Evidence mapPaperPMID 41207901Full record

ArticlePsychopharmacology2025

Investigating antidiabetic drug targets as potential therapeutic modulators for schizophrenia.

Yu-Sheng Huang, Xu Lin, Ya-Juan Xu, Gui-Bing Chen

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Article in Psychopharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1 · What the graph read from it

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3 · Its place in the literature

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Yu-Sheng Huang *Xiamen Xianyue Hospital, Xianyue Hospital Affiliated with Xiamen Medical College, Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, No.387~399 of Xianyue Road, Xiamen, Fujian, 361000, China.ORCID http://orcid.org/0009-0001-8436-3604
Xu Lin *The School of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian, China.ORCID http://orcid.org/0009-0007-4097-2006
Ya-Juan XuThe School of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian, China. 373733112@qq.com.
Gui-Bing ChenXiamen Xianyue Hospital, Xianyue Hospital Affiliated with Xiamen Medical College, Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, No.387~399 of Xianyue Road, Xiamen, Fujian, 361000, China. hjycgb@163.com.ORCID http://orcid.org/0009-0005-0100-7284

Funding

2022 Xiamen City Medical and Health Guidance Project and Guiding 3502Z20224ZD1318
6 · The paper itself

Abstract

rationaleCertain types of antidiabetic drugs (ADs) have been proven to improve cognitive functions and symptom dimensions in schizophrenia (SCZ).

objectivesSchizophrenia is a major contributor to social functional impairment, and antipsychotics (APs) remain the cornerstone of its treatment. Investigating the potential of antidiabetic drugs as APs could significantly advance therapeutic strategies for schizophrenia.

methodsTo assess this potential, we employed an integrated analytical framework that included two-sample Mendelian randomization (MR) using genetic proxies for antidiabetic drug targets, multivariable MR (MVMR), and colocalization analyses. Furthermore, gene and drug enrichment analyses alongside molecular docking studies were performed to elucidate underlying mechanisms and identify candidate drugs. The analysis utilized summary statistics from genome-wide association meta-analyses (GWAS) of schizophrenia, as well as gene expression data from the eQTLGen consortium.

resultsA total of fourteen drug targets were identified among eight major antidiabetic drugs. Notably, RXRB, a target of thiazolidinediones (TZDs), exhibited a strong inverse association with schizophrenia risk (OR: 0.28, 95% CI: 0.21-0.38, P < 0.001). Other significant targets included GPD1 (targeted by metformin), LRP2 (insulin), SLC5A2 (SGLT2 inhibitors), and ABCC8/KCNJ11 and INS (sulfonylureas). Primary and secondary MR analyses confirmed the associations of RXRB, INS, LRP2, and SLC5A2 with gene expression levels. Drug enrichment and molecular docking analyses identified bezafibrate as a promising candidate for repurposing as an AP.

conclusionAntidiabetic drugs may possess therapeutic potential in schizophrenia by modulating specific drug-related pathways.These findings provide new theoretical support for the selection of ADs in patients with schizophrenia comorbid with diabetes, and also offer new insights for the future development of APs.

Indexed as

Antidiabetic drugsDrug targetsGene expressionMendelian randomizationSchizophrenia

Identifiers

PMID41207901

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.