Related Experiment Video

Updated: Mar 20, 2026

Homogeneous Time-resolved Förster Resonance Energy Transfer-based Assay for Detection of Insulin Secretion
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Lipid-lowering and glucose-lowering drug targets differentially modulate antipsychotic treatment efficacy in

Yunqing Zhu1, Rui Yuan1, Zhe Lu1

  • 1Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China.

Cell Reports. Medicine
|March 18, 2026
PubMed

Insights

Genetic risk scores for APOC3 may improve schizophrenia negative symptoms, while GCK scores are linked to less symptom improvement. Volanesorsen/olezarsen show promise, but dorzagliatin requires caution in schizophrenia patients with metabolic issues.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Genetics

Background:

  • Schizophrenia frequently co-occurs with dyslipidemia and hyperglycemia.
  • The impact of metabolic-modifying agents on schizophrenia progression is not well understood.

Purpose of the Study:

  • To investigate the genetic associations between metabolic targets and schizophrenia progression.
  • To evaluate the potential of metabolic-modifying agents in schizophrenia treatment.

Main Methods:

  • Drug-target genetic association study in two independent Han Chinese schizophrenia cohorts.
  • Leveraged metabolic genome-wide association studies to generate genetic risk scores (GRSs) for lipid-modifying and hypoglycemic targets.
  • Genetically proxied proteomics analysis for functional validation.

Main Results:

  • Higher APOC3 GRS associated with reduced triglycerides and improved negative symptoms (PANSS).
  • Higher GCK GRS associated with decreased glucose and less improvement across PANSS scales.
  • Effects on negative symptom recovery were robust in hyperlipidemic/diabetic subgroups.

Conclusions:

  • Volanesorsen/olezarsen targeting APOC3 show potential as adjunctive treatments for schizophrenia.
  • Dorzagliatin targeting GCK warrants caution in schizophrenia patients with metabolic disturbances.
Keywords:
antipsychotic efficacyapolipoprotein C3glucokinaseschizophrenia

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