Abstracts for the Sixth Biennial SIRS Conference Oral Session: Prediction S101 Discussion: Our results using a novel machine learning approach suggest that an ensemble of cognitive, early environmental and genetic features can predict schizophrenia with signifcant accuracy. Our results also give key information on cognitive and environmental factors that can be targeted in early identifcation programs and offer novel insights about genetic loci that may be prioritized in future investigations of the pathophysiology of the disease. However, the near chance-level predictive ability of the genetic modality alone calls for the implementation and testing of more complex models of interaction between multiple risk factors. O9.5. ABERRANT DOPAMINE SYSTEM FUNCTION REVERSED BY THE OREXIN RECEPTOR ANTAGONIST TCS1102 IN A RODENT MODEL OF SCHIZOPHRENIA Stephanie Perez* ,1 , Daniel Lodge 1 1 University of Texas Health Science Center at San Antonio Background: Aberrant regulation of dopamine system function is thought to contribute to psychosis in schizophrenia patients; however, the brain regions associated with this dysregulation have not been conclusively dem- onstrated. We have recently demonstrated that medium spiny neurons in the nucleus accumbens (NAc) receive convergent input from the ventral hippocampus (vHipp) and paraventricular nucleus of the thalamus (PVT). Furthermore, inactivation of either the vHipp or PVT is suffcient to reverse aberrant dopamine system function in rodent models of schizophre- nia. Using, chemogenetic experiments we now provide conclusive evidence that the thalamic input to the NAc plays a role in the regulation of dopa- mine neuron activity. These data demonstrate that the vHipp and thalamus (specifcally the PVT) work in concert to regulate VTA dopamine neuron population activity. Such data are important as they provide evidence that thalamic abnormalities may contribute to the aberrant dopamine system function observed in schizophrenia and suggest that the PVT may be a novel site for intervention in psychosis. To examine this, we explored the orexin system, which is known to provide a dense innervation of the PVT. Methods: Pregnant Sprague Dawley (SD) rats were treated on gestational day (GD) 17 with either methylazoxymethanol acetate (MAM; 22 mg/kg, i.p.) or saline. For Poly I:C, pregnant dams were treated on GD12 (7.5 mg/kg Poly I:C or saline). Male pups weaned on post-natal day 21 in groups of 2–3 until adulthood (>60 days). For chemogenetic experiments, normal SD rats were bilaterally micro-injected with AAV2 vectors (Addgene) express- ing hm3D(Gq)(pAAV-h8yn-HA-hm3D(Gq)-mcherry; 0.5μL) into the PVT or mPFC. Control rats were administered the viral vector lacking the hm3D encoding gene. Prior to testing, CNO (0.75ul; 300uM) was injected into the nucleus accumbens. In vivo extracellular recordings were performed to measure dopamine neuron activity in the VTA. Spontaneously active VTA dopamine neurons were recorded using previously established electrophys- iological criteria. Results: NMDA activation of the PVT induces a signifcant increase in VTA dopamine neuron population activity. MAM- and Poly I:C-treated rats (both verifed rodent models of schizophrenia) consistently display aber- rant VTA dopamine neuron population activity, which is restored by phar- macological inactivation of the PVT with TTX. Chemogenetic activation of PVT neurons projecting to the mPFC do not affect VTA dopamine neu- ron activity; however, activation of PVT neurons projecting to the nucleus accumbens induces a signifcant increase in dopamine neuron population activity. This effect can be replicated in rats that receive microinjections of the endogenous orexin peptide A or B into the PVT. Consequently, dopa- mine neuron function can be restored in MAM-treated rats that received a systemic injection of the orexin peptide antagonist TCS 1102. Discussion: We now demonstrate that orexin receptors are expressed on PVT neurons projecting to the NAc and may serve as a substrate for phar- macological manipulation of this pathway. Here, we provide evidence that both systemic and intracranial (PVT) administration of the orexin receptor antagonist, TCS1102, can normalize aberrant dopamine system function in a rodent model of schizophrenia. Collectively, these data suggest that tar- geting orexin signaling in the thalamus, specifcally, the PVT, may represent a novel site of intervention for psychosis associated with schizophrenia. O9.6. SPECIFIC SYMPTOMS IN ADOLESCENCE PREDICT PSYCHOSIS IN THE NORTHERN FINLAND BIRTH COHORT 1986 Juha Veijola* ,1 , Tuula Hurtig 1 , Graham Murray 2 , Pirjo Mäki 1 1 University of Oulu; 2 University of Cambridge Background: A number of psychological symptoms have been found to pre- dict psychosis. Many studies have found no specifcity to separate symp- toms predicting non-psychotic psychiatric disorders from those predicting psychotic disorders. We were able to conduct prospective study comparing adolescent symptoms predicting non-psychotic psychiatric disorders and psychotic psychiatric disorders. Methods: Members of the of the Northern Finland Birth Cohort 1986 were asked to fll in PROD-screen questionnaire at age 15–16 years. PROD- screen includes 21 items both measuring positive prodromal symptoms, negative prodromal symptoms and general symptoms. We were able to follow 6,514 participants using Finnish Hospital Discharge Register detecting new hospital treated mental disorders till 23 years. Results: The highest prevalence of positive symptoms in the PROD-screen were in the group of subjects who developed psychotic disorder (65% over the cut off) compared to subjects who developed non-psychotic disorder (36%; OR 5.7; 95%CI 2.1–15.4, p<0.001, adjusted for parents’ psychiatric disorder, family structure, family SES, adolescent’s cannabis use and gen- der), and to subjects without any disorder (27%; adjusted OR 6.5; 2.8–15.0, p<0.001). Respective fgures for negative symptoms were 55% in the group of psychotic subjects compared to 30% in subjects with non-psychotic dis- order (3.3; 1.4–7.7, p=0.01) and 24% in the ‘healthy’ (4.1; 1.9–8.6, p<0.001). When comparing separate symptoms in those having psychiatric hospital treatments, we found four positive symptoms and one negative symptom predicting specifcally psychotic disorders. Discussion: In this large prospective population sample both positive and negative symptoms in adolescence associated specifcally with development of frst episode psychosis. O9.7. INDIVIDUALIZED LONG-TERM OUTCOME PREDICTION OF PSYCHOSIS IN AN OBSERVATIONAL STUDY: A MACHINE LEARNING APPROACH Jessica De Nijs 1 , Daniel P.J. van Opstal 1 , Ronald J. Janssen 1 , Wiepke Cahn 1 , Hugo Schnack* ,2 , GROUP Investigators 1 Brain Centre Rudolf Magnus, University Medical Center Utrecht; 2 University Medical Centre Utrecht Background: Schizophrenia and related disorders have heterogeneous out- comes. Predicting long-term psychosis outcome may be helpful in improv- ing treatment decision making. The aim of our study was to develop and validate a long-term outcome prediction model of psychosis in individual patients. Many studies have shown that outcome is related to symptoms, demographic, clinical, cognitive, genetic and environmental data – at the level of correlations. We hypothesized that, using machine learning (ML), it is possible to predict individual long-term outcome based on patterns that are present in these data at baseline. Second, we test if variables that were recently found to be predictive of short-term outcome (European First Episode Schizophrenia Trial (EUFEST), Koutsouleris et al, 2016) can yield accurate long-term outcome predictions in our sample.