetail:whystudyingindividualdifferencesinaddictionmatters...

12:30–1:00 AnnualGeneralMeeting1:00–2:30 LunchandPosters1:30–2:30 Posterpresentations

2:30–3:10

SpecialSymposium:HighestrankedstudentabstractsChair:DrKellyNewell

GeorgiaWattThetherapeuticpotentialofcannabidiol(CBD)inatransgenicmousemodelofAlzheimer’sdisease

SallyGraceIntranasaloxytocinincreasesamygdala

responsestoemotionalfacesinbodydysmorphicdisorder

AsadAliAlteredfetalsteroidogenesisanddysregulatedplacentalimmuneresponseinadevelopmental

vitaminDdeficientratmodelofautism

3:10–4:10

Q&AModerator:Nick

Rheinberger(ABCIllawarra)Chair:A/ProfJeremyCrook

ProfPaulAmminger

IsBiologicalPsychiatryTheGraveyardofPsychiatry?

ProfPatMichie

ProfStephenWood

ProfIainMcGregorProfSureshSundram

4:10–4:30 AfternoonTea4:30–4:45 PrizesandAwards4:45–5:00 ConferenceDiscussant DrVibekeCatts

5:00 ConferenceClose

Welcome 7

Welcome

DearColleagues, OnbehalfoftheLocalOrganisingCommittee(LOC),IwarmlywelcomeyoutotheBiologicalPsychiatryAustralia(BPA)ConferenceinWollongong!Iwouldliketothankoursponsorsfortheirinvaluablesupport.ThankyoutoourMajorSponsor,theIllawarraHealthandMedicalResearchInstituteandtotheFacultyofScience,MedicineandHealthattheUniversityofWollongong.Iwould also like to thank and acknowledge the financial support of our Gold Sponsors, Neuroscience ResearchAustralia (NeuRA), Otsuka/Lundbeck and Creso Pharma and our Silver Sponsor, Janssen. Your generosity ensuresthatthesemeetingsarepossibleandprovidessupportforourmanyEarlyCareerResearchers. IwouldliketothanktheBPA2017LOCandtheBPAExecutiveCommitteeaswellasourgraduatestudents,whohavegreatly assisted in organising our annualmeeting inWollongong. This year’s program highlights the exciting anddiverse range of biological psychiatry research that is being conducted in Australia.We are pleased to have theinauguralBPAPresident,ProfBrianDean,openingourconferenceonSundayevening.WeareequallydelightedtohaveEmeritusProfessorPatMichieandDrJeeKimpresentingtheIsaacSchweitzerLectureandAubreyLewisAwardLecture and congratulate theseoutstandingAustralianbiological psychiatry scientists for these awards. Wehavethreeoutstandingsymposiainthisyearsprogram,togetherwithastudentsymposia,3datablitzsessionsandtwo-daysofposterpresentations.Weareexcitedtoincludeanewadditiontotheprogramthisyear,aninteractiveQ&ApanelmoderatedbyNickRheinbergerfromABCIllawarra,andwould liketothanktheesteemedscientistsonthispanel. The BPA2017 LOCwould like to offer a warmwelcome to the newmembers of our society, and to our currentmemberswewouldliketothankyouforyourcontinuedsupport.Webelieveourprogramwillprovideopportunitiesto hear of the latest developments in biological psychiatry research from leading and emerging Australianresearchers, engage in intellectual discussion and initiate new collaborations in biological-based research intomental illness. BPA2017 also provides an excellent platform for our Early Career Researchers to present theirresearchandinteractwiththeleadersinthefield. Wethankyouforcomingtoourbeautifulcitynestledbetweenthemountainsandtheseaandhopethatyouenjoythemeeting.

KindRegards, KellyNewellChair,LocalOrganisingCommitteeBPA2017Conference

LocalOrganisingCommitteeChair:DrKellyNewell

MrJeremyLum ProfDarrylEylesDrKatrinaGreen DrJeeKim

A/ProfJeremyCrook ProfChaoDengProfNadiaSolowij DrJiameiLianDrYinghuaYu ProfXu-FengHuang

Keynotepresentation:ProfBrianDean 8

Keynotepresentation:TranslatingBiologicalPsychiatryResearchintotheClinic:ARollerCoasterthatisWorththeRide.

ProfBrianDean,TheFloreyInstituteofNeuroscienceandMentalHealthandSwinburneUniversity;InauguralPresidentofBiologicalPsychiatryAustraliaSunday,29thOct,5:00–5:40pmBrianDeancurrentlyholdsthepositionsofHead,TheDivisionofBiologicalPsychiatryandMentalHealthandHead,TheMolecularPsychiatryLaboratoryatTheFloreyInstituteofNeuroscienceandMentalHealth,Parkville and Professorial Research Fellow at the Centre for Mental Health, Swinburne University,Hawthorn,Victoria,Australia.HeisalsoaProfessorintheDepartmentofFloreyNeuroscienceandMentalHealth, University of Melbourne, Australia and Deputy Director of the Victorian Brian Bank Network(Psychiatry).Brian Dean initially trained in the fields of pharmacology and parasitology whilst studying for a HigherNationalDiplomainAppliedBiologyatSunderlandUniversity,UK.AfterobtainingadegreespecialisinginbiochemistryfromtheUniversityoftheSouthbank,LondonhewasacceptedasaLicentiateoftheInstituteofBiology.OnmovingtoAustralia,hewasawardedMasterofScienceandthenaDoctoralDegreefromthe University of Melbourne. Subsequently, he has sort to understand the changes in moleculararchitectureofthehumanbrainthatcauseschizophrenia,bipolardisorderandmajordepressivedisordersaswellasidentifyingmolecularmechanismsofactionofpsychotropicdrugs.BrianDean researchseeks tounderstand thecausesofpsychiatricdisordersasabasisofadvancing theapproachesusedtomanagethetreatmentofpeoplewithsuchdisorders. Hence,amongover235peerreviewedpapershehaspublished therearesignificantbodiesofworkcontributing toanunderstandingtheroleofmuscarinicreceptorsintheaetiologiesandtreatmentofschizophreniaandmooddisorders,therole of cytokine-regulatedpathways in the aetiologies of schizophrenia andmooddisorders andon theneurobiology of suicide. In addition, his laboratory is making a significant effort to develop usefuldiagnosticortheranostictestthatwillassistintheclinicalmanagementofpsychiatricdisorders.BrianDeanisaFellowoftheRoyalSocietyofBiologyandtheCINPaswellasbeingaCharteredBiologist.He has received a number of honours including presenting the University ofMelbourne Beattie SmithLectureandtheASPRLillyOrationaswellasbeingpresentedwiththeUniversityofMelbourneMedal.BrianDean contributes to the advancement of his field of research, particularly in theAsian region, bybeingtheTreasureroftheCINP,aCouncilloroftheAsianCollegeofSchizophreniaResearch(ACSR)andaBoardMemberandChairmanoftheSACoftheRebeccaCooperMedicalResearchFoundation.HewastheInauguralPresidentofBiologicalPsychiatryAustraliaandhasbeenSecretaryoftheASCR,aBoardmemberoftheAsianCollegeofNeuropsychopharmacologyandPresidentoftheMelbourneChapteroftheSocietyforNeuroscience.Hecurrentlyserveson6EditorialBoardsandprovidesAdHocReviewerfor25Journals.

AubreyLewisAwardLecture:Dr.JeeKim 9

AubreyLewisAwardLecture:DevelopmentofMemoryandMotivation

DrJeeKim,DevelopmentalPsychobiologyLaboratory,FloreyInstituteofNeuroscienceandMentalHealth,UniversityofMelbourneMonday,30thOct,9:00–10:00amDr Jee Hyun Kim graduated from the University of New South Wales (UNSW) in Australia with theprestigiousUniversityMedalinPsychology.In2008shecompletedherPhDatUNSWonthedevelopmentofmemoryusingrodentmodels,andwasawardedtheAustralianPsychologicalSocietyAwardforExcellentPhD Thesis in Psychology. After a postdoctoral fellowship atMichiganUniversity (Ann Arbor, USA), shebecametheHeadofDevelopmentalPsychobiologylaboratoryattheFloreyInstituteofNeuroscienceandMental Health/University ofMelbourne in 2013. She has received numerous international and nationalawards including International Society for Developmental Psychobiology Kucharski Young InvestigatorAward, and Australian Psychological Society Early Career Research Award, The International College ofNeuropsychopharmacology Rafaelson Young Investigator Award. She has 52 publications and 1300+citations.Herteamworksonmemoryandforgettingacrossone’slifetime,demonstratingthatemotionalmemoriesareregulateddifferentlydependingonone’sage.Thisworkhasmajorimplicationsforanxietyandaddictiontreatments,especiallyearlyinlife.ShehasbeeninvitedtogiveaTEDxMelbournetalkonthistopic,whichhasnowreached+650,000views(https://www.youtube.com/watch?v=W_t9O5MgisM).

IsaacSchweitzerAwardLecture:Prof.PatMichie 10

IsaacSchweitzerAwardLecture:FromClinicaltoPre-ClinicalResearch–UsingAnimalModelstoUnderstandtheNeurobiologyofSchizophrenia.

Prof.PatMichie,EmeritusProfessorofPsychology,UniversityofNewcastle,Australia.Tuesday,31stOct,9:00–10:00am

Dr.PatMichie is currentlyEmeritusProfessorofPsychologyat theUniversityofNewcastle,Australia.Shepreviously heldprofessorial positions atUWAandMacquarieUniversity. She is an experimentalpsychologistwhoseresearchhasfocusedontheneuralbasisofnormalandabnormalcognition.SheisaFellow of the Academy of Social Sciences of Australia and isthe 2016 recipient of the AustralianPsychological Society’s Distinguished Contribution to Psychological Science Award. Herresearch hasbeencharacterisedbyapplicationoftheoriesandmethodologiesfrombasicresearch incognitionandcognitiveneurosciencetounderstandthenatureofcognitivedeficitsandtheirneuralbasisinindividualsdiagnosed with schizophrenia and those at risk. Her research spans auditory processing deficits,impairedinhibitorycontrolandcognitivecontrolmoregenerallyandusesbothpsychophysicalmethodsto assess performance as well as functional brain imagingmethods such as event-related potentials(ERPs)ofthebrain.ShewasakeymemberoftheAustraliangroupwhowerethefirsttodemonstratethat individuals with schizophrenia exhibit impaired automatic change detection in a background ofauditory regularities, an ERP-derived observation replicatedmany times and one of themost robustfindings in the schizophrenia literature. Her current research is focused on animal models ofschizophrenia.

Pat currently chairs the Research Committee of Orygen, the National Centre of Excellence in YouthMentalHealth,andtheNationalCommitteeofBrainandMind(NCBM)oftheAcademyofSciencesofAustralia.SheispastchairoftheAustralianBrainAlliance,aninitiativeoftheNCBMandtheAcademy.TheAlliance,whichissupportedbytheAustralianPsychologicalSociety,thePsychologyFoundationandtheAustralasianNeuroscienceSocietyandmajorresearchorganisations,aimstosecure investment inAustralianbrainresearchcomparabletootherinternationalinitiatives.

Symposium:Therapeuticpotentialofcannabidioltreatmentforpsychiatricillness. 11

Symposium1:Therapeuticpotentialofcannabidioltreatmentforpsychiatricillness.

Monday,30thOctober,11:00am–12:30pmSpeakers:Dr.KatrinaWeston-Green,UniversityofWollongong;ProfNadiaSolowij,UniversityofWollongong;ProfPaulAmminger,OrygenandUniversityofMelbourne.Chair:ProfNadiaSolowij,UniversityofWollongongDiscussant:ProfPatrickMcGorry,OrygenandUniversityofMelbourneDescription: Cannabidiol(CBD)isanon-intoxicatingcompoundderivedfromthecannabisplantthathascausedarecentsparkofinterestforitspotentialasanoveltherapeuticinpsychiatricillness/psychologicaldisorders.Thissymposiumwillhighlightsomeexcitingdevelopments inAustralianclinicalandpreclinicaltrials with CBD, including: 1) a preclinical investigation of the efficacy of CBD in treating the cognitivedeficitsandsocialwithdrawalsymptomsofschizophrenia inapoly I:Cmodel,withearly insight into thepotential neurochemical mechanisms underlying these benefits; 2) a pragmatic trial of prolonged CBDtreatment in chronic cannabis users, examining potential beneficial effects on cognition, symptoms andbrainneurochemistry;and3)clinical trialsexamining theefficacyofCBD in treatinganxietydisorders inyouth,aswellassafety (toxicology)considerations.ProfessorPatMcGorrywilldiscuss the findings fromthesestudiesinthecontextofthegrowingfieldofyouthmentalhealth,otherstudiesofCBDaroundtheworldandthepotentialforCBDasamedicationoradjuncttreatmenttransdiagnosticallyinpsychiatry.1.Dr.KatrinaWeston-Green,UniversityofWollongongCannabidiol treatment in a poly I:Cmodel of schizophrenia: cognitive behavioural improvements andaltered neurotransmission. Cognitive impairment is a core symptom domain of schizophrenia.Antipsychotic drugs have minimal benefits in treating cognition and can cause serious side-effects.Therefore, novel therapeutic approaches are required. Cannabidiol (CBD), from the cannabis plant,improves memory and learning in numerous pathological states, and has antipsychotic andneuroprotectiveproperties.WeexaminedtheeffectsofCBDoncognitionandneurochemicalsignallingina rodent (poly I:Cprenatal infection)modelof schizophrenia.Pregnantdamswereadministered (GD15)polyI:C(4mg/kg)orsaline(control).Post-pubertal(PND56)offspringwereadministeredCBD(10mg/kg)orvehicle(control)for3weeks(n=12/group).Offspring(PND70)underwentbehaviouraltesting:novelobjectrecognition (recognition memory), T maze (working memory) and social interaction (behaviouralphenotypefornegativesymptoms).Post-mortembrainanalysisisongoing.WehaveexaminedmuscarinicM1 (M1R) and glutamatergicNMDA receptors (NMDAR) in regions of the brain implicated in cognition.Poly I:C impaired recognition andworkingmemory, and reduced social interaction,while CBD restoreddeficits to control-like levels. Poly I:C down-regulated M1R (cingulate cortex, CPu, hippocampus) andNMDAR(PFC,cingulatecortex,CPu)bindingdensities,whileCBDreturnedlevelstonormal.Interestingly,CBD reducedM1RandNMDARbinding inhealthyoffspring.Our findingsdemonstrate that chronicCBDtreatment reduces cognitive and social interaction deficits caused by prenatal poly I:C infection andsuggest a role for muscarinic and glutamatergic signalling in the underlying mechanisms; furtherinvestigation is required. Overall, these results present interesting implications for treating cognitivedeficitsinschizophrenia.

Symposium:Therapeuticpotentialofcannabidioltreatmentforpsychiatricillness. 12

2.ProfNadiaSolowij,UniversityofWollongongProlongedadministrationofcannabidioltochroniccannabisusers:apragmatictrialanditscognitiveandsymptomatic outcomes. Heavy cannabis use is associated with impaired cognition and structural andfunctional brain alterations, including psychosis at the extreme. Significant interest has emerged inunderstandinginteractionsbetweenthetwoprimaryconstituentsofcannabisplantmatter:THCwhichisassociatedwithworseoutcomesandcannabidiol(CBD)whichmayameliorateadverseeffectsofTHCandhasneuroprotectiveandantipsychoticproperties.WeshowedthatexposuretoCBDmayprotectagainstTHC-relatedhippocampalharms,andthatprolongedabstinencemayresultinrecoveryoftheseharms,butmanychroniccannabisusershavedifficultystoppingusing.Currenttreatmentsforcannabisdependenceare inadequate and there is interest in the potential for CBD to be used as an adjunct treatment.Weconducted a pragmatic open-label trial (ISRCTN89498802) of prolonged administration of CBD (200mgdailyfor10weeks)to20cannabisuserswhocontinuedusingcannabisthroughoutthetrial.Ourprimaryaimwas to examine effects on cognition, psychological symptoms and a range of brain functional andstructural measures. Effects on cannabis use patterns were also of interest. After 10 weeks of CBDtreatment, with no adverse effects, participants showed better memory and attention switchingperformance, and reported significantly fewerdepressiveandpsychotic-like symptoms thanatbaseline.Plasma CBD levels correlated with better attention switching performance. This study is the first toexamineCBD treatment in current cannabis users, anddespite the lackof a placebo control group, theresults suggest promising beneficial effects of CBD on psychological symptoms and cognition, in thecontextofongoingcannabisuse.3.ProfPaulAmminger,OrygenandUniversityofMelbourneThe cannabidiol youthanxietypilot study (CAPS): a 12-weekopen-labelpilot studyof cannabidiol foranxietydisorders.Anxietydisordersareamongthemostprevalentpsychiatricconditionsinadolescents.Current evidence-based treatments include cognitive behaviour therapy (CBT) and/or medication.However,treatmentresistanceisasignificantproblem.Onlyaround50%ofchildrenandadolescentsremitfromtheiranxietydisorderswithCBTorpharmacologicalintervention.Therefore,thereisaclearneedtodevelopandexplorenoveltherapeuticagentsforthemanagementofanxietydisordersinthisagegroup.Theaimofthepresentstudyistotestthefeasibility,safety,tolerabilityandtherapeuticeffectsof12-weektreatment with cannabidiol (CBD) to reduce anxiety severity in young people who do not respond tostandard treatment. This is a single-centre (headspace), 12-week open label trial (ANZCTR identifier:ACTRN12617000825358p) of CBD in 30 patients aged 12-25 who do not respond to evidence-basedstandardtreatmentforanxietydisorders.PatientswillreceiveCBDonafixed-flexibleschedule,beginningwith 200mg of CBD per day (adjusted up to 800mg/day). A background intervention of bi-weekly CBTsessions will be offered. The primary outcome is anxiety severity, measured with the Overall AnxietySeverity and Impact Scale atweek 12. Secondary outcomeswill include absence of an anxiety disorderdiagnosis, depressive symptoms, social and occupational functioning, plasma levels of CBD and itsmetabolites and study withdrawal due to adverse events. Data from this study will provide the firstevidenceofthepotentialsafety,tolerabilityandefficacyofCBDforanxietydisordersinyouth.ResultswillbeusedtoinformfurtherevaluationsofCBDforanxietydisordersinlargerstudies.

Symposium:Epigeneticmediatorsofbraindysfunctionandpsychiatricdisorders. 13

Symposium2:Epigeneticmediatorsofbraindysfunctionandpsychiatricdisorders.

Monday,30thOctober,2:30pm–4:00pmSpeakers:DrTerencePang,FloreyInstituteofNeuroscienceandMentalHealth;DrIrinaVoineagu,UniversityofNewSouthWales;DrXiangLi,QueenslandBrainInstitute,UniversityofQueenslandChair/Discussant:ProfAnthonyHannan,FloreyInstituteofNeuroscienceandMentalHealthDescription:Weareinthemidstofanumberofmajorbiomedicalrevolutions.Thegenomicrevolutionisdelivering unprecedented new insights into genetic predisposition for a wide range of behavioural andcognitivetraits,aswellaspsychiatricandneurologicaldisorders.However,brainfunctionanddysfunctionis theresultofcomplexcombinationsofgeneticandenvironmental factors,andepigenetics iscrucial inunderstandinghow ‘natureandnurture’ combine.Theepigenetic revolutionprovidesanadded layerofcomplexity overlaid on genetics and incorporates a nexus of gene-environment interactions. Thissymposiumwilladdresstheroleofepigeneticsinmediatingbrainfunctionanddysfunctioninpsychiatricdisorders. It will cover a range of epigenetic modifications, including DNA methylation, histonemodifications and the regulatory roles of noncoding RNAs. The symposium will incorporate nationalexperts in this field of biological psychiatry. Epigenetic mechanisms mediating key behavioural andcognitiveprocesses,includinglearningandmemory,willbeaddressed.Furthermore,epigeneticsiscrucialtoourunderstandingofbraindevelopmentandhealthyfunction,whichwillbecoveredinthissymposium.Thespeakerswillalsodiscusstherelevanceofepigeneticdysregulationtomajorpsychiatricdisorders.ThistopicwillbeofbroadinteresttoawiderangeofBiologicalPsychiatryAustraliamembers,andotherattendeesoftheAnnualScientificConference.Whethertheprimaryfocusofthesescientistsismolecular,cellular,behavioural,cognitiveorclinical,epigeneticsimpactsonmultiplelevelsofneurobiologyandbiologicalpsychiatry.Furthermore,thesymposiumwilladdressbothbasicandclinicalneuroscience,andislikelytoengagethediverseBPAaudience.1. Dr Terence Pang, Florey Institute of Neuroscience and Mental HealthPaternal Environmental Exposures Induce Transgenerational Epigenetic Effects on Offspring BrainFunction and Psychiatric Endophenotypes. It is now becoming evident that a male’s lifestyle prior toconception can significantly alter the health outcomes of his children. Examples of these potentiallyimpactfulfactorsincludetraumaticstress,ahigh-fatdiet,andexposuretodrugsofabuse.Epidemiologicalevidence traced along the paternal lineage indicates that ancestral exposure to traumatic events elicitsnegative transgenerational response in subsequent generations. Studies of animal models of traumaticstress(maternalseparation,chronicsocialdefeat)havealsofoundlong-termimpactsonoffspringanxietyand stress response. To study the impact of non-traumatic stress (arguablymore relevant to thewiderpopulation), we developed and demonstrated in a mouse model of low-dose chronic corticosteronesupplementationthatthisledtoelevatedanxietyinthemaleF1offspring(Shortetal.,2016).Iwilldiscusshow the transgenerational response is modulated by environmental enrichment (increased cognitivestimulationandphysical activity) andexercise. Thisextendsonourpreviouslydemonstratedbenefitsofenvironmental enrichment in variousmodels of neurological conditions, in part by rescuing anxiety anddepressivephenotypes (Pangetal.,2009;Duetal.,2012;Pangetal.,2013). Iwillalsodiscussourgeneexpression profiling studies of the offspring hippocampus, where we have examined variousmolecularmediators associatedwithanxietypathology.Ourwork suggests thatpaternalpreconception conditions

Symposium:Epigeneticmediatorsofbraindysfunctionandpsychiatricdisorders. 14

indirectlyresultindifferentialregulationofgeneexpressioninoffspringbrainswhichcouldunderlietheirbehaviouralphenotypesandmodulatetheirresponsetoenvironmentalcues.2.DrIrinaVoineagu,UniversityofNewSouthWalesThe Role of the RBFOX1 Splicing Factor and Circular RNAs in Autism Spectrum Disorders. AutismSpectrumDisorders(ASD)areneurodevelopmentalconditionsthatarehighlyheritablebutalsogeneticallyvery heterogeneous. Current genetic data estimates that over 1000 loci contribute to the geneticlandscapeofASD.DespitethegeneticheterogeneityofASD,areplicablemolecularsignatureofASDbrainshasbeen identifiedbyseveral studiesusingdistinctcohorts (Voineaguetal.Nature2011,Liuetal.PlosGenetics2016,Parikshaketal.Nature2016).Oneof thegenesconsistentlydysregulated in thebrainofASDpatientsistheneuronalandmusclespecificsplicingfactorRBFOX1.Severallinesofevidenceindicatethat, RBFOX1 has an effect on transcript abundance. Here we investigate the hypothesis that RBFOX1might affect transcript abundance by regulating the formation of circular RNAmolecules. Circular RNAs(circRNAs) result from non-canonical back-splicing. To investigate the effect of RBFOX1 on circRNAbiogenesis, we overexpressed the neuronal isoform of RBFOX1 in human primary astrocytes. WeperformedRNA-seqon triplicateRBFOX1overexpressionandcontrol samples,withandwithoutRNaseRtreatment,toenrichforcircularRNAmolecules.Weobservedastrong increase incircRNAexpression incellsstablyexpressingRBFOX1.WealsofoundasignificantoverlapbetweenRBFOX1-dependentcircRNAsandcircRNAspreviouslyshown(Zhangetal.Cell.Rep.2016)tobeinduceduponneuronaldifferentiation.These data bring initial evidence for the role of RBFOX1 in regulating the formation of circRNAs in thehumanbrain,amechanismpotentiallycontributingtoitsroleinASD.3.DrXiangLi,QueenslandBrainInstitute,UniversityofQueenslandThedevilisinthedetail:whystudyingindividualdifferencesinaddictionmatters...TheFormationofFearExtinction Memory Requires the Accumulation of N6-methyl-2’-deoxyadenosine in DNA. We havediscovered that the DNAmodificationN6-methyl-2’-deoxyadenosine (m6dA) is dynamically regulated inpost-mitoticneuronsandaccumulatesgenome-wideintheadultbrainofC57Bl6miceinresponsetofearextinction learning.Thedepositionofm6dAdrivesactivity inducedgeneexpressionand isnecessary forthe formation of fear extinction memory. In stimulated primary cortical neurons in vitro, m6dAaccumulateswithintheP4promoterofthegeneencodingbrain-derivedneurotrophicfactor(BDNF)andcreatesanactivechromatinstateandtherecruitmentoftheactivatingtranscriptionfactorYin-Yang1andRNApolymeraseII,whichleadtoincreasedBDNFexonIVmRNAexpression.Theeffectsaremediatedbytheactivityof aputativeadeninemethyltransferase (N6amt1), theknockdownofwhichpreventsm6dAdepositionandrelatedrecruitmentofchromatinandtranscriptionalmachineryat theBDNFP4 locus. Intheadultinfralimbicprefrontalcortex,N6amt1-mediatedaccumulationofm6dApromotestheexpressionofBDNFexonIV,whichisrequiredfortheformationoffearextinctionmemory.Weproposeamodel inwhich the experience dependent accumulation of m6dA at specific GATC sites along gene promoterscreatesanepigeneticstatethatispermissiveforgeneactivation,andplaysakeyroleintheexpressionofgenes associatedwith the formation ofmemory. These findings dramatically expand the scope of DNAmodificationanditsadaptiveroleintheepigeneticregulationofgeneexpressionintheadultbrain,whichhas implications for understanding the pathogenesis of psychiatric disorders.

Symposium:Addictedtoaddiction–isitlackoflove,toomuchstress,orjustyourpersonality(andgenes)?

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Symposium3:Addictedtoaddiction–isitlackoflove,toomuchstress,orjustyourpersonality(andgenes)?

Tuesday31stOctober,11:00am–12:30pmSpeakers:Prof.IainMcGregor,UniversityofSydney;Prof.AndrewLawrence,FloreyInstituteofNeuroscienceandMentalHealth;A/Prof.ChristopherDayas,UniversityofNewcaslteChair:Dr.JiameiLian,UniversityofWollongongDiscussant:Dr.JeeHyunKim,FloreyInstituteofNeuroscienceandMentalHealthDescription:Seekingofrewards,suchassexandfood, isnecessarytopromotesurvival.However, itcanmanifest as addictionwhen it interfereswithdaily functioning.Addiction todrugsof abuse is a chronicbrain disorder characterized by compulsive drug seeking and use that persist despite severe adverseconsequences, and relapse following treatment is high. It is one of the greatest causes of financial andsocietal burden in the world. Therefore, understanding the molecular mechanisms underlying drugaddictionisclinicallyimportant.Oursymposiumwillpresentthelatestfindingsondifferentdrugsofabuse(alcohol, cocaine,methamphetamine)withsignificant implications in the fieldofBiologicalPsychiatrybyleading scientists fromMelbourne, Sydney, and Newcastle. The Discussant Dr Jee Kimwill first set thescenebrieflybyraisingthehottestquestionsinaddictionandillustratingfailures inclinicaltrialstotreataddiction. Professor Iain McGregor will describe his journey in discovering and developing a novelpharmacotherapy exploiting the oxytocin system that may simultaneously cure our substance usedisorders and social anxiety. Professor Andrew Lawrence will then highlight that other neuropeptidesystemssuchas relaxincanbemanipulatedalso tocureaddictionbyreducingstress-inducedrelapseofalcohol seeking. A/Professor Christopher Dayas will then challenge both their work with his researchshowingthatthekeytoreducingaddictionlieswithinindividualdifferencesinmicro-RNAchangesindrug-taking,-seeking,and–relapse.DrKimwillthenleadtheaudienceintoanexcitingdiscussionintowhetherwecancureaddiction,oratleastdrinklesswhenstressed. 1.Prof.IainMcGregor,UniversityofSydneySerendipity and the Hard Slog: an insiders account of the discovery and development of a noveltherapeuticfortreatingaddictionandsocialdeficits.Thepastfewyearshaveseenincreasinginterestintheneuropeptideoxytocinasanovelandeffectiveinterventionforaddictivebehaviourandforpsychiatricdisorders that feature social withdrawal as a central feature (e.g. autism). Early studies in laboratoryanimals showed the capacity of oxytocin to increase prosocial behaviours and to reducemethamphetamine,cocaineandalcoholself-administrationandwithdrawalsymptoms.However,oxytocinitself isunlikely toeverbecomeamainstreamtherapeuticdue to itspoorbrainpenetrationand lackoforal bioavailability. Investigation of non-peptide small molecule oxytocin-like compounds by our grouplead to the serendipitous discovery of SyntheticOxytocin-Like-Compound 1 (SOC-1), a novel compoundthat stimulates brain oxytocin circuitry and has dramatic prosocial and anti-addiction effects in animalmodels. SOC-1 reduces intravenous methamphetamine self-administration and reinstatement ofmethamphetamineseekingbehavior in rats, reducescocaineself-administration in rhesusmonkeys,andalcohol self-administration in baboons. SOC-1 shows favourable pharmacokinetics and a very promisingtoxicityprofile,andfurther testing isbeingcurrentlyundertaken in theUSAandAustralia toenable fasttrackingofPhase1humanclinicaltrials.ThemodeofactionofSOC-1remainssomethingofamystery:it

Symposium:Addictedtoaddiction–isitlackoflove,toomuchstress,orjustyourpersonality(andgenes)?

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stimulatesmagnocellularoxytocincontainingneuronsinthehypothalamusbutdoesnotshowaffinityformore than 100 different receptors and transporters that have been screened, including the oxytocinreceptor. Microarray and activity-based proteomic profiling are currently being conducted to betterelucidatetheactionsofSOC-1onthecentralnervoussystem. 2.Prof.AndrewLawrence,FloreyInstituteofNeuroscienceandMentalHealthPeptide interactions and relapse. Increasingour understandingof thebrain circuits and chemicals thatregulatealcoholintakeandrelapseoffersthepotentialformoretargetedtherapeuticapproachestoassistinrelapseprevention.Stress isakeyprecipitantofrelapse,andrelaxin-3signallingviaRXFP3modulatesboth stress responses and alcohol intake. In iP rats, icv microinjection of a selective RXFP3 antagonistpreventedyohimbine-inducedreinstatementofalcohol-seeking,discretemicroinjectionsimplicateddorsalBNST and central amygdala as loci. Relaxin-3 neurons are predominantly located in the CRF-sensitivenucleus incertus (NI). Intra-NI microinjection of a selective CRF1 receptor antagonist attenuatedyohimbine-induced reinstatementof alcohol-seekingwhereasaCRF2 receptorantagonisthadnoeffect.Afterlong-termvoluntaryalcoholintake,qPCRrevealedthattheexpressionofmRNAencodingbothCRF1and RXFP3 receptors was upregulated in the NI. Furthermore, chronic ethanol intake leads toneuroadaptive changes in CRF and relaxin-3 systems within rat NI. The NI also receives orexinergicinnervation, bilateral NI injections of an OX2 receptor antagonist attenuated yohimbine-inducedreinstatementofalcoholseeking,whileanOX1receptorantagonisthadnoeffect.Orexin-AdepolarizedNIneuronsrecordedincoronalbrainslices,sensitivetobathapplicationofTCS-OX2-29,butnotSB-334867.ThesedatasuggestanexcitatoryorexinergicinputtoNIcontributestoyohimbine-inducedreinstatementofalcoholseeking,predominantlyvia localOX2receptorsignalling.Collectively,thesedataimplicateCRFandorexininputstorelaxin-3neuronsoftheNIinalcohol-seeking.3.A/Prof.ChristopherDayas,UniversityofNewcaslteNon-codingRNAarealevelofmolecularcontrolthatcanpromotebothfinetuningandlastingchangesinsynapticplasticity.Micro-RNAsareaformofnon-codingRNAsthatareshort(21-23nucleotidesinlength)inlengthandpost-transcriptionallyregulatemessengerRNAprimarilythroughtranslationalrepressionortranscriptdegradation.Keystudieshaveshownthatoverexpressionof specificmiRNAwith thestriatumcan profoundly modify drug taking. However, the temporal profile of miRNA dysregulation andcontribution to distinct behaviours across the addiction cycle has not been studied. Accordingly, weexamined theexpressionof candidatemiRNA in thedorsalandventral striatumofanimals identifiedas‘addiction prone’ or resistant either immediately following self-administration training or followingextinction and relapse testing. Cocaine self-administration was associated with changes in miRNAexpressioninaregionallydiscretemannerwithinthestriatum,withthemostmarkedchangesoccurringinthenucleusaccumbenscore.WhenweexaminedthemiRNAprofileofaddiction-proneratsfollowingself-administration,weobservedincreasedlevelsofmiR-212inthedorsomedialstriatum.Afterextinctionandrelapsetesting,addiction-proneratsshowedsignificantincreasesintheexpressionofmiR-101b,miR-137,miR-212andmiR-132 inNAcSh,andmiR-137 inDLS.This study identifies temporally specific changes inmiRNAexpressionconsistentwiththeengagementofdistinctstriatalsubregionsacrossthecourseoftheaddiction cycle. Increased dysregulation of miRNA expression in NAcSh and DLS at late stages of theaddictioncyclemayunderliehabitualdrugseeking,andmaythereforeaidintheidentificationoftargetsdesignedtotreataddiction.

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SpecialSymposium:Highestratedstudentabstracts

Tuesday,31stOct,2:30–3:10pm1.Thetherapeuticpotentialofcannabidiol(CBD)inatransgenicmousemodelofAlzheimer’sdisease.Authors:GeorgiaWatt,KaniShang,HongyunLi,GrettGarnerandTimKarl.Affiliations:WesternSydneyUniversity,NeuroscienceResearchAustralia,UniversityofNewSouthWales,UniversityofWollongong,IllawarraHealthandMedicalResearchInstitute(IHMRI)Background:InAlzheimer’sdisease(AD)pathologicalbrainchangesincludetheaccumulationofamyloid-β(Aβ)andtauhyperphosphorylation causing neurodegeneration, neuroinflammation and oxidative stress. Current ADtreatments do not stop or reverse the disease progression, highlighting the need for more effectivetherapeutic alternatives. The non-psychoactive phytocannabinoid cannabidiol (CBD) has demonstratedanti-oxidant,anti-inflammatoryandneuroprotectiveproperties.Furthermore,chronicCBDtreatment(20mg/kg)hasbeenshowntoreversesocialrecognitionmemorydeficitsinanestablishedmousemodelforAD(i.e.APPxPS1transgenicmice).Thecurrentprojectaimedtodeterminetheeffectof50mg/kgCBDinAPPxPS1mice.Methods:Male APPxPS1 transgenic mice at 12 months of age were treated with CBD (50 mg/kg CBD, dailyintraperitoneal injections)starting3weekspriortobehaviouraltesting(WT-VEHn=10;WT-CBDn=11;APPxPS1-VEH n = 10; APPxPS1-CBD n = 8). A variety of cognitive domains including object and socialrecognitionmemory, spatial memory, and fear-associatedmemory were evaluated following the initialtreatmentperiod.Afterbehaviouraltestcompletion,braintissuewascollectedandsolubleandinsolubleAβ40andAβ42levelswereanalysedbyELISAasamarkerforADbrainpathology.Results:Vehicle treated male APPxPS1 mice demonstrated impaired social recognition memory and impairedreversal learning in the cheeseboard task. These deficits were absent in AD mice undergoing CBDtreatment. The ELISA results indicated that soluble Aβ42 levels were not affected by CBD treatment.However,therewasatrendforCBDtoreduceinsolubleAβ40levelsinthehippocampusinAPPxPS1mice.Conclusions:Thisstudy investigatedthetherapeutic-likeeffectsof50mg/kgCBDoncognitionandbrainpathologyofAPPxPS1transgenicmales.ChronicCBDtreatmentcouldreversedeficitsinsocialrecognitionmemoryandspatial learning in thecheeseboard task.Furthermore,CBDtreatment trendedto reduce insolubleAβ40levelsinthehippocampus.

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2.Intranasaloxytocinincreasesamygdalaresponsestoemotionalfacesinbodydysmorphicdisorder.Authors:SallyGrace,IzelleLabuschagne,MatthewHughes,DavidCastleandSusanRossellAffiliations:SwinburneUniversityofTechnology,AustralianCatholicUniversity,MelbourneUniversityBackground:Patientswithbodydysmorphicdisorder(BDD)areimpairedatrecognisingfacialemotionsandhaveshownabnormal brain activity in regions involved in face and emotion processing. Past research hasdemonstratedthattheneuropeptideoxytocinincreasesbehaviouralperformanceonfaceprocessingtasks,aswell asmodulates amygdala responses toemotional faces inhealthy subjects and thosewith clinicaldisorderssuchassocialanxietyandautism.Methods:Here,weaimedtoassessamygdalaresponsestoemotivefacesinasampleof20maleandfemalepatientswithBDDand22matchedhealthycontrolparticipants.Inarandomized,double-blindplacebo-controlledwithin-subject functional MRI study, we measured group differences in amygdala activation to anemotionalfacematchingtaskoffearful,angry,disgusted,sad,surprisedandhappyfacesfollowingacuteintranasaladministrationofOXT(24IU)andplacebo.Results:Oxytocin elicited differential effects within the left amygdala, with the BDD group showing increasedamygdala responses to surprised and threatening faces (anger & fear) following intranasal oxytocin,whereasdecreasedamygdalaresponseswereobservedinthehealthycontrolgroup.Conclusions:Our resultsprovidenewevidence thata singleadoseofoxytocinhasamodulatoryeffectonamygdalaresponsestoemotivefacesinBDD.Theseobservationsmayreflectoxytocin-inducedsalienceprocessingofemotivefacesandsubsequentlyenhancefaceemotionprocessinginmaleandfemaleBDDpatients,whichhaveimportantclinicalimplicationsforthedisorder.

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3.AlteredfetalsteroidgenesisanddysregulatedplacentalimmuneresponseinadevelopmentalvitaminDdeficientratmodelofautism.Authors:AsadAli,XiaoyingCuiandDarrylEylesAffiliations:QueenslandBrainInstitute,BrisbaneBackground:EmergingevidencesuggeststhatmaternalordevelopmentalvitaminDdeficiency(DVD-deficiency)isariskfactor for autism.Awell-establishedassociationhas alsobeen foundbetweengestational infection andincreased incidenceofautism.Postmortemstudieshaverevealedthatbrainsfromautisticchildrenhaveincreased inflammatorycytokines. Inaddition importantdevelopmentalneurosteroidshavebeenshownto be significantly increased in the amniotic fluid of childrenwho develop autism. Vitamin D has beenshown to both promote anti-inflammatory actions in placenta and regulate expression of severalsteroidogenicenzymesinvitro.HereweinvestigatetheeffectsofDVD-deficiencyonfetalsteroidogenesisandplacentalimmunefunctions.Methods:DVD-deficiencywas induced by feeding vitamin D deficient diet to female Sprague-Dawley rats for theperiodof6weeksbeforemating.Foetuseswerecollectedatgestationalday18.Malefetusespositionedbetweentwoneighbouringmales(2M-males)ordownstreamtoamalefetus(1M-males)wereselected.Theexpressionofsteroidogenicenzymesandcertainautism-candidategeneswereexaminedbyReal-TimePCRinmatchingfetalbrainsandplacentas.BaselinelevelsofcytokinesweremeasuredbyELISA.Placentalresponsetotheinflammatoryagentslipopolysaccharidesandpolyinosinic-polycytidylicacid(polyI:C)wasalsoexaminedwhenplacentawascultured.Datawasanalysedbymultivariateanalysis.Results:DVD-deficiencyreducedaromataseexpressionin2M-malebrainscomparedtosimilarpositionedcontrols(p=0.031).Theprogesteronecatabolicenzymecyp21a1(p=0.04),foxp2(p=0.023)andvitaminDactivatingenzymecyp27b1 (p=0.049)wereall significantly reduced in2MDVD-deficientbrains. Inplacenta,DVD-deficiencyreducedexpressionofcatechol-O-methyltransferase(p=0.005). Incontrasttobrains,cyp27b1wasup-regulatedinDVD-deficientplacentas(p=0.001).DVDdeficiencydidnotaffectbaselinecytokinesinbrainorplacenta.HoweverwhenactivatedwithpolyI:C,DVD-deficientplacentasfrommalefetuseshadhigherconcentrationofIL-6(p=0.025)and1L-1β(p=0.020)thencontrolplacentas.Conclusions:Therefore 3 potential autism-related processesmay operate in the DVD-deficient developing brain andplacenta.A)Thealterationsinthearomataseandcyp21a1expressionsmaypossiblyenhancetestosteroneand progesterone production in DVD-deficient male brains. B) Down-regulation of catechol-O-methyltransferaseleadstoreduced2-methoxyestradiolawell-knowncauseofpreeclampsia.C)Increasedproduction of IL-6 and 1L-1β in poly I:C activated DVD-deficient placentas suggests that vitamin Ddeficiency is sufficient to causedysregulationof placental immune regulation against viral infections. Inconclusion, developmental alterations in steroidogenesis, autism-candidate genes and dysregulatedplacentalimmuneresponseprovideplausiblemechanismslinkingDVD-deficiencyandautism.

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Monday,30thOct,10:00am–10:30am1.There’ssomethingfishyabouthisbehaviour:Howdoesomega-3statusinfluenceaggressionandcognitivefunctionandwhatcanbedonetoensureabetterfuture?Authors:BarbaraMeyerandMitchellByrneAffiliations:SchoolofMedicine,UniversityofWollongong;SchoolofPsychology,UniversityofWollongongBackground:Dietinfluencesmentalhealthandbehaviour.Omega-3(n-3)fattyacidsplayapivotalroleinmentalhealthandbehavioural self-regulation.Theoldepithet “youarewhatyoueat”extendsbeyondphysicalhealthandbodymorphology,withincreasingdatademonstratingthatdietinfluencesbothcognitivefunctionandbehaviour.Thisisparticularlyrelevantinoffenderpopulationswherepoordietscombinewithhigherthanaverage incidence of mental health problems. This presentation outlines the biological plausibility ofomega-3 supplementation as an intervention for behavioural disorders (aggression) and mental healthdifficulties(ADHD).Methods:Thepilotfeasibilitystudywasadoubleblindcross-sectionalstudyutilisingbehavioural,psychometricandbiologicalmeasures.136adultmaleprisonerswererecruitedfromSouthCoastCorrectionalCentre(SCCC),NSWAustralia.A7pointcategorisationwasusedtoquantifylevelsofaggressivebehaviour(4weeks)fromindividualSCCCcasenotes,wherebyhigherscorescorrespondtoincreasinglyaggressivebehaviour.Studyparticipants completed the Aggression Questionnaire (AQ) and the Brown’s Attention Deficit DisorderScales(BADDS),providedabloodsampleforerythrocytefattyacidanalysisusinggaschromatographyandtheomega-3indexwascalculated.Results:The baseline omega-3 index ranged from 2.3% to 10.3% with a median of 4.7%, indicating that someparticipants already had substantial omega-3 intake. Assessment of aggressive and attention deficitbehaviour revealed that therewerenegativecorrelationsbetweenbaselineomega-3 indexandbaselineaggression categorisation scores (r=-0.21, P=0.016); total AQ score (r=-0.234, P=0.011); Anger (r=-0.222p=0.016);HostilityAQ(r=-0.239,P=0.009); indirectaggression(r=-0.188p=0.042);totalBADDS(r=-0.263,p=0.005);Activation (r=-0.224,p=0.016);Attention (r=-0.192,p=0.043);Effort (r=-0.253,p=0.007);Affect(r=-0.330,p=0.000)andMemory(r=-0.240,p=0.010).Conclusions:Thestudydemonstratedthatthereisahighvariabilityinomega-3statusofaNSWprisonpopulation,andinmateswithloweromega-3indexweremoreaggressiveandhadhigherADDscores.Thispilotfeasibilitystudyhasledtoasuccessful$1.8MNHMRCPartnershipGrantthatincludesamulticentretrialofn-3andaggressivebehaviourinadultmaleprisonersaswellastranslationintopolicyandpractice.

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2.VitaminDdeficiencyreduceshippocampalsubfieldvolumeanddisruptsright-hippocampalstructuralconnectivity:evidencefrommouseandhumandata.Authors:MamunAl-Amin,RK,Sullivan,NyomanD.Kurniawan,YeonsilMoon,Seol-HeuiHanandTHJBurne.Affiliations:QueenslandBrainInstitute,UniversityofQueensland;CentreAdvancedImaging,UniversityofQueensland; Department of Neurology, Konkuk University Medical Centre, Seoul; Australia andQueenslandCentreforMentalHealthResearch.Background:Converging evidence fromhuman epidemiological and rodent studies suggest that vitaminD deficiencyimpairs cognition. Here we examined the impact of adult vitamin D (AVD) deficiency on hippocampalsubfield volume and structural connectivity in BALB/c mice. We also analysed previously collectedstructuralanddiffusionweightedMRIdataofelderlypersonshavingmildcognitive impairment(MCI)tocomparewithanimalfindings.Methods:AdultmaleBALB/cmice(10weeksold)werefedacontroldiet(1500IUvitaminD3/kg,n=16)ordeficientdiet(0IUvitaminD3/kg,n=16)foradurationof20weeks.Weusedtheactiveplaceavoidance(APA)testtomeasurespatial learningandmemory formation.WeacquiredstructuralanddiffusionMRI imagesofmousebrainusinga16.4Tscanner.Weused“mrtrix3”and“FSL”forpre-processingofdiffusionimage.Weused “Freesurfer” formotion correction,whole brain and hippocampal subfield segmentation.We alsoused network based statistics to identify connections and networks that are altered in vitamin Ddeficiency.Results:WeobservedthatAVD-deficientmicehadasignificantly(p<0.05)lowerlatencytoentertheshockzoneinAPA test.We found a significant (p<0.05) reduction of total hippocampal volume in human but not inmouse.Humanhippocampalsubfieldvolumeanalysisshowedasignificant(p<0.05)reductionofCA1,CA3,CA4,subiculumandfimbriavolumes.Bycontrasts,mousedatashowedasignificant(p<0.05)shrinkageofCA1subfield.Moreover,wefounddisruptedstructuralbrainconnectivityon29nodesinmiceand12brainnodeson theelderlyAVD-deficienthuman.Bothspeciesshowedthat theright-hippocampus is thecorehubofthedisruptednetwork.Conclusions:Consistent with several previous studies, we found that AVD deficiency impaired spatial learning andmemoryformation.Theaffectedmousebrainregionsareinvolvedinmemory,navigation,fear,emotionalstimuli processing. In humans, there were reductions in hippocampal subfield volume and disruptedstructural connectivitywere associatedwith bothmemory impairment and AVD deficiency. Our resultsindicate a vulnerability in hippocampal subfield volume and connectivity associated with vitamin Ddeficiencyinmiceandhumans.

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3.Dosensoryintegrationdeficitsrepresentabiomarkerforschizophrenia?Authors:OliviaCarter,HayleyDarke,ChristinaDamicoucas,MatthewMitchell,KeriSteenbergandSureshSundram.Affiliations:UniversityofMelbourne,MonashUniversityBackground:Visualdysfunctioniscommonplaceinschizophreniaandoccursalongsidecognitive,psychoticandaffectivesymptomsof thedisorder.A substantial bodyof evidencehas repeatedlydemonstrated impairments intheintegrationof“low-level”visualfeaturesinpatientswithschizophrenia.Thishasledsometosuggestthat visual integration impairmentsmay serve as a potential biomarker for this disorder. Despitemanysymptomsofschizophreniaoccurringinarangeofdisorders,visualintegrationdeficitsarerarelytestedinbroaderpatientpopulations.Methods:Thepresent study assessedpatientswith a rangeof psychotic andnon-psychotic disorders andhealthycontrolsonavarietyoftasksassessingvisualcontrastdetection,visualmotionintegration,visualcontourintegration,auditorytonedetection,andauditorytoneintegration.Acrossthedifferentmeasuresatotalof 239 psychiatric inpatients (schizophrenia spectrum disorder n=114; bipolar affective disorder n=44;majordepressionn=38andotherpsychiatricconditionsn=33)and74healthycontrolswereassessed.Results:Comparedwithhealthycontrolsandnon-psychoticpatients,psychoticpatients trans-diagnosticallywereimpairedonthesensoryintegrationtasks(visualmotion,visualcontourandauditoryintegration)howevertheywereunimpairedinsimplevisualorauditorydetection.Impairmentinvisualmotionintegrationwascorrelatedwiththeseverityofpositivesymptomsindependentofdiagnosis,andcouldnotbeaccountedforbyareductioninprocessingspeed,inattentionormedicationeffects.Conclusions:Our results demonstrate that impaired sensory integration is not specific to schizophrenia, as haspreviously been assumed. Instead, sensory integration deficits are closely related to the presence ofpositivesymptomsindependentofdiagnosis.Thefindingthatequivalentintegrativesensoryprocessingisimpairedinauditionisconsistentwithhypothesesthatproposeageneraliseddeficitofneuralintegrationinpsychoticdisorders.

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4.KetogenicdietnormalizesbehaviouralabnormalitiesinachronicneurodevelopmentalmurinemodelofschizophreniaAuthors:Ann-KatrinKraeuter,ZoltanSamyaiandMaartenvandenBuuseAffiliations:JamesCookUniversity,LaTrobeUniversityBackground:Schizophrenia is a chronic neurodevelopmental disorder effecting around1%of theworld’s population.Current medications have poor efficacy with detrimental side effects. Current research associatesschizophrenia with a dysfunctioning glucosemetabolism. Viral infection during pregnancy activates thematernal immune system, increasing schizophrenia incidences in the offspring through altering braindevelopment. Therefore, we are proposing a metabolic based approach, Ketogenic diet (KD), for thetreatment of schizophrenia. KD has been used since 100 years safely for the treatment of childhoodrefractoryepilepsy.WeaimtouseKDasanalternative fuel source toglucose inaneurodevelopmentalmousemodelofschizophrenia.Methods:Pregnant females were injected i.v. on gestation day 9 with Polyinosinic:polycytidylic acid (Poly I:C) toactivatethemothersimmunesystem.Maleandfemaleoffspringwereplacedbetween5-6weeks(duringadolescence) on Standard diet or KD. Animals remained for 3weeks on their randomly assigned diets,whichwasfollowedbyabatteryofbehaviouralassays.Animalsweretestedbehaviourallyfor locomotoractivity(openfield),sociability(3chambersociability),repetitivebehaviour(marbleburying)andsensorymotorgating(prepulseinhibitionofstartle).Results:Ketogenic diet normalized locomotor activity and sociability in both genders. Repetitive behaviour wasonlyincreasedinmalePolyI:Canimals,whichwasnormalizedbytheKetogenicdiet.NoeffectofPolyI:Cwasfoundinfemaleanimals.Inmalesincombinationwith0.25mg/kgMK-801agreatersensitivitytotheNMDA-receptorantagonistwas foundwithinthePoly I:Cgroup,whichwasnormalizedbytheKetogenicdiet.Conclusions:Our findings show that KD was effective in reversing neurodevelopmental changes induced by thematernal immuneactivationmodel.However, furtherresearch isneededtoestablishthe implicationsofKDinthematernal immuneactivationmodeloncognition.Thisraisesthepossibilitythatametabolicallybasedapproachcanbeusedeffectivelyinthetreatmentofchronicschizophrenia.

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5.Theeffectsofmid-lategestationalmaternalimmuneactivationinratsonschizophrenia-relatedbehaviourAuthors:LaurenHarms,ArielDunn,AnitaGray,RebeccaTattoli,PatriciaTMichieandDeborahMHodgsonAffiliations:PriorityCentreforBrainandMentalHealthResearch,UniversityofNewcastleBackground:Prenatalinfectionisariskfactorforschizophreniainoffspringandisbelievedtobemediatedbymaternalimmuneactivation(MIA)inresponsetoaninfection.PreviousstudiesinourlabinvestigatingtheeffectofMIA during mid or late gestation found sensorimotor gating deficits and transient working memoryimpairments, but did not observemany other behavioural changes consistentwith an animalmodel ofschizophrenia.Therefore,thecurrentstudyaimstodeterminewhetherMIAatanothergestationaltime-pointleadstosignificantchangestoschizophrenia-relatedbehaviour.Methods:Polyinosinic:polycytidylicacid (PolyI:C)was injected to induceMIA inpregnantWistar ratsatgestationalday(GD)14.Controldamsweregivensalineinjections.Theresultingoffspringwereraiseduntiladulthoodand their behaviours with relevance for schizophrenia and other psychiatric disorders were examined,including the elevated plus maze behaviour, social interaction, sucrose preference, open field activity,sensorimotorgatingandlocomotorsensitivitytothepsychomimeticdrugsamphetamineandMK-801.Results:MIA-exposed rats were more sensitive to the locomotor-stimulating effects of the psychomimeticamphetamine (F(1, 29) = 8.00, p = .008) , an effect most pronounced after a high dose (2.5mg/kg) ofamphetamine.Inaddition,MIA-exposedratsexhibitedreducednovelobjectpreferenceinthenovelobjectrecognitiontestoflearningandmemory(F(1,38)=9.57,p=.004).Botheffectsweremorepronouncedinmale rats. MIA exposure at GD14 did not affect sensorimotor gating, locomotor responsivity to thepsychotomimetic MK-801, social interaction, sucrose preference, elevated plus maze or open fieldbehaviour.Conclusions:These findings indicate that theMIAmodelmaybeuseful for further investigationof schizophrenia-likecognitivedeficitsandpsychotic-likebehaviour,butisunlikelytobeusefulforthefurtherinvestigationofnegativesymptom-likebehaviour.

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Monday,30th12:30–1:00pm1.Raloxifenemodulatesdopamine-relatedtranscriptsinthemidbraininmaleratsAuthors:TertiaPurves-Tyson,DannyBoerrigterandCyndiShannonWeickertAffiliations:SchizophreniaResearchLaboratory,NeuRA;SchoolofPsychiatry,UNSWBackground:The selective estrogen receptor modulator, raloxifene, improves cognition in schizophrenia and mayameliorate psychosis. Dopamine (DA) dysregulation contributes to cognitive deficits and psychosis inschizophrenia. It is not known if themolecularmechanisms of raloxifene include changes in dopamineregulationatthedopaminecellbodies.WehypothesisedthatraloxifenemodulatesDA-relatedtranscriptsin the substantia nigra (SN) and ventral tegmental area (VTA) in healthy male rats, and that this mayunderpinraloxifene-inducedchangesinDA-relatedbehaviours.Methods:AdultmaleWistarrats(n=~12/group)weregivendailysubcutaneousinjectionsofraloxifene(5mg/kg)orvehicle for 4 weeks. DA synthesis enzyme, tyrosine hydroxylase (TH) and dopamine transporter (DAT)mRNAswereassessedbyqPCRintheSNanddopaminereceptor(DRD2short,DRD2long,DRD1,DRD3)andcatabolicenzyme(MAOA,COMT)transcriptsintheSNandVTA.DatawasanalysedwithStudent’sttests.Results:In the SN, therewas no change in THmRNA, but an increase in DATmRNAwith raloxifene treatment.DRD2S,DRD2LandDRD3transcriptswereincreasedbyraloxifeneinboththeSNandVTA.Incontrast,wedidnotdetectaraloxifene-relatedchangeinDRD1mRNAinthemidbrain.MAOandCOMTmRNAswereincreasedbyraloxifeneinbothregions.Conclusions:Since we have found significant reductions in DAT and DRD2 mRNA in the midbrain of people withschizophrenia,thesestudiesshowpotentialforraloxifenetorestoregeneexpressionofmoleculesthatarereduced in the midbrain in schizophrenia. Furthermore, raloxifene also increases catabolic enzymetranscripts thatmaycontribute to reducingextracellularor intracellulardopamine levels. Future studieswillinvestigateDA-relatedtranscriptsinstriatumandcortexanddeterminewhetherraloxifenepreservescognitioninaratmodelofschizophreniathatexhibitscognitivedeficits.

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2.Effectsofcannabidioltreatmentuponhippocampalsubfieldvolumesincurrentcannabisusers.Authors:CamillaBeale,SamanthaBroyd,YannChye,ChaoSuo,MuratYucelandNadiaSolowijAffiliations: School of Psychology, University of Wollongong; Illawarra Health and Medical ResearchInstitute, University ofWollongong; Brain andMental Health Laboratory,Monash Institute of CognitiveandClinicalNeurosciences,MonashUniversity.Background:Chroniccannabisuseisassociatedwithneuroanatomicalalterationsinthehippocampus,aregionwithahigh density of cannabinoid type 1 receptors. Cannabis is comprised of two primary constituents,Δ-9-tetrahydrocannabinol(THC)andcannabidiol(CBD).WhileadverseimpactsaregenerallyattributedtoTHC,there isemergingevidence thatCBD isneuroprotectiveandmayameliorate suchharms.Wepreviouslyfound that cannabisusers regularly smoking cannabis containingCBDdidnot show typicalhippocampalvolumetricloss.ThecurrentstudyexaminedwhetherprolongedadministrationofCBDtoregularcannabisuserscanreversethecharacteristicbrainharmsassociatedwithcannabisuse.Methods:Eighteen regular cannabis users participated in a 10-week trial of daily administrationof 200mgCBD incapsule form,withnochangetotheirongoingpatternofcannabisuserequired.Participantsunderwentstructural magnetic resonance imaging (MRI) at baseline and post-treatment, and attended weeklymonitoringsessionsinvolvingbloodsamplecollectiontoassayCBDlevelsinplasma.T1-weightedimageswereprocessedusing anovel automated longitudinal hippocampal segmentation tool available throughFreeSurfersoftware(version6.0).Wholehippocampalandtwelvesubfieldvolumeswerequantifiedforleftand right hemispheres separately. Paired t-tests were conducted to assess volumetric change frombaselinetopost-treatment.Results:No significant change was observed in total left or right hippocampal volume, nor in nine subfields.However, changes were detected in the subicular complex (comprising presubiculum, subiculum andparasubiculum). Left subicular complex volume showed a significant increase (p=.017). Heavy and lightuser groups (median split on cumulative lifetime cannabis exposure; range 140–8700 occasions) werefurtherassessed.Increaseinleftsubicularcomplexvolumewassignificantinheavy(p=.005)butnotlightusers(p=.37).Inheavyusers,greaterincreaseinleftsubicularcomplexvolumewassignificantlyassociatedwithhigherCBDplasmalevelsduringthefinalweekofthetrial(r=.854,p=.030).Conclusions:This studyreportsoutcomes fromthe first trialofprolongedCBDadministration tocannabisusers.CBDtreatmentpromotedgrowthinthesubicularcomplexofthe lefthippocampus,despiteongoingcannabisuse.SignificantincreaseinsubicularvolumeinheavybutnotlightuserssuggeststhatCBDtreatmentmayconfergreatertherapeuticeffectstothosemoreheavilyengagedincannabisuse.CorrelationswithCBDplasma levels in this group suggest a CBD treatment-specific effect on subicular growth, a subregionimplicatedinarangeofcognitiveprocesses.ThesefindingssupportthecontentionthatCBDmayfacilitateneuroprotectionandrecoveryfromcannabisrelatedharms.

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3.DecreasedhippocampalresponsivenesstomuscarinicM1receptorpositiveallostericmodulationinasub-groupofsubjectswithschizophrenia.Authors:ShaunHopper,GeoffreyMarkPavey,MadharaUdawela,AndreaGogosandBrianDeanAffiliations: The Florey Institute of Neuroscience and Mental Health; Cooperative Research Centre forMentalHealth;CentreforMentalHealth,SwinburneUniversityBackground:CholinergicmuscarinicM1 receptor (CHRM1) positive allostericmodulators (PAM) are receptor specificandrepresentapromisingschizophreniatreatment.Ourdata,usingtheCHRM1PAMBQCA,suggestasub-groupofsubjectswithschizophreniawhohaveamarkedlossofcorticalmuscarinicreceptors(MRDS)willnot respond to such treatment. Our mRNA data suggest that CHRM4, not CHRM1, is lower in thehippocampusfromsubjectswithMRDS;wethereforehypothesizedthatBQCAeffectivenesswouldnotbealteredinthehippocampusofMRDSsubjects.Totestthis,wedevelopedanauto-radiographicmethodtomeasureBQCAeffectivenessinsubjectswithMRDSinthehippocampus.Methods:Frozenhippocampaltissuesections(20μm)from40subjects(20MRDSand20subjectswithschizophreniaand no decrease in cortical muscarinic receptors (non-MRDS)) and 20matched non-psychiatric controlsubjects were incubated for 2 hours with [3H]nmethylscopolamine ([3H]NMS; 0.4nM) in the absence(total),andpresence(non-specific)ofACh(10mM);specificbindingwasthedifferencebetweentotalandnon-specificbinding.Wealsomeasured[3H]NMSbindingpartiallydisplacedbyACh(1mM)inthepresenceor absence of BQCA (3μM); the difference between these is the BQCA effect (measure of CHRM1availability).Results:[3H]NMS binding was lower in schizophrenia in all sub-fields (dentate gyrus (molecular/granular layers(M/G)andpolymorphiclayer(PL));cornuammonis(CA)1-3(alveuslayer–pyramidallayer(a-p),lacunosummoleculare–stratum radiatum (lm-r)); and the subiculum (polymorphic/pyramidal layers (PP),molecularlayer(ML));p<0.01allregions)comparedtocontrol.BQCAmodulationofCHRM1wassignificantlylowerinM/Gdentategyrus (p<0.05)andboth layersof thesubiculum (PP:p<0.05;ML:p<0.05) in schizophreniacompared to control. [3H]NMSbinding (p<0.01 all regions) and theBQCAeffect (p<0.05 for all regions)werelowerinallsub-fieldsinMRDS,butnotnon-MRDS,comparedtocontrols.Conclusions:WefounddecreasedCHRM1availabilityinthehippocampusfromsubjectswithMRDS.Thesedatarefuteour hypothesis of no decrease in CHRM1 availability in the hippocampus and suggest that the lower[3H]pirenzepinebindingwehavepreviouslyreported in thehippocampusofsubjectswithschizophreniaincluded, at least as a component, a decrease in CHRM1 inMRDS. This could have implications for theefficacyofallostericmodulatorsastreatmentsforsomepatientswithschizophrenia,highlightingtheneedforpersonalisedtherapeutics.

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4.MaternalFluoxetinetreatmentaltersoffspringbehaviourandNMDAreceptorsubunitprofileatadolescenceAuthors:SamuelJMillard,JeremeySLum,FrancescaFernandez,KatrinaWeston-GreenandKellyANewellAffiliations: School of Medicine, Illawarra Health and Medical Research Institute, University ofWollongong;AustralianCatholicUniversityBackground:8-10% of pregnancies are prescribed antidepressants,most commonly the selective serotonin reuptakeinhibitor (SSRI), such as Fluoxetine. Human studies suggest that SSRI treatment during pregnancy mayincreaseoffspringriskofdevelopingneurodevelopmentaldisorders.HumanstudiesareconfoundedbythedifficultyofseparatingtheeffectsofmaternaldepressionfromtheeffectsofSSRIexposure. Intheadultbrain SSRI treatmenthasbeen shown toalter functioningofNMDA receptor andassociated scaffoldingprotein,PSD95;littleisknownhoweveroftheeffectsofSSRIexposureonthedevelopingbrain.Methods:TheaimofthisstudywastoevaluatetheeffectsofmaternalFluoxetinetreatmentonoffspringbehavioursand neurobiology of relevance to neurodevelopmental disorders, using a rodent model of depression.Sprague-Dawley (SD) and Wistar-Kyoto (WKY; depression model) dams were treated with Fluoxetine(10mg/kg/day) or vehicle, from gestational day 0 until postnatal day 14. Once offspring reachedadolescence, behaviour was assessed using the elevated plus maze (EPM) and forced swim test (FST)(n=10-14/group),afterwhichbrainswerecollectedforwesternblotanalysis.Results:Fluoxetine exposed offspring exhibited increased anxiety-like behaviours in the EPM, evident throughdecreased time spent in open arms (-90%, p<0.001). Additionally, Fluoxetine exposed offspring showedincreasesindepressive-likebehaviour,evidentthroughincreasesinimmobilitytime(+28%,p<0.05)intheFST.ImmunoblotdatarevealedthatFluoxetineexposedoffspringexhibitedreducedrelativeproteinlevelsof NMDA receptor subunits, NR1 (-12%, p<0.05) and NR2A (-13%, p<0.05) in the prefrontal cortex andreduced levels of PSD95 in both the PFC (-17%, p<0.05) and ventral hippocampus (-18%, p<0.05) atadolescence.Theeffectsofmaternalfluoxetinetreatmentonoffspringwerelargelyindependentofstrain.Conclusions:Our results demonstrate that maternal SSRI exposure has the potential to alter the neurobiology andbehaviour of exposed offspring at adolescence, irrespective of the presence of innate depressivephenotypes.FurtherstudiesinvariousmodelsofmaternaldepressionarerequiredtoconfirmthefindingsandestablishtheeffectsofFluoxetineexposureonthedevelopingbrain.Giventheincreasingnumberofantidepressantsprescribedtopregnantwomen,thesefindingswarrantfurtherinvestigation.

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5.EpigeneticregulationofdopaminergicneuronaldifferentiationbyvitaminDAuthors:RenataPertile,XiaoyingCuiandDarrylEylesAffiliations:QueenslandBrainInstituteBackground:Histonemodifications are epigeneticmarks critical for neuronal development. ThehistonedemethylaseJMJD3 removes the H3K27me3 repressive mark from the chromatin of neuronal genes. This acts topromote neurogenesis and dopaminergic neuron differentiation. JMJD3 repression is a key epigeneticmechanism in early neurogenesis, which maintains cells in a stem cell fate until the proper ligand ispresent. We have shown previously that vitamin D alters the ontogeny of dopaminergic neurons.Intriguingly,vitaminDhasbeenshowntoincreaselevelsoftheJMJD3gene.However,thereiscurrentlynoevidencelinkingvitaminDwithepigeneticmarksrelevanttodopaminergicneurons.Methods:WehaveevaluatedtheeffectofvitaminDontheepigeneticeventsoccurringduringthedifferentiationofdopaminergicneurons.Tothisend,weusedquantitativePCRtoanalysethelevelsofexpressionofJMJD3,thevitaminDreceptor(VDR)andtyrosinehydroxylase(TH)inourSH-SY5YcellmodelinwhichtheVDRisoverexpressed. The SH-SY5Y/VDR+ cells were treated with vitamin D or a vehicle control for 48h. TheexpressionofH3K27me3wasanalysedusinganimmunofluorescencetechnique.Results:Our quantitative PCR results show that treatment with vitamin D increases levels of the JMJD3 gene.Furthermore, this increase correlates with increased expression of VDR and TH following the 48htreatment in SH-SY5Y/VDR+ cells. The quantification of mean fluorescence of H3K27me3 suggests thatvitamin D does not reduce the overall expression of H3K27me3 in these cells. However, the cells thatexpress high levels of VDR also appear to present lower levels of H3K27me3, as observed by theimmunofluorescenceintensity.Conclusions:These results reveal that vitaminDalters theexpressionof thehistonedemethylase JMJD3 inneurons.This further suggests that vitaminDmayplay a role in alteringepigeneticmarks inneurons, and it is apotentialmechanism bywhich vitamin D drives the differentiation of dopaminergic neurons. Alongsidepreviousresults,thesefindingsleadustohypothesizethatintheabsenceofvitaminD–inthevitaminDdeficient model for instance - JMJD3 gene expression is likely to remain repressed resulting in animpairmentofdopaminergicneuronsdifferentiation.

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DataBlitz3

Tuesday,31Oct,10:00–10:30am1.Withdrawalfromthehelpoffriendsandfamilyindepression:LinkstoplasmacortisolandoxytocinlevelsAuthors:SusanJThomasandTheresaLLarkin Affiliations: School ofMedicine, Faculty of Science,Medicine and Health and the Illawarra Health andMedicalResearchInstitute,UniversityofWollongongBackground:Background: Depressed individuals often refuse or withdraw from help, a phenomenon termed help-negation,which is a risk factor forpooroutcomesand suicide.Mostprevious researchhas investigatedpsychosocialfactorsincludingstigmaascausesofhelp-negation,howeverthesedonotadequatelyexplainthe problem. Because help-negationworsenswith symptom severity,we hypothesised that itmight belinked to neurobiological changes associated with depression itself. We investigated the relativecontributions of cortisol, a stress hormone linked to depression, and oxytocin, a pro-social hormone,alongsidepsychosocial factors, tohelp-seeking intentions inparticipantswithmajordepressivedisorder(MDD)andhealthycontrols.Methods:Methods:Wequantifiedmorningplasma cortisol andoxytocin levels, severity of psychopathology, helpseeking intentions, suicidal ideationandperceivedsocial support in59untreatedadultsmeetingDSM5criteria for MDD, and 60 healthy controls. Cortisol and oxytocin were quantified using a Milliplexfluorescencemagneticbeadimmunosorbentassay.Between-groupanalysesofvariance,correlationalandhierarchicalmultipleregressionanalyseswereemployed.Results:Results:Help-seekingintentionswerelowerindepressedthanhealthyparticipants,negativelycorrelatedto cortisol and symptomseverityandpositively correlated tooxytocin.Cortisolnegatively, andoxytocinpositively, predicted informal, but not formal, help-seeking intentions, after controlling for symptomseverityandpsychosocialfactors.Conclusions:Conclusions:Neuroendocrinechangesassociatedwiththeprogressionofdepressionmaycontributetothewidespreadhelp-negationobservedinMDD,particularlyfrominformalsourcessuchasfriendsandfamily.Approacheswhichincorporatebiologicalaswellaspsychosocialfactorsmayallowfornovel,targetedandmoreeffectiveearlyinterventions.

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2.DeficitsinsomatostatinandSSTR2mRNAsinorbitofrontalcortexinschizophreniaAuthors:TasnimRahman,TertiaPurves-TysonandCyndiShannonWeickertAffiliations:NeuroscienceResearchAustraliaBackground:Increased inflammatorymarkers are found in the orbitofrontal cortex (OFC) and dorsolateral prefrontalcortex(dlPFC)inasubsetofpeoplewithschizophrenia.SomatostatinmRNAisreducedinOFCanddlPFCinschizophrenia. In dlPFC, reductions of somatostatinmRNA are exacerbated in cases classified as havinghighinflammation.Somatostatininhibitsneurotransmissionviasomatostatinreceptors(SSTRs)andSSTR2mRNAisreducedin layersVandVIofdlPFCinschizophrenia.Wehypothesizedthatschizophreniacaseswill have lower SSTR2mRNA in layersV andVI, and that caseswithhigh inflammatory statuswill haveexacerbatedchangesinsomatostatinandSSTR2mRNA.Methods:Previous two-step clustering of pro-inflammatory cytokine gene expression in OFC cohort yielded thefollowinggroups:lowinflammationcontrols(control;33cases),lowinflammationschizophrenia(SCZ-low;27cases),andhighinflammationschizophrenia(SCZ-high;11cases).SomatostatinandSSTR2mRNAsweredetected by in situ hybridisation autoradiography. Laminar density values derived from the films werecomparedusingrepeated-measureANCOVAs(covariatesused:post-morteminterval,ageofdeath,RIN).Results:In OFC, somatostatin mRNA was reduced in both schizophrenia groups compared to control(F(2,59)=21.78, p<0.001), where SCZ-high had less somatostatin mRNA than SCZ-low (p<0.05).SomatostatinmRNAwas reduced in Layers I andVI of SCZ-high compared to both SCZ-low and control(p<0.05; laminaxgroup interactioneffect: F(7.13,210.17)=24.11). Layers II-IValsohad less somatostatinmRNA in both schizophrenia groups compared to control (p<0.05). In Layer V, somatostatinmRNAwasreducedinbothschizophreniagroups,however,waslowerintheSCZ-highcomparedtoSCZ-low(p<0.05).SSTR2mRNAwasreducedinbothschizophreniagroupscomparedtocontrol(p<0.01;F(2,67)=8.40)acrossalllamina.Conclusions:ThisstudyindicatesthatreductionsinsomatostatinmRNAaremorelikelytooccurindeepcorticallaminainhighinflammatoryschizophreniacases,butthatreductionsinsomatostatinmRNAinsuperficiallaminaarefoundinpeoplewithschizophreniaregardlessofinflammatorystatus.SSTR2mRNAreductionsextendto the OFC, however they do not appear to be exaggerated in schizophrenia cases that have elevatedinflammatory markers. We conclude that people with schizophrenia may have reduced somatostatin-mediated inhibitoryneurotransmission in theOFC regardlessof thecurrent stateofneuroinflammation,andthatincreasedinflammationmayexacerbatethisdeficitbydecreasingsomatostatingeneexpression.

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3.MaternalvitaminDtreatmentreversesmaternalimmuneactivationinducedalterationsinmesencephalicneurogenesisAuthors:WeiLuan,LukeAHammond,UrsMeyerandDarrylWEylesAffiliations: Queensland Brain Institute, University of Queensland; Institute of Pharmacology andToxicology,UniversityofZurich-Vetsuisse,Zurich.Background:Dopaminedysregulation isa featurepresent in themajorityofpatientswithschizophrenia.Weproposetheaberrantontogenyofmesencephalicdopamine(mesDA)systemsasacommoncausalpathwayforthepathogenesisofschizophrenia.WeaimtotestwhethermaternaladministrationofvitaminDcouldrescuethe aberrantdopamineneurodevelopment inducedbymaternal immuneactivation (MIA)usingdouble-strandviralmimicRNA(polyinosinic:polycytidylicacid,poly(I:C)).Methods:Weadministratedpoly(I:C)orsaline,andtheactivehormoneformofvitaminD(1,25OHD)oritsvehicle(cornoil)topregnantC57BL/6mousedamsatgestationalday(GD)9.Twodayslater,GD11,weassessedmesDAneurodevelopmentusingimmunochemistryandautomatedimageanalysisofCellProfilersoftware.Four mesDA factors were employed for immunohistochemical analysis, including LIM homeoboxtranscription factor 1 alpha (Lmx1a), SRY-related HMG-box2 (Sox2), nuclear receptor related 1 protein(Nurr1), and tyrosine hydroxylase (TH). Four subgroups of early mesDA cells were therefore analyzed:mesDAprogenitors,post-mitoticmesDAneurons,immatureandmaturemesDAneurons.Results:The results revealed that MIA and 1,25OHD treatment reduced mesDA progenitors (Lmx1a+Sox2+),however, 1,25OHD treatment increased mature mesDA neurons (Nurr1+TH+). Single-cell quantificationshowed that 1,25OHD treatment increased the expressionof Lmx1a,Nurr1 andTH in individualmesDAcells,butnotofSox2.MIAtreatmentinsteadhadnoobviouseffectsontheexpressionofthesefactors.Conclusions:Inconclusion,ourdatademonstratestheneuroprotectiveeffectsof1,25OHDonearlymesDAneurogenesis possibly via its upregulation of mesDA factors, counteracting against the acute negativeeffectsofMIAtreatment.

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4.Network-basedcorticalthinningintreatmentresistantschizophreniaAuthors:CassandraWannan,CaliBartholomeusz,VanessaCropley,ChadBousman,EleniGanella,IanEverall,ChristosPantellisandAndrewZaleskyAffiliations:MelbourneNeuropsychiatryCentre,DepartmentofPsychiatry,UniversityofMelbourneandMelbourneHealth;Orygen,theNationalCentreofExcellenceinYouthMentalHealth;theCentreforYouthMental Health, University of Melbourne; Brain and Psychological Sciences Research centre, SwinburneUniversity;TheUniversityofMelbourne,DepartmentofGeneralPractice;theCooperativeResearchCentre(CRC) for Mental Health; Florey Institute for Neurosciences and Mental Health; Centre for NeuralEngineering,UniversityofMelbourne.Background:Evidence suggests that thatbrain regionswith themost extensive cortical thinning in schizophrenia arestrongly connected. However, unlike early and established schizophrenia, few studies have examinedcortical thickness in TRS, and none have examined this from a network perspective. The current studyaimedto(i)characterisecorticalthinninginTRS,and(ii)examinewhetherthestrengthofcortico-corticalconnections was greater between brain regions showing significant cortical thinning in individuals withTRS.Methods:Cortical thickness was compared in 148 brain regions between 47 individuals with TRS and 54 healthycontrols. The average structural connectivity strength between pairs of regions with significant corticalthinning inpatientswas computedand thencomparedwith theaverage structural connectivity in5000groups of randomly chosen regions in patients and controls. Corticocortical connectivity in regions ofreducedthicknesswasthencomparedbetweenTRSpatientsandhealthycontrols.Results:Corticalthicknesswasreducedin106outof148brainregionsinTRSpatients,withthegreatestreductionsobservedinfrontal,temporal,cingulate,andinsularregions(falsediscoveryrate-correctedp<.05).BothTRS patients and healthy control subjects showed significantly greater structural covariance in corticalregions that were thinner in TRS patients, compared to randomly selected regions (p <.00001). TRSpatients also had significantly stronger structural covariance than healthy control subjects in regions ofreducedthickness(p<.00001).Conclusions:These findings support the notion of network-based cortical thinning in the disorder, with regions ofreduced thickness demonstrating greater structural connectivity not only in TRS individuals, but also inhealthypeople.

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5.ChangesinperipheralimmunecelltraffickingmoleculesinschizophreniaAuthors:HelenQCai,ThomasW.Weickert,VibekeS.Catts,MaryanneO’Donnell,CherrieGalletly,DennisLiuandCynthiaShannonWeickertAffiliations: Schizophrenia Research Laboratory, Neuroscience Research Australia; School of Psychiatry,University of New South Wales; Discipline of Psychiatry, School of Medicine, University of Adelaide;NorthernAdelaideLocalHealthNetwork.Background:Irregular inflammatory processes such as endothelial dysfunction have been implicated in thepathophysiology of schizophrenia. Intercellular adhesion molecule (ICAM1), a marker of endothelialdysfunctionwitharole in immunecelltrafficking, isupregulatedinpost-mortembrainsofschizophreniapatients.However, less isknownabouttheexpressionof ICAM1’scognate ligands, lymphocytefunction-associatedantigen-1(LFA1)andmacrophage-associatedantigen-1(MAC1),whichareexpressedonwhitebloodcells,inschizophrenia.Methods:WhitebloodcellmRNAexpressionofICAM1,LFA1andintegrinalphaM(ITGAM),whichencodesacrucialsubunitofMAC1,weremeasuredwithquantitativePCRusingFluidigmBiomarkHD™in86patientswithschizophreniaand77healthycontrols.SolubleICAM1wasalsomeasuredinplasmafrom78patientswithschizophrenia and 73 healthy controls using a Luminex immunoassay. Further, white blood cell countsavailable frompatientswereusedtodetermineanyassociationsbetweenthe ligandsandspecificwhitebloodcellpopulations.Results:LFA1 mRNA was reduced by 11.4% in patients with schizophrenia (t(155) = 3.396, p < 0.01), whereasITGAMmRNAwaselevatedby13.5%inpatientswithschizophreniacomparedtocontrols(t(153)=-3.287,p<0.01).ICAM1mRNAwasunchanged(t(156)=-1.526,p=0.129),howeversICAM1proteinwashigherinplasma of patients with schizophrenia by 29.2% (t(140) = -3.988, p < 0.01). Neutrophil counts werepositively correlatedwith ITGAM(r=0.58,p<0.01)andnegatively correlatedwithLFA1 (r= -0.46,p<0.01)inpatients.Conclusions:No change in ICAM-1mRNA expression inWBC, but increased sICAM-1 protein in plasmamay suggestincreasedsheddingof sICAM-1 fromcellsaspartof immuneresponse regulation.Different immunecellpopulationsmaybetraffickedintotissueastheICAM1ligandsITGAMandLFA1expressionsarechangedinoppositedirectionsinschizophrenia.Schizophreniamaybeassociatedwithalteredimmunecelltrafficking.

PosterSession1:Monday30thOctober 35

PosterSession1

Monday,30thOct,1:30–2:30pmP1.Theeffectofoestrogeniccompoundsonpsychosis-likebehaviourinfemaleLongEvansrats

Authors:AlyssaSbisa,MaartenvandenBuuseandAndreaGogosAffiliations:FloreyInstituteofNeuroscienceandMentalHealth;LaTrobeUniversityBackground:17β-estradiol (17β) treatment has shown benefit for schizophrenia symptoms, however long-term usemay be associatedwith negative side effects. Selective estrogen receptormodulators (SERMs), such asraloxifene(RAL)andtamoxifen(TAM),havebeenproposedassuitablealternativesto17β.An isomerof17β, 17α-estradiol (17α), is considered less carcinogenic, and non-feminising inmales, however little isknown about its potential as a treatment for schizophrenia. However, the mechanism underlying thetherapeutic action of SERMs and 17α remains unclear. We aimed to investigate the ability of theseestrogeniccompoundstoattenuateacutepharmacologicalmodelsofpsychosis.Methods:We measured two widely used behaviours: psychotomimetic drug-induced hyperlocomotion anddisruptionofprepulse inhibition (PPI). FemaleLongEvans ratswereeither intactSHAM,ovariectomised(OVX),orOVXandchronicallytreatedwith17β,17α,RALorTAM.Results:Only17βtreatmentattenuatedlocomotorhyperactivityinducedbymethamphetamine.17β-treatedratswere also protected againstmethamphetamine- and apomorphine-induceddisruption of PPI. The otherestrogenic compounds had mixed or lesser effects. TAM-treated rats were protected againstmethamphetamine- and apomorphine-induced PPI disruption, however RAL-treated rats were onlyprotectedagainstapomorphine-induceddisruption.BaselinePPIwassignificantlyreducedfollowingOVX,andthisdeficitwasreversedbyallestrogeniccompounds.Further,PPIinOVXratswasincreasedfollowingadministrationofapomorphine.Conclusions:Thisstudyconfirmsaprotectiveeffectof17βintwopsychosis-likebehavioursinrats,whileTAMshowedbeneficial effects against PPI disruption. In contrast, 17α and RAL showed little effect on attenuatingdopaminergic-inducedpsychosis-likebehaviours.

PosterSession1:Monday30thOctober 36

P3.MaternalfluoxetinetreatmentincreasesmGluR5expressionintheamygdalaofadolescentoffspringAuthors:KimarnieBaskerville,SamuelJMillard,JeremySLumandKellyANewellAffiliations:SchoolofMedicine,UniversityofWollongong;IllawarraHealthandMedicalResearchInstituteBackground:Approximately 10% of pregnant woman are prescribed antidepressant drugs such as the selectiveserotonin reuptake inhibitor (SSRI), Fluoxetine (Prozac), for the treatment of depression. Emergingevidence suggestsmaternal fluoxetine treatment increases the risk of neurodevelopmental disorders inoffspring,howevertheneurobiologicalunderpinningsremainunclear.Wehavepreviouslyfoundevidenceofanincreaseinanxiety-relatedbehaviourinfluoxetine-exposedoffspring,usingarodentmodel.DuetotheroleofmGluR5signalling intheamygdala inmodulatingfearandanxiety,thisstudyaimedtoassesswhethermGluR5proteinexpressionintheamygdalaisalteredfollowingprenatalfluoxetineexposure.Methods:Wistar-Kyoto (establishedmodelofdepression)andSprague-Dawley (healthymodel) rodentdamsweretreatedwith10mg/kg/dayfluoxetinefromgestationalday0topostnatalday14.Brainsofmaleoffspringwere collected at adolescence (postnatal day 42) and the amygdala dissected. RelativemGluR5 proteinlevels were measured via immunoblotting under non-reducing conditions to promote mGluR5 dimerintegrity.Rawvalueswerenormalizedtoβ-actinandapooledsampletoaccountforgel-gelvariability.Results:Immunoblots revealed3distinctbands formGluR5dimer (250-260kDa), andonedistinctband forbothmGluR5 monomer (150kDa) and β-actin (37-50kDa). Maternal fluoxetine treatment increased mGluR5dimer (+13.5%; p=0.009) and monomer (+31.4%; p=0.053) in the amygdala of adolescent offspringcompared to vehicleexposedoffspring. Therewerehowevernoeffectsof rat strainonmGluR5andnostrainxtreatmentinteractions.Conclusions:Thesefindingssuggestthatantidepressanttreatmentduringpregnancyaltersglutamatergicproteinsintheamygdala of adolescent offspring. Considering the role ofmGluR5 in the amygdala, these changesmaycontributetotheanxiety-likephenotypeobservedinfluoxetine-exposedoffspring.

PosterSession1:Monday30thOctober 37

P5.MaternalimmuneactivationinduceschangesinmicrogliaIBA1+immunoreactivityinthewhitematterofthecorpuscallosumofadultratsAuthors:RyanDuchatel,CrystalMeehan,LaurenHarms,PatriciaMichie,MarkBigland,DougSmith,RohanWalker,PhillipJobling,DeborahHodgsonandPaulTooneyAffiliations:UniversityofNewcastleBackground:Prenatal immune challenge is an environmental risk factor for the development of psychiatric illnessesincluding schizophrenia. Modelling this epidemiological link in animals shows that maternal immuneactivation(MIA)iscapableofinducinglong-lastingdeficitsinbrainstructure,functionandbehaviourintheoffspring. Microglia activation and cytokine upregulation have been proposed to play key roles in theneuropathologyofschizophrenia.WehypothesisedthatMIAinduceschangesinmicrogliaandcytokinesinthebrainsoftheadultoffspring.Methods:MIAwasproducedbyinjectingPolyI:CintopregnantWistarratsonGD10orGD19;braintissuefromtheoffspringwascollected12weeksofage.Iba1,Gfap,TNF-αandIL-1βmRNAlevelsinthecingulatecortexwere determined by quantitative RT-PCR from fresh frozen tissue of adult offspring ofGD10 andGD19PolyI:C dams compared to controls. Microglia IBA1+ immunoreactive material (IBA1+-IRM) / astrocyteGFAP+-IRMwasmeasuredinoffspringofGD10orGD19PolyI:Cdamscomparedtopooledcontrolsinthecingulatecortex (C-CTX)andwhitematterof thecorpuscallosum (CC)using immunohistochemistryandcumulativethresholdanalysis.Results:TherewasnochangeinIba1,Gfap,IL-1βandTNF-αmRNAlevelsintheC-CTXinoffspringexposedtoMIA.WhilstMIAhadnoeffectonIBA1+-IRMinC-CTX,asignificantmaineffectonIBA1+-IRMwasobservedintheCC,withpost-hocanalysesidentifyingasignificantincreaseinIBA1+-IRMatGD19(p=0.017),butnotGD10.MIAhadasignificantmaineffectonGFAP+-IRMintheCCTX,withpost-hocanalyses identifyingastrong trend towards increased GFAP+-IRM in the offspring of GD19 PolyI:C (p = 0.054), but not GD10PolyI:Cdams.NochangeinGFAP+-IRMwasobservedintheCC.Conclusions:These findings suggest that late gestationMIA is capable of causing subtle alterations tomicroglia andastrocytes. How these findings relate to the pathophysiology of schizophrenia requires furtherinvestigation.

PosterSession1:Monday30thOctober 38

P7.Earlyantipsychotictreatmentinjuvenileratselicitslong-termalterationstotheadultserotoninreceptorsAuthors:MichaelDeSantis,Xu-FengHuangandChaoDengAffiliations:IllawarraHealthandMedicalResearchInstitute;SchoolofMedicine,UniversityofWollongongBackground:Antipsychoticdrugprescriptionanduseinchildrenhasincreasedsignificantlyoverthepastdecade.Thisisdespite a lack of insight into potential long-term effects of treatment during this criticalneurodevelopmental timeperiod on adult brain functioning.Whilst initial studies have uncovered long-term alterations to adult behaviours following early antipsychotic treatment, further investigations intopotential changes to neurotransmitter systems are necessary. The current investigation utilised anestablishedanimalmodelforearlyantipsychotictreatmentwitharipiprazole,olanzapineandrisperidoneinmaleandfemalejuvenilerats,toinvestigatepotentiallong-termchangestotheadultserotonin(5-HT)neurotransmittersystem.Methods:Maleandfemalejuvenilerats(n=6/group)weretreatedwitharipiprazole,olanzapineandrisperidonefrompostnatal day (PD) 22-50 equating to the human childhood-adolescent timeperiod.Adult animalswerethensacrificedonPD106.Levelsof5-HT1A,5-HT2Aand5-HT2Creceptorsweremeasuredintheprefrontalcortex (PFC), caudate putamen (CPu), nucleus accumbens (NAc) and hippocampus viawestern blot andreceptorautoradiography.Results:Inthemalecohort,aripiprazoledecreased5-HT2AlevelsinthePFCandhippocampus,whilst5-HT2Cwasdecreased in the PFC, and increased in hippocampus. Olanzapine decreased 5-HT2A levels in thehippocampusand5-HT2ClevelsinthePFC,whilstrisperidonedecreased5-HT1AlevelsinthePFCandNAcand 5-HT2A levels in the PFC and hippocampus, whilst increased 5-HT2C levels in the hippocampus.Analysisofthefemalecohortuncoveredlessereffects,withdecreased5-HT1AlevelsfollowingaripiprazoletreatmentintheNAcand5-HT2Alevelsinthehippocampusfollowingolanzapinetreatment,whilstearlyrisperidonetreatmentdecreased5-HT2Alevelsinthehippocampus.Conclusions:Theseresultssuggestthatearlytreatmentofvariousantipsychoticsinjuvenileratsmaycausegenderandbrainregionalspecificchangesin5-HT2Aand5-HT2Creceptorsintheadultbrain.

PosterSession1:Monday30thOctober 39

P9.Variationinlaboratoryhousingconditionsimpactsondrug-inducedlocomotioninratsAuthors:SuzyAlexander,EmiliaLefevre,DarryEylesandThomasH.J.BurneAffiliations:QueenslandBrainInstitute,UniversityofQueenslandBackground:Variationsinhousingconditionsareknowntoimpactonrodentbehaviour.Inparticular,theuseofMK-801to elicit a locomotor response is particularly sensitive to environmental conditions, with alterations inresponseinducedbystress,novelty,dietarymanipulations,priorhandling,arenasizeandpriorexposureto some anaesthetic agents. With so many environmental variables altering the response of MK-801inducedlocomotionouraimwasto identifytheimpactofexposuretounexpectedlaboratoryconditionsduringrepeatedtestinginadultrats.Methods:WeusedadultSpragueDawley rats tested in2different sizedopen fieldsandcollected locomotordatausingEthovisionvideotrackingduring1)habituationtoanovelfield(45cmx45cm)andaftersalineorMK-801, or 2) immediately following administration of saline orMK-801, in a 60cm x 60cmopen field.We retrospectivelycodeddatafordifferentlaboratoryconditions.Theseconditionsincludedexposuretootherratinjectionprocedurespriortotestingandarefurbishmenteventintheanimalfacility.Results:ForExperiment1, ratsexposed toother rats receiving IP injectionsprior to testing led toan increase inMK-801inducedlocomotion,comparedtonon-exposedratsfromthesamegroup,onthedayofexposureand again 24hours later. This exposurehadnoeffect on saline-treated rats or on the initial 30-minutehabituationtotheopenfieldoneitherday.ForExperiment2,femaleratsexposedtotherefurbishmentofanadjacentroomintheanimalfacilityhaddecreasedMK-801inducedlocomotorresponsescomparedtotheirnon-exposedequivalents,whilemalerats treatedwith saline had decreased locomotor responses comparedwith their performance 14 dayspriortocommencementofrefurbishment.Discussion:Reporting housing conditions has become more standardised in rodent behaviour but additionallaboratory variables can have a large impact on behaviour. These results suggest that both baselineperformanceanddrug-inducedlocomotionissusceptibletoenvironmentallaboratoryconditions.Ifpossible,minimisingalterationsinenvironmentallaboratoryconditionswouldbeidealbutissometimesunavoidable. Minimising administering rat injection procedures around other rats or avoiding testingduring refurbishment events would be highly recommended. However, even using control animalsmatchedfortimeofdaymayunderestimatetheeffectofunforeseenconditionsonbehaviouraloutcomes.Weconcludethatcleardocumentationandconsiderationofanychangeinenvironmentalconditionsmayaccountfor,orhelpreducethevariabilityinbehaviouraldata.

PosterSession1:Monday30thOctober 40

P11.TheeffectofchronicantidepressanttreatmentonNMDA,AMPAandGroupImGlureceptorsinthecingulatecortexAuthors:EmilySzafranek*,RebeccaWebby*,JeremyLum,NicholasStorr,JessicaNealonandKellyANewell*:EqualcontributionAffiliations:SchoolofMedicine,UniversityofWollongong;IllawarraHealthandMedicalResearchInstituteBackground:Antidepressant drugs (ADD) target monoaminergic neurotransmitter systems, but typically require 3-4weeks for therapeutic response. Emerging evidence suggests downstream effects on the glutamatergicsystem,particularlytheNMDA,AMPAandGroupImetabotropic(mGluR1,mGluR5)glutamatereceptors,could be central to the antidepressant effects. In line with this, antagonists or negative allostericmodulators (NAMs) of mGluR5 have shown promise for the rapid treatment of depression in animalmodels. This study aimed to determine whether chronic antidepressant drug treatment influencesmGluR5,NMDAandAMPAproteinexpressionandhowthiscomparestoanmGluR5NAM.Methods:AdultfemaleSprague-DawleyratsweretreatedwiththeADDsfluoxetine(10mg/kg;aselectiveserotoninreuptakeinhibitor),imipramine(10mg/kg;atricyclicantidepressant),MPEP(3mg/kg;anmGluR5NAM)orvehicle (saline) for 5 weeks. Their brains were collected and cingulate cortex dissected. Immunoblotanalyseswereperformed todetermine the levelof expressionofmGluR1,mGluR5,NR1 (theobligatoryNMDAsubunit)andtheAMPAGluA1subunit(n=6/group).Results:FluoxetineandImipraminetreatmentbothcausedanincreaseinmGluR1monomerscomparedtocontroltreated rats (+63% and +37% respectively; p<0.05) and a reduction inmGluR1 dimers (-33% and -30%respectively; p<0.05) following 5 weeks of treatment, while MPEP treated rats showed no change inmGluR1protein.FluoxetinetreatmentadditionallyincreasedmGluR5monomers(+220%;p<0.0%),butnotdimers, compared to control treated rats. There were no effects of fluoxetine, imipramine or MPEPtreatmentonNR1orGluA1proteinexpressioninthecingulatecortex.Conclusions:TheseresultsrevealthattheADDsfluoxetineandimipraminebothaltertheexpressionofmGluR1inthecingulatecortex,afteraperiodofchronictreatmentandsuggestthattraditionalantidepressantdrugsmaymediatetheireffectsviachangestoGroup1mGluRs inthisregion.Further investigation intohowthesemolecular changes relate to depressive-like behaviours and whether these changes extend to otherrelevant brain regions such as the hippocampus will be important to characterise their mechanism ofactionanddefinemoreeffectiveandrapidtreatmenttargetsfordepression.

PosterSession1:Monday30thOctober 41

P13.StressinducedbehaviouraldeficitsamelioratedbyganaxolonetherapyinmaleguineapigoffspringAuthors:GabrielleK.Crombie,HannahK.Palliser,JuliaC.Shaw,DebraM.Hodgson,DavidW.WalkerandJonathonJ.HirstAffiliations: School ofBiomedical Sciences andPharmacy, FacultyofHealth andMedicine,University ofNewcastle;HunterMedicalResearchInstitute,MothersandBabiesResearchCentre;SchoolofPsychology,UniversityofNewcastle;SchoolofHealthandBiomedicalScience,RMITUniversity.Background:Neurosteroids promote neuronal survival andmyelination in the developing brain. Perinatal stress, andassociated neurosteroid disruption, is known to impair neurodevelopment and lead to behaviouraldisorders. Human studies have shown a relationship between early life stress and attention deficithyperactivity disorder (ADHD) in offspring. ADHD is characterised by symptoms of inattention,hyperactivityand impulsivity.Weproposethatdisturbances in thematurationof theGABAergicsystem,throughperinatalstress,maypromoteexcitationwhichcanhavedamagingeffectsontheimmaturebrainand leadtothesedisorders.Additionally,weproposethatreplacementofneurosteroids inearly lifewillreducetheseadverseoutcomes.Methods:Guineapigpupswereexposedtoprenatalstress(maternalstrobelightexposurefor2hrsadayonGA50,55, 60and65; term71days), postnatal stress (maternal separation for2hrsonpostnatal days2-8)or acombination of both stressors (dual stress). Pups were administered ganaxolone, a syntheticallopregnanolone analogue, twice daily (5mg/kg) on days 2-8. Pups underwent open field and elevatedplusmazebehaviouralassessmentonday9,toassessforhyperactivebehaviour.Brainswerecollectedonday30forquantificationofGABAAsubunitreceptormRNAexpressionbyrealtimePCRandmaturemyelinbyMBPimmunostaining.Results:Maleguineapigsexposedtoperinatalstressdisplayedan increase inhyperactivebehaviourat9daysofage.Thishyperactivebehaviourwasobservedasincreasedspeedtravelled,andincreasedentriesinto,anddistance travelled, in the inner zone of the open field arena. These males also displayed increasedlocomotion intheopenfieldandelevatedplusmazebehavioural test.Ganaxoloneadministration inthefirstweekoflifereturnedbehaviouralparametersofthedualstressgrouptowardthatofcontrolguineapigs. GABAAR subunit mRNA expression was increased and mature myelination decreased in thehippocampusofmalesexposedtoprenatalstress.Conclusions:Perinatal stress leads to changes in GABAergic pathways that may contribute to reduced myelination,altered GABAA subunit expression and behavioural deficits in the exposed offspring. Neurosteroidsupplementation using ganaxolone treatment following dual stress ameliorates later hyperactivebehaviourinmaleoffspring.

PosterSession1:Monday30thOctober 42

P15.TheeffectsofhandlingtechniquesonthebehaviouralphenotypeofageneticmousemodelforschizophreniaAuthors:StefanGuerra,CynthiaShannonWeickertandTimKarlAffiliations:SchoolofMedicine,WesternSydneyUniversity;SchoolofPsychiatry,UniversityofNewSouthWales;NeuRA,Randwick,Australia.Background:Handling of laboratory mice has a noticeable effect on both the wellbeing of the test animal and thereliability of experimental test results. So far, handling studies have been limited to common strains oflaboratorymice.However,itisofutmostimportancetoassesshandlingeffectsingeneticmousemodelsfor human diseases. Here, we determined the impact of two types of handling (e.g. tail versus tubehandling)on the face validityof anewlyestablished transgenicmousemodel for the schizophrenia riskgeneneuregulin1(i.e.typeIIINrg1overexpressingmice;Nrg1IIItg).Methods:Nrg1IIItgandwildtype-likelittermatecontrolmiceofbothsexesareinitiallyassignedtoeitherhandlinggroup,thosebeingthestandardtailhandlingmethodortheuseofaPVCtunnel.Animalsareexposedtotail /PVChandling for10daysbeforebehavioural testing commences.A comprehensivebatteryof testparadigmswith relevance to schizophrenia is applied:open field, elevatedplusmaze, socialpreference,prepulseinhibitionandfearconditioningtests.Micearealsohandledwiththeirassignedmethodbetweentestdaysassotheeffectsdoesnotdiminishoverthefulltestperiod.Results:ThisprojectiscurrentlyongoingandtestingwillbecompletedbyearlyOctober.Conclusions:Resultswillhavebeenanalysedbymid-October.

PosterSession1:Monday30thOctober 43

P17.Thetime-dependenteffectsofolanzapinetreatmentonthegluco-metabolicdisordersandhepaticAKT/GSK3β/PPARαpathwayinratsAuthors:JiameiLian,Xu-FengHuangandChaoDengAffiliations:SchoolofMedicine,UniversityofWollongong;IllawarraHealthandMedicalResearchInstitute BackgroundOlanzapineiseffectivelytotreatschizophreniaandothermentaldisorders.However,itisassociatedwithgluco-metabolicside-effects;howevertheunderlyingpathogenesismechanismsarestilllargelyunknown.The peroxisome proliferator-activated receptor (PPAR) is associated with the type II diabetes andmetabolicsymptomsincludingobesityandinsulinresistance.PPARαisbelievedtoparticipateinfattyaciduptake, balancing glucose homeostasis, mainly in the liver. The glycogen synthase kinase 3β (GSK-3β)activity isattenuatedafterphosphorylationbyAKT,whichcontributestothe insulinstimulatedglucagonsynthesis.Therefore,theaimofthisstudywastoinvestigatethetime-dependenteffectsofolanzapineongluco-metabolicsideeffectsandhepaticmechanismsinaratmodel.MethodsFemale Sprague Dawley rats (201-225g) were administered with olanzapine (2 mg/kg， t.i.d.) for2,3,4,5,7,9weeks.Plasmawastakenforinsulin,glucoseandlipidanalysisbyELISAoraKoneLabanalyser.ProteinlevelswereexaminedbyWesternBlot.ResultsOlanzapinesignificantly increasedbodyweightgain, food intake, liverweight,white fatpad.Olanzapinesignificantlyaltered theplasmaglucose, insulin, cholesterol,non-esterified fattyacid levelscompared tocontrols in a time-dependent manner. Furthermore, the activation of hepatic PPARα, AKT and GSK-3βphosphorylationwerealsoobservedbyolanzapineadministration,withtime-dependentdifference.ConclusionsTherefore, this study suggested that olanzapine induced gluco-metabolic disorders, at least partiallyattributedtothehepaticAKT/GSK/PPARαsignallingpathway.

PosterSession1:Monday30thOctober 44

P19.ManipulationofdevelopingdopamineneuronsinmicewithtargetedSiRNAtransfectionAuthors:JamesP.Kesby,WeiLuanandDarrylW.EylesAffiliations:QueenslandBrainInstitute,TheUniversityofQueensland,QueenslandCentreforMentalHealthResearch,TheParkCentreforMentalHealth.Background:Schizophrenia is a chronic psychiatric disorder with a poorly understood aetiology. Dopamine is aneurotransmitter that has been implicated in the cause and treatment of schizophrenia. Thus,understanding the consequences of altered dopamine neuron development represents a coredevelopmentaldrugtargetinschizophrenia.WeareusinginuteroelectroporationforthetransfectionofsiRNAintodevelopingdopamineneuronsinmice.Methods:Pregnantmicewereanaesthetisedandtheuterinehornsexposed.Areporterplasmidencodingayellowfluorescentprotein(pCAGeYFP,1.5ug)andsiRNAtargetedagainstdopaminespecification/differentiationfactors was injected into the mesencephalic ventricle of E11 mice embryos. Electroporation wasaccomplishedusinga tripleelectrodeconfiguration. Fiveelectricalpulses (amplitude,30V;duration,50ms;intervals,950ms)wereadministered.EmbryoswereharvestedatE13andexpressionoftargetfactorsweredeterminedusingquantitativeimmunofluorescence.Results:Our data demonstrates the feasibility of this technique to target dopamine progenitors in the ventralmesencephalon. Moreover, we will present evidence demonstrating the specific downregulation ofdopaminetargetfactorsbytransfectionofsiRNAintodopamineprogenitors.Conclusions:These data suggest that the transient manipulation of factors at early stages of dopamine neurondevelopmentispossiblewiththeuseofinuteroelectroporation.Thisworkwillallowustogainabetterinsightintotheroleofspecificdifferentiationfactorsindopamineneurondevelopment.

PosterSession1:Monday30thOctober 45

P21.Modellinganautismriskfactorinrats,theimpactofperinatalimmunechallengesongastrointenstinalinflammationandintegrityAuthors:SharonHollins,LukeBrock,RafaelBarreto,PatriciaMichieandDeborahM.HodgsonAffiliations: School of Psychology, University of Newcastle; Priority Centre for Brain andMental HealthResearch,UniversityofNewcastle;HunterMedicalResearchInstitute.Background:Autism SpectrumDisorder (ASD) often presentswith numerous comorbidities correlated to its severity,including immunesystemandgastrointestinal (GI)disorders.Researchsuggeststheseabnormalitiesmaybeinvolvedintheaetiology,pathogenesisandpathophysiologyofASD,however,thebiologicalpathwaysinvolvedareunknownGiventhatanimalmodelsofmaternalimmuneactivation(MIA)havedemonstratedASD-like peripheral and neural findings, if analogous GI integrity and immune phenotypes were alsodemonstrated,themodelpresents itselfasapotentialtoolto investigatetheetiology,pathogenesisandpathophysiology of ASD gut-brain interactions, potentially presenting the GI tract as a target for novelpsychiatrictreatmentoptions.Methods:PregnantratswereexposedtoPolyI:C (MIA)atgestationalday(GD)10and19.Asegmentofcolonwasextractedfromoffspringonpostnataldays (P)7and84andtissuewasexaminedforexpressionoftightjunction protein and proinflammatory cytokinemRNA. A segment of the jejunum and distal ileumwasremovedfromP7offspringforhistologicalstudies.Cross-sectionswereselectedandembeddedinparaffin.Full-thicknesssectionsof5μmwereobtainedatdifferentlevelsandstainedwithhaematoxylinandeosin.Thehistologicaldamagewasevaluatedbyapathologistobserver,whowasblinded to theexperimentalgroups.Results:P7 MIA offspring exhibited alterations in tight junction proteins as well as proinflammatory immunemarkers. P84 offspring exhibited subtle alterations in tight junction proteins however no alterations ininflammatorymarkerswereobserved.Specifically,MIAoffspringexhibitedsignificantlyreducedexpressionoftheproinflammatoryimmunemarkerInterleukin6(IL-6)atP7butnotP84.IncreasedexpressionoftightjunctionproteinsTightJunctionProtein1(TJP1),TightJunctionProtein(TJP2)andOccludin(OCLN)wereobservedatP7,whiledecreasedexpressionofTJP2wasobservedatP84.HistologicalevaluationshowednoarchitecturaldamageorsignsofinflammationinP7MIAoffspring.Conclusions:We found thatMIA alters the expression of pro-inflammatory cytokines and GI tight junction proteinsduringearlydevelopment,withalterationsdiminishingthroughoutadulthood.Thesefindingssuggestthatperinatal immune challenge can have a significant impact on neonatal GI inflammation and integrity.Changes inexpressionof intestinal tight junctionproteinand IL-6mRNAatP7suggestMIAmay lead toearly changes in brain-gut signalling. Although histological evaluation showed no signs of architecturaldamageor inflammation,our results suggest thisanimalmodelmayprovideauseful tool to investigategut-brainaxisdeficitsunderlyingtheGIandimmuneaberrationsseeninASD.

PosterSession1:Monday30thOctober 46

P23.OlanzapinedecreasedhypothalamicPOMCexpressionviaH1Rand5-HT2CRantagonismAuthors:YuanyiXie,PengZheng,MinminHu,YinghuaYuandXu-FengHuangAffiliations:CentreforTranslationalNeuroscience,SchoolofMedicine,UniversityofWollongong;IllawarraHealth andMedical Research Institute; Department of Pathogen and Biology and Immunology, XuzhouMedicalUniversityandJiangsuKeyLaboratoryofImmunityandMetabolism,Xuzhou,Jiangsu,China.Background:olanzapine decreases energy expenditure and increases food intake while the mechanism is not fullyunderstood.HypothalamicPOMCplaysanimportantroleregulatingbothenergyexpenditureandintake.Using hypothalamic POMC-GFP neurons, this study investigated the effect of olanzapine on POMCexpressionwith/withoutH1Rand5-HT2CRagonists.Methods:Methods:WehaveusedhypothalamicPOMC-GFPcell line inthisstudy.First,wetestedtheeffectof50μMolanzapineininhibitionofPOMCexpression.Wetestedtheeffectofolanzapineundertheconditionofno, low and high glucose treatment. Then the cells were treated with olanzapine+FMPH, olanzapine +lorcaserin and controls including FMPH and lorcaserin only. After 6 hours of various concentrations oftreatments,cellswerecollectedandanalysedbyflowcytometryandflexstantion.Results:Results:(1)Wefoundthat50μMolanzapinereducedPOMCexpressionby30%in6hours.Nodifferenceof POMC expression was detected under various glucose concentrations. (2) Secondly, we found thatolanzapinecandecrease50%ofPOMCexpression. (3)Thirdly,FMPH(aH1Ragonist)and lorcaserin (a5HT2CRagonist) increasedPOMCexpressionby30%and70%, respectively. (4) Furthermore,olanzapine-inducedinhibitoryeffectonPOMCcanbereversedbyFMPHandlorcaserin.Conclusions:Conclusions: This study indicated thatolanzapine reducedhypothalamicPOMCexpression viabothH1Rand 5-HT2CR antagonism. EitherH1Ror 5-HT2CR agonist could partially reverse the inhibitory effect ofolanzapine-induceddown-regulationofhypothalamicPOMCexpression.

PosterSession1:Monday30thOctober 47

P25.D2ReceptorhyperactivityincreasesD2R-DISC1interactionandimpairsneuritegrowthintheprefrontalcortexAuthors:PengZhang,MinminHu,YunayiXie,YinghuaYuandXu-FengHuangAffiliations:CentreforTranslationalNeuroscience,SchoolofMedicine,UniversityofWollongong;IllawarraHealth andMedical Research Institute; Department of Pathogen and Biology and Immunology, XuzhouMedicalUniversityandJiangsuKeyLaboratoryofImmunityandMetabolism,Xuzhou,Jiangsu,China.Background:D2 receptor (D2R) hyperactivity and DISC1 dysfunction are associated with psychosis and neuronaldevelopment.AlthoughbothinvivoandinvitrostudiesconnectedDISC1tothedopaminergicsystem,theactual roleofDISC1 inmediatingD2R signallingwasnotelucidated. This studywas to investigate if theD2R-DISC1 complex formation induced by D2R over-activation has morphological effects in corticalneurons.Methods:(1)WeculturedprimaryprefrontalcorticalneuronsfromDISC1locusimpairment(LI)miceandwildtypemice (WT) at postnatal day 0; (2)After 7 daysof culturing, theneuronswere treatedwithD2Ragonist(quinpirole,100uM)orpre-treatedwithpartialagonist(aripiprazole,10uM)orantagonist(haloperidol,10uM); (3) Fluorescence resonance energy transfer (FRET)was applied to examineprotein interaction; (4)Westernblotwasused toquantifyproteinexpression. (5)HEK293cells transfectedwithD2R-EGFPandDISC1-mCherryplasmidswereusedtostudyDISC1interaction.Results:Thisstudyshowedthat(1)OveractivationofD2Rbyhighdosageofquinpiroleinhibitedneuritegrowthofprimary prefrontal neurons of DISC1 LI andWTmice; (3) GSK3β phosphorylationwas decreased in theprefrontalcorticalneuronsofDISC1LImice,whilequinpirolefurtherreducedit;(4)D2Ragonistquinpiroleinduced increasing interaction of D2R and DISC1 in prefrontal cortical neurons; (5) Haloperidol andaripiprazolewereunable to reverseneurite impairment inducedbyquinpirole inDISC1LImice inwhichD2R-DISC1 complex was fully abolished; (6) Quinpirole increased DISC1-mCherry aggregation andpromotedthetransferofaggregatesinHEK293cells.Conclusions:Inthisstudy,over-activationofD2RincreasedD2R-DISC1complexformationandinhibitedneuritegrowthin the prefrontal cortical neurons. Further, D2R-DISC1 complex is involved in the therapeutic effects ofantipsychoticdrughaloperidolandaripiprazoleonneuritegrowthandGSK3βphosphorylation.ThisstudysuggeststhatDISC1aggregationinducedbyD2Rover-activationmayberelatedtoneuronaldevelopment.Thus,manipulationofD2RandDISC1complexformationmightbeanoveltherapeutictargetforimprovingneuronalconnection.

PosterSession1:Monday30thOctober 48

P27.ElevatedPeripheralC-reactiveProteinLevelsinPeoplewithSchizophreniaAuthors:RoxanneCadiz,HayleyNorth,DannyBoerrigter,ThomasW.WeickertandCynthiaShannonWeickertAffiliations: Schizophrenia Research Laboratory, NeuRA; School of Psychiatry, Faculty of Medicine,UniversityofNewSouthWales.Background:There is increasing evidence implicating a pathogenic role of inflammation in schizophrenia: a severepsychiatricdisorderforwhichnobiomarkerscurrentlyexist.AnelevatedlevelofC-reactiveprotein(CRP)in the blood serum and plasma is commonly used as amarker for systemic inflammation.WhilemoststudiesofperipheralCRPinschizophreniareportincreasedlevels,thereareconflictingresultsinthefield.WeanalysedCRP levels in twodistinct cohortsandhypothesized thatCRPwouldbeelevated inpeoplewithschizophreniacomparedtohealthycontrolswithinbothcohorts.Methods:Bloodwascollectedfrompatientsandcontrolsintwodifferentcohorts.Inthe“CASSI”cohortplasmawascollected from thebloodof healthy controls (n=97) andpatientswith schizophrenia and schizoaffectivedisorder(n=87)fromSydneyandAdelaide. Inaseparatecohort,the“ASRB”cohort,serumfromhealthycontrols (n=644) and people with schizophrenia (n=374), schizoaffective disorder (n=58) or atypicalpsychosis (n=44)wasreceived fromtheAustralianSchizophreniaResearchBank (ASRB).CRP levelswerequantifiedusingCRPHigh-SensitivityELISAfromIBLInternationalandanalysedinIBMSPSSVersion24.Results:IntheCASSIcohort,CRPlevelsinplasmaweresignificantlyhigherinpeoplewithschizophreniacomparedtocontrols(Mann-WhitneyU=1439,p<0.0001;meansschizophrenia3.41mg/L,control1.79mg/L).SerumCRP levelswerealso significantlyhigher inpeoplewith schizophrenia compared tocontrols in theASRBcohort (Mann-Whitney U=104889.5, p<0.0001; means schizophrenia 3.33 mg/L, controls 1.80 mg/L).WithinbothschizophreniaandcontrolgroupsfromtheASRBcohort,CRPlevelsweresignificantlyhigherinfemalesthanmales.Findingsof increasedCRP intheschizophreniagroupremainedsignificantwhenweco-variedforgender.Conclusions:Our findings support the growing literature demonstrating a strong link between inflammation andschizophrenia. Thedata suggests thatCRP levelsmaybeusedas apotential biomarker for peoplewithschizophrenia and suggests future investigations into the benefits of adjunctive anti-inflammatorytreatments.

PosterSession1:Monday30thOctober 49

P29.Theassociationbetweensystolicbloodpressurevariabilitywithdepression,cognitivedeclineandwhitematterhyperintensities:the3CDijonMRIstudyAuthors:PhillipJTully,StephanieDebetteandChristopheTzourioAffiliations: School of Medicine, University of Adelaide; Bordeaux Population Health Research Center,BordeauxUniversityBackground:Accumulating evidence links blood pressure variability (BPV)withwhitematter hyperintensities (WMH)and stroke. The longitudinal association between BPVwith late onset depression and cognitive declineremainsunexplored.Methods:Prospective cohort study of 2812 participant’s age≥ 65 years (median age 72 years, 63.6% female)without dementia or stroke. Serial clinic visits assessed blood pressure, cognitive function, depressiondisorder,anddepressivesymptoms.Abrainmagneticresonanceimaging(MRI)substudywasperformedin1275personstoexaminepossibleassociationswithWMH.Results:TheinteractionbetweensymptomaticlateonsetdepressionandsystolicBPVwasassociatedwithcognitivedeclineontheIsaacSetTest(β-4.45;95%CI-8.92to-.16,p=.04),BentonVisualRetentionTest(β-.89;95%CI-1.77to-.01,p=.049),MiniMentalStateExamination(β-1.08;95%CI-1.86to-.30,p=.007)andFinger Tapping Test (β -7.53; 95% CI -13.71 to -1.34, p = .017) . TheMRI substudy demonstrated thatsystolicBPVwasassociatedwithcognitivedeclineviainteractionswithdepressionandtotalWMHvolume.Conclusions:The findings show that the interaction between systolic BPV with symptomatic depression and WMHincreases cognitive decline in persons≥ 65 years of age. Future work could extend these findings byexaminingsystolicBPVinrelationtocognitivedeclineandWMHinolderpopulationswithdepression.

PosterSession1:Monday30thOctober 50

P31.CortisolandoxytocinaredifferentiallycorrelatedwithspecificpsychopathologysymptomprofilesAuthors:TheresaLarkinandSusanThomasAffiliations:UniversityofWollongong,IllawarraHealthandMedicalResearchInstituteBackground:The stress-associated hormones cortisol and oxytocin are both implicated in psychological health anddisease, but with contrasting effects. In particular, dysregulation of the hypothalamic–pituitary-adrenal(HPA)axis isamajorcontributortodepression.TheHPAaxis isactivatedduringstress,withconsequentincreasedcortisolsecretion.Oxytocinissecretedinresponsetohighcortisol levelstoattenuatetheHPAstress response.Accordingly, cortisol is associatedwith psychopathologies including stress andhostility,whileoxytocinisinverselycorrelatedwithanxiety.Weaimedtodeterminewhethercortisolandoxytocinare differentially correlated with distinct symptom profiles of psychopathology in depressed and non-depressedindividuals.Methods:Plasma cortisol and oxytocin concentrations were quantified in healthy participants and participantsmeetingDSM5criteriaformajordepressivedisorder.Bloodwassampledbetween9and11amtoaccountfordiurnalvariationsincortisolsecretion.Cortisolandoxytocinwerequantifiedsimultaneouslyinplasmausing a fluorescence magnetic bead immunosorbent assay (Milliplex). Participants completed the BriefSymptomInventory(BSI),a53-itemself-reportmeasureofmostmajorformsofpsychopathologywithninedomains (Somatization, Obsessive-Compulsive, Interpersonal Sensitivity, Depression, Anxiety, Hostility,Phobic anxiety, Paranoid ideation, Psychoticism) and three global indices. Pearson’s correlations andStudent’st-testswereperformed.Results:Datawerecollectedfor60non-depressedparticipants(58%female;meanage31.8±11.0years)and63depressedparticipants(56%female;meanage31.9±14.5years).Oxytocinwassignificantlylower(158±140 versus 262 ± 159 pg/mL) and cortisol was significantly higher (252 ± 103 versus 107 ± 65 ng/mL)amongdepressedversusnon-depressedparticipantswithnogenderdifference.CortisolwassignificantlycorrelatedwithallsubscalesoftheBSI.OxytocinwassignificantlybutinverselycorrelatedwithDepression,Paranoid ideation and Psychoticism. Oxytocinwasmore variable than cortisol (co-efficient of variation:89%versus33%).Conclusions:These results provide further insight into the differential associations of cortisol and oxytocin withpsychiatricsymptomsubtypes.EvidenceofHPAaxisdysregulationandaroleofoxytocinwereapparentindepression,withdepressedparticipantshavingmore thandouble theplasmacortisol concentrationandapproximatelyhalf theplasmaoxytocin concentration levelsof controls. Cortisolwas amore consistentbiomarker across a broad range of psychopathologies. The oxytocin results are in line with emergingresearchthatsuggestsoxytocin is implicated inpsychopathologiesrelatedtosocialdiscomfort, includingdepressionandpsychoses,andwithgrowinginterestinusingsyntheticoxytocinasanadjuncttherapy.

PosterSession1:Monday30thOctober 51

P33.AllostaticloadanddepressivesymptomsinpatientswithmajordepressivedisorderAuthors:MaximusE.Berger,Robert-PaulJuster,SabineWestphal,BernhardBogerts,KoljaSchiltz,SabineBahn,JohannSteinerandZoltanSarnyai

Affiliations:Laboratory of PsychiatricNeuroscience, Australian Institute of Tropical Health andMedicine (AITHM), 1James Cook Drive, Townsville, QLD 4811, Australia; Columbia University Medical Center, ColumbiaUniversity, New York; Institute of Clinical Chemistry and Pathobiochemistry, University of Magdeburg,Leipziger, Germany; Department of Forensic Psychiatry, Psychiatric Hospital of the Ludwig-MaximiliansUniversity München, Nußbaumstr. 7, D-80336 München; Department of Chemical Engineering andBiotechnology,UniversityofCambridge,UKBackground:Activation of the hypothalamic-pituitary-adrenal (HPA) axis and subsequent sensitisation ofneuroendocrine, immune and oxidative pathways are thought to contribute to the pathophysiology ofmooddisorders.Previousstudiesindicatedthatallostaticload(AL)maybeelevatedinlate-lifedepressionandindicativeoffuturedepressiveepisodesinpopulation-basedstudiesbutitisunclearifallostaticloadiselevatedinmajordepressivedisorder(MDD).Methods:WeassessedAL in inpatientswithMDD(n=31)andhealthycontrols (n=28).Biomarkers fortheAL indexwere selectedbasedon (1) representationof severalphysiological systems including thecardiovascular,neuroendocrine,immune,andmetabolicsystems,(2)useinpreviousALresearch,and(3)associationswithdisease risk.We adopted a scaledAL algorithmwhereby eachmarkerproportionally contributes to theoverallALindex.UnadjustedandadjusteddifferencesbetweenpatientswithMDDandcontrolsinALweretested with ANCOVA and partial correlations were used to test associations of AL with psychometricvariables.Results:Unadjustedbetween-groupcomparisonofpatientswithMDDandhealthycontrols showedhigherAL inpatientsrelativetocontrols(3.92±1.30vs.2.59±1.42,p<0.001).However,thisdifferencebecamenon-significantwhenageandsmokingwereenteredascovariates(F(1,55)=2.153,p=0.15).WetestedifALwascorrelatedwith psychometric variables using partial correlations and found that AL at baselinewas notassociatedwithHAMDscores(adjustedR=-0.217,p=0.27)orGAFscores(adjustedR=0.010,p=0.96).Conclusions:Multisystemdysregulation,measuredasAL,isnotincreasedinhospitalisedpatientswithMDDcomparedto controlswhenageand lifestyle factors are taken intoaccount. These findings contrastwithpreviousstudiesthatfoundelevatedALinlatelifedepression.ALmaybeassociatedwithdepressiononlyinolderpopulationsortheassociationmaybemediatedbyhealthbehaviours.

PosterSession1:Monday30thOctober 52

P35.IncreasedcirculatingglucocorticoidreceptorcofactorFKBP5mRNAinschizophreniaAuthors:C.H.Lee,D.Sinclair,C.S.WeickertandT.W.WeickertAffiliations:SchoolofPsychiatry,UniversityofNewSouthWales,NeuRA,Sydney;UniversityofTasmania,HobartBackground:Adecreaseoftheglucocorticoidreceptorandanincreaseinitsco-factorFKBP5hasbeenfoundinseveralbrain regions involved with cognition in people with schizophrenia. A number of single nucleotidepolymorphismswithintheFKBP5genehavebeenassociatedwithpoorercognitiveperformanceinstressrelated disorders, such as major depressive disorder and schizophrenia. We sought to determine theextent towhichperipheral FKBP5mRNA levels are increased inpeoplewith schizophrenia andwhetherFKBP5 rs4613916 impacts peripheral mRNA levels in controls and people with schizophrenia. We alsotestedtheextenttowhichFKBP5rs4613916predictscognitiveability.Methods:PeripheralFKBP5mRNAlevelsandgenotypeforFKBP5rs4713916weredeterminedin77healthycontrolsand93peoplewithschizophrenia,usingTaqmanmRNAexpressionassay(hs01561006_m1)andTaqmanSNPgenotypingassay,respectively.Cognitiveassessmentscoreswereadjustedforage,converted intozscores,andgrouped intofivecognitivedomains:verbalmemory,workingmemory, language,processingspeed,andperceptualorganization.Results:Significant elevation in peripheral FKBP5 mRNA was found in people with schizophrenia compared tohealthycontrols,t(156)=-2.97,p<0.01.TherewasnostatisticallysignificantmaineffectofgenotypeorinteractionbetweenFKBP5rs4613916genotypeanddiagnosisonperipheralFKBP5mRNAlevels,F(2,143)=0.94,p=0.39.Therewasasignificantgenotypeeffectonlanguageinhealthycontrols,F(2,74)=4.90,p=0.01, such that risk allele AA homozygotes (n=11) performed significantly worse than GG homozygotes(n=35)(p=0.02).Conclusions:TheincreaseinperipheralFKBP5mRNAlevelsidentifiedinpeoplewithschizophrenia,maybesuggestiveofanoveractivestressresponsepathwayandbluntednegativefeedbackability.TheonesinglenucleotidepolymorphismexaminedintheFKBP5genemaynotbeamajordeterminantforthelevelofFKBP5mRNAlevelsinthebloodofhealthycontrolsandpeoplewithschizophrenia.However,geneticvariationinFKBP5appearstorelatetolanguageabilityinhealthyadults.

PosterSession1:Monday30thOctober 53

P37.DysregulatedadultneurogenesisandgliogenesisinthehumansubependymalzoneinpsychiatricdiseaseAuthors:ChristinWeissleder,HayleyF.North,MareeJ.WebsterandCynthiaShannonWeickertAffiliations: Schizophrenia Research Laboratory, Neuroscience Research Australia, Randwick NSW 2031,Australia; School of Psychiatry, Faculty ofMedicine,University ofNewSouthWales, SydneyNSW2052,Australia;LaboratoryofBrainResearch,StanleyMedicalResearchInstitute,MD20815,USA

Background:The human subependymal zone (SEZ, also subventricular zone) adjacent to the caudate nucleus is thelargestreservoirofnewlyborninhibitoryinterneuronsandglialcellsintheadultbrain.PrecursorcellscanberecruitedforbrainrepairhenceimpairedneurogenesisintheSEZmayaccountfordeficitsininhibitoryinterneurons inpsychiatricdiseases.Wehypothesized thatadultneurogenesisandgliogenesiswouldbereducedinthehumanSEZinschizophreniaandbipolardisordercomparedtocontrols.Methods:Post-mortemtissuewasobtainedfrom33schizophrenia,32bipolardisorderand33controlcasesfromtheStanleyMedicalResearch Institute.SEZtissuewasdissectedfrom60µmthicksectionsforRNAisolationand cDNA synthesis. Gene expression was measured by quantitative polymerase chain reaction andincludedmarkersofneuralstemcells (GFAPδ),transitamplifyingprogenitors(Ki67),neuronalprecursors(ASCL1), immature neurons (DCX), astrocytes (VIM, pan-GFAP), oligodendrocytes (OLIG2) andmicroglia(IBA1).Results:GFAPδ,ASCL1andpan-GFAPmRNAsweredecreased in schizophrenia (24%,p=0.03;20%,p<0.0001and32%, p=0.007, respectively) and bipolar disorder (24%, p=0.009; 32%, p=0.004 and 22%, p=0.01,respectively)comparedtocontrols.Ki67andIBA1mRNAsweredecreasedinbipolardisordercomparedtocontrols(23%,p=0.02and26%,p=0.007).NosignificantdifferencesinDCX,VIMandOLIG2mRNAsweredetectedbetweendiagnosticgroups(allp>0.14).Conclusion:Schizophrenia and bipolar disorder shared deficits in neural stem cell, neuronal precursor and matureastrocyte expression suggesting that the production of new cells may be impaired across psychiatricdiseases. Bipolar disorder showed unique deficits in cell proliferation and microglia indicating disease-specific alterations in the adult SEZ. Impaired neurogenesis and gliogenesis may contribute to theneuropathology of psychiatric diseases and provide a potential target for the development of newtherapeutic treatments. Future work will determine protein levels of cell-type specific markers andexaminetheexpressionoffactorsthatregulatecellproliferationandfatedeterminationinthehumanSEZ.

PosterSession1:Monday30thOctober 54

P39.Glialexcitatoryaminoacidtransporter1(EAAT1)mRNAisincreasedintheprefrontalcortexofsubjectswithschizophreniaAuthors:GeorgiaParkin,MadharaUdawela,AndrewGibbonsandBrianDeanAffiliations:MolecularPsychiatryLaboratories,TheFloreyInstituteofNeuroscienceandMentalHealth;TheCRCforMentalHealth;TheCentreforMentalHealth,SwinburneUniversityBackground:Astrocytedysfunctionhasbeenimplicatedinarangeofpsychiatricillnesses,includingmajordepressivedisorderandschizophrenia.UsinganAffymetrix™microarray,weobserveda36%increaseinexpressionofthepredominantlyastrocyticglutamatetransporterExcitatoryAminoAcidTransporter1(EAAT1)intheprefrontalcortex(Brodmann’sarea(BA)9)fromsubjectswithschizophrenia(Scarretal,2017).TheaimofthecurrentstudyistodeterminewhetherchangesinEAAT1mRNAlevelsarepresentwithinothercorticalregionsfromsubjectswithschizophrenia.Methods:ThehumanCNStissueusedinthisstudywasobtainedfromtheVictorianBrainBankNetwork.cDNAwassynthesizedfromRNAthatwasextractedpostmortemfromBA44ofsubjectswithschizophrenia(n=27)andhealthycontrols(n=29).EAAT1mRNAlevelsweremeasuredusingtheBio-RadiQ5qPCRDetectionSystemwithSYBRGreen1dyetechnology.Reactionsweremeasuredintriplicatewithresultsnormalisedtothegeometricmeanofthreestablyexpressedreferencegenes–glyceraldehyde3-phosphatedehydrogenase(GAPDH),transcriptionfactorB1,mitochondrial(TFB1M)andS-phasekinase-associatedprotein1A(SKP1A).Results:NormalisedlevelsofEAAT1mRNAweresignificantlyhigherinBA44fromsubjectswithschizophreniacomparedtoageandsexmatchedcontrols(MannWhitneytest,p=0.0004).EAAT1mRNAlevelswerenotrelatedtosex,suicidecompletion,durationofillness,typeordoseofmedication.Conclusions:OurdatasuggeststhatawidespreadincreaseinEAAT1mRNAintheprefrontalcortexmaybeinvolvedinthepathophysiologyofschizophrenia.Thesefindingsareimportantastheysupportaroleforastrocytesinglutamatergicdysfunctioninschizophreniaandmayhaveimportantimplicationsforthetreatmentofthedisorder.

PosterSession1:Monday30thOctober 55

P41.PeripheralmicroRNA-mRNAinteractionsinindividualswithschizophreniaAuthors:MichaelGeaghanandMurrayCairnsAffiliations: University of Newcastle; Centre for Brain and Mental Health, Hunter Medical ResearchInstitute;SchizophreniaResearchAustraliaBackground:Schizophreniaisasevereneuropsychiatricdisorder,characterisedbypositiveandnegativesymptoms,andcognitivedeficits.Highthroughputtechnologiesincludingmicroarrays,andmorerecentlynext-generationsequencing have identified numerous genetic variants and transcriptional signatures associated withschizophrenia. In particular, microRNAs (miRNAs) have been found differentially expressed in bothperipheral and post-mortem grey matter tissue in schizophrenia, and one of the most significantschizophrenia-associatedvariantsoccurswithintheMIR137genetic locus.Thesesmall,non-codingRNAsare potent regulators of translation, can target awide variety of transcripts, and are thus of particularinterestinpolygenicdisorderssuchasschizophrenia.Methods:Weobtainedperipheralbloodmononuclear cell (PBMC) samples from36 individualswith schizophreniaand 15 healthy controls. After isolating total RNA from these samples, we utilised RNA sequencing toexamineboththemiRNAandmRNAexpressionprofiles.Rawreadswerealignedto thehumangenome(hg38), annotated, counted and analysed for differential expression using an open source softwarepipeline. Correlations between miRNA and mRNA expression were found and matched to predictedTargetScanmiRNA-mRNAinteractionsusingthemiRCombRpackage.Results:16miRNAsand25genesweredifferentiallyexpressed(adjustedp<0.05);mostmiRNAs(13outof16)weredownregulated, while the vast majority of mRNAs (21 out of 25) were upregulated. When males andfemaleswereanalysed separately,we found38miRNAsand90genesdifferentiallyexpressed inmales,while females only showed 1 differentially expressed gene (no miRNAs reached significance). SeveralmiRNAs inmaleswere found to significantly correlatewithdifferentially expressed genes. Furthermore,many differentially expressed genes and miRNAs have previously been linked to schizophrenia andneuronalfunction.Conclusions:These results contribute to a growing body of evidence that suggest peripheral miRNA and mRNAexpressionisalteredinschizophrenia.WeidentifyageneraldownregulationofmiRNAsandupregulationof mRNAs in peripheral tissue in schizophrenia. Several significant correlations between miRNAs andmRNAspreviouslylinkedtoschizophreniaandbrainfunctionsuggestpotentialmiRNA-mRNAinteractionsthatmaybesignificantfordiseasepathophysiology.

PosterSession1:Monday30thOctober 56

P43.DevelopmentofandEGFPknock-inhumandopaminergiccellmodelusingCRISPR-CAS9systemAuthors:XiaoyingCui,DiXia,RenateAparecidaNedelPertileandDarrylEylesAffiliations: Queensland Brain Institute, University of Queensland; Institute of Molecular Biology,UniversityofQueenslandBackground:It is hypothesized that alterations in the development of the dopaminergic system are central toschizophrenia.Animalmodelsofschizophrenia,includingdevelopmentalvitaminDdeficiency,haveshowndelayedordiminisheddopaminesystemdevelopment.Furthermore,theadditionofvitaminDpromotesthe differentiation of dopamine neurons. To determine the effect of vitamin D on the functional andelectrophysiological properties of dopaminergic neurons, we generated a genomic knock-in cell model.Thiswasachievedbyfusinggreenfluorescentprotein(GFP)intotheendogenoustyrosinehydroxylase(TH,dopamine neuronal marker) sequence using the Clustered Regularly Interspaced Short PalindromicRepeats(CRISPR)-associatedprotein9(Cas9)system.Methods: The guide (g)RNAs against TH terminals were designed using the Zhang lab website(http://crispr.mit.edu/).ThedonorvectorwasconstructedfromtheEGFPgeneflankedbyshorthomologyarms(1kbeach)toinserttheEGFPgeneaftertheTHsequence.ThisproducedEGFPfusedin-framewithTH protein. The pU6Cas9-mCherry and TH-EGFP donor plasmids were transfected into humanneuroblastoma cells SHSY5Y using electroporation. mCherry-positive cells were sorted using flowcytometry.TheincorporationofEGFPingenomewasassessedbyPCRandcellsweredifferentiatedwithretinoicacid(RA,10μM).Results:PCRamplificationof the junctionbetweentheTHsequenceandEGFPwasdetectedfromgenomicDNA.This indicates that Cas9 mediates double strand break-induced homology-direct repair (HDR) with thetargeted plasmid sequence. Seven days after RA-induced differentiation, EGFP-expressing cells wereobserved. ImmunofluorescencewasusedtofurtherconfirmthattheseEGFPcellswereTH-positive.ThisfindingindicatesthesuccessfulfusionofEGFPwiththeendogenousTHprotein.Conclusions:Wedemonstratedthatatargetedknock-inmethodcouldbeusedinhumandopaminergiccellstoinducethe fusion of EGFPwith endogenous TH. This cellmodel could be used formany purposes including 1)tracing the differentiation and maturation of dopaminergic neurons; 2) examining the functional orelectrophysiological properties of these dopaminergic neurons, and 3) assessing the effect ofneuromodulators such as vitamin D specifically within dopaminergic neurons. These de novo targetedknock-in constructs could be also applied in human IPS cells to further explore the development ofdopaminecells.

PosterSession1:Monday30thOctober 57

P45.StructuralnetworkscharacterisemethylphenidateresponseinyouthwithADHDAuthors:KristiGriffiths,MichaelKohn,SimonClarke,LeanneWilliamsandMayureshKorgaonkarAffiliations:BrainDynamicsCentre,Westmead Institute forMedicalResearch,TheUniversityofSydney;AdolescentandYoungAdultMedicine,WestmeadHospital;PsychiatryandBehaviouralSciences,StanfordUniversity.Background:While MPH is largely successful in treating the symptoms and cognitive impairments associated withADHD, in approximately 30%of cases it is either ineffective or causes intolerable side-effects. The exactbiologicalreasonsforthisindividualvariabilityinresponsetomethylphenidateareunclear.Hereweusedgraph theory to determinewhetherwhole-brainwhitematter connectivity differed inMPH respondersversusnon-responders.Methods:Thirty-six children and adolescentswithADHD completed baseline brain imaging in a 6weekMPH trial(internationalStudytoPredictOptimizedTreatmentResponseinADHD;iSPOT-A).Treatmentresponsewasdefinedas>25%improvementfrombaselineontheADHD-RatingScale.An84x84structuralconnectivitymatrixforeachindividualwasconstructedfromDTItractographybetween84parcellatedcorticalandsubcorticalregions.Graphtheorywasusedtocomputemetricsthatcharacterizeboththeglobalorganizationof anatomical networks (characteristic path length, clustering coefficient and global efficiency) and theparticipation(degree)oflocalnodeswithinthenetwork.Results:MPHresponders(R,n=20)exhibitedincreasedpre-treatmentglobalefficiencyrelativetonon-responders(NR,n=16).Locally,NRhadhigherparticipationoftherightsuperiortemporalandsupramarginalregions,whileRhadgreaterparticipationoftheleftcaudateandamygdala.LowerrightSupramarginalandhigherleftcaudateparticipationwasassociatedwithgreaterreductionofinattentivesymptoms(r=.447,p=.006;r=-.423,p=.01),while higher amygdala nodal degreewas associatedwith greater hyperactivity symptomreduction(r=-.574,p<.001).Conclusions:InADHD,patternsofstriatalorganizationandconnectivitymaybeusefulfordistinguishingthosewhoareunlikely to respond to MPH. Structural covariance provides a novel method for examining theneurobiologicalbasisforMPHresponseinADHD.

PosterSession1:Monday30thOctober 58

P47.RegionalbrainnetworkorganizationdistinguishesthecombinedandinattentivesubtypesofAttentionDeficitHyperactivityDisorderAuthors:JacquelineSaad,KristiR.Griffiths,MichaelR.Kohn,SimonClarke,LeanneM.WilliamsandMayureshS.KorgaonkarAffiliations: Brain Dynamics Centre, The Westmead Institute for Medical Research, The University ofSydney; Discipline of Psychiatry, University of Sydney Medical School: Westmead Hospital; Centre forResearch into Adolescents’ Health, Department of Adolescent and Young Adult Medicine, WestmeadHospital;PsychiatryandBehaviouralSciences,StanfordUniversity

Background:AttentionDeficitHyperactivityDisorder(ADHD)ischaracterizedclinicallybyhyperactive/impulsiveand/orinattentive symptoms which determine diagnostic subtypes as Predominantly Hyperactive-Impulsive(ADHD-HI), Predominantly Inattentive (ADHD-I), andCombined (ADHD-C).Neuroanatomically thoughwedonotyetknowiftheseclinicalsubtypesreflectdistinctaberrationsinunderlyingbrainorganization.Methods:Weimaged34ADHDparticipantsdefinedusingDSM-IVcriteriaasADHD-I(n=16)orasADHD-C(n=18)and28 matched typically developing controls, aged 8-17 years, using high-resolution T1 MRI. To quantifyneuroanatomical organization we used graph theoretical analysis to assess properties of structuralcovariance between ADHD subtypes and controls (global network measures: path length, clusteringcoefficient, and regional network measures: nodal degree). As a context for interpreting networkorganizationdifferences,wealsoquantifiedgraymattervolumeusingvoxel-basedmorphometry.Results:EachADHDsubtypewasdistinguishedbyadifferentorganizationalprofileofthedegreetowhichspecificregionswereanatomicallyconnectedwithotherregions(i.e.,in“nodaldegree”).ForADHD-I(comparedtobothADHD-Cand controls) thenodaldegreewashigher in thehippocampus.ADHD-I alsohadahighernodal degree in the supramarginal gyrus, calcarine sulcus, and superior occipital cortex compared toADHD-C and in the amygdala compared to controls. By contrast, the nodal degree was higher in thecerebellum for ADHD-C compared to ADHD-I and in the anterior cingulate, middle frontal gyrus andputamencomparedtocontrols.Conclusions:ADHD-Calsohadreducednodaldegreeintherolandicoperculumandmiddletemporalpolecomparedtocontrols.Theseregionalprofileswereobservedinthecontextofnodifferencesingraymattervolumeorglobalnetworkorganization.OurresultssuggestthattheclinicaldistinctionbetweentheInattentiveandCombinedsubtypesofADHDmayalsobereflectedindistinctaberrationsinunderlyingbrainorganization.

PosterSession1:Monday30thOctober 59

P49.Theeffectsofcannabismolecule,cannabidiol(CBD),ondopaminergicsignalling:AsystematicreviewoftheliteratureAuthors:Wan-HaoLeeandKatrinaWeston-GreenAffiliations: Neuropharmacology and Molecular Psychiatry Laboratory and Centre for TranslationalNeuroscience, School of Medicine, University of Wollongong; Illawarra Health and Medical ResearchInstitute;CentreforMedicalandMolecularBioscience,FacultyofScience,Medicine&Health,UniversityofWollongongBackground:Cannabidiol (CBD) is one of the major constituents of the cannabis plant. Recent studies havedemonstratedawiderangeoftherapeuticbenefitsofcannabidiol(CBD),includingantipsychotic,andpro-cognitiveeffects.Indeed,werecentlyshowedthatCBDattenuatesnegativeandcognitivesymptomsinapolyI:Cmodelofschizophrenia;however,theunderlyingmechanismsareunknown.Dopamine(DA)playsa pivotal role in normal brain function and the pathophysiology of schizophrenia. This study aimed toexaminetheeffectsofCBDondopaminesignalinginthebrain.Methods:Weconducteda systematic reviewof the literature inaccordancewithPRISMAguidelinesusing studiesdatingfromthecommencementofrecordstoAugust2017.Majorelectronicdatabases(Scopus,MedlineandPubmed)weresearchedusingthekeywords,‘dopamine’AND‘cannabidiol’, inthetitle,abstractandkeywords.Theexclusioncriteriawasstudiesthatwere(i)notfullypublishedarticlesand(ii)studiesthatadministeredimpuretreatments(egCBD+THCorbotanicextracts)withoutaCBD-onlycontrolgroup.Results:Eighteen studieswere included for qualitative synthesis (cell (n=3), healthy rodents (n=11), Parkinson’sdisease models (PD) (n=3), amphetamine-sensitized rodents (n=1)). CBD increases DA uptake insynaptosomes in a dose-dependent manner. In healthy rodents, CBD increased DA levels (nucleusaccumbens (NAc)) and decreased DA precursor/metabolites (L-DOPA, DOPAC, HVA) (NAc, pre-frontalcortex, striatum). Conversely, acutematernal CBD decreases hypothalamicDA in adult offspring. In PD,CBDrestoresDAand tyrosinehydroxylase (TH) levels (CPu),butnot levelsofTH (in substantianigra)orDOPAC (CPu). CBD prevents amphetamine-increased DA neuronal firing (VTA) but decreases firing inhealthyrats.Conclusions:Overall,CBDdoesexertactionsonthedopaminesignalingpathways inthebrain.CBDtendsto increaseDA,possiblybyincreasingDAuptakeandreducingDAturnoverinthehealthybrain.Maternal(acute)CBDexposurecaninducelong-termDAchangesintheadultoffspringbrain.CBDrestoressomeDAimbalancesinPDandprotectsagainstamphetaminetreatment.Thisreviewcanbeusedtoaididentificationofgapsinknowledge,whichwillhelpguidefuturemechanisticstudiesonthetherapeuticbenefitsofCBD.

PosterSession2:Tuesday31stOctober 60

PosterSession2

Tuesday,31stOct,1:30–2:30pmP2.BehaviouraleffectsofhighfatdietinearlyadulthoodinNrg1transmembranedomainmutantmiceAuthors:JerzyZieba,MargaretJMorrisandTimKarlAffiliations: Neuroscience Research Australia; Schizophrenia Research Institute; School of MedicalSciences,UniversityofNewSouthWales;SchoolofMedicine,WesternSydneyUniversity.Background:Schizophrenia patients are often obese or overweight. Poor dietary choices are a factor in thisphenomenon.Poordiethascomplexconsequencesforthementalstateofpatients.Furthermore,femaleadultmiceofanestablishedmodelfortheschizophreniariskgeneneuregulin1(transmembranedomainNrg1:Nrg1TMHET)showabehaviouralresponsetohighfatdiet(HFD),includingattenuationofcognitivedeficits. As sex effects are described for Nrg1 mutant mouse models and adolescence is a period ofincreasedsensitivitytoenvironmentalriskfactors,we investigatedwhetherHFDprovidedearly in lifetobothsexesmodulatesschizophrenia-relevantbehaviours.Methods:MaleandfemaleNrg1TMHETandcontrollittermateswereexposedtoeitherHFDorastandardchowdiet(CHOW)(N=12-16)for8weeksstartinginlateadolescence.Afterthisinitialperiod,micewerekeptontherespective dietary conditions and tested in behavioural domains relevant to schizophrenia includinglocomotionandexploration inopenfield (OF)socialpreferenceandsociabilitybehaviours,sensorimotorgating(i.e.prepulseinhibition(PPI),andassociativelearninginthefearconditioningtask(FC).Results:AllmiceonHFDweighedsignificantlymorecomparedtoCHOWmiceregardlessofgenotype.InOF,Nrg1TMHETmiceofbothsexesexhibitedincreasedlocomotionandreducedanxiety.Infemales,therewasasignificant ‘habituation’by ‘diet’ interactionwithHFD increasingthe locomotorhabituation intheOF. InPPI,Nrg1TMHETmalesandfemalesdisplayedareducedacousticstartleresponse.InFC,astrongtrendfor a ‘diet’ by ‘genotype’ interactionwas detected for freezing inmaleswithHFD impairing associativememoryforthecueinNrg1mutants.Therewereno‘genotype’or‘diet’effectsonsocialbehaviours.Conclusions:Inthecurrentstudy,maleandfemaleNrg1TMHETmicedisplayedincreasedexplorativebehavioursandlocomotion confirming previous findings. Additionally, Nrg1 mutants exhibited a lower response to anacousticstartlestimuluscomparedtocontrolanimals.HFDhadamoderatelystrongernegativeimpactonfear-associated memory in Nrg1 TM HET males. Adolescent HFD did not augment the majority ofbehaviours assessed. This resilience of late adolescent Nrg1mutant mice, who are susceptible to HFDeffects in adulthood, is similar to what has been found in previous studies evaluating the effects ofcannabisexposureacrossdevelopment.

PosterSession2:Tuesday31stOctober 61

P4.IncreasedTHinthedorsalstriatum:AnewanimalmodelofschizophreniaAuthors:AlicePetty,XiaoyingCuiandDarrylEylesAffiliations:QueenslandBrainInstitute,QueenslandCentreforMentalHealthResearchBackground:Increased dopamine synthesis and release in the dorsal striatum is one of the strongest neurochemicalfindings in patientswith schizophrenia. This finding has been reliably documented through PET studies.Intriguingly,thisabnormalityisalsofoundpriortoschizophreniaproper,inthe‘prodromal’period,thoughto a lesser extent. Thus the progressive nature of this abnormality suggests theremay be awindowofopportunity for therapeutic intervention. In order to develop interventions however, greaterunderstanding of the transition from the prodrome to schizophrenia is necessary. We have thereforedevelopedananimalmodelofthisprodromalabnormality.Methods:Weusedanadeno-associatedviral(AAV)vectortoinsertageneticconstructintothesubstantianigraparscompacta (SNpc) of adolescent rats. The construct contains tyrosine hydroxylase (TH) and GTPcyclohydrolase1(GCH1);ratelimitingfactorsindopaminesynthesis.ThecontrolvectorisGCH1alone.TheSNpc innervates the dorsal striatum. Sixweeks after the injection (in adolescence - P35), animalsweretestedforamphetamine-induced locomotion(0.6mg/kgAMPH),pre-pulse inhibition(PPI)and“negative”symptomtests.Neurochemistryof thedorsal striatum(medialand lateralportions),nucleusaccumbens(NAc)andprefrontalcortex(PFC)wasanalysedwithHPLCandrtPCR.Results:AnimalsinjectedwiththeTH+GCH1vectorshowedincreasedamphetamine-inducedhyperlocomotion,anddecreased%PPIcomparedtocontrols.Theseanimalsalsofailedtoshownormalsocialnoveltypreference,but showed typical open field locomotion, sucrose preference, and spontaneous alternation behaviour.Neurochemical analysis revealed that, as expected, virally-generated huTH was found primarily in thedorsal striatum (68%) compared to the NAc (32%). This indicates preferential infection of the SNpccompared to the VTA in themidbrain. This treatment had no effect on basal levels of dopamine or itsmetabolites.Theexpressionofarangeofdopamine-relatedgeneswasalsounchanged.Conclusions:We have generated a model of increased expression of the TH enzyme preferentially in the dorsalstriatum. This treatment resulted in abnormal amphetamine-induced locomotion and PPI; behavioursclearly reflecting the“positive”symptomsofschizophrenia.Theseanimalsalsoexhibiteddeficientsocialnovelty preference, representing a “negative” symptom of schizophrenia. Further experiments areundergoingtoexaminetheexactnatureofthechangesinducedbytheadditionoftheTHenzymetothedorsal striatum.We now have amodel to potentially understand how themost robust neurochemicalfindinginschizophreniamayresultinitskey“positive”symptoms.

PosterSession2:Tuesday31stOctober 62

P6.Brainderivedneurotrophicfactorreversesdopaminemediateddeficitsinprepulseinhibitioninearlylifestressmodelsofschizophrenia`Authors:EmilyJ.Jaehne,ElaineMeiSanChongandMaartenvandenBuuseAffiliations:SchoolofPsychologyandPublicHealth,LaTrobeUniversity,MelbourneBackground:Schizophreniaisadevastatingmentalillnesscausedbygeneticandenvironmentalfactors.LevelsofBrain-DerivedNeurotrophic Factor (BDNF) havebeen shown to be reduced in post-mortembrain tissue frompatients with schizophrenia. BDNF may therefore be a potential therapeutic target for schizophrenia;however the mechanisms by which it affects behavioural changes relevant to schizophrenia, remainunclear.Weusedtwodevelopmentalanimalmodelsofschizophrenia,maternal immunestimulationandsocial isolation rearing, to investigate the role of BDNF in the regulation of prepulse inhibition (PPI), amodelofsensorimotorgatingwhichisreducedinschizophrenia.Methods:PregnantLong-Evansratsweretreatedwiththeviralmimetic,polyI:C,andmaleoffspringwerecomparedin adulthood to control offspring. PPI testing included the BDNF receptor agonist, 7,8-dihydroxyflavone(7,8-DHF,10mg/kg),aswellasthedopaminereceptor-stimulatingdrug,apomorphine(APO,1mg/kg),orthe dopamine releasing drug, methamphetamine (METH, 2 mg/kg) to induce a schizophrenia-like PPIdisruption. A second cohort of rats were reared in social isolation from weaning to adulthood andcomparedtogroup-housedcontrols.Results:Acute administrationofAPO causeda significant reductionof PPIwhichwasnot significantly altered inpoly I:C rats.However, inpoly I:Coffspringonly,7,8-DHFsignificantly reversed theeffectofAPOonPPI(Control baseline 54 ± 2%, APO 20 ± 4%, APO+DHF 16 ± 2%; poly I:C baseline 54 ± 3%, APO 16 ± 3%,APO+DHF35±3%;p<0.05).AsimilartrendwasobservedaftertreatmentwithMETHaswellasinsocialisolationrats.Conclusions:Thesefindingssuggestthat7,8-DHFhastheabilitytoreversedopamine-mediateddeficits inPPI inearlylifestressmodelsofschizophrenia.ThishighlightsthetherapeuticpotentialoftargetingBDNFsignallingforthetreatmentofschizophrenia.

PosterSession2:Tuesday31stOctober 63

P8.Usingmouseoperanttaskstoinvestigatetheneuralmechanismsunderlyingreward,motivationandchoiceinschizophreniaAuthors:Kyna-AnneConn,ThomasHJBurneandJamesPKesbyAffiliations:QueenslandBrainInstitute,TheUniversityofQueenslandBackground:Thenegative symptomsof schizophrenia include impairedmotivationandcognitiondeficits, andoneofthe most robust pathophysiological findings is aberrant striatal dopamine function. The striatum isinvolvedwiththecoordinationofmotor-andaction-planning,decision-making,reinforcementandrewardperception.Byunpickingspecificpathwaysinthisregionandassessingtheircontributiontomotivationalandcognitivedysfunction,wecanbettertargetinterventionstoimprovedailyfunctioning.Therefore,theaim of my PhD project is to use operant tasks that permit the exploration of reward, motivation andchoice,and,thedetectionofdifferencesduetostriataldopaminedysfunctioninmice.Methods:By combining twoexisting operant tasks inmice, theOutcome-specificDevaluation Task (ODT) and theProgressiveRatioBreakpointTask (PRBT),wecandissectmotivationalandcognitiveperformance in~50days of training and testing. Using 16 adult male C57BL/6J mice, the amalgamated tasks have beenestablished to detect individual variations in reward valuation (value testing), goal-directed actionselection (choice testing) and incentive motivation (breakpoint testing). We can also assess a reversallearningcomponentintheODTtoexaminecognitiveflexibility.MicearealsotestedwithamphetaminetodeterminethesensitivitytodetectchangesinsystemicdopamineonthePRBT.Results:Wewereable toseparaterewardvaluation,goal-directedactionselectionand incentivemotivation inasingle throughput test battery. Detecting differences due to changes in systemic dopamine are alsoexaminedinthisstudyvalidatingthefutureaimstomanipulatemajordopaminergicstriatalpathwaysthathavebeenimplicatedinschizophrenia.WiththeprospectiveapplicationofthechemogenetictoolDesignerReceptorsExclusivelyActivatedbyDesignerDrugs(DREADDs)usedtomodulatereceptoractivityinvivo,inthemeso-limbicandnigrostriatalpathwaysinparticular,wewillbeabletodissecttheroleofthesecircuitsinmotivation,rewardvaluation,cognitiveflexibilityandgoal-directedaction.Conclusions:My project will contribute significantly to understanding the overlap between the negative (lack ofmotivation)andcognitive(impaireddecisionmaking)symptomsseeninpatientswithschizophrenia.Theinteractions between these symptoms are poorly understood, are known to contribute to functionalimpairmentsandreducedqualityoflife,andtherearecurrentlynoefficacioustreatments.Inaddition,theODT and PBRT have identical task equivalents in humans, making this behavioural test battery highlyrelevant for crossspecies translational studies. This work will also increase our knowledge about brainmechanismsthatareinvolvedwithcomplexbehaviours,suchasmotivationanddecision-making.

PosterSession2:Tuesday31stOctober 64

P10.RationaleandmethodsoftheroleofestrogeninmodulatingexecutivefunctionintheratAuthors:KaraJaeschkea,AnreaGogosandThomasH.J.BurneAffiliations:Queensland Brain Institute, University of Queensland; Florey Institute of Neuroscience andMentalHealth,UniversityofMelbourneBackground:Numerousstudieshavesuggestedthatestrogen isneuroprotectiveagainstcognitivedysfunction inboththemale and female brain. Cognitive deficits, particularly executive deficits, are key drivers of adversefunctional outcomes in neuropsychiatric disorders. However, they remain currently unresolved bypharmacological and behavioural intervention. While several models have been developed to assessexecutivefunctioning,mostarenon-automatedandlabourintensive.Thus,thisstudyaimstodevelopanautomatedoperanttaskinrodentsthatmimicsthehumanintra-/extra-dimensional(ID/ED)tasktolookattheroleofsexandestrogeninneurobiologicalcomponentsofexecutivefunction.Methods:Twodissociablecomponentsofexecutivefunctionwillbemeasuredinthistask:reversallearningandset-shifting within the same dimension (intra-dimensional) or between different dimensions (extra-dimensional).Duringthistask,ratswillbetrainedduring∼5dailysessionsandthentestedover∼10dailysessions.Twodimensionswillbeusedinthistaskandstimulicanbesimpleorcompound.Performanceonthistaskwillbeusedtodeterminetheeffectsofsex(maleversusfemaleSpragueDawley(SD)rats)andestrogen (ovariectomisedorsham-operatedwith17β-estradiol (25mg)orvehicleviaasilastic implant infemaleSDrats)onexecutivedeficits.Results:This taskwill beused toexplore the roleof sex andestrogen in executive function. Themainoutcomevariables are intra-dimensional and extra-dimensional set-shifting and reversal learning ability. This taskaims to provide the possibility to test the effects of various neural, pharmacological and behaviouralmanipulationsondiscretemeasuresofexecutivefunction,includingaccuracy,perseverativeresponsesandresponselatencies.Conclusions:The neural circuits underlying behaviour during reversal learning and set-shifting are highly conservedacrosshumans,nonhumanprimatesandrodents.Thus,thisoperanttaskaimstoprovideface,constructand predictive validity for executive deficits present in neuropsychiatric disorders. It aims to addresslimitationsofexistingtasksbyreducingextensivetrainingperiodsandomissionrates,andcontrollingbodypositionbyusingcentralnosepoketoself-initiateatrial.Thistaskhasthepotentialtobeusedbyavarietyof fieldstoassesscognitivephenotypesandspecificdifferences(i.e.sex)ortreatments (i.e.estrogen) inanimalmodelsrelevanttoneuropsychiatricdisorders.

PosterSession2:Tuesday31stOctober 65

P12.BaselinephenotypeofImmp2Iknockout-mice:AmodelforTourettesyndromeAuthors:FabianKreilaus,RoseChesworth,ValsammaEapen,RaymondClarkeandTimKarlAffiliations:SchoolofMedicine,WesternSydneyUniversity;SchoolofPsychiatry,FacultyofMedicineandInghamInstituteUniversityofNewSouthWales;NeuroscienceResearchAustraliaBackground:Tourette Syndrome (TS) is a neurodevelopmental disorder, characterised bymotor and vocal tics. TS isoften co-morbid with other conditions including obsessive compulsive disorder and possibly autismspectrumdisorder.ThegeneticfactorsrelevanttothedevelopmentofTSareyettobefullyunderstood.AtargetedgeneassociationstudyinTSpatientshasidentifiedanassociationbetweenTSandamutationinthe inner mitochondrial membrane peptidase subunit 2 (IMMP2L) gene. Germline knockout (KO) ofImmp2l inmice results inmitochondrialdysfunction, increase ischemicbraindamageand infertility.TheimpactofImmp2lonbehaviourisunknown.Methods:Inthisstudy,weaimedtocharacterisethebehaviouralconsequencesofImmp2ldeletioninbothmaleandfemaleadultmice(C57/BL6background).HeterozygousandhomozygousImmp2lKOmicewerecomparedto control littermates in a battery of behavioural tests relevant to TS including open field (OF), socialinteraction (SI), novel object recognition (NOR),marble burying (MB) and prepulse inhibition (PPI). Theeffectofacutedexamphetamine(5mg/kg)onopenfieldbehaviourwasalsoinvestigated.Results:Underbaseline conditions, the time spent in the centre zoneof theOFwas significantly longer inmalehomozygous KOmice compared to controlmales indicating an anxiolytic-like phenotype. Total distancetravelled was not significantly different across genotypes but homozygous KO mice showed a fasterrecovery from the dexamphetamine-induced locomotor stimulation compared to heterozygous KO andcontrolmice.TheNORtest indicatedadeficit inmaleheterozygousandhomozygousmalestoexploreanovel objectwhen compared to controlmice. These behavioural changeswere not detected in femalemice.FurthertestsincludingPPI,SIandMBarecurrentlybeinganalysed.Conclusions:Deficiency in Immp2ldecreased theanxiety responseofmalehomozygousKOmice, compromised theirobject recognitionmemory,andmodulated the locomotor response todexamphetamine.TheeffectsofImmp2ldeficiencyappearedgene-doseandsexdependent.Themodulatedresponsetodexamphetaminein homozygous KO mice suggests a potential role of Immp2l in controlling dopamine-related brainmetabolism. These preliminary results indicate that this model may possess partial face validity forpreclinicalresearchintoTSpathophysiologyandtherapy.

PosterSession2:Tuesday31stOctober 66

P14.EffectofenvironmentalriskfactorsonelectrophysiologicalfeaturesrelatedtoschizophreniaAuthors:ArielDunn,LaurenHarms,JuanitaTodd,RossFulham,AarongWong,DeborahHodgson,UlrichSchallandPatriciaMichieAffiliations:SchoolofPsychology,UniversityofNewcastle;PriorityResearchCentreforBrainandMentalHealthResearch,UniversityofNewcastle;SchoolofMedicineandPublicHealth,UniversityofNewcastleBackground:Maternalimmuneactivation(MIA)inresponsetogestationalinfectionisariskfactorforthedevelopmentofschizophreniainoffspring.PreviousstudieshaveshownthatMIAinratsandmice,inducedbythenon-infectious viral mimic Poly(I:C), produces a variety of schizophrenia-like behavioural, cognitive andmorphologicalalterations.However,itwasunknownifMIAalteredelectrophysiologyinrats.Thecurrentstudy therefore investigated the impact of MIA on two electrophysiological features altered inschizophrenia,gammaactivityandmismatchnegativity(MMN).Furthermore,ourstudyinvestigatedthesefeaturesinbothmaleandfemalerats.Methods:PregnantWistarratswereexposedtoeitherPoly(I:C)(MIA)orsalineduringlategestation(gestationday19).Offspringunderwentsurgeryinadulthoodtoimplantskullelectrodeswhichwereusedtoassesstheneurophysiological phenotypes of gamma activity and MMN. Gamma activity was measured using anauditorysteadystateresponse(ASSR)task,whileMMNwasmeasuredviaanoddballandmany-standardscontrolparadigm.Results:MIAratshadreducedgammapower(p=.018)andphase-locking(p=.020)between30and50Hz.Nosexeffectswere found forgammaactivity.MMN-like responseswere foundand femaleanimalshadhigheroverall responses than males early in the MMN waveform, a novel finding (p = .029). No significanttreatmenteffectswerefoundforanyMMNcomponent.Conclusions:Amultiple hitmodel ofMIA, or a two-hitmodel of a variety of risk factorswill be implemented in thefuturetoinvestigatemorereliableandrobustelectrophysiologicalalterations,aswellasbehaviouralandcognitive alterations. Our findings of sex differences suggest that animal research should consistentlyincludebothsexestoimprovethevalidityofcurrentmodelsofschizophrenia.

PosterSession2:Tuesday31stOctober 67

P16.Postnataldevelopmentoftheendocannabinoidsystemintransmembranedomainneuregulin1mutantmice,ageneticmousemodelofschizophreniaAuthors:RoseChesworth,LeonoraLong,CyndiShannonWeickertandTimKarlAffiliations:SchoolofMedicine,WesternSydneyUniversity;NeuroscienceResearchAustraliaBackground:Cannabisuseisawell-establishedcomponentriskfactorforschizophrenia,particularlyinindividualswithgenetic predisposition for the disorder. Alterations to the endocannabinoid system have been found inpost-mortembrain tissueof schizophreniapatients. Thus,weassessedwhethermolecularalterations inthe development of the endocannabinoid signalling pathway were associated with genetic mutationswhichincreaseriskforschizophreniaMethods:Weanalysedtranscriptsencodingkeymoleculesoftheendocannabinoidsysteminageneticmousemodelforschizophreniaknowntohaveincreasedsensitivitytocannabisexposure(heterozygoustransmembranedomainNeuregulin1mice:Nrg1TMHET).TissuefromtheprelimbiccortexandhippocampusofNrg1TMHETmiceandwildtype-likelittermates(n=8-12/genotype/age)wascollectedatpostnataldays7,10,14,21, 28, 35 and 161. Quantitative polymerase chain reaction was conducted to assess mRNA levels ofcannabinoidreceptor1(CB1),andenzymesforthesynthesisandbreakdownoftheendocannabinoid2-arachidonoylglycerol(2-AG).Results:HippocampalandcorticalmRNAexpressionofdiacylglycerol lipasealpha (DAGLα),monoglyceride lipase(MGLL)andα/β-hydrolasedomain-containing6(ABHD6)wasdynamicacrosspostnataldevelopment,withonlyminorchangesinCB1mRNAfoundacrosspostnataldevelopmentinthehippocampus.Nrg1TMHETmRNAexpressionwasnotdifferentfromcontrolmiceforanyendocannabinoidmarkerinvestigated.Conclusions:Here,weprovideadetaileddevelopmental trajectoryof keyendocannabinoid system transcripts in themousebrain.Nrg1TMHETmutationdidnotalter thedevelopmental trajectoryof theendocannabinoidmarkersassessed,suggestingothermechanismsmayberesponsibleforcannabinoidsusceptibilityinthesemice.

PosterSession2:Tuesday31stOctober 68

P18.Maternalimmuneactivationadverselyaffectstheontogenyofdopamineneurons:IsvitaminDneuroprotective?Authors:SuhailahAli,LeonLuanandDarrylEylesAffiliations:QueenslandBrainInstitute;QueenslandCentreforMentalHealthResearchBackground:Dopaminedysregulationisoneofthemajorhypothesesunderlyingthepathophysiologyandtreatmentofschizophrenia,whichmayresultfromearlyalterationsindopamineontogeny.Twowell-establishedanimalmodels – maternal immune activation (MIA) using Poly(I:C) treatment, and developmental vitamin Ddeficiency (DVD) – both showan initial reduction in factors crucial for dopaminergic development. Thissuggests a convergent aetiologicalmechanism,which is supportedbyour recentevidence showing thatvitamin D can ameliorate schizophrenia-related behavioural phenotypes in the Poly(I:C) model. Wetherefore want to investigate whether vitamin D is acting to correct the abnormal dopaminergicdevelopmentinducedbyPoly(I:C).Methods:Pregnant mice were co-administered the active vitamin D hormone simultaneously with Poly(I:C) atgestationalday9andembryoswerecollectedattwodevelopmentaltime-points,E11andE14.Inordertoexaminedopamineontogeny,weusedimmunohistochemistrytoanalysetheexpressionoffourdopaminelineagemarkers–Lmx1a,Sox2,Nurr1andTH–whichcanbeusedtodistinguishdopamineprogenitors,immature neurons and mature neurons. Using spinning-disk confocal microscopy coupled with anoptimisedCellProfileranalysispipeline,wewereabletoidentifyindividualdopaminergiccellsandquantifytheexpressionofthesemarkers,alongsidecellnumber,shape,sizeandspatialposition.Results:Wehave so farobtainedpreliminary results for theexpressionof Lmx1aandSox2 inE11embryos.OurinterpretationsarecurrentlylimitedasweremainblindtotreatmentgroupsuntiltheNurr1andTHimageshave been analysed. Poly(I:C) had a significant effect on the number and nuclear shape of progenitors(Lmx1a+Sox2+),whilevitaminDhadasignificanteffectontheexpressionofLmx1ainprogenitorsandthelateralpositionofpostmitoticcells(Lmx1a+Sox2-).NointeractionsbetweenPoly(I:C)andvitaminDwereobserved.Conclusions:Poly(I:C) and vitaminD appear to be having independent effects on dopaminergic development at E11.However,we have yet to analyse Nurr1 and TH in the E11 embryos,whichwill allow us to distinguishbetween immature and mature neurons. We are also currently processing the E14 embryos, whichrepresentsatime-pointwhendopamineneurogenesisisalmostcomplete.Wehopetousethesefindingstobetterunderstandhowdifferentenvironmental risk factors forschizophreniaconvergeondevelopingdopaminergicsystems.

PosterSession2:Tuesday31stOctober 69

P20.Post-weaningsocialisolationimpairsfearextinctionrecallinadolescenceAuthors:KatherineDrummondandJeeHyunKimAffiliations:TheFloreyInstituteofNeuroscienceandMentalHealthBackground:Early life chronic stressmay increase an individual’s vulnerability to develop anxiety disorders andmayreduce the efficacy of treatment by subsequent behavioural therapies. Social isolation stress duringpubertyisarelevantmodelofadolescentchronicstress.Thisstudyaimstoinvestigateinratstheeffectsonpost-weaningsocialisolationonadolescentfearextinctionbehaviour.Methods:At21daysofagemaleandfemaleSpragueDawleyratswerehousedin3’sorinisolationforthreeweeks.Thenallratsreceiveda6whitenoise(10s)–footshock(1s,1mA)pairings.Thenextday,allratsreceived60presentationsofthenoisewithoutshock(i.e.extinction).Ondaythree,extinctionrecallwastestedwithrodentspresentedwiththeanoise-alonetrial(2mins)intheextinctioncontext.Results:Isolationhousinghadnoeffects on conditioning andextinction acquisition compared to grouphousing.However, at extinction recall test, both female andmale isolation-housed rats froze higher than grouphousedrats(*post-hoctestsfollowinginteraction,p<0.05;**t-testp<0.05).Conclusions:This demonstrates that social isolation stress can impair fear extinction recall in adolescence. Betterunderstandingofthemechanismsthatunderliethisimpairmentmayleadtonoveltreatmentstoassistinpreventionandtreatmentofanxietydisorders.

PosterSession2:Tuesday31stOctober 70

P22.ElevatedimmunecellmarkersintheneurogenicsubependymalzoneinschizophreniaAuthors:HayleyNorth,ChristinWeissleder,MareeWebsterandCynthiaShannonWeickertAffiliations: Schizophrenia Research Laboratory; Neuroscience Research Australia; School of Psychiatry,UniversityofNewSouthWales;LaboratoryofBrainResearch,StanleyMedicalResearchInstituteBackground:Research indicatesadysregulationofadultneurogenesisandapathogenic roleofneuroinflammation inschizophrenia and bipolar disorder. The greatest extent of post-natal neurogenesis occurs in thesubependymal zone (SEZ; also termed subventricular zone). Immune cells trafficked to the brain canreleasemolecules that impact neurogenesis; andwehypothesized thatmolecular indicators of immunecell levels in the SEZ would be increased in psychiatric disorders. If immune cells infiltrate the SEZ inschizophrenia and bipolar disorder, thismay be associatedwith reducedmarkers for neural stem cells(GFAPδ)andneuronalprecursorcells(ASCL1)foundintheSEZinthesedisorders.Methods:Post-mortemcaudatetissuewasobtainedfrom32schizophrenia,29bipolardisorderand32controlcasesfromtheStanleyMedicalResearch Institute.SEZtissuewasdissected from60μmthicksections~2mmdeep to the lateral ventricle surface for RNA isolation and cDNA synthesis. We tested for diagnosticdifferences in gene expression of immune cell markers CD14 (monocytes), CD163 (perivascularmacrophages) and FCGR3A (natural killer cells) with quantitative polymerase chain reactions usingFluidigmBiomarkHDTM.Results:CD163was increased inschizophreniacomparedtocontrols (161%,p=0.01)andbipolardisorder (158%,p=0.01).FCGR3AandCD14werenotsignificantlydifferentacrossdiagnosticgroups(p=0.10andp=0.49),butplannedcontrastsshowedincreasedFCGR3Ainschizophreniacomparedtocontrols(47%,p=0.05).Inschizophrenia,CD163correlatedpositivelywithGFAPδ (r=0.55,p=0.001)andnegativelywithASCL1(r=0.40,p=0.03);andFCGR3AcorrelatedpositivelywithGFAPδ(r=0.57,p=0.001)butnotASCL1.Inbipolardisorder, CD163 was not significantly correlated with GFAPδ or ASCL1; whereas FCGR3A correlatedpositivelywithGFAPδ(r=0.636,p<0.001)butnotASCL1.Conclusions:WefindthefirstevidenceofincreasedmarkersofperivascularmacrophagesandnaturalkillercellsintheSEZinschizophrenia,whichweplantofurtherexplorewithimmunohistochemistry.NochangesinimmunecellmarkerswerefoundintheSEZ inbipolardisorderdespitepreviousfindingsofneuroinflammation inother regions. Our data is consistent with increased neuroinflammation in schizophrenia and thecorrelationsbetweenmarkersforimmunecellsandneurogenesisintheSEZmayhaveimplicationsforthedysregulationofneurogenesisinschizophrenia.

PosterSession2:Tuesday31stOctober 71

P24.Anassessmentofpresynapticmarkers,vGluT1andsynaptophysin,inthenucleusaccumbensinschizophreniaAuthors:SamaraBrown,JeremySLumandKellyANewellAffiliations:SchoolofMedicine,UniversityofWollongong;IllawarraHealthandMedicalResearchInstituteBackground:Thenucleusaccumbens(NAc)isimplicatedinthepathologyofschizophreniahowevertherehasbeenlittledirectinvestigationofthisregioninschizophreniasubjects.TheNAcreceivesinputsfrommultipleregionsofthebrain,includingtheprefrontalcortexandhippocampus,withemergingevidencesuggestingalteredprojectionsontotheNAcinschizophrenia,particularlyglutamatergicprojections.Thepurposeofthisstudywas to use a large postmortem cohort to measure the presynaptic markers, vGluT1 (a marker ofpresynapticglutamatergicterminals)andsynaptophysin(amarkerofpre-synapticdensity), intheNAc inschizophrenia.Methods:Postmortem NAc samples from 30 schizophrenia and 30 control subjects, matched for age at death,postmortem interval and brain pH, were obtained from the NSW Brain Tissue Resource Centre. Therelative protein levels of vGluT1 and synaptophysin were assessed via western blot and normalised toGAPDH. T-tests and ANCOVA were used to compare between schizophrenia and control subjects.Correlation analyses were used to determine any associations between vGluT1 and synaptophysin andclinicalvariablesincludingestimatedlifetimeantipsychoticdrugdoseanddurationofillness.Results:ProteinlevelsofvGluT1andsynaptophysinintheNAcwerenotsignificantlydifferentbetweencontrolandschizophreniasubjects.Asexpectedhowever,vGluT1andsynaptophysinwerepositivelyassociatedintheNAc in both control (r=0.875 p<0.001) and schizophrenia subjects (r=0.610; p<0.001). There was noassociationbetweenvGluT1orsynaptophysinandestimatedlifetimeantipsychoticdrugintakeordurationofillness.Conclusions:Thepresent studydoesnotprovideevidence for presynaptic glutamatergic abnormalities in theNAcofschizophrenia subjects. The lack of change in VGluT1 suggests there are no changes in cortical andhippocampalglutamatergicprojections toNAc inschizophrenia,howeverwecannotruleoutchangestospecificsubdivisionsoftheNAc(iecorevshell)orinotherpresynapticglutamatergicmarkers(e.g.vGluT2).

PosterSession2:Tuesday31stOctober 72

P26.IncreaseinPrefrontalCortexandDecreaseinStriatumofDopamineTransporterhavethePossibilityofSupportingDopamineHypothesisinSchizophreniaAuthors:HirotakaSekiguchi,GeoffPaveyandBrianDeanAffiliations:TheFloreyInstituteofNeuroscienceandMentalHealthBackground:Thedopaminehypothesis inschizophreniahasbeendiscussedforseveraldecades.Ithasbeenproposedthatinschizophreniathereisahypodopaminergicstateintheprefrontalcortexandahyperdopaminergicstate in the striatum; thehyperdopaminergic state in the striatumdue to synaptic dopamineelevation,particularly in the dorsal striatum. The dopamine transporter (DAT), which is a regulator of dopamineconcentrationthroughthereuptakeofdopaminefromthesynapticcleftbythepre-synapticneuron,isoneofthemoleculesthatmaybeinvolvedinthedopaminergicpathophysiologyofschizophrenia.Therefore,wemeasuredlevelsofDATinthecortexandstriatum.Methods:LevelsofDATweremeasuredinthegraymatterfromfrontalpole(Brodmann’sarea(BA)10)andstriatumfrom15subjectswithschizophreniaand15controlsusinginsituradioligandbindingof[3H]mazindol(15nM)displacedbymazindol(1μM)quantifiedusingautoradiography.Klüver-Barrerastainedsectionswerereferred in order to detect the boundary between the gray matter and the white one within BA10.Approval to collect human tissuewas obtained from the Ethics Committee of the Victorian Institute ofForensicMedicine.Results:Levelsof[3H]mazindolwerehigherinBA10fromsubjectswithschizophrenia(t=3.11;df=19.77;p=0.0055;Cohen’sd=1.14)but lower inthedorsalstriatumfromthosewiththedisorder (t=3.61;df=25;p=0.0013;Cohen’sd=1.40).Conclusions:Thechanges in levelsof [3H]mazindol implythat levelsofDATarethathigher inBA10but lower inthestriatum from subjects with schizophrenia. We hypothesis that higher levels of DAT in BA10 could becontributing to low synaptic dopamine whereas lower levels of striatal DAT in the striatum could becontributingtoahyperdopaminergicstateinthatCNSregions.

PosterSession2:Tuesday31stOctober 73

P28.IncreasedCypAexpressionintheanteriorcingulatecortexofsubjectswithmajordepressivedisorderAuthors:KateMcPherson,AndrewGibbons,AndreaGogosandBrianDeanAffiliations:TheFloreyInstituteofNeuroscienceandMentalHealthBackground:Agrowingbodyofevidencesuggeststhat inflammatoryprotein levelsarealtered intheCNSofpatientswith mood disorders. Cyclophilin A (CypA), a major immunosuppressant drug target, regulates theexpression of several key inflammatory proteins. Furthermore, drugs that bind to CypA can inducedepressive side effects in patientswith inflammatory disorders. However, it is unclearwhether CypA isinvolved in thepathophysiologyofmooddisorders.We investigatedwhether CypAmRNAexpression isalteredinsubjectswithmajordepressivedisorder(MDD)orbipolardisorder(BD),comparedtocontrolsinBA24,abrainregionthatisimportantincontrollingmood.Methods:Humanpost-mortembraintissuewasobtainedfromtheVictorianBrainBankNetwork.RNAwasextractedfromBA24(anteriorcingulatecortex)tissue,obtainedpost-mortemfromsubjectswithMDD(n=20),BD(n=18),andnon-psychiatriccontrols(n=20).TheRNAwasreversetranscribedandexpressionlevelswerequantified using qPCR with SYBR green chemistry in a Bio-Rad iQ5 Real-Time PCR Detection System.Reactionswereperformedintriplicate,andrelativequantitiesofCypAmRNAexpressionwerenormalizedtothegeometricmeanquantitiesoftwostablyexpressedreferencegenes;GAPDHandSKP1.Results:CypAmRNA expression was increased in BA24 fromMDD subjects compared to controls (p < 0.0001).Therewasnosignificantdifference inCypAmRNAexpression inBDcomparedtocontrols.Furthermore,therewasnosignificantvariationinage,post-morteminterval,andsexacrossdiagnosticcohorts.BrainpHwashigherintheMDDcohortcomparedtothecontrolandBDcohorts(p=0.0005).However,CypAmRNAexpression did not correlate with pH. Therefore, this is not likely to impact interpretation of the dataacrossdiagnoses.Therewasno relationshipbetweenCypAmRNAexpressionand suicide completionorantidepressantuse.Conclusions:WehaveshownthatthelevelofCypAmRNAexpressionisincreasedinBA24fromsubjectswithMDDbutnot subjectswithBD. These findings indicate that increasedexpressionofCypA could contribute to thepathophysiologyofMDD.ThediagnosticspecificityofthesefindingshasimplicationsforunderstandingthebiochemicaldifferencesunderlyingMDDandBD.

PosterSession2:Tuesday31stOctober 74

P30.RegulationoftheD2R-DISC1complexformationandtheneuriteoutgrowthbyantipsychoticdrugsAuthors:MinminHu,PengZheng,YuanyiXie,ZehraBoz,HongqinWang,YinghuaYuandXu-FengHuangAffiliations:DepartmentofPathogenBiologyandImmunology,XuzhouMedicalUniversityandJiangsuKeyLaboratory of Immunity and Metabolism, Xuzhou, Jiangsu, China; School of Medicine, University ofWollongong;IllawarraHealthandMedicalResearchInstituteBackground:Schizophrenia is a chronic mental illness, which is characterized by episodes of psychotic symptoms,cognitive impairments and social behaviordisorders.DopamineD2 receptor (D2R) is themain targetofantipsychoticdrugs.HaloperidolisaD2RantagonistandaripiprazoleisD2Rpartialagonist.D2RbelongstotheG-protein-coupledreceptorfamily.Recently,ithasbeenshownthatD2RcanformaproteincomplexwithDisruptedinschizophrenia(DICS1),whichregulatestheglycogensyntheseskinase3(GSK3)signalingpathway.However,theroleoftheD2R-mediatedsignalingeventsintheactionsofantipsychoticsremainsunclear.Methods:(1)DesignandconstructthefusionproteinofD2R-GFP,D2Rmut-GFPandDISC1-mCherry;(2)Transfectionof plasmids intoHEK293 cells; (3) Fluorescence microscopy and Western blot to confirm the proteinexpression; (4) Fluorescence resonance energy transfer (FRET) analysis to investigate the effect ofHaloperidolandAripiprazoleonthe interactionbetweenD2RandDISC1 inHEK293cells;and(5)DetecttheeffectofHaloperidolandAripiprazoleonRetinoicAcid-inducedneuriteoutgrowthinSHSY5Ycells.Results:Establishment of D2R-GFP, DISC1-mCherry, D2R-GFP+DISC1-mCherry, D2R mut-GFP +DISC1-mCherry inHEK293 cells; (2) D2R agonist quinpirole overstimulation induced a significant increase of D2R/DISC1complex formation; (3) D2R antagonist Haloperidol and Aripiprazole prevented D2R/DISC1 complexformation;(4)HaloperidoldecreasedtheneuriteoutgrowthoftheSHSY5Ycells.Conclusions:Antipsychotics drugs, Haloperidol and Aripiprazole, can block the complex formation between D2R andDISC1.Also,HaloperidolinhibitedtheneuriteoutgrowthofSHSY5YCells.

PosterSession2:Tuesday31stOctober 75

P32.MultidimensionalanalysisofgeneexpressionindifferentiatedhumanneuroblastsafterwholecelldepolarisationAuthors:DylanKiltschewskilandMurrayCairnsAffiliations:SchoolofBiomedicalSciencesandPharmacy,FacultyofHealth,TheUniversityofNewcastle;Priority Research Centre for Brain and Mental Health Research, Hunter Medical Research Institute;SchizophreniaResearchAustraliaBackground:Dysregulationofthesignalingassociatedwithneuronalexcitationandconnectivityisacommonfeatureofpsychiatric disorders including schizophrenia, addiction and autism spectrum disorders. While theseprocessesinvolvespatiallyandtemporallyrestrictedpatternsofmRNAtranslation,theposttranscriptionalregulatorymechanismsthatfacilitatethisarepoorlyunderstood.Togainfurtherinsight,weexploredthetranslational dynamicsof depolarisation in adifferentiatedhumanneuroblast culture systemusinghighthroughput ribosome profiling and reconciled this with associated changes in mRNA abundance andmiRNAexpression.Methods:SH-SY5Y neuroblastoma cultures were differentiated with all-trans retinoic acid (0.1μM) for 7 days.Membraneexcitationwas inducedby incubationwithHank’sBalancedSaltSolution,supplementedwithdepolarisingconcentrationsofKCl(100mM).Afteratotalof4stimulus–restcycles,cellswereharvested1hour followingthefinalstimulus inthepresenceof thetranslational inhibitorcycloheximide.Changes inmRNAabundance and translationwere determinedby sequencing bothmRNAand ribosomeprotectedtotal RNA fragments. These were then comparedwithmiRNA expression examined through small-RNAsequencing. All libraries were produced and sequenced (NextSeq500) according to the manufacturer’sinstructions(Illumina).Results:Ribosomeprofiling revealedover1230genesweresubject toa significant (p<0.05,q<0.1),excitationassociated change in translational activity after depolarization. Interestingly, integrative analysis withmRNA steady-state expression data indicated themajority of differentially translated genes (85%)wereprimarilyregulatedatthetranslationallevel.TheanalysisofmiRNAexpressionsuggestedthemajorityofsignificantmiRNA:mRNAinteractionsaffectedsteadymRNAlevelsratherthantranslationdirectly.hsamiR-1271-5pandhsa-miR-125b-5pwereidentifiedasmajorregulatorsofdepolarisationassociatedtranslation,whichcorrelatedwithsubsetsofmRNAsatboththetranscriptionalandtranslationallevels.Conclusions:Theseresultsprovidecompelling insights intodynamicregulationofexcitation-associatedneuronalgeneexpression. Translational activity 1 hour after membrane excitation appears to be highly regulated,howeverwithminimal influence frommRNAabundance andmiRNAexpression.We suspect changes intranslational activity may show stronger correlation with interactions between mRNA and the RNAinduced silencing complex, with correlation analysis suggesting miRNA primarily influence mRNAabundanceatthewhole-celllevelatthistime-pointpost-depolarisation.Theseinsightsintotheregulationof neural activity-associated translation and the role of posttranscriptional gene regulation are tounderstandthechangesinthissystemobservedinpsychiatricdisorders.

PosterSession2:Tuesday31stOctober 76

P34.OlanzapineinhibitsmitophagyandupregulatesROSinNPY-expressinghypothalamicneuronalcellsAuthors:ZehraBoz,YinghuaYuandXu-FengHuangAffiliations:IllawarraHealthandMedicalResearchInstitute,UniversityofWollongongBackground:Olanzapine is a commonly prescribed second-generation antipsychotic. However a major side-effectassociated to olanzapine are metabolic disorders such as; extreme weight-gain and diabetes. Themechanism underlying antipsychotic-inducedmetabolic dysfunction remains unknown.Mitophagy is anintra-cellularmechanismactivateduponcellularstresssuchasnutrientdeprivationoroxidativestress.Thismechanism moderates stress via “recycling” damaged or prolonged mitochondria for energyreplenishment while retaining the integrity of the cell. This study aimed to investigate the effects ofolanzapineonhypothalamicmitochondriaandparticularlymitophagy.Methods:HypothalamicNPY-expressingmHypOA-59neuronal cellswere culturedat37°C inaCO2 incubatorwithDMEM 5796, supplemented with 1% penicillin/streptomycin and 10% fetal bovine serum. Cells wereseededin6-wellplatesovernight,at70%confluencycellsweretreatedwithvariousdosesofolanzapineinserum-freeDMEMfor24hrs.CellswerewashedwithPBSandstainedwitheitherMitotrackerGreenFM(200nM)for30minutesorMitosoxred(5μM)for20minutes.PlateswerethenimagedforfluorescenceusingtheincucyteZOOMorDMi8fluorescentmicroscopeandthentrypsinizedforflowcytometryanalysis.Results:Our results demonstrate that olanzapine significantly increased mitochondrial mass with MitotrackerGreeninmHypOA-59cellsaftera24hrtreatmentinadose-dependentmanner;50μM(p<0.001),100μM(p <0.001), 150μM (p <0.001) compared to the control group. We also found a significant increase insuperoxideanion(O2-)withMitosoxredinadose-dependentmanner,50μM(p<0.05),100μM(p<0.01),150μM(p<0.05);anindicatorofmitochondrialreactiveoxygenspecies(ROS)andoxidativestress.Conclusions:Increasedmitochondrialmassornumberasaresultsofolanzapinetreatmentsuggestsanimpairmentinmitochondrialclearanceormitophagy.MitochondriaarethemainsourceofROSproductioninacellandthe most undesirable form of ROS is the superoxide anion (O2-). Therefore, olanzapine causesmitochondrial stress to the cell, whichmay inhibitmitophagy ultimately lead to apoptosis - cell death.Chronic hypothalamic ROS release is involved type 2 diabetes and other neurodegenerative diseases.Hence, our findings imply that olanzapine causes detrimental effects in the metabolic regulation ofhypothalamicneurons.

PosterSession2:Tuesday31stOctober 77

P36.Decreased5-HT2cRandGHSR1adimerizationbyolanzapinecontributestoincreasedhypothalamicNPYandobesityside-effectsAuthors:YinghuaYu,XiaoqiChen,TiantianJin,KatrinaWeston-Green,XueqinSong,KuiyangZhengandXu-FengHuangAffiliations: Jiangsu Key Laboratory of Immunity andMetabolism,Department of PathogenBiology andImmunology,XuzhouMedicalUniversity,Xuzhou,Chine;IllawarraHealthandMedicalResearchInstitute;SchoolofMedicine,UniversityofWollongong;DepartmentofEndocrinology,ZhongnanHospitalofWuhanUniversity,Wuhan,ChinaBackground:Bothantagonismofserotonin2creceptors(5-HT2cR)andactivationofghrelinreceptortype1a(GHSR1a)signallinghavebeenidentifiedasamaincauseofsecondgenerationantipsychotic(SGA)inducedobesity.Recently,the5-HT2cRwasreportedtoregulateGHSR1asignallingviaa5-HT2cRandGHSR1ainteraction.This study investigatedwhether theobesogenic SGAolanzapinealters this5-HT2cR/GHSR1a interaction,affectingorexigenicneuropeptidesignalinginthehypothalamus.Methods:Primaryhypothalamicneurons,mHypoA-59andmHypoA-NPY/GFPcellsweretreatedwitholanzapine(25and50μM),5HT2cRantagonist (SB242084,10,50and100μM)andolanzapine (50μM)+5HT2cRagonist(lorcaserin, 10 and 50μM). We used immunofluorescence and confocal Fluorescence Energy Transfer(FRET)technologytocharacterizetheinteractionof5-HT2cRandGHSR1ainhypothalamicneurons.FRETefficienciesforthesensitizedemission(SE)werecalculatedandanalysedbyFRET-SEWizardSoftware.TheGHSR1a signaling molecules, pAMPK, FOXO1, UCP2 and pCREB were measured by Western blot. TheorexigenicneuropeptideY(NPY)expressionlevelswerequantifiedfollowingolanzapineand/orlorcaserintreatmentsbytheFlexStation.Results:We found that the 5-HT2cR dimerized with the GHSR1a in primary hypothalamic neurons using FRETtechnology,whichenablesmeasurementofreceptordimerizationatasinglecelllevel.Olanzapineandthe5-HT2cRantagonist,SB242084,decreasedtheinteractionbetween5-HT2cRandGHSR1a,inturnactivatingGHSR1asignalling(pAMPK-UCP2-FOXO1/pCREB)inhypothalamicneurons.The5-HT2cRagonist,lorcaserin,counteractedthereducedinteractionbetween5-HT2cRandGHSR1acausedbyolanzapine.Furthermore,lorcaserin prevented olanzapine’s activation of GHSR1a signalling and orexigenic NPY levels inhypothalamicneurons.Conclusions:Taken together, these findings suggest that the inhibitory effect of olanzapine on 5-HT2cR andGHSR1adimerizationcouldbepreventedbya5-HT2cRagonist,whichrestoreshypothalamicNPYtonormallevels.Theseresultsmayhavebroaderimplicationsfortheuseofa5-HT2cRagonistinclinicaltrialstocounteracttheobesityside-effectsofSGAswithstrong5-HT2cRantagonisticprofiles.

PosterSession2:Tuesday31stOctober 78

P38.TheeffectsofelectricalstimulationandconductivepolymeronhypothalamicneuronsinpsychiatricdisordersAuthors:SitiNaquiaAbdulRahim,Xu-FengHuang,GordonWallace,KerryGilmoreandJeremyCrook

Affiliations: Intelligent Polymer Research Institute, Illawarra Health and Medical Research Institute,UniversityofWollongong;ARCCentreforExcellenceforElectromaterialsScience;CentreforTranslationalNeuroscience;DepartmentofSurgery,StVincentsHospital,UniversityofMelbourneBackground:The unique mechanical, electrical and chemical properties of conducting polymers (CPs), such aspolypyrrole(Ppy),makethesematerialsattractiveforbiomedicalapplications.Apreviousstudyhasshownamelioration of schizophrenia (Sz) deficits with in vitro electrical stimulation (ES) mediated by CP.However,themechanismselicitedbyESatthecellularandmolecularlevelremainunclear.Giventheroleof hypothalamus in the pathogenesis and treatment of psychiatric disorders, including the therapeuticeffectsofdeepbrainstimulationortranscranialdirectcurrentstimulation,wehavestudiedtheeffectofESandCPinaninvitrophencyclidine(PCP)modelofSz.Methods:PCP-treated anduntreated adultmousehypothalamic neuronswere seededonto Ppy filmsdopedwithdodecylbenzenesulfonate (DBS) and electrically stimulated for 8 hours/day over three days at 0.25mA/cm2 current density and 250 Hz frequency. Phenotypical assessment was performed usingimmunocytochemistryandneuronalmarkerswerequantifiedwithquantitativerealtimepolymerasechainreactionandflowcytometry.Results:Immunostaining showed that ES increased neurite outgrowth of the adult hypothalamic neurons,comparedtonon-EScontrols.ThemRNAexpressionofMAP2andDlg4,alongwithproteinexpressionofMAP2,were increased inES cells (P<0.05).PCP treatment significantly reduced themRNAexpressionofMAP2incellsculturedonstandardtissuecultureplastic,howeverthePCPtreatmentalongwithPCP+EStreatmentincreasedtheneuronalmRNAandproteinmarkersincellsculturedonPpy-DBS.Conclusions:ESviaPpy-DBSenhancesneuriteoutgrowthofhypothalamicneurons.Interestingly,Ppy-DBSaloneandincombination with ES, reversed the effect of PCP on the cells. This is consistent with reports of CPsamelioratingreducedneuriteoutgrowthsinSzknockoutmodels.ThisstudyconfirmstheeffectivenessofESandsuggeststhepromisingcapabilityofCPsinalleviatingneuraldeficitsinSzmodels.

PosterSession2:Tuesday31stOctober 79

P40.Symptomprofiles,hormones,andqualityoflifeinmajordepressivedisorderAuthors:TangAiLing(Claire),SusanJThomasandTheresaLarkinAffiliations:SchoolofPsychology,FacultyofSocialSciences,UniversityofWollongong;SchoolofMedicine,FacultyofScience,MedicineandHealth,UniversityofWollongongBackground:Qualityoflife(QoL)isemergingasabetterindicatorofhealththansymptommeasuresalone.Depressionisaheterogeneousconditioninvolvingphysicalandpsychologicalsymptoms,andsubstantial impairmentin QoL. However, little research has examined which symptom types have greatest impacts on QoL.Additionally,thereisalackofunderstandingabouttherolesbiologicalfactorsplayinQoLindepression.This study aimed to examine relationships between depressive symptoms and QoL. Additionally, theinterplaybetweencortisol,oxytocinandQoLwasinvestigatedindepression.ItwashypothesisedthatkeyhormoneslinkedtodepressionwoulddifferentiallypredictQoLlevels.Methods:Firstly, 570 community members completed the World Health Organization Quality of Life-BREFquestionnaire, encompassing Physical, Psychological, Social and Environmental domains; and the BeckDepression Inventory II, measuring psychological and physical symptom profiles. Secondly, 60 adultsmeetingDSM-5 criteria formajor depressive disorder (MDD) and60healthy controls providedmorningplasma samples and completed questionnaires. Cortisol and oxytocin were quantified using aMilliplexfluorescencemagneticbeadimmunosorbentassay.SymptomprofileswerecorrelatedwithQoL-domains.Between-group ANOVAs compared depressed with healthy participants. QoL domain scores werecorrelated with cortisol and oxytocin levels. Multiple regression analyses were performed to examinerelationshipsbetweenvariables.Results:In the community study, as hypothesised, relationships were found between QoL and symptomaticprofiles,anddifferentsymptomprofileswere foundtopredict specificdomains inQoL. In thebiologicalstudy,asexpected,participantswithMDDhadlowerQoLthanhealthycontrols.Additionally,cortisolandoxytocinlevelsweredifferentiallyassociatedwithspecificQoLdomains.OxytocinwaspositivelycorrelatedwiththeQoLdomainsofPsychologicalhealthandSocialrelationships.CortisolwasnegativelycorrelatedwithalldomainsofQoL.BothoxytocinandcortisoluniquelypredictedvarianceinQoLaftercontrollingforsymptomseverityanddemographicvariables.Conclusions:These findings provide new information about the relationships between specific types of depressivesymptomsonQoL.Additionally,thisstudyconfirmspreviousfindingsoflowerQoLinMDD,andprovidesnovel evidence for neuroendocrine pathways linked to QoL which may be affected in MDD. ThesepathwaysmayhelptoexplainthelargeburdenofMDDanditseffectsonQoL.Inconclusion,multifacetedapproachestoQoLinmentalhealthmayleadtogreaterunderstandingoftheunderlyingmechanisms,andin turn, to improved and tailored preventions and treatments. Further, limitations and suggestions forfutureresearcharediscussed.

PosterSession2:Tuesday31stOctober 80

P42.Problematiceatingbehavioursandweightgaininmajordepressivedisorder:TheroleofleptinAuthors:JessicaMills,SusanJThomas,TheresaALarkin,ChaoDengandNageshBPaiAffiliations: School of Medicine, Faculty of Science, Medicine and Health, University of Wollongong;IllawarraHealthandMedicalResearchInstituteBackground:Appetiteandweightchangesarecoresymptomsofmajordepressivedisorder(MDD),andthosewithMDDare at an increased risk of obesity, cardiovascular disease andmetabolic disorders. Understanding themechanisms of appetite dysregulation and overeating may allow for improved interventions aimed atpreventingweightgainandchronicdiseases inat-risk individuals.Leptinpromoteshungersatiety,andisassociatedwithmood.Leptindysregulationandresistancearenotedinobesity;howevertheroleofleptinin weight changes in MDD is not established. This study investigates relationships between leptin,depressivesymptomprofiles,appetite,problematiceatingbehavioursandweightchangesinMDD.Methods:Plasmaleptinlevels,psychopathologyandbiometricswerecomparedbetweenparticipantsmeetingDSM-5diagnosticcriteriaforMDD(n=63)andhealthycontrols(n=60).MDDparticipantsweresub-categorisedby their symptoms into those with increased, decreased or unchanged appetite and/or weight. EatingbehaviourstylesandfoodaddictionmeasureswereexaminedinasubsetofparticipantswithMDD,usingtheDutchEatingBehavioursQuestionnaireandtheYaleFoodAddictionScale.Results:Participants with MDD had significantly higher leptin levels than controls, and females overall hadsignificantly higher leptin levels thanmales. ParticipantswithMDDwith increased appetite/weight hadsignificantly higher leptin levels than thosewith decreased or unchanged appetite/weight. Leptin levelswerepositivelycorrelatedwithBMIandwaistcircumference.Leptinlevelswerealsopositivelycorrelatedwith Emotional and Restrained eating subscales of theDutch Eating BehavioursQuestionnaire, and theIncreasedfoodintakesubscaleoftheYaleFoodAddictionScale.OnequarterofthedepressedsubsetmettheYalecriteriaforfoodaddiction.Further,femalesreportedmorecomforteatingbehavioursthanmales.Conclusions:ThecurrentstudyprovidesnewinformationregardingrelationshipsbetweenleptinandsymptomprofilesinMDD.Additionally,novellinkswereidentifiedbetweenleptin,problematiceatingbehavioursandfoodaddiction.Theresultsindicatethatleptinisassociatedwithincreasedweight,appetiteandanthropometricrisk factors for cardiovascular disease and metabolic syndrome in MDD, particularly in females. Therelationshipsobserved in thecurrentstudy indicatepromisingareasof future research investigating riskfactorsforweightgainandpotentialearly interventionsaimedatpreventingweightgain inthoseatriskduetoMDD.

PosterSession2:Tuesday31stOctober 81

P44.AlteredfunctionalsegregationofinsulacortexinpatientswithtreatmentresistantschizophreniaAuthors:YeTian,ChadBousman,ChristosPantellisandAndrewZaleskyAffiliations:MelbourneNeuropsychiatryCentre,DepartmentofPsychiatry,TheUniversityofMelbourne;TheCooperativeResearchCentre(CRC)forMentalHealth;CentreforNeuralEngineering,DepartmentofElectricalandElectronicEngineering,UniversityofMelbourneBackground:Using resting-state functionalMRI (fMRI), insula cortex canbe subdivided into spatially contiguous sub-regionsthatarecharacterizedbydistinctpatternsof functionalconnectivitywiththecortex.Whileearlystudies indicate a bipartite subdivision comprising posterior and anterior sub-regions, recent studiesprovide evidence of a tripartite clustering inwhich anterior insula is further subdivided into dorsal andventral components. Given that insula is associated with psychological processes in perception, self-awareness and cognitive function, which is severely disturbed in patients with treatment-resistantschizophrenia (TRS).We aimed to test whether insula would demonstrate altered or absent functionalsegregationinthiscohort.Methods:Resting-state fMRIwasacquired in50TRSpatientsand52matchedcontrols.Aconnectional fingerprintwasmapped for each insula voxel by correlating its resting-state activity with all other cortical voxels.HierarchicalclusteringbasedonWard’s linkagewasthenusedtodelineateclusters individually.Clusterscomprised voxels that were functionally connected to common cortical targets, representing putativeinsula sub-regions. The optimal number of clusters was found with Silhouette criterion. To defineconsensus group-level clustering, Newman’s spectral community detection algorithm was employed tomapprobabilisticsegmentations.Between-groupdifferencesinthefunctionalconnectivityofsub-regionsweretestedusingvarianceandcluster-basedstatistics.Results:Cluster analysis indicated that the left and right insula each comprise two sub-regions in patients andcontrols;ananteriorsubregionthatisfunctionallyconnectedtothefronto-temporalcortexandaposteriorsub-regioncharacterizedbyparieto-occipitalconnections.Thisbipartitesubdivisionexhibitedsignificantlyless consensus across patients than controls (right: P=0.0038, left: P=0.002), suggesting altered insulasegregationinschizophrenia.Inpatients,theanteriorinsulawassignificantlymorestronglyconnected to sensory-motor and occipital cortex, while the posterior insula showed more extensiveconnectivitytoprefrontalcortex(PFWE<0.025).Thedysconnectivitybetweenanteriorinsulaandanteriorcingulatecortexwascorrelatedwithemotionalwithdrawal(r=-0.51,P<0.001).Conclusions:TRS patients have impaired functional coupling between anterior and posterior subdivisions and otherlarge-scale brain networks, including default mode network, central executive network, sensory-motornetwork as well as language/auditory processing related brain regions. These disturbances werewidespreadwithinandacrosshemispheresassociatedwithperceptual,emotionalandcognitivesystems,suggestingacrucialroleoftheinsulainthepsychopathologyofTRS.

PosterSession2:Tuesday31stOctober 82

P46.AssessmentofmultipleclassesofraregeneticvariantsinextendedfamilieswithbipolardisorderimplicatepostsynapticdensitygenesAuthors:ClaudioToma,AlexDShaw,Richard JNAllcock,AnnaHeath,KerrieDPierce,PhilipBMitchell,PeterRSchofieldandJaniceMFullertonAffiliations: Neuroscience Research Australia and Schizophrenia Research Institute, Randwick, NSW;SchoolofPathologyandLaboratoryMedicine,UniversityofWesternAustralia;BlackDogInstitute,PrinceofWalesHospital,SydneyBackground:Bipolardisorder(BD) isacomplexpsychiatricconditionwithhighheritability, thegeneticarchitectureofwhich likely comprises both common variants of small effect and rare variants of higher penetrance.Multiplex families with high density of illness provide an opportunity to map novel risk genes orconsolidateevidenceforexistingcandidates,byidentifyinggenescarryingpathogenicrarevariants.Methods:Weperformedwholeexomesequencing(WES)in15BDfamilies(117subjects:72affected,28unaffectedrelatives), augmentedwith copy number variant (CNV)microarray data, to examine contributions of: i)predicted pathogenic SNVs and likely-gene disruptive variants shared in affected versus unaffectedrelatives;ii)genome-wideburdenoflikely-gene-disruptivevariants;iii)denovovariants;iv)rareCNVs;andv) rare highly penetrant variants under family-specific linkage peaks. Linkage analysis and haplotypereconstructionusingWES-derivedgenotypesenabledeliminationoffalse-positiveSNVs,CNVinheritance,andcandidategeneprioritisation.Results:Rare predicted pathogenic variants shared amongst ≥3 affected relatives were over-represented inpostsynaptic density (PSD) genes (P=0.002, PBonf=0.024), with no enrichment in unaffected relatives.Burdenoflikely-gene-disruptivevariantswasnodifferentinaffectedversusunaffectedrelatives(P=0.24),but correlated significantlywithageofBDonset (P=0.017). Thenumberofdenovovariants inaffectedversus unaffected offspring was no different (P=0.23).We identified novel BD candidate genes: the X-linked IRS4witha stopmutation inall 5affected siblingswhichmappedwithina family-specific linkagepeak,anddeletionsacrosstheprotocadherinfamilyofgenes,whichacttomediateneuronalconnectivity.Conclusions:Genetic approaches that combine WES, CNV and linkage analyses in extended families is an effectivemethod for detection of potential pathogenic variation, pinpointing genes and pathways that maycontribute to thepathophysiologyofBD.Weobservedheterogeneitywithinandbetween families,withallelesofmodest effect and reducedpenetrancebeing themost likely geneticmodel.Ahighburdenofbrain-expressedloss-of-functionvariantsmayexpeditesymptomonsetinBDindividuals,andfurtherinvestigationofthisrelationshipwithothermeasuresofBDseverityarewarranted.

PosterSession2:Tuesday31stOctober 83

P48.Sex-specificassociationsofandrogenreceptorpolyglutaminerepeatlengthwithtestosteroneandstresssymptomsinschizophreniaAuthors:SamanthaOwens,TertiaDPurves-Tyson,ThomasWWeickertandCynthiaShannonWeickertAffiliations: Schizophrenia Research Laboratory, Neuroscience Research Australia; School of Psychiatry,FacultyofMedicine,UniversityofNewSouthWales.Background:Shorterandrogenreceptor(AR)polyglutamine(CAG)repeatlengthconfersmoreefficientARfunctionandis associatedwith lower circulating testosterone andmore depressive symptoms inmales. Inmenwithschizophrenia, testosterone is associated with negative symptoms and impaired emotion processing,suggesting that androgen signalling may be involved. We hypothesised that the relationship betweencirculatingtestosteroneandCAGrepeatlengthwouldbedisruptedinschizophreniaandshorterCAGrepeatlengthwouldbeassociatedwithmorenegativeandemotionalsymptomsinschizophreniapatients.Methods:Serumtestosteronewasmeasuredin97(59male/38female)schizophreniapatientsand87(46male/41female) healthy controls. CAG repeat length was determined from genomic DNA using capillaryelectrophoresis. Symptom severity was assessed using the Positive and Negative Syndrome Scale andnegative emotional states were evaluated using the Depression and Anxiety Stress Scale (DASS).Spearman’scorrelationswereperformedbetweenCAGrepeat lengthandperipheraltestosteronelevels.SymptomandemotionalstateratingswereanalysedbyCAGrepeatlengthgroup(short≤21/long>21)andsexusingmultivariateanalysisofvariance.Results:CirculatingtestosteronelevelsandCAGrepeatlengthweresignificantlyandpositivelycorrelatedinmalecontrols (ρ=0.429, p=0.008) and female patients (ρ=0.429, p=0.01), but were not correlated in femalecontrols (ρ=-0.163, p=0.322) ormale patients (ρ=0.101, p=0.454). Therewas a trend for a CAG repeatlength x sex interactiononDASS subscale scores [V=0.078, F(3,88)=2.491, p=0.065]. Stress scoresweresignificantly higher in male patients with short compared to long CAG repeat lengths [t(55)=2.436,p=0.018].Conclusions:Sex-specific alterations of the relationship between CAG repeat length and testosteronewere found inschizophrenia patients and may indicate that abnormal androgen signalling contributes to diseasepathogenesis.SexsteroidmodulatingtherapiesmaybebeneficialforstresssymptomsinasubsetofmaleschizophreniapatientswithmorerobustARsignalling.

PosterSession2:Tuesday31stOctober 84

P50.DecreasedserumacidlevelsaftertreatmentindrugnaivebipolarpatientsduringamanicepisodeAuthors:Jing-XuChen,Li-GangZhang,Hong-MeiChen,Yun-LongTan,Fu-DeYangandXu-FengHuangAffiliations:BeijingHui-Long-GuanHospital,PekingUniversity,China;SchoolofMedicine,IllawarraHealthandMedicalResearchInstitute,UniversityofWollongongBackground:Evidence suggests that UA levels may contribute to the pathophysiology and therapeutics of bipolardisorder(BPD). The aimof this studywas to evaluatewhetheruric acid(UA) levelswere associatedwithclinicalpropertiesandthechangesinUAlevelsaftertreatmentinBPDduringthemanicepisode.Methods:Drug-naive, first-episodemanicpatients (34men,43women)and76ages-andgender-matchedhealthysubjectswereenrolled.YoungManiaRatingScale(YMRS)andserumUAlevelswereevaluatedatbaselineandattheendof8-weektreatmentwithquetiapineandsodiumvalproateinpatients.Results:UAlevels inmanicphasewerehigherthanthose inremittedphasebutallofthemhadhigherUAlevelscompared to controls (378.55±99.08, 323.57±73.53, 290.89±72.18umol/L, respectively). No significantrelationwasfoundbetweenYMRSscoresandUAleveleitheratbaselineorattheendpoint.WhiletherewasasignificantcorrelationbetweenthedecreaseinUAlevelsandthatinYMRSscoresinthesepatients(r=0.250).Conclusions:OurresultssuggestthatserumUAlevelsmightnotonlybeastatemarkerofseverityofmaniabutalsobeatraitmarkerinbipolarpatientsanditmaybeanimportanttargetfordevelopingimprovedtherapeutics.

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