Preliminary Study of Baseline Demographic Moderators of Behavioral Change during Cognitive Enhancement Therapy for Early Course Schizophrenia

Background and Purpose: A recent confirmatory trial demonstrated continued support for Cognitive Enhancement Therapy (CET) in the treatment of early course schizophrenia (Wojtalik et al., 2021). A natural next step in the optimization of CET for this population is the identification of moderators of treatment response. This secondary analysis sought to identify potential demographic moderators of cognitive, functional outcome, and symptom change during two social work-developed interventions, CET compared to Enriched Supportive Therapy (EST).

Methods: The current research utilized data from 102 (CET: n = 58, EST: n = 44) outpatients with early course schizophrenia who participated in an 18-month confirmatory, multi-site (Pittsburgh: n = 53; Boston: n = 49) randomized trial of CET. Assessments were completed at baseline, 9, and 18 months. Composite indexes were calculated for cognition, functional outcome, and symptomatology. Potential baseline demographic moderators included age, sex, race, education, employment status, IQ, illness duration, substance abuse history, and antipsychotic medication dose and adherence. Mixed-effects models, adjusting for study location, were conducted to identify any significant group (CET vs. EST) x time (baseline, 9, and 18 months) x baseline demographic interactions.

Results: No significant moderators were identified for differential cognitive change. Sex was a trend-level moderator of trajectory differences in cognition (p = .064), but at the completion of treatment males and females did not significantly differ in their responses to the treatments (p = .698). Race emerged as a significant moderator of differential functional outcome change (p = .028), such that White individuals had a large response to CET (d = .95) and Non-White individuals had a large response to EST (d = .89). Race also moderated differential change in symptoms at 18 months (p = .041). Non-White individuals in EST had the largest improvement in symptoms (d = .63) followed by White participants in CET (d = .56). Illness length (p = .027) and history of substance abuse (p = .034) also moderated differential symptom change at 18 months. Irrespective of illness duration (e.g., 1 SD above or below the mean), participants in CET had large symptom improvements (d > .80) while those in EST slightly declined (d < -.07). Participants with substance abuse histories responded the strongest to CET regarding symptom improvement (d = .70). EST participants without substance abuse histories had the next largest improvement in symptoms (d = .56).

Conclusions and Implications: This preliminary investigation has provided initial evidence that sex, race, illness duration, and past substance abuse may be key moderators of response to cognitive remediation among individuals in the early course of schizophrenia. Understanding responses to CET among subgroups has implications for the personalization of this treatment and warrants further understanding of treatment moderators.

Wojtalik, J. A., Mesholam-Gately, R. I., Hogarty, S. S., Greenwald, D. P., Litschge, M. Y., Sandoval, L. R., Shashidhar, G., Guimond, S., Keshavan, M. S., & Eack, S. M. (2021). Confirmatory Efficacy of Cognitive Enhancement Therapy for Early Schizophrenia: Results from a Multi-Site Randomized Trial [Manuscript submitted for publication].