174.1 Neurocognition and Transition to Psychosis: Baseline Functioning in the Second Phase of the North American Prodrome Longitudinal Study

Background: Neurocognition is a central characteristic of schizophrenia and other psychotic disorders. Identifying the pattern and severity of neurocognitive functioning during the “near-psychotic,” prodromal, clinical high-risk (CHR) state is necessary to develop accurate predictors of psychosis and more effective, early interventions. Our goal was to identify core neurocognitive dysfunctions associated with the CHR phase, measure the ability of neurocognitive tests to predict the transition to psychosis, and determine whether the neurocognitive deficits are robust or explained by potential confounders. Methods: A case–control study carried out by a consortium of 8 university-based, outpatient programs studying the psychosis prodrome in North America. Baseline neurocognitive functioning was collected from 2008 to 2012 in the second phase of the North American Prodrome Longitudinal Study (NAPLS-2). CHR individuals (n = 689) and healthy controls (HCs, n = 264), ages 12–35 received testing. We evaluated neurocognitive differences between those who did and did not transition to psychosis, differences between medicated and unmedicated groups, and time to conversion. Nineteen neuropsychological tests and four factors derived from factor analysis were studied. Results: The factors were Executive Function/Visual-Spatial, Verbal, Attention/Working Memory (WM), and Declarative Memory. Amongst widespread mild to moderate impairments, CHR individuals were significantly impaired compared to HCs on Attention/WM and Declarative Memory. CHR converters had large Declarative Memory and Attention/Working Memory deficits (Cohen’s d = ~.8, P < .001) compared to controls and were significantly worse on these dimensions than non-converters. In Cox regression, impaired Declarative Memory and high Verbal (premorbid) ability in addition to age, site, and positive psychotic symptoms, significantly predicted time to conversion in those who later transitioned to psychosis. The pattern of impairments could not be accounted for by premorbid or current general cognitive ability, medications, current depression, alcohol or cannabis abuse. Conclusion: Neurocognitive impairment is a robust characteristic of CHR individuals, especially those who later develop psychosis. Tests tapping Verbal and Visual Declarative Memory and attention/WM were most sensitive to imminent psychosis among those at CHR. Interventions targeting the enhancement of neurocognitive functioning are warranted in this population.