Candidates for drug repurposing to address the cognitive symptoms in schizophrenia

• Published in: Progress in neuro-psychopharmacology & biological psychiatry 2023-01, Vol.120, p.110637-110637, Article 110637
• Main Authors: Koch, Elise, Kauppi, Karolina, Chen, Chi-Hua
• Format: Article
• Language: English
• Subjects: Cognition; Computational Biology; Drug Repositioning; Female; Genetics; Humans; Male; Medicin och hälsovetenskap; Network medicine; Neuroprotective Agents - therapeutic use; Protein-protein interactome; Proteins; Schizophrenia; Schizophrenia - complications; Schizophrenia - drug therapy; Schizophrenia - genetics; Sex differences
• ISSN: 0278-5846; 1878-4216; 1878-4216
• DOI: 10.1016/j.pnpbp.2022.110637

In the protein-protein interactome, we have previously identified a significant overlap between schizophrenia risk genes and genes associated with cognitive performance. Here, we further studied this overlap to identify potential candidate drugs for repurposing to treat the cognitive symptoms in schizophrenia. We first defined a cognition-related schizophrenia interactome from network propagation analyses, and identified drugs known to target more than one protein within this network. Thereafter, we used gene expression data to further select drugs that could counteract schizophrenia-associated gene expression perturbations. Additionally, we stratified these analyses by sex to identify sex-specific pharmacological treatment options for the cognitive symptoms in schizophrenia. After excluding drugs contraindicated in schizophrenia, we identified 12 drug repurposing candidates, most of which have anti-inflammatory and neuroprotective effects. Sex-stratified analyses showed that out of these 12 drugs, four were identified in females only, three were identified in males only, and five were identified in both sexes. Based on our bioinformatics analyses of disease genetics, we suggest 12 candidate drugs that warrant further examination for repurposing to treat the cognitive symptoms in schizophrenia, and suggest that these symptoms could be addressed by sex-specific pharmacological treatment options. •This is the first study using a network medicine approach incorporating gene expression data to identify repurposing candidates to treat the cognitive symptoms in schizophrenia.•Based on our bioinformatics analyses of schizophrenia genetics related to cognitive functioning, we identified 12 drug repurposing candidates, most of which have anti-inflammatory and neuroprotective effects.•Due to gene expression differences in male and female patients, four of those 12 drugs were identified in females only, three were identified in males only, and five were identified in both sexes, suggesting that the cognitive symptoms in schizophrenia could be addressed by sex-specific pharmacological treatment options.