11.2022 - 02.2026

Common and rare genetic variants and clinical variables associated to the risk of antipsychotic-induced extrapyramidal symptoms or weight gain in persons with schizophrenia or bipolar disorder - VARASE

Antipsychotics (AP) are the cornerstone of the psychopharmacological treatment of schizophrenia and bipolar disorders. However, they can induce extrapyramidal symptoms (EPS) and weight gain, which can lead to discontinuation of treatment. Therefore, one of the main challenges for the prescriber is the selection of a safe and effective treatment. Pharmacogenomics can allow the clinician to select the most appropriate drug to optimize therapeutic efficacy and minimize the risk of adverse events. Genomic association studies (GWAS) were conducted to explore common single nucleotide polymorphisms (SNPs) associated with AP-induced EPS and weight gain, but the results are inconclusive. Furthermore, no study has been conducted so far to investigate the role of rare genetic variants, such as copy number variations (CNVs) and truncated protein variants (PTVs) in AP-induced EPS or weight gain. Therefore, the present research project aims to investigate whether common and rare genetic variants are associated with the risk of developing EPS or weight gain in patients treated with AP. For this purpose, patients with schizophrenia or bipolar disorder, recruited into workpackage 3 of Spoke 5 and treated with AP for at least 3 months, will undergo a clinical evaluation to ascertain the onset of EPS and the increase in body weight after treatment with AP. Common and rare genetic variants will be identified by GWAS, exome sequencing and long-reading genome-wide sequencing. A polygenic risk score (PRS) will be calculated. Associations between clinical/demographic variables, SNPs, CNV, PTV, PRS and AP-induced EPS or weight gain will be explored, explored using linear or logistical regressions. Significant associations are expected to be identified to predict the risk of EPS or AP-induced weight gain. These findings would help implement pharmacogenomic testing in clinical practice to prevent AP adverse events.

These findings would help implement pharmacogenomic testing in clinical practice to prevent AP adverse events.

Settori Scientifico Disciplinari

MED/25  PSYCHIATRY

Spoke 5 : Mood and Psychosis