Distinct contributions of schizophrenia and neurotransmitter pathway genetic liability to neurocognition and antipsychotic efficacy in drug-naïve first-episode schizophrenia - PubMed
3 hours ago
- #polygenic risk score
- #neurocognition
- #schizophrenia
- Higher schizophrenia polygenic risk score (SZ-PRS) predicts schizophrenia diagnosis and poorer baseline executive function and working memory in patients, but not in healthy adults.
- Pathway-specific polygenic risk scores (pPRSs) for neurotransmitter systems (e.g., serotonin, GABA) show weaker associations with diagnosis and baseline cognition but better predict treatment outcomes.
- Higher serotonin-pPRS predicts greater improvement in depressive symptoms, while higher GABA-pPRS predicts greater improvement in overall symptoms during weeks 4-24 of antipsychotic treatment.
- Exploratory analyses suggest treatment response varies across antipsychotics and is differentially associated with pPRSs, supporting personalized treatment stratification.
- Findings indicate distinct contributions of genome-wide and pathway-specific genetic liabilities to schizophrenia phenotypes, highlighting their potential integration for personalized medicine.