Lipid-lowering and glucose-lowering drug targets differentially modulate antipsychotic treatment efficacy in schizophrenia - PubMed
5 hours ago
- #metabolic-modifying agents
- #genetic risk scores
- #schizophrenia
- Schizophrenia is often comorbid with dyslipidemia and hyperglycemia.
- A drug-target genetic association study was conducted in two Han Chinese schizophrenia cohorts (N = 2,111/292 for discovery/validation).
- Higher APOC3 GRS (inhibited by volanesorsen/olezarsen) is linked to attenuated triglycerides and improved negative symptoms (PANSS β = 1.23).
- Higher GCK GRS (activated by dorzagliatin) is associated with decreased glucose but less improvement in PANSS total (β = -1.70).
- Causal associations of GCK were replicated in an independent validation cohort.
- APOC3 and GCK effects on negative symptom recovery are robust in hyperlipidemic/diabetic subgroups.
- Volanesorsen/olezarsen are potential adjunctive candidates; dorzagliatin warrants caution in schizophrenia with metabolic disturbance.