Mediating Effects of Social Cognition on the Relationship between Neurocognition and Functional Outcome in Early Course Schizophrenia: Implications for Cognitive Enhancement Therapy

Background and Purpose: Cognitive remediation for early course schizophrenia, such as Cognitive Enhancement Therapy (CET), are the most promising interventions to facilitate cognitive improvement and reduce long-term functional disability. CET is a social work-developed comprehensive approach to cognitive remediation, such that it targets both neuro- and social cognition, along with functioning. For continued optimization of programs like CET, it is critical to develop a strong understanding of the mechanistic relationships among the primary treatment targets. The current study examined the mediating effects of social cognition on the relationship between neurocognition and functional outcome in a large sample of individuals with early course schizophrenia.

Methods: This secondary study used baseline data from 102 outpatients with early course schizophrenia who participated in an 18-month multi-site trial of CET (Pittsburgh: n = 53; Boston: n = 49). A comprehensive battery of field standard measures assessed neurocognitive and social-cognitive performance, and functional outcome. Composite indexes were calculated for each of these three outcome domains. A path analysis approach was conducted in R using the mediation package to determine the average causal mediation effect (ACME) between neurocognition (predictor) and functional outcome (outcome) mediated by social cognition (mediator). Significance of ACME was tested using bootstrapping with 5,000 permutations and the models adjusted for study location. The mediating effects of the overall social-cognitive composite and individual subdomains of social cognition (emotional intelligence, facial emotion recognition, theory of mind, and social inference) were explored.

Results: Significant positive associations were observed between neurocognition and social cognition (b = 0.68, p = <.001), along with social cognition and functional outcome (b = 0.23, p = 0.032). The direct effect of neurocognition on functional outcome was non-significant (b = -0.18, p = .221), whereas the indirect effect of social cognition on this relationship was significant (ACME: b = 0.16, p = 0.042). A similar pattern was observed for social inference. Higher neurocognitive performance significantly predicted stronger social inference (b = 0.35, p <.001), and stronger social inference predicted better functional outcome (b = 0.59, p <.001). The direct effect of neurocognition on functional outcome remained non-significant (b = -0.23, p = .074), whereas the indirect effect of social inference was significant (ACME: b = 0.20, p<.001). No other individual subdomains of social cognition had a significant indirect effect on the relationship between neurocognition and functional outcome. Reverse causal models with neurocognition as the mediator were explored and non-significant (all ACME p’s > 0.088).

Conclusions and Implications: The results provide important insights to the mechanistic relationships among the primary targets of CET in early schizophrenia. The mediation models suggest that the impact of neurocognitive impairment on poor functional outcome occurs, in part, through social cognitive impairment, particularly social inference challenges. The findings provide continued support for the provision of comprehensive approaches to cognitive remediation, such as CET, in the early course of schizophrenia. Furthermore, the observation of social inference as a particular mechanism of functional status has implications for cognitive remediation strategies to specifically target this domain in the early course population.