(F=7.33 p=0.009) and more confused (F=14.31 p=0.0005) follow-ing theMIST than following the SMCT, giving support to the effectivenessof the stress paradigm. Preliminary PET data suggests a significantdifference between groups in the AST (F=6.30 p=0.005), with CHRand SCZ having larger [11C]-(+)-PHNO displacement in response to theMIST, as comparedwithHV.No significant differencewasobtained in theSMST (F=3.16 p=0.0.06) or the LST (F=1.53 p=0.23).Discussion: Sensitization is one of the fewproposedmechanisms for thehyperdopaminergic state in psychosis: DA sensitization to stress duringadolescence and early adulthood may progressively set the stage forenhanced DA release, which when combined with other relevant riskfactors, may result in enhanced vulnerability for psychosis. This study isthe first to test stress-induced DA release in CHR and SCZ, andmay haveimportant theoretical and clinical implications regarding efforts to abortor delay conversion to psychosis.

doi:10.1016/j.schres.2010.02.204

THE ROLE OF GLUCOCORTICOIDS IN THE EMERGENCE OFPSYCHOSIS: POTENTIAL GENETIC AND EPIGENETIC MECHANISMS

Elaine Walker, Michael Compton, Dan ShapiroEmory University Atlanta, Ga, USA

Background: Advances in the field of molecular genetics havebroadened our understanding of the mechanisms involved inepigenetic processes. Hormones, including glucocorticoids, play asignificant role in the signaling cascades that alter the expression ofgenes governing neuronal function. In particular, the HPA axisinvolves a neurohormonal signaling process, via glucocorticoidreceptors in the brain that is influenced by both environmentalfactors and intrinsic developmental 'programs'. Research onpatients with schizophrenia and other psychotic disorders indicatesHPA hyperactivity that may be related with symptom severity. Todate, glucocorticoid secretion during the prodrome, prior to clinicalonset, has not been examined. We present data on the relation ofglucocorticoid secretion with progression to psychosis in prodromalyouth, and genetic factors that might contribute to this progression.Methods: Longitudinal data on cortisol secretion were obtained on130 adolescents who were followed for 4 years. Of these, 56 metcriteria for the prodrome to psychosis as measured by theStructured Interview for Prodromal Syndromes (SIPS), 36 werehelp-seeking but not prodromal, and 38 were healthy controls.Genotyping was conducted for several candidate genes that havebeen linked with the expression of psychosis, including COMT andBDNF. Diagnostic status was measured over the course of 4 yearswith the Structured Clinical Interview for DSM (SCID).Results: There is a significant longitudinal increase in cortisolsecretion through the course of adolescence, and it is morepronounced among individuals who meet criteria for the prodrome.Further, when comparing the 14 prodromal youth who converted toAxis I psychotic disorder with those who did not, the longitudinalincrease is greater for those who converted within 4 years ofbaseline. Data on the role of candidate genes in modulatingdevelopmental changes in HPA activity are also presented.Discussion: Neurodevelopmental changes in the HPA axis thatincrease glucocorticoid secretion during adolescence appear to belinked with conversion to psychosis. Potential neural mechanismsmediating the relation between HPA activity and prodromal progres-sion will be discussed. In particular, plausible genetic and epigeneticfactors in the neuropathological cascade, as well as implications forfuture research on preventive intervention, will be considered.

doi:10.1016/j.schres.2010.02.205

WHY TRANSITION TO PSYCHOSIS IS NOT THE WHOLESTORY - NEUROCOGNITIVE MARKERS OF TRANSITION ANDPOOR FUNCTIONAL OUTCOME SEVEN TO 14 YEARSAFTER IDENTIFICATION AS ULTRA-HIGH RISK AT THEPACE CLINIC

Ashleigh Lin1,2, Alison R. Yung2, Warrick Brewer2, Barnaby Nelson2,Annie Bruxner2, Daniela Spiliotacopoulos2, Christina Broussard2,Magenta B. Simmons2, Christos Pantelis1, Patrick McGorry2,Stephen J. Wood1

1Melbourne Neuropsychiatry Centre, University of MelbourneMelbourne, Victoria, Australia; 2ORYGEN Research Centre Melbourne,Victoria, Australia

Background: The progression from ultra-high risk (UHR) to frankpsychosis remains unclear. Early predictors may help to bettertarget intervention, although it is still unknown whether neuro-cognitive indicators when at risk can be used to predict transition topsychosis. This follow-up study investigated baseline markers oftransition to psychosis and poor functional outcome in a group ofindividuals identified as UHR at the Personal Assessment and CrisisEvaluation (PACE) Clinic seven to 14 years prior.Methods: Transition data was collected from the first 198 individualswho were seen at PACE (from 1994 - 2000). Psychopathological,neuropsychological and functional outcome datawas collected on 120of these individuals. Most of them had received neurocognitiveassessment at baseline. Using Cox regression survival analysis (fortransition to psychosis) and logistic regression modelling (forfunctional outcome),we identified neurocognitivemarkers at baselinethatpredicted the transition to psychosis andpoor functional outcome.Results: Lower visual memory scores at baseline (odds ratio=0.94,95% CI 0.90 – 0.98, p=0.001) significantly predicted the transitionto psychosis. The overall model was significant, χ2=10.62, df=1,p=.001. The data, however, showed a number of individuals withvery poor functional outcome, some of whom had never transi-tioned to psychosis. This group of individuals was defined by poorquality of life, low global assessment of functioning (GAF) scores,and higher negative symptoms. Poor functioning individualsshowed significantly worse baseline neurocognitive function acrossverbal and verbal memory neurocognitive domains. When neuro-cognitive variables were modelled, the best model for predictingpoor functional outcome (χ2=22.08, df=3, p<.001) includedpoorer verbal memory for stories (odds ratio=0.76, 95% CI 0.63 –

0.92, p=.004) and visual memory (odds ratio=1.24, 95% CI 1.03 –

1.48, p=.02) and slower psychomotor speed (odds ratio=1.06,95% CI 0.98 – 1.15, p=0.17). When psychopathology scores atbaseline were added to the model described above, the model waseven stronger in predicting poor functional outcome, χ2=32.47,df=4, p<.001. Poorer verbal memory for stories (odds ratio=0.70,95% CI 0.55 – 0.90, p=.005) and lower mania scores (oddsratio=0.60, 95% CI 0.40 – 0.91, p=.015) significantly predictingpoor functioning at follow-up. The model also included higher BPRSpsychotic subscale scores (odds ratio=0.1.44, 95% CI 0.98 – 2.11,p=.06) and SANS scores (odds ratio 1.08, 95% CI 1.00 – 1.12,p=.07), although these were not significant. Individuals withverbal IQ (odds ratio=6.30, p=.007) or verbal memory indexscores (odds ratio=14.00, p=0.001) at baseline that were onestandard deviation or more below the meanwere significantly morelikely to be functioning very poorly at follow-up.Discussion: Many individuals identified as UHR may not transitionto psychosis, but still experience poor functional outcome and lowquality of life. Poor neurocognitive performance when at UHR ismore strongly related to poor functional outcome than transition tofrank psychosis. Verbal memory performance when at UHR mayhelp differentiate those most likely to experience a poor functionaloutcome from those who have a better outcome. The data suggest

Abstracts174