White matter abnormalities in first episode psychosis: a DTI study

105 Pages·2013·1.63 MB·English

EurArchPsychiatryClinNeurosci(2013)263(Suppl1):S7–S111
DOI10.1007/s00406-013-0433-0
ABSTRACTS
4th European conference on schizophrenia research: together
for better treatment and care
PL-01 Toward new approaches to classifying psychotic emphasis to heterogeneity andunmet therapeutic needs. At the psy-
chopathology level this involves deconstructing the syndrome into
spectrum disorders: the NIMH Research Domain
pathologydomainssuchasavolitionorimpairedcognition.Asetof
Criteria Project
suchdimensionsispresentedinSection3ofDSM-5.Asecondpar-
adigm involves deconstruction into phenotypes assessed with
PL-01-001 neuroimaging,electrophysiologyorneuropsychologymethods.These
Towardnewapproachestoclassifyingpsychoticspectrum measures may ‘‘map on’’ to the behavioral constructs that NIMH is
disorders:theNIMHresearchDomainCriteriaProject developing as an alternative approach focused at the neural circuit
level. A third paradigm involves the life course of mental illness
B.N.Cuthbert(NIMH-NationalInstituteofMentalHealth, evolvement with stages for primary prevention and early detection
Bethesda,USA) withsecondaryprevention.Therapeuticdiscoveryforthetwostages
is substantially different from therapeutic development aimed at
Abstract: Clinical research over the past several years has increas- treating a fully expressed psychotic disorder. A developmental,
ingly revealed marked heterogeneity and excessive co-morbidity of interactive model integrating causal pathways and stages and
psychiatric disorders as currently defined. Recent studies have also includingdifferentialdiagnosisofdisordersassociatedwithpsychosis
demonstratedsignificantoverlapsingeneticriskacrossthespectrum willbepresented.Implicationsfornoveltherapeuticdevelopmentwill
of psychotic disorders, as well as across mood-anxiety disorders. bediscussed.
These issues represent barriers to accurate diagnosis and the devel- Policyoffulldisclosure:WilliamCarpenterreceivedgrants/research
opment of appropriately focused treatments. In response to such supports from NIH and Stanley Medical Research Institute. For one
concerns,theNationalInstituteofMentalHealth(NIMH)developed consultationWilliam Carpenter receivedafeefromRoche. William
the Research Domain Criteria project (RDoC), to ‘‘develop, for CarpenterreceivedfinancialsupporttoattendtheECSRfromESAS.
researchpurposes,newwaysofclassifyingmentaldisordersbasedon
dimensions of observable behavior and neurobiological measures.’’
This talk will summarize the rationale and current status of RDoC,
PL-03 Structure and function of the human brain
withanemphasisonhowresearchwithintheRDoCframeworkcan
contributetonewwaysofparsingthespectrumofpsychoticdisorders at the level of receptors and neural systems: a basis
and to the development of more precisely targeted preventive and for psychiatric research
treatmentinterventions.
Policyoffulldisclosure:None.
PL-03-001
Structureandfunctionofthehumanbrainatthelevelof
receptorsandneuralsystems:Abasisforpsychiatricresearch
PL-02 Shifting paradigms for therapeutic discovery
K.Zilles(RWTHAachenUniversityDepartmentofPsychiatry,
PL-02-001 Aachen,Germany)
Shiftingparadigmsfortherapeuticdiscovery
Abstract:Transmitterreceptorsarekeymoleculesofneurotransmis-
W.T.CarpenterJr.(UniversityofMarylandSchoolofMedicine, sioninthebrain.Theyplayacrucialroleinvariouspsychiatricand
PsychiatricResearchCenter,Baltimore,USA) neurological diseases. The analysis of the regionally heterogeneous
expression of transmitters and receptors not only provides novel
Abstract:Schizophrenia,asclassifiedinICDorDSM,isadisorder. insightintothemolecularbasisofinformationprocessinginthebrain,
The assumption that schizophrenia is a unitary disease entity per- butisaprerequisiteforunderstandingthepathophysiologicalmech-
meatesmostresearchdesigns,andregulatorybodiesapprovingdrugs anisms underlying impaired brain functions. Moreover, the regional
verify efficacy for thediagnostic class rather thanspecific symptom heterogeneity of receptor expression is important for understanding
domains.Butschizophreniahasthestatusofaclinicalsyndromewith the effects and side-effects of widely used drugs on different func-
substantialheterogeneitybetweenpatientsonvirtuallyallaspectsof tional systems in the brain. Structure and function of numerous
etiology, pathophysiology, psychopathology, treatment, course and receptors were intensively analysed during the past decades at the
functional outcomes. While psychopharmacology development has cellular and molecular level, but the role of receptors in complex
been primarily targeted for schizophrenia, psychosocial treatment neural systems, e.g. perception and processing of different sensory
development has more specific clinical targets in psychopathology modalities, action control, language, emotion, or attention is not
(e.g., CBT for negative symptoms) or function (e.g., supported sufficiently understood. It willbe demonstrated thatstructurally and
employmentforoccupationalimpairment).Recentdevelopmentsgive functionally defined areas and functional systems of the human
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S8 EurArchPsychiatryClinNeurosci(2013)263(Suppl1):S7–S111
cerebralcortexarecharacterizedbydifferentandregionallyspecific S-01BeyondDSM-5andICD-11:howshouldpsychotic
expressionlevelsofsinglereceptorsanduniquebalancesbetweenthe disorders be conceptualized and diagnosed
expressionlevelsofmultiplereceptors.Inmostcases,receptor-based
in the future?
definitionsofcorticalunits(‘‘areas’’)perfectlymatchmicroscopically
defined regions and cortical layers detectable in cytoarchitectonical
observations, structural connectivity or functional neuroimaging S-01-001
studies. Receptor studies also revealed hitherto unknown cortical Functionalimpairment:amandatorycriterionformental
areassubserving various cognitivefunctions. Furthermore,ouranal- disorders?
ysisofthedifferentexpressionlevelsofmultiplereceptors(upto20
different receptorbindingsitesforglutamate, GABA,acetylcholine, W.Gaebel(DepartmentofPsychiatryandPsychotherapy,Medical
noradrenaline,dopamine,serotoninandadenosine)ineachsinglearea FacultyHeinrich-Heine-UniversityDuesseldorf,LVR-Klinikum,
reveals a regionally and functionally specific balance between the Duesseldorf,Germany)
variousreceptors,i.e.the‘‘receptorfingerprint’’ofaneuronalstruc-
ture. Consequently, drugs with receptor-specific agonistic and Objective: ICD-11 and DSM-5 differ in the role of functional
antagonistic effects can influence perception, processing of sensory impairmentsforthediagnosisofamentaldisorderingeneral.Whilea
stimuli,emotionsandcognition.Insharpcontrasttoprimarysensory DSM-5diagnosisofamentaldisorderincludesfunctionalimpairment
areas, the higher sensory areas display lower densities of GABAA, asamandatorycomponent,ICD-11doesnot.
muscarinic M2 and a2 receptors, but markedly higher densities of
otherreceptors.Motorandmultimodalcorticesdisplayacompletely • ToclarifythereasoningbehindthedecisionoftheAPAandWHO
different pattern. Examples of selected psychiatric diseases will be toincludeornottoincludefunctionalimpairmentasamandatory
showninthislecture.Principalcomponentandclusteranalysesofthe diagnosticcriterion.
receptor fingerprints of numerous cortical areas reveal a receptor- • Topresent arguments for andagainst the inclusion of functional
basedsegregationintovariousfunctionalsystems.Thefingerprintsof impairment in the diagnostic criteria for mental disorders, also
the areas representing a complex functional system are similar and withrespecttofutureclassificationstrategiessuchastheResearch
differ from those of other systems. Furthermore, the fingerprints DomainCriteria(RDoC)project.
reveal ahierarchical organization ofthecortical areas bothbetween
Methods:Presentationofproandconarguments.
andwithinthefunctionalsystems.
Results:WHOprefersfunctionalcriterianottobeincludedamongthe
Policyoffulldisclosure:None.
clinical criteria (Reed et al., 2011) and suggests using the Interna-
tional Classification of Functioning (ICF) to assess and code such
functional impairments. This recommendation is based on findings,
that functional impairments are not always present in persons with
PL-04 Twenty years of early intervention in psychosis: schizophreniaandthattheyarenotdisorder-specific.Accordingtoa
how critical is the critical period hypothesis? WHO study, their occurrence in persons with psychosis-like experi-
ences in the general population does not inevitably indicate
schizophrenia or other mental disorders (Nuevo et al., 2010). APA
PL-04-001
holdsthatfunctionalimpairmentsareessentialfeatures,presentina
Twentyyearsofearlyinterventioninpsychosis:howcriticalis
substantial majority of persons that suffer from psychotic disorders,
thecriticalperiodhypothesis?
particularly in schizophrenia. The inclusion of functioning should
better separate schizophrenia from people in the general population
M.Birchwood(SchoolofPsychology,UniversityofBirmingham,
who have delusions and hallucinations (van Os et al., 2009).
Birmingham,UnitedKingdom)
Conclusion: DSM-5 has retained the mandatory criterion of func-
tionalimpairment,whileICD-11willprobablynotincludefunctional
Abstract: Early intervention in psychosis is approaching its 20th
impairment. The question of caseness with and without mandatory
birthday.SpecialisedservicesweredevelopedintheUKinformedby
functional impairments in the diagnostic criteria will be one of the
the ‘‘critical period hypothesis’’[1, 2]. In 2001, the UK government
researchissuesfortheupcomingICD-11fieldtrials.
committedamajorinvestmentinspecializedservicesforfirstepisode
References:
psychosis,usingasatemplatetheserviceinBirmingham,whichhad
NuevoRetal.,TheContinuumofPsychoticSymptomsintheGeneral
been ongoing since 1994. The model has been replicated across the
Population:ACross-nationalStudy.SchizophreniaBulletin2010;38:
wholecountrywithwell inexcess of150teams inoperation.Trials
475–485.
and health economic analysis have confirmed their effectiveness in
Reed GM et al., The WPA-WHO Global Survey of Psychiatrists’
improving outcome during the ‘critical period’ Our National EDEN
AttitudesTowardsMentalDisordersClassification.WorldPsychiatry
projectsevaluatetheeffectivenessofthesespecializedteamsinroutine
2011;10:118–31.
practiceinbothurbanandruralsettingswithover5sitesand20teams.
Policy of full disclosure: Wolfgang Gaebel received grants/research
Thesedatahighlighttheimpactbutalsothelimitationsofthemodeland
supportsfromLundbeckInstitute(FacultyMember).
inthislectureIwillreviewthesefindingsandproposeamodelforthe
‘nextgeneration’ofearlyinterventionservices,includingtheproposalto
settheseservicesinthecontextofayouthmentalhealthframework. S-01-002
References: Howtodistinguishbetweensymptomsofamentaldisease
Birchwood, M Macmillan,J F Early Intervention in Schizophre- andimpairmentsof(social)functions
nia\BR[Aust N Z J Psychiatry September 1993 vol. 27 no. 3
374–378. A.Heinz(PsychiatryandPsychotherapyCharite´,Berlin,Germany),
Birchwood M, Todd P, Jackson C. Early intervention in psychosis. Friedel,Eva
The critical period hypothesis. Br J Psychiatry 1998;172(33)
:53–59. Abstract:Modernpsychiatricclassificationsavoidtheterm‘‘disease’’
Policyoffulldisclosure:None. andinsteaddescribe‘‘disorders’’ofmentalfunctioning.However,the
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EurArchPsychiatryClinNeurosci(2013)263(Suppl1):S7–S111 S9
term ‘‘disorder’’ is rather broad and it has been criticized that it S-01-004
includes illness experiences as well as common forms of human Cankeysymptomsofschizophreniabematchedtobrainsystems?
sufferingthatarenotrelatedtomedicaldiseases(e.g.thediscussion
about how long and severe grief has to be in order to count as a W.Strik(UniversityHospitalofPsychiatry,UniversityofBern,Bern,
mental disorder). With respect to schizophrenia, symptoms of the Switzerland),Th.Dierks
maladythatimpairessentialpsychicfunctionsnecessaryforsurvival,
forexamplecommentingandimperativevoicesthattellthepatientto Abstract:Keysymptomsofschizophreniaaredelusionsandhalluci-
commitsuicideandwhichhefeelscompelledtofollow,canbedis- nations,butalsoformalthoughtandmovementdisorders.Psychiatry
tinguished from the subjective experience of the illness and the isstillinfluencedbytheattitudeofKurtSchneiderandKarlJaspers,
impairmentofsocialparticipation,whichisusuallyreferredtoasthe who intended the highest brain functions like emotions and thought
sickness. Outside of psychiatry, medical care usually focuses on such‘‘faraway’’(Schneider)fromneuralactivitythatitwouldnever
aspects of the disease only, i. e. on the cure of dysfunctions of an bepossibletostudythem bymeansofneuroscience.Thisparadigm
organthatareessentialforits purpose(e.g.thecureofthecauses hassilentlyshifted,however,sincethenewmethodsofbrainimaging
and consequences of heart failure). Rehabilitation that aims at a allowstudyingstructureandfunctionofthe‘‘workingbrain’’during
restoration of social participation and hence at a reduction of the the highest brain functions. While today it appears possible to
sickness aspects of a malady is usually carried out in separately understand the brain activation patterns during specific neuropsy-
financed rehab centres. In psychiatry, sickness aspects are usually chological tasks exploring executive functions, working memory,
treated within the medical system, thus contributing to a blurred mild cognitive impairments or theory of mind, the involved brain
distinctionbetweendiseasesymptomsontheonehandandaspects systemsandtherelationshipwiththekeysymptomsofschizophrenia
of sickness manifest as impaired social participation on the other. remain unclear. Based on examples of the ‘‘symptom catching’’
We describe the theoretical distinction between disease, sickness approach to brain imaging, the presentation will show that charac-
andillnessanddiscusskeysymptomsofschizophreniawithrespect teristic psychotic symptoms like hallucinations, formal thought and
to this systematic distinction. We suggest not to confuse the movement disorders can be matched on functional and structural
description levels of disease and sickness. On the other hand, any changes of specific brain systems, meaningful for the respective
maladythatistobetreatedwithinthemedicalsystemshouldconsist subjectiveandbehaviouralphenomena.
of both disease symptoms as well as indicators of harm such as Policyoffulldisclosure:None.
individualsufferingorotherillnessexperiencesoranimpairmentof
socialparticipation.
Policyoffulldisclosure:None.
S-02 Preventive outpatient treatment approaches
for schizophrenia-associated violence and delinquency
S-01-003 S-02-001
Aretherespecificsymptomsthatguideschizophrenia Themultifactorialbasisofviolenceinschizophrenia
diagnosis?
S.Hodgins(Universite´ deMontre´alPsychiatrie,Montreal,Canada)
S.Galderisi(Dept.ofPsychiatry,UniversityofNaplesSUN,
Naples,Italy) Objective: To provide a review of knowledge of violent behaviour
among people with schizophrenia and who are developing
Objective: Definition and diagnostic criteria for schizophrenia have schizophrenia.
always struggledwith thedifficulty toidentifysymptomsthatcould Methods:Aliteraturereview.
beregardedascharacteristicofthedisease.Thepriorityassignedto Results: Initially, the distinction will be made between violent
Schneiderian first-rank symptoms has recently been questioned and behaviour that occurs during an acute psychotic episode, usually
theywillnotreceiveunevenweightinginICD-11andDSM-V. whenapatientishospitalizedinvoluntarily,andviolencethatoccurs
Methods: However, in the attempt to identify specific aspects of in the community. Violence that occurs on psychiatric wards rarely
schizophrenia, the definition proposed in the present draft of the leadstocriminalprosecution.Inanacuteepisodeasmanymalesas
chapter‘‘SchizophreniaSpectrum andOtherPrimary PsychoticDis- femalesengageinaggressiontowardsothers,andthemainassociated
orders’’maintainstheICD-10sentence‘‘Thedisturbanceinvolvesthe factor is positive symptoms. The aggressive behaviour dissipates
most basic functions that give the normal person a feeling of indi- within days as neuroleptic medication takes effect. Once positive
viduality, uniqueness, and self-direction’’, and includes ‘‘distortions symptoms are reduced, a structured assessment is required to assess
of self-experience’’ among core symptoms of the disorder, together theriskforviolentbehaviourwhendischargedtothecommunityand,
withpersistentdelusionsandhallucinationsandthoughtdisorder. if there is a risk, the associated factors. Interventions aimed at
Results: The presentation will summarize evidence suggesting non reducingthesefactorswouldbeintegratedintothedischargeplan.By
specificity of Schneiderian first-rank symptoms and will review the contrast, aggression towards others that occurs in the community
present status of three psychopathological domains often referred to leadstocriminal prosecutionssometimes, butnotalways.Themain
as ‘‘core aspects of schizophrenia’’: anomalies of the sense of self/ factors associated with aggressive behaviour and violent crimes
self-awareness, cognitive dysfunctions and impairment of social occurring in the community are male sex, a history of conduct
cognition/interpersonalrelationships. problemsincechildhood,andsubstancemisuse.Suchbehaviourstend
Conclusion:Itisdifficult,forthetimebeing,todrawconclusionson to be repetitive. Importantly, almost all patients with schizophrenia
thefailureexperiencedsofartodemonstratespecificityofthese‘‘core whowillcommitacrime,offendbeforefirstepisode.
aspects’’. Whether theoretical and methodological limitations of Conclusion: Thus, at first episode clinics, once the acute episode of
availablestudiescanbeovercomeandchangethispictureisanissue psychosis is reduced, an assessment can be undertaken to assess
openfordiscussion. conduct problems in childhood/adolescence, prior offending, and
Policy of full disclosure: Honoraria/Consultation fees from Amgen- substance misuse. When such factors are present, interventions
Dompe´ andEli-Lilly. directlytargetingtheproblemareneededtoreducetheriskoffurther
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S10 EurArchPsychiatryClinNeurosci(2013)263(Suppl1):S7–S111
violentbehaviour.Somepatientswithanopriorhistoryofaggressive Methods: In the catchment area of Ansbach, patients with a mental
behaviour do engage in violence towards others. Assuring that illness showing a high-risk profile to commit a severe crime (i.e.
patients are not using drugs, are taking prescribed medications, are violence, sexual offences) are offered home visits and continuous
engagedinmeaningfulactivities,andarereceivingsupervision,will appointmentsinthenew‘‘ForensicPreventiveOutpatientClinic’’by
preventviolentbehaviour. amulti-professionalteam.Therapieswhichareoffered:
Policyoffulldisclosure:None.
• Psychotherapeutic and anti-psychotic drug treatment (including
depot-medication)viahomevisitsorforensicoutpatientclinic
• Grouptherapyintheoutpatientclinic
S-02-002 • Psycho-education(patientandfamily)
Apsychoeducationalinterventionprogrammetoreduce • Active risk-management -Therapy focusing on individual risk
compulsoryhospitalreadmissionintheCantonofZurich factors
Results:TheoutpatientclinicstartedinFeb2012andtakescarefor
B.Lay(UniversityofZurichResearchInstituteofClinicalandSocial
about 50 high-risk patients, now. The goal is to treat about 100
Psychiatry,Zurich,Switzerland),T.Scho¨nenberger,M.Bleiker,
patients.Besidethetreatment,theprojectisevaluatedwithreference
S.Lengler,C.Blank,W.Ro¨ssler
to:
Objective:Thehighnumberofinvoluntaryplacementsofpeoplewith • Risk-profilebeforeandduringtreatment
mental disorders constitutes a major health issue in many European • Drop-outrate,compliance,adherence,illnessseverity,patientand
countries.Inviewoftheethicalandpersonalrelevanceofcompulsory familysatisfaction,globalfunctioning,etc.
admission for the patients concerned and given the far-reaching
effects in terms of health care costs, innovative interventions to Furthermorethepatientsarecomparedtoacontrolsampleofpatients
improve the current situation are much needed. Therefore, an inter- whoareoutofthecatchmentarea.
vention programme is conducted currently at four psychiatric Conclusion: First results dealing with the above named parameters
hospitalsintheCantonofZurichthataimstoreducethenumberof areverypromisingandwillbepresentedbesideacasehistory.
involuntary psychiatric hospitalisations and to increase patients’ Policyoffulldisclosure:None.
empowermentandtreatmentsatisfaction.
Methods: This programme consists of individualized psycho-educa-
tionfocusingonbehaviourspriortoandduringillness-relatedcrisis, S-02-004
the distribution of a crisis card and, after inpatient admission, a Acomplex-therapeuticinterventionprogrammefor
24-month preventive monitoring of individual risk factors for com- schizophreniaoutpatientstargetedatreducingviolent
pulsory readmission to hospital. Detailed follow-up assessments of offendingandcompulsorydetentioninDu¨sseldorf,
service use, psychopathology and patient perceptions are scheduled NorthRhine-Westphalia
12 and 24months after discharge. For the whole study a period of
5yearsisscheduled.
C.Luckhaus(Heinrich-HeineUniversityDepartmentofPsychiatry
Results:Intotal,238patientshavebeenincludedintherandomized
andPsychotherapy,Duesseldorf,Germany)
controlledtrial(119patientseachintheinterventionandthecontrol
group). Up to now, 140 of them are participating in the programme
Objective:Toconceptualize,adaptandapplyamultimodaltreatment
for a period of 12months. Patients with a variety of psychiatric
programmeforschizophreniapatientsasafollow-upafterdischarge
diagnoses are included, many of them displaying comparatively
from compulsory general psychiatric hospitalization. To assess the
problematic behaviour (characterised by aggression, suicidal behav-
feasibility of applying the intervention, and to analyse its effective-
iour, substance abuse, low social adjustment and social difficulties).
nessandefficacyontheprimaryendpointofcompulsoryreadmission
Data suggest that most of the participants have experienced a high
duetoendangeringbehaviourandmulti-domainsecondaryendpoints.
number of previous hospitalizations, many of them involuntary.
Methods:Atotalof79subjectswithschizophrenia,schizoaffectiveor
Psychopathology, previous health care use, perceived coercion and
maniac disorder (ICD-10), who have received compulsory general
socialbackgroundofpatientswithschizophrenia(vs.otherdiagnoses)
psychiatric hospital treatment, are to be enrolled in a prospective
willbepresented.
outpatientinterventiontrial.Theinterventionismultimodal,includes
Conclusion: The current study will provide further insight into pro-
patient tracking and is adaptable to individual needs. It comprises
cessesandfactorsthatcontributetocompulsoryadmission.Afterallit
psychiatric, psychotherapeutic, social support and risk management
allowsforaprospectiveanalysisoftheeffectivenessofthisinnova-
modules.Theinterventionphaseis6months,followedbya6-month
tiveinterventionprogramme.
catamnestic follow-up. At baseline, post-intervention and post-fol-
Policyoffulldisclosure:None.
low-up, standardized variables of re-admission, anamnestic key
information, aggressive behaviour, delinquency, psychopathology,
social functioning, social and neuro-cognition are assessed and
S-02-003 comparedtoapatientgroupreceivingtreatmentasusualatapartner
Apreventiveoutpatientclinicforhigh-risk-of-violencepatients hospital.Primaryendpointistherateofreadmissiontogeneralpsy-
intheregionofAnsbach,Bavaria chiatrichospitalcare.Secondaryanalysesregardrespectiveratesand
predictorsofviolentbehaviour,delinquencyandforensicdetention.
J.Nitschke(BezirksklinikenAnsbachForensicPsychiatry,Ansbach, Results: Preliminary interim analysis of 77 screened patients shows
Germany),C.Luckhaus goodfeasibilityofstudyandtreatmentdesignwitharecruitmentrate
of57%andanadherencerateof94%.Aggressivebehaviourhaving
Objective: The preventive outpatient clinic aims to reduce possible ledtoinitialgeneralpsychiatrichospitaltreatmentislargelymoderate
future crime committed by schizophrenic high-risk patients by pro- with preponderance of threatening behaviour or aggression towards
viding risk assessments to patients who are referred by general objects.Psychiatriccomorbidityismostlylimitedtosubstanceabuse.
practitioners,psychiatrists,ortheirfamilies.Furthermoretheproject So far, the total readmission rate is below 50%, the rate of com-
aimstoprotectpotentialvictims. pulsory readmission is 12.5%. The total amount of intervention
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EurArchPsychiatryClinNeurosci(2013)263(Suppl1):S7–S111 S11
contactsperstudyparticipantrangesbetween3and43.Bothhighand Objective:Apathycanbedefinedasaquantitativereductioningoal-
lowutilisersareamongthereadmittedgroup. directedbehaviour.Thus,itshouldbepossibletounderstandapathy
Conclusion: The study and treatment design appears feasible for asadisturbanceofmotivationaland/orcognitiveprocesses underly-
schizophrenia,schizoaffectiveandmaniacpatientswithanincreasedrisk inggoal-directedbehaviour.Herewepresenttwostudiesaddressing
for violence. A high degree of outpatient adherence can possibly be distinct components of goal-directed behaviour. In study 1 we
reachedbyamultimodaltreatmentapproachthatisadaptedtoindividual investigate dysfunctional effort-cost computations as a central moti-
needsandincludesapatienttrackingcomponent.Preliminaryinterim vational process in relation to apathy. In study 2 we investigate a
analysis points to a preponderance of voluntary versus compulsory dysfunctional generation of options for action as a key cognitive
readmissionsamongpatientsreceivingthistypeofintervention.Both processunderlyingapathy.
highandlowtreatmentutilisersareamongthereadmitted. Methods:Inbothstudiesin-andoutpatientswithschizophreniawere
Policyoffulldisclosure:Thisstudyissupportedbyagrantfromthe included. A detailed psychopathological and neurological assess-
MinistryofHealthoftheStateofNorthRhine-Westphalia,Germany. ment was performed. Apathy was defined as the sum of the
avolitionandanhedonia/asocialitysubscoresoftheSANS.Instudy
1 until now 10 patients with schizophrenia have performed an
effort-based decision-making task, in which effort was opera-
S-03 Apathy in schizophrenia: clinical, experimental
tionalisedasphysicalgripforce.Inthefinalsample30patientswill
and therapeutic approaches be included. In study 2 20 patients have performed a new task
requiring the generation of options for action in ill-structured
S-03-001 everyday situations.
Apathyinfirstepisodepsychosis:similaritiesanddifferences Results:Pilotdatafromstudy1suggestthatapathyisrelatedtoa
tootherbraindisorders steeper discounting of monetary reward value, when physical
effort is required. In other words, patients with apathy are less
willing to commit effort for the same amount of reward than
A.Faerden(UllevalUniversityHospital,Oslo,Norway)
patientswithoutapathy.Instudy2patientswithapathygenerated
fewer options for action in ill-structured situations than patients
Abstract:Apathyisoneofthenegativesymptomsthatrecentlyhave
without apathy. Importantly, this relationship remained signifi-
receivedincreasedinterestduetoitspossibleroleindevelopmentof
cant even when controlling for processing speed and global
poor psychosocial functioning in psychotic disorders. Negative
cognitive impairment.
symptoms are present already when people come into treatment for
Conclusion: Overall, these initial results suggest that different pro-
the first episode of psychosis (FEP), but there is limited knowledge
cesses underlying goal-directed behaviour and their disturbances in
aboutapathyinFEP.Apathyisalsoasymptomfoundinotherbrain
apatheticsyndromescanbedelineatedinpatientswithschizophrenia.
disorders. By comparing results from studies in these disorders we
Separation of these processes provides avenues for further research.
may get a better understanding of apathy in FEP that can lead to
Forexample,reducedmotivationanddysfunctionaleffort-costcom-
development of new treatments. The aim of this presentation is to
putations can be modelled in animals with the aim of developing
present current knowledge of apathy across disorders and suggest
pharmacologicaltreatmentapproaches.Thisismoreproblematicwith
possible mechanisms behind apathy in FEP. Papers were retrieved
respecttothecognitiveprocessesrelatingtoapathy.Putativeoptions
after a Pub Med search with the key words apathy, psychosis, and
for improvement of these processes include the stimulation of the
braindisorders.Apathywaspresentin50%ofFEPpatients,23%of
subserving cortical regions orpsychological approaches such astar-
those with possible Parkinson‘s disease (PD) and between 20 and
getedtraining.
50% in those with possible or in the early stage of Alzheimer‘s
Policy of full disclosure: This work has been funded in part by the
disease (AD). For FEPpatient’s level ofapathy decreased atfollow
VolkswagenFoundation(Hannover,Germany)throughtheEuropean
up,forPDandADtherewasanincrease.Foralldisordersapathyhad
Platform for Mind Sciences, Life Sciences and the Humanities. SK
ahighcorrelationwithpoorpsychosocialfunctioningandtwostudies,
hasreceivedroyaltiesforcognitivetestingandtrainingsoftwarefrom
oneinFEPandoneinADfoundapathytopredictpoorfunctioningat
Schuhfried (Mo¨dling, Austria) and speaker honoraria from Roche
1-yearfollowup.Forallthreedisordersapathywasmoreassociatedwith
(Basel,Switzerland).
malegender.Alsoacrossdisordersapathywasassociatedtopoorper-
formanceonneurocognitivetestsofexecutivefunction.Thereseemtobe
commonalitiesacrossdisordersregardingmalegender,earlyappearance
indiseaseprocess,associationto—andpredictionofpoorfunctioning S-03-003
andassociationstopoorexecutivefunction,butnotothercognitiveareas. Roleoffrontostriatalandfrontoparietalnetworksinapathy
Thispointstoacommonmechanismforapathyregardlessofetiology,
butwithdifferencestofurtherdevelopmentovertime.Apathymayseem
A.Aleman(UniversityofGroningenDepartmentofNeuroscience,
tobemoreunstableinFEPthanotherdisorders,whichmaygiveriseto
Groningen,Netherlands)
differenttreatmentopportunities.Moreknowledgeisneededregarding
howtheaffective-,cognitive-andmotorsystemsareaffectedinapathyin
Abstract:Apathyconcernsaquantitativereductionofvoluntary,goal-
ordertocomeupwitheffectfulltreatments.
directed behaviours that impairs daily functioning. It is a prominent
Policyoffulldisclosure:None.
andseverelydebilitatingaspectofseveralpsychiatricdisorders,most
notably schizophrenia. Little is known regarding the neuroscientific
basis of apathy, however. Clinically, it has been suggested that two
S-03-002 forms of apathy can be distinguished: cognitive apathy (CA) which
Apathyasadisturbanceofmotivationalandcognitiveprocesses concerns reduced initiative to start daily activities, and social-emo-
subservinggoal-directedbehaviour tional apathy (SEA) which concerns reduced interest in otherwise
gratifying activities. Both are not primarily due to depression and
S.Kaiser(UniversityofZurichPsychiatricHospital,Zurich, both involve a reduced activation of the behavioural activation sys-
Switzerland) tem. I discuss the hypothesis that CA is primarily a dysfunction of
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S12 EurArchPsychiatryClinNeurosci(2013)263(Suppl1):S7–S111
cognitivecontrolandself-initiatedaction,whereasSEAisprimarilya S-04 The mild encephalitis hypothesis of schizophrenia
failure to signal the salience of positive events. Two neuroanatomi- updated: low level neuroinflammation, autoimmunity,
cally distinct routes may underlie these two forms of apathy in
volume transmission, treatment approaches
schizophrenia: a dorsal frontostriatal circuit including also the right
parietal cortex for CA and a more ventral frontostriatal circuit
including the reward system for SEA. The first route may involve S-04-001
abnormalities of glutamate neurotransmission, whereas the second Antiinflammationandpsychoimmunomodulation
route involves abnormal dopamine transmission. Preliminary evi- inschizophrenia
dencefromstudiesinschizophreniaandneurodegenerativedisorders
willbeaddressed. E.Weidinger(Dept.ofPsychiatry,LMUMunich,Munich,Germany),
Policyoffulldisclosure:None. N.Mu¨ller
Abstract: A persistent (chronic) infection as aetiological factor in
schizophreniaisdiscussedsincemanyyears.Researchpointsoutthatnot
onesinglepathogenbuttheimmuneresponseofthemotherisrelatedtothe
S-03-004
increasedriskforschizophrenia.Interestingly,infectionsandautoimmune
Bilateralrepetitivetranscranialmagneticstimulationfornegative
disordersincreasetheriskforalaterdiagnosisofschizophreniaina‘dose-
symptomsofschizophrenia:findingsfromadouble-blind
dependent’wayalsoinlaterlife.Severalreportsdescribedincreasedserum
randomizedcontrolledtrial
IL-6levelsinschizophrenia.IL-6isaproductofactivatedmonocytesandof
theactivationofthetype-2immuneresponse.Moreover,severalmarkersof
J.Dlabac-DeLange(UniversityMedicalCenter,Groningen, thetype-1immuneresponsearedecreasedinthemajorityofschizophrenic
Netherlands),L.Bais,A.Aleman,H.Knegtering patients, while signs of activation of the type-2 immune response are
described accordingly in schizophrenia. Mechanisms involved in the
Objective: Previous studies have reported on the efficacy of inflammatoryprocessinschizophreniawillbeoutlinedincludingtheroleof
repetitive transcranial magnetic stimulation (rTMS) treatment for microglia cells, the macrophages of the brain. Antipsychotic effects of
negative symptoms of schizophrenia, however the results were cyclo-oxygenase-2inhibitorshavebeenstudiedinschizophrenia.Acritical
inconsistent. This study aimed to investigate whether longer overviewonresultsofthesestudieswillbepresented.COX-2inhibition
treatment duration in combination with 10Hz bilateral stimula- showedbeneficialeffectsmostlyinearlystagesofthedisease.Thedata
tion of the dorsolateral prefrontal cortex enhances treatment regardingchronicschizophreniaarecontroversial,possiblyinpartdueto
effects. methodologicalreasons.Inthemeantime,twometa-analyseswerepub-
Methods: A double-blind randomized controlled trial was per- lished on this topic showing that the use of COX-2 inhibitors in
formed in 32 patients with the diagnosis of schizophrenia or schizophrenia show beneficial effects, especially in early stages of the
schizoaffective disorder, and moderate to severe negative symp- disease or in first manifestations. The therapeutic effects of short-term
toms (PANSS negative subscaleC15). Patients were randomly studies(5–8weeks)dependfromthedurationofdisease,inourinterpre-
allocated to a 3-week course of real (n=16) or sham (n=16) tationfromthechronicityoftheinflammatoryprocess.Furthertherapeutic
rTMSofthebilateraldorsolateralprefrontalcortex,atafrequency strategiesbasedonimmune-modulatoryeffectswillbediscussed,too.
of 10Hz in 10-second trains, with an inter-train interval of 50s. Policyoffulldisclosure:None.
Patients were stimulated during 20min at 90% of the motor
threshold.TheprimaryoutcomemeasurewasthePANSSnegative
symptom score and the Scale for the Assessment of Negative S-04-002
Symptoms(SANS)totalscore.Subjectswereevaluatedatbaseline, AutoimmunitytoNMDAreceptorsinschizophrenia
end of treatment, at 4weeks and at 3months follow-up. For
analysis of the primary outcome a repeated measures analysis of B.Lennox(DepartmentofPsychiatry,UniversityofOxford,
variancewasconducted,withthebaselinescoresasacovariate.To WarnefordHospital,Oxford,UnitedKingdom)
investigate if the effect was independent of depressive symptoms
we added the post treatment Montgomery Asberg Depression Objective: Autoantibodies associated with central nervous system
RatingScale(MADRS)asacovariate.Analysisuntil4weeksand encephalopathies have been defined over around the last decade to
3monthswere conducted. now include those directed against the voltage-gated potassium
Results: Analysis until 4weeks follow-up shows a significant channel (VGKC) complex, glutamic acid decarboxylase (GAD) and
improvement on the SANS (p=0.04) in the TMS group (n=16) the N-methyl, D-aspartate receptor (NMDAR).NMDAR-antibodies
as compared to the sham group (n=16). Analysis of the apathy wereinitiallydescribedinaparaneoplasticencephalitisaffectingyoung
subscale of the SANS also shows a significant improvement womenwithovarianteratomas.Removalofthetumourwithconcurrent
(p=0.04) in the TMS group. In preliminary results (TMS group immunotherapiesoftenimprovedtheclinicaloutcomes.Thecorefea-
n=14, sham group n=16) until 3months follow-up this effects tures of the disease include behavioural changes, delusions, memory
seems to have diminished in both the SANS (p=0.14) and the disturbances,seizures,andamovementdisorder.Weaimedtodescribe
apathy subscale of the SANS (p=0.15). There was no significant whetheraproportionofpatientswithpsychosis,withoutotherfeaturesof
differencebetweenthetwogroupsonthePANSSnegativesymptom encephalitisalsohadantibodiestoNMDAreceptors.
score in the course of follow-up until 4weeks (p=0.38) and Methods:Wetestedtheserumofpatientswithafirstepisodeofpsychosis
3months(p=0.32). usingacellbasedassayexpressingNR1/NR2bsubunitsoftheNMDA
Conclusion: Bilateral prefrontal rTMS appears to have beneficial receptor.
effect on negative symptoms of schizophrenia during 4weeks post Results:6.5%ofourinitialcohortofpatientshadantibodiesagainst
treatment. After 4weeks the effect diminishes. Limitations of the theNMDARorVGKCcomplex.Afurthercohortofpatientshasbeen
studyincludesmallsamplesizeanduncertaintyaboutrTMSoptimum identified through clinical testing. All 16 patients with NMDAR
treatmentparameters. antibodieshadprimarypsychiatricdiagnoses,andnoneprogressedto
Policy of full disclosure: Jozarni Dlabac-de Lange received an become encephalopathic. Six patients have been treated solely with
unconditionalresearchgrantbyAstraZeneca. immunotherapyandpsychoticsymptomshaveimproved.
123
EurArchPsychiatryClinNeurosci(2013)263(Suppl1):S7–S111 S13
Conclusion: A proportion of patients with schizophrenia may have Objective: During the past two decades, the construct of a clinical
pathogenic antibodies against the NMDA receptor, and be treatable high risk (HR) state for psychosis, has evolved to capture the pre-
withimmunotherapy. psychotic phase, describing people presenting with potentially pro-
Policyoffulldisclosure:None. dromal symptoms. The aim of this presentation is to reframe the
diagnostic,prognosticandtreatmentvaliditydataoftheHRstate.
Methods:ConceptualreviewofHRstudiesaddressinginclusioncri-
S-04-003 teria, epidemiology, transition criteria, outcomes, clinical and
Volumetransmissionbalancingwiring(e.g.synaptic)transmission functional characteristics, neurocognition, neuroimaging, predictors
of psychosis development, treatment trials, socioeconomic aspects,
K.Fuxe(KarolinskaInstitute,Stockholm,Sweden),D.Borroto- nosography and future challenges in the field. This is supported by
Escuela recentmeta-analysesinthefield.
Results: Independent of the psychometric instrument employed to
Abstractnotreceivedinduetime. diagnoseHRsubjects,thereismeta-analyticalmeantransitionriskof
18%(95%CI12–25)after6monthsoffollow-up,22%(95%CI
17–28) after 1year, 29% (95% CI 23–36) after 2years and 36%
S-04-004 (95%CI30–43)after3years.MostofHRsubjects(73%)whowill
Themildencephalitishypothesisofschizophreniaupdated goondeveloppsychosiswilltransittowardsschizophreniaspectrum
psychoses. Longer follow-up outcomes are not well defined but HR
K.Bechter(BKHGuenzburg/UlmUniversityPsychiatryII, individuals may continue to develop psychotic disorders up to
Guenzburg,Germany) 10yearsafterinitialpresentation.InadditiontoHRsymptoms,many
have comorbid diagnoses, in particular anxiety, depression (meta-
Objective: Schizophrenia seems to be a heterogeneous disorder. analyticalestimateof40%comorbidratefordepressivesymptoms)
Infections and autoimmune disorders are risk factors. Low level thatareclinicallydebilitating,andhighlevelsofnegativesymptoms,
neuroinflammation(LLNI)maybeinvolved. occupational difficulties as well as substantially compromised sub-
Methods: Accordingtothemildencephalitis(ME)hypothesis,LLNI jective quality of life. The HR symptoms are associated with
representsthecorepathogeneticmechanisminaschizophreniasubgroup, widespread mildcognitivedeficits,fallingatalevelthatisinterme-
possiblytriggeredbyinfections,autoimmunity,toxicity,ortrauma. diate between healthy individuals and those diagnosed with
Results:A‘latehit’andgene–environmentinteractionarerequiredto schizophrenia. Meta analytical estimates indicated that HR individ-
explainmajorfindingsaboutschizophrenia,andbothaspectswouldbe uals who convert to psychosis show more severe neurocognitive
consistentwiththeMEhypothesis.Schizophreniariskgenesstayrather deficitsatbaselinethannon-convertersinparticularinverbalfluency
constantwithinpopulationsdespitearesultinglownumberofprogeny, and memory domains. Meta-analyses of structural imaging studies
suggesting advantages associated with risk genes, e.g., an improved indicated that volumetric reductions in temporal, cingulate, insular,
immune response, which may act protectively within changing envi- prefrontal and parahippocampal cortices are associated with later
ronments.Specificschizophrenicsymptomsmayarisewithinstancesof development of psychosis. Functional neuroimaging has shown
LLNIwhencertainbrainfunctionalsystemsareinvolved,inadditionto changes in activation in HR samples that are intermediate between
beingshapedbypre-existingliabilityfactors.Prodromephaseandthe firstepisodepatientsandhealthycontrols.Brainspectroscopystudies
transitiontoadiseasedstatusmayberelatedtoLLNIprocessesemerging have suggested some differences in metabolite concentration. Neu-
andvaryingovertime.Contributingfactorsaregenes,environment,and rochemicalstudiesfoundelevatedstriataldopaminesynthesisinHR
immunesystem.MEcouldrepresentacommonpathogeneticlinkforthe individualsthatisgreaterinthosewholatertransitiontopsychosis.At
distributed brain dysfunction, dysconnectivity, and brain structural aclinicallevel,themostpredictivesymptomsofpsychosistransition
abnormalitiesobservedinschizophrenia.Preliminarycriteria for sub- arethepresenceofbaselinenegativesymptoms,poorfunctioningand
grouping neurodevelopmental, genetic, ME, and other types of psychosocial dysfunction. Preventive interventions in psychosis are
schizophreniasareproposed.ArareexampleofMEschizophreniamay feasible and indicate clinically meaningful advantages of focused
beobservedinBornadiseasevirusinfection.LLNImayincludedys- treatment (psychological, psychopharmacological or neuroprotective
function of the blood–brain barrier, the blood–CSF barrier, CNS- interventions) as compared to the respective contrast groups. Meta-
endogenousimmunity.ThevolumetransmissionmodeislinkedtoCSF analytical estimates of randomized controlled trials in HR subjects
signalling,whichmayextendintoperipheraltissuesviatheCSFoutflow indicatedasignificanteffectofactivetreatments,withariskratioof
pathwayalongbrainnervesandperipheralnerves,anditmayexplainthe 0.34(from23%to7%,p\0.001)andaNTTof6inthefocused
peripheraltopologyofsomeneuronaldysfunctionsfound,likeinolfac- treatmentsversusthecontrastgroupat1year.
tory dysfunction, dysautonomia, and even pathology in peripheral Conclusion:ThefieldofHRresearchinpsychosisisexcitingandIi
tissues,i.e.,themusclelesionsfoundin50%ofcases. has potential to shed light on the development of major psychotic
Conclusion: Considering investigations ofCSF, the ME schizophre- disorders and to alter their course. It also provides a rationale for
niasubgroupmayconstituteapproximately40%ofcases. service provision tothose in need ofhelpwho could notpreviously
Policyoffulldisclosure:None. access it, and the possibility of changing trajectories for those with
vulnerabilitytopsychoticillness.
Policyoffulldisclosure:None.
S-05 Approaches for predicting development
of psychosis
S-05-002
Theepidemiologicperspectiveofriskidentificationandpsychosis
S-05-001 prediction
PrognosticandtherapeuticvalidityoftheAttenuatedPsychosis
Syndrome I.Kelleher(RoyalCollegeofSurgeonsinIreland,DeptPsychiatry,
EducationandResearchCentre,BeaumontHospitalDublin,Dublin,
P.Fusar-Poli(King’sCollegeLondonInstituteofPsychiatry, Ireland),AileenMurtagh,CharleneMolloy,SarahRoddy,MaryC.
Dept.ofPsychosisStudies,London,UnitedKingdom) Clarke,MichelleHarley,MaryCannon
123
S14 EurArchPsychiatryClinNeurosci(2013)263(Suppl1):S7–S111
Objective: While a great deal of research has been conducted on preventivemeasures,clinicalcriteriahavebeendevelopedandeval-
prodromalrisksyndromesinrelationtohelp-seekingindividualswho uated. Incidence rates associated with these criteria in help-seeking
present to the clinic, there is a lack of research on prodromal risk samples are several times higher than the incidence rates in the
syndromesinthegeneralpopulation.Thecurrentstudyaimedfirstly general population. Yet, rates vary considerably across studies and
to establish whether prodromal risk syndromes could be detected in thus,improvedpredictionstrategiesarerequired.
non-help seeking community-based adolescents and secondly to Methods:Modelsproposedintheliteratureaswellasdataonfileare
characterize this group in terms of Axis-1 psychopathology and discussedwithregardtotheircapacityforadvancingprediction.
generalfunctioning. Results: Narrowing criteria results in an unfavourable loss of sensi-
Methods: We conducted in-depth clinical interviews with a popula- tivityandthus,exclusionofindividuals,whomaypotentiallybenefit
tion sample of 212 school-going adolescents in order to assess for from preventive measures. This effect is avoided by strategies
prodromal risk syndromes, Axis-1 psychopathology and global combinghighlysensitivedetectiontoolswithapproachesenablingan
(social/occupational)functioning. approximationoftheindividualrisk.Promisingapproacheshavebeen
Results:Between0.9%and8%ofthecommunitysamplemetcri- suggested based on risk stratification by clinical as well as neuro-
teriaforarisksyndrome,dependingonvaryingdisabilitycriteria.The biological variables. In particular, neurophysiological parameters of
risk syndrome group had a higher prevalence of co-occurring non- information processing may enhance risk estimation not only
psychotic Axis-1 psychiatric disorders (OR 4.77, CI regardingmagnitude,butalsoregardingtimetoevent.
95=1.81–12.52;p\0.01)andpoorerglobalfunctioning(F=24.5, Conclusion: A multi-step procedure comprising a sequence of risk
df=1,p\0.0001)comparedtocontrols. detection and risk stratification seems to be the most promising
Conclusion: Individuals in the community who fulfill criteria for approach for individualized risk estimation as a major step towards
prodromal risk syndromes demonstrate strong similarities with clin- needs-adaptedprevention.
ically-presentingrisksyndromepatientsnotjustintermsofpsychotic Policyoffulldisclosure:None.
symptom criteria butalso interms ofco-occurring psychopathology
andglobalfunctioning.
S-06 The risks and benefits of antipsychotic
Policyoffulldisclosure:None.
polypharmacy: clinical relevance and development
of evidence
S-05-003
Predictingpsychosisinclinicalpractice:outcomeofpatientsseen S-06-001
inanNHSProdromeClinic AntipsychoticdrugtargetoccupancyinPETstudies:lessons
forcombiningantipsychotics?
M.Marshall(LancashireCareNHSFoundationTrust,Dept.
ofPsychiatryUniversityofManchester,Manchester,United G.Gru¨nder(RWTHAachen,Aachen,Germany)
Kingdom),C.Johnson,K.Neelam,R.Drake
Objective: Binding of antipsychotics to D2-like dopamine receptors
Abstract: English Early Intervention Services (EIS) are responsible in the human brain has been extensively studied with positron
forthecareofallpeoplewithafirstepisodeofpsychosiswhopresent emission tomography (PET). For most of the available new com-
fromgeographicallydefinedcatchmentareas.However,oftenEISare pounds the D2 receptor occupancy can be easily derived from a
referred patients who have not had a first episode of psychosis, but plasma concentration of a particular drug. However, occupancy of
who may be experiencing prodromal symptoms. We describe a ser- neither the D2 nor any other receptor has ever been studied under
vice evaluation of an NHS clinic that was set up to assess such treatmentwithacombinationof(antipsychotic)drugs.Amodelhow
patients. The clinic is unusual for England in that it adopted an suchvaluescouldbecalculatedfrom theavailable datawillbepre-
assessmentapproachthatincluded:theComprehensiveAssessmentof sentedhere.
At Risk Mental States (CAARMS), the Schizophrenia Proneness Methods: Values for the maximum attainable receptor occupancy
Questionnaire(SPI-A),measurementofNeurologicalSoftSigns,and (Emax)andtheserumconcentrationpredictedtoprovide50%ofthe
ameasureofschizotypy.Wedescribealong-termfollowupof174 maximumattainablereceptoroccupancy(EC50)fromourownseries
patients assessed in the clinic, which investigated the predictive of [18F]fallypride PET studies with amisulpride, aripiprazole, clo-
accuracy of this combined approach. Our findings suggest that a zapine, quetiapine and ziprasidone as well as published values for
combined approach to assessment is feasible in an ordinary clinic olanzapine andrisperidonewillbe usedasinput foramathematical
setting and provides an accuracy of prediction that is substantially modelwhichisbasedonthelawofmassaction(Michaelis–Menten
betterthananysingleinstrument. kinetics), with occupancy [%]=(Emax x [C])/(EC50+[C])
Policyoffulldisclosure:Noconflictofinterest. ([C]=plasmaconcentration),andwhichtakesintoconsiderationthe
competition of two (or more) different compounds with different
affinities.
Results: Calculations of D2 receptor occupancy values under treat-
S-05-004
ment with clinically common antipsychotic combinations (e.g.,
Howtoimprovethepredictionofpsychosis
clozapine/aripiprazole; clozapine/amisulpride; amisulpride/olanza-
pine)willbepresented.
S.Ruhrmann(UniversityofColognePsychiatryandPsychotherapy,
Conclusion:ThemodelillustratesthatstriatalD2receptoroccupancy
Cologne,Germany)
quickly exceeds the threshold level associated with increasing inci-
dence of extrapyramidal side-effects (approximately 80%
Objective:Avalidandreliableidentificationofindividualsbeforethe
occupancy),whentwocompoundswithmoderatetohighaffinityare
outbreakofapsychosisisthoughttoenableaneffectivepreventionof
combined.Italsodemonstratesthatthepotentialbeneficialeffectsof
this group of disorders or at least a significant improvement of its
combination treatment can hardly be attributed to (increased) D2
course.Asriskdetectionbyfamilyburdenisassociatedwithbothlow
receptoroccupancy.Rather,theyhavetobeascribedtomechanisms
specificity and low sensitivity, and thus not sufficient for effective
beyondD2antagonism.
123
EurArchPsychiatryClinNeurosci(2013)263(Suppl1):S7–S111 S15
Policy offulldisclosure: Alkermes, Bristol-Myers Squibb,Cheplap- efficacy, is widely used in routine clinical practice. Antipsychotic
harm, Eli Lilly, Forest Laboratories, Gedeon Richter, Lundbeck, (AP) polypharmacy, the combination of two or more APs, in
Otsuka,Roche,Servier. schizophreniaispracticedaroundtheworld,althoughthepercentage
variesamongcountries,continentsandtherapeuticsetting(inpatient/
outpatient).
S-06-002 Methods: The AMSPstudy is a drug safety program forthe contin-
Whentoswitchorcombine:timecourseforresponse uous assessment of severe ADR in psychiatric inpatients under the
inantipsychoticdrugtreatment naturalistic conditions of routine clinical treatment. Today, 20years
after the initiation of AMSP, 60 institutions from Austria, Germany
andSwitzerlandparticipateintheprogram.Ontworeferencedaysper
M.Ja¨ger(UniversityUlm/BKHGuenzburg,Ulm,Germany)
hospitalandperyear,thefollowingdataarerecordedforallpatients
onthewardsunderAMSPsurveillance:alldrugsappliedonthatday
Objective: Antipsychoticdrugshavebeenusedformorethanahalf
withthedailydosageforpsychotropicdrugs,ICDdiagnosis,age,and
century.Theaimofthepresentanalysesweretodescribethecourse
sex.DataisstoredatthestudycentreinHannover.
of positive and negative symptoms during inpatient treatment and
Results: From 2003 to 2011 we collected reference-day-data from
examine remission and response rates under routine clinical care
6986 inpatients being treated for a F20 ICD-10 diagnosis. Psycho-
conditions.Furthermore,weaimedtoexaminethepredictivevalidity
tropicmonotherapywasfoundonlyin23.38%ofoursample.Most
of early improvement and to identify the criterion that bests define
inpatientsinoursamplereceivedoneAP(52.58%),althoughstilla
earlyimprovement.
large proportion of them received two (35.26%) or more APs. The
Methods:WithintheframeworkoftheGermanResearchNetworkon
percentage of inpatients being prescribed one AP-agent was more
Schizophrenia 218 patients suffering from schizophrenia were
commoninSwitzerland(61.34%)thaninGermany(49.62)orAus-
assessedwiththePositiveandNegativeSyndromeScale(PANSS)at
tria (40.23%). Clozapine and olanzapine were most common APs
admission and at biweekly intervals until discharge from hospital.
prescribedasmonotherapyinoursample.CombinationsoftwoAPs
Patients were treated under naturalistic conditions. Remission was
showedgreatvarietyanddifferencesbetweencountriesinpreference
defined according to the symptom-severity component of the con-
of AP-combinations could be seen. In prescriptions with two AP-
sensus criteria (Remission in Schizophrenia Working Group) as a
agents clozapine (27.2%) and risperidone (21.61%) were most
ratingofthreeorlessintherelevantPANSSitemsatdischarge,and
commonlyfound.
response as a reduction of at least 20% in the PANSS total score
Conclusion: Since AP polypharmacy is common practice among
fromadmissiontodischarge.
clinicians, future guidelines should give guidance regarding pre-
Results:Themeandurationofinpatienttreatmentwas54.8days.Of
scription ofrational combinations in thetreatment ofschizophrenia.
thetotalsample,78.5%achievedthecriteriaforresponseand44.6%
Therefore further studies on seeming putative combinations of AP-
thoseforremission.MeanPANSStotalscoresdecreasedfrom72.4at
treatmentareneeded.
admission to 52.5 at discharge. A reduction in PANSS total scores
Policy of full disclosure: Have received honoraria from Affiris,
was found from visit to visit, up to week 8. The most pronounced
AstraZeneca, Novartis, Pfizer and Servier, served as consultant for
declinewasobservedwithinthefirst2weeksoftreatment.Receiver
AstraZeneca,andasaspeakerforAstraZeneca,Bristol–MyersSquib
operating characteristic (ROC) analyses showed that early improve-
andJanssen-Cilag.
ment(reductionofthePANSStotalscorewithinthefirst2weeksof
treatment) predicts remission (AUC=0.659) at discharge. A 20%
reduction inthePANSStotal scorewithinthefirst2weeks wasthe
mostaccuratecut-offforthepredictionofremission(totalaccuracy: S-06-004
65%;sensitivity:53%;specificity:76%). ARCTtoassessthebenefitsofOlanzapineandAmisulpride
Conclusion: The treatment under naturalistic conditions of ‘‘real combinationtreatment(COMBINE):designandmethods
world’’patientssufferingfromschizophreniaappearstobebeneficial
intermsofclinicaleffectiveness.However,aconsiderablenumberof C.Schmidt-Kraepelin(LVR-KlinikumDuesseldorf,Department
patientsdespiteachievingresponsefailtoachievesymptomremission ofPsychiatryII,Duesseldorf,Germany)
during inpatient treatment, underlining the need for optimizing cur-
rent available treatment. Furthermore, the findings of clinical drug Objective: This lecture presents the study rationale and design of a
trials that early improvement is a predictor of subsequent treatment multi-centretrialtoaddresstheissueofantipsychoticpolypharmacy
response were replicated in a naturalistic sample. Further studies in Schizophrenia patients. The prevalence of antipsychotic combi-
should examine whether patients without early improvement benefit nationtreatmentishighinclinicalpracticeworldwide.Thisisdespite
fromanearlychangeofantipsychoticmedication. clinical guidelines doing not recommend such regimen and there is
Policyoffulldisclosure:M.Ja¨gerreceivedremunerationsandfinancial little evidence about potential risks and side effects. Combination
supportforcongressesfromAstraZeneca,EliLillyundJanssen-Cilag. treatment has shown some superiority to monotherapy concerning
efficacy but results are limited since they exclusively involved the
combination with clozapine. Therefore we consider it essential to
S-06-003 study the efficacy of synergistic atypical antipsychotic drugs. Olan-
Thedevelopmentofmultipleantipsychoticcombination zapine has a similar chemical structure and a comparable receptor
treatmentincomparisonbetweenEuropeancountries:findings binding profile as clozapine. Amisulpride has proven favourable
fromtheAMSPproject therapeutic outcome when applied in combination with clozapine.
Whencombinedtogetherweexpectcomplementingreceptorbinding
A.Konstantinidis(Div.ofBiologicalPsychiatry,University properties to enhance efficacy and reduce side effects. Hypothesis:
ofVienna,Vienna,Austria),J.Cordes,D.Degner,T.Schuhmann, Patientswith combination treatmentof OlanzapineandAmisulpride
S.Kasper show higher improvement on the Positive and Negative Symptom
Scaleafter8weeksversuseithermonotherapy.
Objective:Psychotropicpolypharmacy,althoughrelatedwithahigher Methods:Thedesignincludesarandomized,double-blindcontrolled
risk for adverse drug reactions (ADR) and lacking data regarding trialcurrentlybeingexecutedat7centresinGermany.Thereisone
123
S16 EurArchPsychiatryClinNeurosci(2013)263(Suppl1):S7–S111
combinationtreatmentarmandtwomonotherapytreatmentarmswith S-07-003
flexible dosage of oral amisulpride 400–800mg/day and oral olan- Dysfunctionsofthemotorsysteminschizophrenia
zapine 10–20mg/day. Sample size was calculated to n=39101,
assuminganeffect-sizeof0.50withapowerof90%andatwo-sided S.Walther(UniversityBern,Dept.ofPsychiatry,Bern,Switzerland)
ttestwithsignificancelevelof0.025.
Results:RecruitingforthistrialhasstartedJune2012.UptoJanuary Objective: Schizophrenia patients suffer from a variety of motor
17th,201342patientshavebeenrandomized.Theendofthetrialis symptoms,includingparkinsonism,catatonia,neurologicalsoftsigns,
expectedtobeinMarch2015(lastpatientout). abnormalinvoluntarymovementsandpsychomotorslowing.
Conclusion: We expect results to enhance evidence for rational Methods: Literature review of prevalence rates and presentation of
approachestowardsantipsychoticcombinationtreatment. ownresults.
Policyoffulldisclosure:None. Results: Parkinsonism and abnormal involuntary movements are
intrinsic to schizophrenia, but may also be evoked by antipsychotic
treatment. Reduced motor activity is associated with negative
symptoms,catatoniaandpsychomotorslowing.Furthermore,40%of
S-07 Dimensional concepts of psychosis
schizophreniapatientsareimpairedingestureperformance,whichis
related to executive and basic motor function. Mild motor distur-
S-07-001 bances are found in the majority of patients, while severe
Dimensionsofpsychoticsymptomsandbrainphysiology dysfunctions are limited to a minority. Our neuroimaging studies
suggest that hypokinesia is caused by defective cortico-subcortical
W.Strik(UniversityHospitalofPsychiatry,UniversityofBern,Bern, motor loops in schizophrenia. Taken together, a dimensional
Switzerland),SebastianWalther,AlexanderWopfner,Katharina approach to schizophrenia motor symptoms seems promising. A
Stegmayer,DanielaHubl,HelgeHornandThomasDierks purelydescriptiveassessmentofmotorsignsispreferredovertheory-
ladencategorization.Usingobjectivemotorparametersallowsfinding
Abstract: Classical descriptions of schizophrenia are based on the neuralcorrelatesofabnormalmotorbehaviour.
concept of dissociation of higher brain functions, i.e. between Conclusion: The motor dimension of schizophrenia is linked to dis-
Thinking, Feeling and Will (E. Bleuler). This implies a relative tinctdisturbancesinthecerebralmotorsystem.Targetedmodification
independence oftherespective brainfunctionsand,inabrain-phys- of the defective motor system might become a relevant treatment
iological view, interacting but structurally and functionally distinct option in patients suffering from schizophrenia with predominant
brain systems. The dimensional approach to psychotic symptoms is motorfeatures.
appealing to study such a concept, due to the often supposed conti- Policyoffulldisclosure:None.
nuity from symptoms to normal, and to the distinct symptom
domains. In principle, dimensions allow quantifying the degree of
deviation from normal, and to rigorously refer them to a respective
normalbrainfunction.Inasystems-physiologicalview,normalbrain
S-07-004
functions can be understood as the emergent property of brain sys-
Thelimbicsystemandpositivesymptomsofschizophrenia
tems in a functional, homeostatic balance. In this perspective,
deviations can be described as an imbalance between the inhibitory
andtheexcitatorycomponentsoftherespectivecircuitry,resultingin A.Heinz(PsychiatryandPsychotherapyCharite´,Berlin,Germany),
adysfunctionalinhibitionordisinhibitionoftheoutput,alongwitha Schlagenhauf,Florian;Friedel,Eva;Ha¨gele,Claudia
reduced reactivity to external inputs. Although a systematic dimen-
sionalapproachhasnotbeenpossibletoberealizedinDSM-5dueto Abstract: It has long been suggested that dopaminergic dysfunction
insufficientdataandpracticalreasons,inpsychiatricneuroscienceitis plays a key role in the pathogenesis of schizophrenia. Here, we
increasinglyapplied.Basedonbrainimagingresultsobtainedwitha describe empirical studies in animals and in humans that model
dimensional approach to brain physiological changes during psy- dopaminergicneurotransmissionasasignatureforrewardprediction
chotic symptoms, evidence for the existence of three specific errors and suggest that increased phasic dopamine release during
symptom dimensions related to the classical descriptions and to acutepsychosisattributessaliencetootherwiseirrelevantstimuliand
specificbraincircuitrieswillbeshown. canthuscontribute to delusionalmood. Weshowhowthisideahas
Policyoffulldisclosure:None. originallybeentestedonincentivedelaytasks,inwhichaconditioned,
reward predicting cue, appears to be drowned in increasingly noisy
ventral striatal neurotransmission. We further describe how reversal
learningtaskscanbeappliedtodirectlymodelrewardpredictionerrors
S-07-002
andlinkedtoventralstriatalactivation.Thisventralstriatalactivationasa
Thoughtandlanguagedisordersinpsychosis
neuronalsignatureforrewardpredictionerrorsseemstobedysfunctional
in unmedicated patients suffering from schizophrenia. However, it
T.Kircher(Philipps-UniversityMarburgDepartmentofPsychiatry, appearstobeabsolutelynecessarytostrictlymodelbehaviouralperfor-
Marburg,Germany) mance,becauseunmedicatedpatientswithacutepsychosiscanfailto
understandtaskstructureandhencelackoffunctionalactivationdoesnot
Abstracts: Speech and language disorders, such as concretism and necessarilyreflectabiologicalimpairmentbutrathersimplyresultsfrom
formalthoughtdisorder(FTD)arecoresymptomsofSchizophrenia. notperformingthetaskasrequired.Thesameistrueforstudieswith
We will review clinical rating scales of FTD and introduce a new, medicatedpatients,whereblockadeofdopamineD2receptorsbyneu-
validatedscale.Further,brainimagingdatawillbereviewed,relating roleptic medication profoundly alters ventral striatal activation in
speech and language dysfunctions, such as FDS and concretism in schizophrenia.Ourstudiesshowthatventralstriataldysfunctionisakey
Schizophreniatoneuralnetworks.Theimpactofgeneticvarianceand aspect of acute psychosis, while altered prefrontal activation patterns
NNDAreceptorblockagewithKetamineonbrainactivationwillbe appear to be associated with the severity of psychosis rather than
reviewedwithaparticularstressonspeechandlanguageparadigms. schizophreniaperse.
Policyoffulldisclosure:None. Policyoffulldisclosure:None.
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