LAUSR

Abstract Aim Schizophrenia research emphasizes identification of people at risk of psychosis. 22q11DS, associated with increased risk for schizophrenia, is a window for studying emerging psychosis. Such efforts require systematic evaluation of subthreshold psychotic symptoms that can inform the general population. Our goal is to compare youths with 22q11DS to non-deleted youths with similar clinical features. We also examined comorbidity for psychiatric disorders, neurocognitive profile and, neuroimaging in a subsample. Methods 150 youths with 22q11DS and 150 non-deleted youths (9-24 years) matched on age and sex, stratified for presence of psychosis-spectrum features were evaluated for psychosis (SIPS) and other psychopathologies. Youths and caregivers were evaluated separately. Consensus ratings were analyzed with item-wise comparisons, factor analysis, and differential item functioning. The Penn computerized neurocognitive battery was administered and 3T imaging obtained for a subsample. Results Subthreshold psychotic symptoms were common, with 85% of youths with 22q11DS endorsing one or more symptoms. Most commonly rated items were ideational richness (47%) and trouble with focus and attention (44%). Similar to non-deleted samples, factor analysis showed a 3-factor solution with positive, negative and disorganized components. Youths reported more positive symptoms and caregivers more negative symptoms. For equivalent overall symptom severity, youths with 22q11DS were significantly more likely than non-deleted to have impaired tolerance for stress. Neurocognitive deficits were evident and decreased brain parameters that may be linked in GWAS to genes implicated in schizophrenia. Conclusion Subthreshold psychotic symptoms are common with variable manifestation. Comorbidity, cognitive deficits and aberration in brain parameters are evident and may be associated with genes implicated in schizophrenia. Longitudinal studies are essential as well as larger scale studies.