Research report: Genome-wide association study identifies PPP2R2B as a modifier of positive symptom improvement in schizophrenia patients treated with aripiprazole

A six-week genome-wide association study found that the single-nucleotide polymorphism rs2125443 in PPP2R2B was significantly associated with improvement in positive symptoms among patients with schizophrenia receiving aripiprazole. The association was measured on the Positive and Negative Syndrome Scale, or PANSS, and had a reported statistical significance of p = 2.89 × 10⁻⁸. The researchers examined patients treated with aripiprazole and reported that the PPP2R2B signal was associated with reduction of positive symptoms.

The supplied study abstract does not state the sample size, participant demographics, effect size, allelic frequencies or replication results, so the magnitude and breadth of the association cannot be assessed from the available evidence. It also does not report whether the association extended to negative symptoms or to outcomes beyond the six-week treatment period. PPP2R2B encodes a regulatory subunit of protein phosphatase 2A, or PP2A, and interacts with the dopamine D2 receptor, encoded by DRD2 .

Activity of the D2 receptor is thought to be associated with positive symptoms of schizophrenia. In the study’s gene-interaction analysis, the regulatory effect attributed to PPP2R2B appeared more pronounced in genotype groups characterized by higher DRD2 activity. Together with the study’s examination of dopaminergic synaptic signaling, the authors proposed that PP2A/PPP2R2B could serve as a mediator within a DRD2–PP2A/PPP2R2B–AKT1 signaling pathway.

In that model, PPP2R2B may participate in the modulation of dopamine signaling during aripiprazole treatment. The findings provide evidence that rs2125443 is associated with positive-symptom improvement in the six-week aripiprazole study population. They do not establish rs2125443 as a clinically actionable biomarker, and the abstract provides no basis for using it to guide treatment selection.

More broadly, the study connects a measured clinical pattern—reduction in positive symptoms on PANSS—with a gene that interacts with a dopamine-signaling receptor, while leaving the precise causal and clinical significance of the association unresolved.

Subject of Research: Genetic association with positive-symptom improvement during six weeks of aripiprazole treatment in schizophrenia

Article Title: Genome-wide association study identifies PPP2R2B as a modifier of positive symptom improvement in schizophrenia patients treated with aripiprazole

Article References: Wang, X., Lu, Z., Zhang, Y., Sun, Y., Lu, T., Yan, H., & Yue, W. (2026). Genome-wide association study identifies PPP2R2B as a modifier of positive symptom improvement in schizophrenia patients treated with aripiprazole. BMC Psychiatry. https://doi.org/10.1186/s12888-026-08765-9

Image Credits: AI Generated

DOI: 10.1186/s12888-026-08765-9

Keywords: schizophrenia, aripiprazole, PPP2R2B, rs2125443, genome-wide association study, positive symptoms, PANSS, dopamine D2 receptor, PP2A, AKT1, Genome-wide, association