194. Neuromelanin-Sensitive MRI as an Early Indicator of Dopamine Dysfunction in Individuals at Risk for Psychosis

Abstract

(HC) participants aged 12-35 (average = 19.0 ± 4.5 years). Linear and nonlinear curves were fit to relationships between social cognitive variables and age. Differences in age effects between CHR and HC were modeled as interaction terms. Duration of a prodromal syndrome prior to baseline and medication history were tested for interactions with age effects. Results: Emotion perception and social perception age trajectories did not differ by group. Theory of mind age trajectory, particularly for sarcasm items, had a lower slope for CHR than HC. CHR diverged from HC from mid-adolescence onward (starting to differ between approximately ages 15 and 17.5), with a minimum observation window of 4 years required to detect correlations with age. Age trajectory for theory of mind was unrelated to the presence or duration of a prior prodromal syndrome but did interact with medication history, wherein participants with an antipsychotic or antidepressant medication history did not differ from HCs. Only antipsychotic-and antidepressant-naive CHR participants showed a smaller slope for theory of mind, with differences from HC increasing with advanced age. Conclusion: In the current study, all social cognitive abilities increased during adolescence, but development of theory of mind appeared blunted for CHR participants starting in mid-adolescence. This difference, however, was only true for participants without an antipsychotic or antidepressant medication history, which could suggest benefits of early treatment or subgroups within CHR for whom social cognition is affected differently. These cross-sectional results require longitudinal replication and further inquiry into the relationships between treatment history and social cognitive development. Current results suggest that factors related to risk for psychosis may moderate adolescent social development, and that interventions targeting social cognition may be particularly helpful at this stage. Background: Clinical criteria for Ultra-High Risk of psychosis (UHR) show moderate specificity for the prediction of the first psychotic episode (FEP), with an average true positive rate of approximately 30% at 3 years. We have recently developed a multimodal probabilistic model using the odds ratio form of Bayes' rule that achieved sensitivity=73% and specificity=96% for FEP combining clinical data and biological data in a small sample of UHR patients. To validate this approach, we built a similar model using cognitive and clinical data from the Personal Assessment and Crisis Evaluation ("PACE 400") study. Methods: 430 UHR patients presenting to a specialist psychosis service in metropolitan Melbourne, Australia, were identified using the Comprehensive Assessment of At-Risk Mental State (CAARMS). Transition to FEP occurred in 114 within 13 years of presentation. Demographic and clinical data were available for the full cohort and cognitive data for 258 cases. Positive and negative likelihood ratios (LRs) for FEP were calculated for clinical and cognitive variables with statistically...

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