Targeting Processing Speed Deficits to Improve Social Functioning and Lower Psychosis Risk in Adolescents at Clinical High Risk for Psychosis

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Project Summary Prevention of schizophrenia has primarily focused on adolescents and young adults who are considered to be at clinical high risk (CHR) for psychosis. These youngsters display subtle clinical symptoms that are similar to psychosis but not as intense, and therefore considered to still be amenable to early intervention. Initial prevention efforts used anti-psychotics as the primary preventive agents but these were shown to be largely ineffective. More recent approaches have focused on the remediation of the cognitive deficits that are readily apparent and predictive of future illness in CHR adolescents. However, while cognitive remediation has shown substantial promise for improving cognitive deficits and improving outcomes in patients with schizophrenia, it has not yet been markedly successful with CHR youth. The proposed study will test an innovative internet- based remotely-delivered Specific COgnitive REmediation plus Surround (or SCORES) intervention for CHR adolescents ages 14-20 years old that targets early processing speed deficits as measured at the neuropsychological level with the processing speed domain from the NIMH-Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) consensus cognitive battery. The proposed SCORES treatment package is grounded in a theoretical framework, supported by findings from our group and others, where processing speed deficits contribute to poor social functioning, which in turn leads to an increased risk for psychosis. We specifically selected cognitive remediation because it directly targets a core cognitive mechanism, processing speed, which is a rate limiting factor to higher order behaviors and clinical outcome in CHR adolescents. To overcome past difficulties in applying a cognitive remediation treatment to CHR teenagers, we have developed a platform to support our targeted processing speed training, which involves reducing the heterogeneity of the CHR study population (including a reduced age range, narrowed clinical criteria, and targeting individuals with pre-existing processing deficits). In addition, we have adding a novel support surround component which is expected to increase enjoyment and promote retention. In the single-arm R61 phase, a 2-year proof of concept study, 30 CHR individuals will receive SCORES for 10 weeks(4hrs per wk/40 hrs total) with a midpoint assessment at 20 hours (5 weeks) to demonstrate target engagement and identify the optimal dose of SCORES needed to engage the target. In the R33 phase, a 3 year pilot study, we will replicate target engagement in a new and larger sample of 54 CHR individuals randomized to SCORES (optimized dose)or to a Video GameControl condition to firmly establish the centrality of processing speed. In addition, the R33 phase will determine if changes in target engagement are associated with improved social functioning and decreasing attenuated positive symptoms.