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Au)smSpectrumDisorders

-anupdate

Maj-Bri<Posserud,MD,PhD

HaukelandUniversityHospital

Overview

•  Stateortraitandthedualityoflight–  Thecurrentdiagnos)csystem

•  Implicitassump)onsandimplica)onsforASD

•  DSM-5changes

•  Consequencesofthe”either–or”stance•  Thenuisanceofimpairmentandthediagnos)cdilemma

•  Comorbidityandimpairment•  TheESSENCEmodel

•  Implica)onsfortreatmentandprognosis

•  Newmedicaltherapeu)calapproaches

Par)cleorWave?

Electrondiffrac)onpa<ern. www.physicstogo.org

Stateortrait?

State

•  Discrete•  Separate•  Dependent•  Categorical

Trait

•  Con)nuous•  Overlapping•  Inherent•  Dimensional

Implicitassump)onsinthecategorical

classifica)onsystem:

•  Disordersareatsomeleveldiscreteen))es.Differingfromnormalityinkindratherthanbydegree

•  Thedisorderasadysfunc)on.Impairmentisadiagnos)cfeature,linkingdisordertocons)tu)onaldysfunc)on

•  Theendogenousnatureofdisorders.Disordersareseenascharacteris)csoftheindividualratherthanaresultoftheinterac)onbetweentheindividualandtheenvironment

Sonuga-Barke,1998

DSM-IVdiagnos)ccriteria

•  «qualita)veimpairmentinsocialinterac)on»

•  «qualita)veimpairmentsincommunica)on»

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Copyright restrictions may apply."

Constantino, J. N. et al. Arch Gen Psychiatry 2003;60:524-530.

Distribution of Social Responsiveness Scale (SRS) scores as a function of sex (n = 1576)

0

500

1000

1500

2000

2500

3000

3500

4000

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42ASSQ score

Parents

Teachers

ASSQsymptomdistribu0on

PosserudMB,LundervoldAJ,GillbergC.JChildPsycholPsychiatry.2006

WheelwrightS,Baron-CohenS,GoldenfeldN,DelaneyJ,FineD,SmithR,WeilL,WakabayashiA.

BrainResearch,2006

SystemizingQuo0ent-Revised

Copyright restrictions may apply."

Lundstrom, Chang, Råstam, Gillberg, Larsson, Anckarsäter, Lichtenstein . Arch Gen Psychiatry 2012;69:46-52.

Estimates of Genetic and Environmental Effects for the 4 Cutoffs of ASD symptom levels

Thevalidityofcategories«Diagnos)ccategoriesdefinedbytheirsyndromesshouldberegardedasvalidonlyiftheyhavebeenshowntobediscreteen))eswithnaturalboundariesthatseparatethemfromotherdisorders»

«valid—meaning“well-founded…sound…againstwhichnoobjec)oncanfairlybe

brought”»

«Atpresentthereisli<leevidencethatmostcontemporarypsychiatricdiagnosesarevalid….Thisdoesnotmean,though,thatmostpsychiatricdiagnosesarenotusefulconcepts.Infact,manyofthemareinvaluable.But,becauseu)lityogenvarieswiththecontext,statementsaboutu)litymustalwaysberelatedtocontext,includingwhoisusingthediagnosis,inwhatcircumstances,andforwhatpurposes.»

«Ifnodetectablediscon)nui)esinsymptomsarefoundinlargetractsoftheterritoryofpsychiatricdisorder,itislikelythat,soonerorlater,ourexis)ngtypologywillbeabandonedandreplacedbyadimensionalclassifica)on»

AmJPsych,2003.RobertKendell,M.D.,AssenJablensky,M.D.

DSM-5Au)smSpectrumDisorder

Dimensionalityintroduced•  onespectrum

•  severitygradient-3levels–  Requiringverysubstan)alsupport

Criteria:A.  Persistentdeficitsinsocialcommunica)onandsocialinterac)on

acrosscontexts

B.  Restricted,repe))vepa<ernsofbehavior,interests,orac)vi)es

C.  Symptomsmustbepresentinearlychildhood

D.  Symptomstogetherlimitandimpaireverydayfunc)oning

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DSM-5Au)smSpectrumDisorder

Dimensionalityintroduced•  onespectrum

•  severitygradient-3levels–  Requiringverysubstan)alsupport

Criteria:A.   Persistentdeficitsinsocialcommunica)onandsocialinterac)on

acrosscontextsB.  Restricted,repe))vepa<ernsofbehavior,interests,orac)vi)es

C.  Symptomsmustbepresentinearlychildhood

D.  Symptomstogetherlimitandimpaireverydayfunc)oning

DSM-5Au)smSpectrumDisorder

Dimensionalityintroduced…

…buts)llcategoricallyseparatefrom

Normality!

…andimpairmentexplicit!

Pseudo-dimensionalview Dimensionalview

«Humanbeingsarenaturalcategorisers»

•  Categorisingskillspresentintheinfantby3-4months

•  Thecategorisa)oninfluencespercep)on–  Increaseddis)nc)venessbetweencategories–  Increasedsimilaritywithincategories

Sonuga-Barke,1998

Brightness

“thepupillaryphysiologicalresponsereflectsthesubjec)vepercep)onoflight”Laeng,Endestad.PNASfeb2012

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Where is disordered?

HieronymousBosch,GardenofEarthlyDelights

ASD in the Bergen Child Study

•  High scorer ASSQ: 2.7% •  DAWBA: 0.48% •  DISCO minimum prevalence: 0.21%

–  Estimated 0.87% •  Probably > 1% if including higher functioning children with

“traits” and considering false negatives

•  Norway 2015: 1.1% of children above 12 yrs of age (Pål Surén, personal communication)

StateorTrait–orboth?

Implicitassump)onsinthecategorical

classifica)onsystem:

•  Disordersareatsomeleveldiscreteen))es.Differingfromnormalityinkindratherthanbydegree

•  Thedisorderasadysfunc)on.Impairmentisadiagnos)cfeature,linkingdisordertocons)tu)onaldysfunc)on

•  Theendogenousnatureofdisorders.Disordersareseenascharacteris)csoftheindividualratherthanaresultoftheinterac)onbetweentheindividualandtheenvironment

Sonuga-Barke,1998

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Impairment

•  Intrinsicrequirementfordiagnosis

•  However,thesamedegreeofsocialinep)tudewillleadtovaryingdegreesofimpairmentdependingoncontext

à Thediagnosisisnotconstant!

•  Althoughvitalfordiagnosis,unspecificandnotrelatedtotheunderlyingtaxonortrait

HeatherKuzmich America�sNextTopModel2007

«I�msorry.Myeyeswander.I�vebeenworkingreallyhardtokeepeyecontactforawhile»

A different perspective

ASPIESFORFREEDOM.COM

“Weknowthatau-smisnotadisease,andweopposeanya5emptsto"cure"someoneofanau-smspectrumcondi-on,oranya5emptstomakethem'normal'againsttheirwill.Wearepartofbuildingtheau-smculture.Weaimtostrengthenau-smrights,opposeallformsofdiscrimina-onagainstaspiesandau-es”

“arealcurewouldbeunethical,andthecurrentmythofthecureisharmful”

“…the"au)smastragedy"pointofview…carrieswithittheideathatapersonissomehowseparablefromau)sm,andthatthereisa"normal"persontrapped

"behind"theau)sm”

“Beingau)s)cissomethingthatinfluenceseverysingleelementofwhoapersonis-

fromtheinterestswehave,theethicalsystemsweuse,thewayweviewtheworld,

andthewayweliveourlives.Assuch,au)smisapartofwhoweare”

“To "cure" someone of autism would be to take away the person they are, and replace them with someone else.”

“…fundingfor"cure"researchisunlikelytoeverproducearesult.Inthemean)me,

supportservicesforau.s.cpeopleareunderfunded…”“Thecurementalityalsoinfluencesculturaltreatmentofau)s)cpeople.Many

parentsfocusontheideaoffindingacurefortheirchild,andmayneglectactualhelp

andsupportintheprocess”

“..teachingchildrenthattheyare"broken"andneedtobe"fixed"haslong-term

consequencesfortheirmentalhealth.”

Implicitassump)onsinthecategorical

classifica)onsystem:

•  Disordersareatsomeleveldiscreteen))es.Differingfromnormalityinkindratherthanbydegree

•  Thedisorderasadysfunc)on.Impairmentisadiagnos)cfeature,linkingdisordertocons)tu)onaldysfunc)on

•  Theendogenousnatureofdisorders.Disordersareseenascharacteris-csoftheindividualratherthanaresultoftheinterac)onbetweentheindividualandtheenvironment

Sonuga-Barke,1998

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“Idon'tknowwhat"normal"is,butIknowthatpeoplelikemearetheminority,notthemajority.Sothat,inoursociety,iswhatcons)tutes"abnormal"(ratherinsul)ngIwouldsay!).“

LukeJackson,

Freaks,GeeksandAsperger’sSyndrome:Ausersguidetoadolescence

Personalityordisorder?

•  Schizoid,avoidant,obsessive-compulsivePD•  commoninadultswithASDinchildhood

•  Broaderau)smphenotype•  OgenfoundinASDparentsandsiblings

•  Loner,lonewolf•  Ogenfoundin(distant)rela)ves

•  Hermit,recluse,hikikomori(Japan)

•  Geeks,nerds

Categoricalstance

•  Over/underdiagnosingunavoidable!– Restric)vediagnos)ccriteria

•  Manychildrenwithimpairmentwillgoundiagnosedandnotreceivehelp

– Widediagnos)ccriteria•  Manychildrendiagnosedwholaterwillfunc)onwellandshowsocialabilitywithinthenormalrange

•  Clearmessage

•  (over)Simplifying

Diagnosingandtes)ngASD

•  Developmentaldisorder•  Butlowgeneralawarenessofsocialdevelopment

•  BorderlinecasesAREchallenging!•  Neuropsychology

•  Noverygoodtestsofsocialfunc)on…•  Me)culous,slow,overlydetailed

•  Repe))ve,stereotypepa<erndifficultto”see”inhigh-

func)oningindividuals

•  UnevenprofilecommonBUTnotypicalIQprofile!

Jointa<en)on

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Ismomfollowing? Socialdevelopmentintoddlers

•  Socialimita)on-1month

•  JointA<en)on-6-7month

•  GazeMonitoring-9month

•  SocialReferencing-10month

•  PretendPlay-18month

Diagnosingandtes)ngASD

•  Developmentaldisorder•  Butlowgeneralawarenessofsocialdevelopment

•  BorderlinecasesAREchallenging!•  Neuropsychology

•  Noverygoodtestsofsocialfunc)on…•  Me)culous,slow,overlydetailed

•  Repe))ve,stereotypepa<erndifficultto”see”inhigh-

func)oningindividuals

•  UnevenprofilecommonBUTnotypicalIQprofile!

Diagnosingandtes)ngASD

•  Developmentaldisorder•  Butlowgeneralawarenessofsocialdevelopment

•  BorderlinecasesAREchallenging!•  Neuropsychology

•  Noverygoodtestsofsocialfunc)on…•  Me)culous,slow,overlydetailed

•  Repe))ve,stereotypepa<erndifficultto”see”inhigh-

func)oningindividuals

•  UnevenprofilecommonBUTnotypicalIQprofile!

Subthresholdcases

•  Diagnosismaydomoreharmthangood•  Lackofimpairment

•  Dilu)ngtheconceptofASDiftooliberal

•  Prognosisprobablygood?!?•  Butmayencounterdifficul)es

•  Manyfeelostrasized

•  Lifelongsearchforunderstanding–whyamIdifferent?

à Psychoeduca)onà Watchfulexpectancy

•  Intervenewhennecessary

Clearupmisunderstandings!

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Dealingwithdichotomy

•  Diagnos)clabels,notgravestoneepitaphs•  Bepragma)c

•  Psychoeduca)on•  Includingdimensionality

•  UnderstandingandAcceptanceforall•  Respecttheindividualandhis/herways

•  IndividualizedapproachFernellE,HedvallÅ,WesterlundJ,HöglundCarlssonL,ErikssonM,BarnevikOlssonM,

HolmA,NorrelgenF,KjellmerL,GillbergC.ResDevDisabil.2011

DarrouC,PryR,PernonE,MichelonC,AussillouxC,BaghdadliA.Au)sm.2010

OtherDSM-5changes

•  Thetriadofimpairmentsbecomesadyad

–  Communica)onimpairmentisremovedasseparate

criterion

•  Communica)onincludedinsocialimpairment

•  Languageproblemsdiagnosedseparately

•  Newdisorder:Socialcommunica)ondisorder

•  ADHDandASDmaybecomorbid

•  Hyper-orhyporeac)vitytosensoryinputorunusualinterestsinsensoryaspectsofthe

environment

ASDandcomorbidity

Background

•  Youthwithau)smspectrumdisorders(ASD)haveahighlevelof«comorbid»problems.

•  Follow-upstudieshavedemonstratedpooradultfunc)oningforchildrenwithASD

•  Thestudiesare«historical»•  Largeandcon)nuouschangesindiagnos)ccriteriaand

conceptofASD.

•  Heterogeneousgroup

•  Comorbidproblems/disordersinfluencesboth:•  disability/leveloffunc)oning•  serviceuse,diagnos)cworkandtreatment

ASD,comorbidityandimpairment

•  Howcommonis«pure»ASDinapopula)onbasedsample?

•  Is«pure»ASDassociatedtoimpairment?

•  CouldtheextensivecomorbidityseeninclinicalASDbeduetoreferralbias?–  IfpureASDdoesnotrelatetoimpairment,thiswouldresultina«Berksonbias»

•  TowhatdegreeisimpairmentinASDcausedbycomorbidproblems?

•  Gendereffects?

Bergen Child Study Correlations between problem domains:

Emo Peers ASSQ Lang Tics OCD CD ODD Ina< Hyper EatD

SDQemo 1 0.40 0.45 0.30 0.20 0.41 0.38 0.43 0.38 0.32 0.18

SDQpeers 0.40 1 0.60 0.40 0.26 0.27 0.36 0.36 0.42 0.37 0.18

ASSQ 0.45 0.60 1 0.57 0.53 0.51 0.46 0.52 0.56 0.60 0.30

Lang 0.30 0.40 0.57 1 0.36 0.32 0.29 0.33 0.51 0.42 0.15

Tics 0.20 0.26 0.53 0.36 1 0.29 0.23 0.28 0.32 0.38 0.18

OCD 0.41 0.27 0.51 0.32 0.29 1 0.22 0.31 0.34 0.34 0.35

Conduct 0.38 0.36 0.46 0.29 0.23 0.22 1 0.67 0.50 0.53 0.14

ODD 0.43 0.36 0.52 0.33 0.28 0.31 0.67 1 0.56 0.59 0.15

Ina<en)on 0.38 0.42 0.56 0.51 0.32 0.34 0.50 0.56 1 0.66 0.11

Hyperac)vity 0.32 0.37 0.60 0.42 0.38 0.34 0.53 0.59 0.66 1 0.16

Ea)ng

disorder0.18 0.18 0.30 0.15 0.18 0.35 0.14 0.15 0.11 0.16 1

Emo Peers ASSQ Lang Tics OCD CD ODD Ina< Hyper

1 0.45 0.46 0.31 0.23 0.39 0.32 0.35 0.36 0.24

0.45 1 0.69 0.43 0.30 0.29 0.44 0.43 0.46 0.37

0.46 0.69 1 0.57 0.55 0.41 0.53 0.58 0.62 0.56

0.31 0.43 0.57 1 0.31 0.29 0.26 0.24 0.52 0.28

0.23 0.30 0.55 0.31 1 0.29 0.24 0.26 0.35 0.36

0.39 0.29 0.41 0.29 0.29 1 0.18 0.23 0.29 0.24

0.32 0.44 0.53 0.26 0.24 0.18 1 0.78 0.52 0.60

0.35 0.43 0.58 0.24 0.26 0.23 0.78 1 0.54 0.66

0.36 0.46 0.62 0.52 0.35 0.29 0.52 0.54 1 0.63

0.24 0.37 0.56 0.28 0.36 0.24 0.60 0.66 0.63 1

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Impairmentandcomorbidproblems:

Ina<en)on

Hyperac)vity

ODDsymptoms

Learningproblems

Emo)onalproblems

Explainedmorethan60%of

theimpairment!

EarlySymptoma0cSyndromesElici0ngNeurodevelopmentalClinicalExamina0ons-Gillberg2010

Christopher Gillberg, 2010

ESSENCEconceptMajorproblems(leadingtocontactwithhealthservices)inoneor(mostly)severalofthefollowingdomainsbeforetheageof5:

•  Generaldevelopment

•  Motorcontrol/Percep)on/Sensoryproblems

•  Language/Communica)on

•  Ac)vitylevel/impulsecontrol

•  A<en)on

•  Socialinterac)on

•  Behavior

•  Mood/temper

•  Sleep

•  Ea)ng

ASDIDADHD

ODD

SLI,dyslexia…

Why ESSENCE? •  Humans are natural categorisers, our categories influence

the way we think and what we percieve! •  Builds on neurodevelopment and networkbased

understanding of the brain/psyche •  Recognizes that early diagnostics is difficult. •  Abroad approach is always required!

•  A narrow approach will probably not help. •  Specialized clinics counterproductive – collaboration and

coordination of services vital!

•  Lifelong perspective AlessandroSerre{,ChiaraFabbri

Sharedgene0csamongmajorpsychiatricdisorders

TheLancetVolume381,Issue987520131339-1341

h<p://dx.doi.org/10.1016/S0140-6736(13)60223-8

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Thep-Factor

”thepdimensionmayrepresentlowtohigh

psychopathologyseverity…Thiscollec)onof

observa)onsimpliesthatpisadimensionthat

unitesalldisordersandhasneurologicalroots.”

Caspietal.2013,ClinicalPsychologicalScience

5-15-FTF–FivetoFigeen

•  www.5-15.org•  Coversawiderangeofimportantassociated

neuropsychiatricproblems•  Sensoryproblems

•  Motor(fineandgross)problems

•  Space,)meandbodyawarenessproblems

•  Perceptualproblems

•  Parentques)onnaire•  Nordicnorms

•  Freelyavailable•  Nowdeveloping2-5andadultretrospec)vereport

5-15–exampleitems:

Hardiffusoppfatningav)d,foreksempelomtrenthvormyeklokkaer,omdeterformiddagellere<ermiddag,omdeter)d

forågå)lskolenellererhelg.

Harusikkerkroppsoppfatning(usikkerpakroppensstørrelsei

forhold)lomgivelsene,støtermotellervelter)ngutenåmene

det).

Støterbor)andremenneskeritrangeromellernårdemøtes.

DevelopmentalCoordina)onDisorder”theCinderellaofdevelopmentaldisorders”

•  ”Clumsychildren”(butabout2/3con)nuehaving

problemsasadults)

•  1-5%...•  Social,academic,familyproblems

•  Feedingproblems

•  Languageproblems

•  Accidents•  Secondaryhealthproblems

•  Mentalhealth–anxiety,isola)on,depression

•  Soma)chealth-pain,damages,wearandtear

h<p://www.cmaj.ca/content/suppl/2006/08/24/175.5.471.DC1/why-missiuna-online_appendix_2.pdf

Missiuna,Gaines,&Soucie.CMAJ2006

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Whyeveryofficeneedsatennisball:Anewapproachtoassessingtheclumsychild MotorproblemscommoninASD

•  Hypotoniain51%•  Apraxiain34%•  Generalmotordelay

•  Poorcoordina)on•  Posturalproblems

•  Reducedmobility

•  Stereotypicalmovements

Matsonetal.2011,RIDD

5-15exampleitemsonmotorskills:

Harproblemermedåkasteellertaimotball.

Harproblemermed/likerikkeådeltailagidre<

somfotball,håndballellerbasketball

Snublerellerfalleroge.

Harproblemermedåsamle,håndtereeller

se<esammensmå)ng.

Sølerogepåklærneellerbordetnårhan/hun

spiser.

Neurological”sogsigns”

•  Dysdiadochokinesia•  Poorsta)canddynamicbalance

•  Poorcoordina)on(alterna)ngmovements)

•  Muscletonus(hyper/hypotonic)

•  ”Medbevegelser”

•  Tremor

•  Rigidity•  ”Uhensiktsmessigebevegelser”

•  Poorpropriocep)on•  Ataxia,apraxia•  Sensorydysfunc)on•  Troublejudgingdistances/coordina)ng

Otherimportantcomorbidi)es

•  Learningdifficul)es

•  ADHD•  NB!Disregardcompletelyabilitytoconcentrate/focuson

preferred/favouriteac)vi)es

•  MayperformexpertlyatCPT,TOVAetc,butatenourmous

expense

•  Socialphobia,phobiasandfears•  CBTworks,butneedsmodifica)on.E.g.CopingCat,ASDCoolkids

•  Tics/Toure<es/OCD•  Egodystoniamaybeambivalent…

•  Depression

NocureforASD…?

Vilken förkylningstyp irriterar digmest?

Förkylda män som uppträder som att de fåtten dödlig sjukdom.

Föräldrar som släpar med sina förkylda barnöverallt.

Arbetskamrater som går till jobbet när de ärförkylda.

Hypokondrikerna som hela tiden måsteprata om hur de mår och sjukskriver sig såfort de blir lite förkylda.

Snuviga människor som inte har vett att hållaför mun och näsa när de hostar och nyser påbussen eller tåget.

Förkylda människor på långresan som intetar hänsyn till medpassagerarna genom attbada i handsprit och försöka snyta sig på toa.

RÖSTA VISA RESULTAT

Dela FACEBOOK 18394 TWITTER 54 MEJLA

O

FAKTA: AUTISM

13 SEPTEMBER 2013 06:04

Svenskar kan ha knäcktautismgåtan

Svensk forskning kan leda till bot mot autism.Lovande studier har gjorts på både djur och människor.– För tio år sen hade jag sagt att det var omöjligt. Nu har jag sett det med egna

ögon. Då måste man ändra uppfattning, säger psykiatriprofessor ChristopherGillberg.

mkring 95 000 svenskarlider av autism. Autismkan vara mycket

handikappande och har längeansetts obotligt. Men ny svensk-fransk forskning visar att vissaformer av autism, orsakade avgenförändringar, kan behandlas.

Forskarna upptäcker löpandefler genförändringar. Nyligen harman börjat screena svenskaautistiska barn. Ungefär 20procent får i dag veta att de hargenförändringar, men den andelenökar hela tiden. Nästa år är detsannolikt 25 procent, trorChristopher Gillberg, som ärprofessor i barn- ochungdomspsykiatri vid Göteborgsuniversitet. Han och andraautismforskare har nyligen skrivitom detta i tidskriften Naturemedicine och på fredagpresenterar forskaren ThomasBourgeron de nya rönen vidGillbergcentrum i Göteborg.

Uppkopplingen strular

Genförändringarna leder till att olika proteiner i hjärnan inte fungerar som deska. Förenklat kan man säga att proteinernas felfunktion stör nervcellerna ihjärnan, hindrar signalerna i hjärnan från att gå fram ordentligt.

- Försök på både djur och människor med autism visar att man inte får den

ERBJUDANDE: Prova 2 nummer avMin Hälsa för 29 kr Få inspirationoch tips för ett skönare liv!

Räkna ut ditt BMI –hur hälsosam är du?BMI-test Se resultatet här!fungerar för både män och kvinnor.

TEST: Hur fet är dupå världsskalan?

LOGGA IN

SÖK PÅ HÄLSOLIV

sök på hälsoliv

HÄLSA VIKT PSYKOLOGI TRÄNING SÖMN SEX & RELATIONER

AN

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NS:

En procent av Sveriges befolkning harnågon form av autismspektrumtillstånd.Typiskt är att man har svårt med ömsesidigsocial kommunikation och interaktion samtbegränsade repetitiva beteenden,intressen och aktiviteter.Autism beror ofta på kombinationer avvariationer/mutationer i arvsmassan. Oftafinns då autistiska drag i släkten.Ibland kan infektioner eller andra skadorunder fosterlivet leda till autism. D-vitaminbrist hos mamman är en ny ochomdiskuterad riskfaktor förautismutveckling.

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FragileX•  MostcommoninheritedcauseofID

•  Ca1/10.000

•  Largestsingle-genecauseofASD•  FMR1atXchromosomewithCGGrepeats

–  45-54greyzone–  55-200premuta)oncarriersàtremor,ataxia,headache,anxiety,hypertension(1-3/1000)

•  Produc)onofFMRPstopsinfullmuta)on•  FMRPmainfuncionistonega)velyregulateproteintransla)onatthesynapse

•  Metabotropicglutamaterecareupregulatedàexaggeratedlong-termdepression

GABAfuncioninFragileX

•  ImbalanceglutamateandGABA

•  GABAsystemdownregulated•  Oversensi)vitytosensorys)muli

•  Seizures•  Anxiety,socialwithdrawal

à GABAagoniststriedintreatment•  Acamprosate(Campral®alkoholavhengighet),

Ganaloxone(analogofallopregnanolone),Gaboxadol,

Vigabatrin,Arbaclofen…

THEGABAEXCITATORY/INHIBITORYDEVELOPMENTAL

SEQUENCE:APERSONALJOURNEYYehezkelBen-Ari

Evolu)onaryshigfromE-GABAtoI-GABA

Oxytocinpeakatbirthtoinducelabour

•  ExtremelylowCliclevelsàstrong

GABAmediatedinhibitoryoverweight•  Anoxyprotec)on•  Painkiller•  SignalthatshigsfetallyhichicCllevelstoadultlowicCllevels?

•  Atypicalagita)veresponsetobenzodiazepinesclassicalinASD

Bumetanide

NKCC1antagonist

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”Mighttheoxytocin-mediateddeliveryshig

beasignalthatresetstheclockleadingto

long-las)ngconsequencesifitfails?”

Tyzioetal.Sciencefeb.2014

Summary

•  ASDisaheterogeneouscondi)on•  Bothatraitandstate(s)

•  Milderformsareprevalentandmergeinto

”normality”•  Flexibilityindiagnos)cprac)ceisimportant

•  Comorbidi)esoverlookedbutprobablycrucial

forQoLandprognosis

•  Newknowledgefromneurosciencegenerates

exci)ngpossibletargetsfortreatment

Thankyou!