Predicting Social Cognitive Outcomes in Adolescent-Onset Schizophrenia: A Hierarchical Analysis of Pharmacogenetic, Clinical, and Environmental Factors

Association between *CYP2D6* metabolizer phenotype (normal vs reduced) and social cognition performance (theory of mind, empathy) in adolescents with schizophrenia

This cross-sectional study (73 adolescents with schizophrenia, 58 controls) analyzes the link between CYP2D6 metabolizer phenotype and social cognition deficits. Reduced CYP2D6 metabolizers show poorer theory of mind performance and more severe negative symptoms. CYP2D6 status is a significant independent predictor of theory of mind (β = 0.178, p = 0.005), while its effect on empathy is fully mediated by negative symptom severity. The authors advocate pharmacogenetic stratification in early-onset schizophrenia.

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The association between reduced CYP2D6 metabolism and socio-cognitive deficits is interesting but remains correlative: the cross-sectional design and modest sample size preclude causal inference, and the effect could be mediated by exposure to CYP2D6-metabolized antipsychotics. The model explaining 88.8% of variance raises overfitting concerns. To be regarded as an exploratory lead rather than an established genotyping indication.