Pharmacogenetics of Antipsychotic Treatment in Schizophrenia

Pharmacogenetics explores how inherited genetic variation influences individual responses to antipsychotic medications in schizophrenia. By profiling variants in genes that encode drug targets, metabolising enzymes and transporters, researchers aim to predict both therapeutic efficacy and risk of adverse effects. Common single-nucleotide polymorphisms (SNPs) in dopamine and serotonin receptor genes, cytochrome P450 enzymes and drug-efflux transporters have been linked to differences in drug plasma levels, receptor occupancy and symptom improvement. Recent advances in high-throughput genotyping and genome-wide association studies (GWAS) have enabled the development of polygenic risk scores that aggregate the small effects of numerous loci into a single predictive measure. Although these approaches hold promise for guiding antipsychotic selection and dosing, translation into routine clinical practice remains limited by modest predictive accuracy, under-representation of diverse populations and the need to integrate non-genetic factors such as age, sex and comorbidities. Ongoing efforts to combine pharmacokinetic models with pharmacodynamic markers and to validate genetic panels in large, multi-centre cohorts aim to advance precision medicine in psychiatry, reduce trial-and-error prescribing and improve outcomes for people with schizophrenia worldwide.

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Pharmacogenetics of Antipsychotic Treatment in Schizophrenia publication trend

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Technical terms

Pharmacogenetics: The study of inherited genetic variation in drug-metabolising enzymes, targets and transporters that affects individual responses to medications.

Single-nucleotide polymorphism (SNP): A common genetic variant at a single DNA base position that may influence gene function or regulation.

Genome-wide association study (GWAS): An analysis that scans the genome for SNPs associated with a particular trait, such as drug response or disease risk.

Polygenic risk score (PRS): A composite measure that sums the effects of multiple risk alleles to estimate an individual’s genetic predisposition to a trait or outcome.

Treatment-resistant schizophrenia (TRS): A form of schizophrenia characterized by inadequate response to at least two antipsychotics of adequate dose and duration, often treated with clozapine.

References

1. Prediction of antipsychotics efficacy based on a polygenic risk score: a real-world cohort study. Frontiers in Pharmacology (2024).
2. Impact of Pharmacogenetic Testing on Clozapine Treatment Efficacy in Patients with Treatment-Resistant Schizophrenia. Biomedicines (2024).
3. Genome-wide association study identified six loci associated with adverse drug reactions to aripiprazole in schizophrenia patients. Schizophrenia (2023).