Precision medicine for psychotic disorders: objective assessment, risk prediction, and pharmacogenomics.

Autor: Hill MD; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.; Indianapolis VA Medical Center, Indianapolis, IN, USA., Gill SS; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA., Le-Niculescu H; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.; Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA., MacKie O; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.; Indianapolis VA Medical Center, Indianapolis, IN, USA., Bhagar R; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA., Roseberry K; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA., Murray OK; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA., Dainton HD; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.; Department of Neurology, Medical University of South Carolina, Charleston, SC, USA., Wolf SK; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.; Department of Neurology, Ohio State University Medical Center, Columbus, OH, USA., Shekhar A; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.; Office of the Dean, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Kurian SM; Scripps Health, La Jolla, CA, USA., Niculescu AB; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA. anicules@iupui.edu.; Indianapolis VA Medical Center, Indianapolis, IN, USA. anicules@iupui.edu.; Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA. anicules@iupui.edu.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2024 May; Vol. 29 (5), pp. 1528-1549. Date of Electronic Publication: 2024 Feb 08.
DOI: 10.1038/s41380-024-02433-8
Abstrakt: Psychosis occurs inside the brain, but may have external manifestations (peripheral molecular biomarkers, behaviors) that can be objectively and quantitatively measured. Blood biomarkers that track core psychotic manifestations such as hallucinations and delusions could provide a window into the biology of psychosis, as well as help with diagnosis and treatment. We endeavored to identify objective blood gene expression biomarkers for hallucinations and delusions, using a stepwise discovery, prioritization, validation, and testing in independent cohorts design. We were successful in identifying biomarkers that were predictive of high hallucinations and of high delusions states, and of future psychiatric hospitalizations related to them, more so when personalized by gender and diagnosis. Top biomarkers for hallucinations that survived discovery, prioritization, validation and testing include PPP3CB, DLG1, ENPP2, ZEB2, and RTN4. Top biomarkers for delusions include AUTS2, MACROD2, NR4A2, PDE4D, PDP1, and RORA. The top biological pathways uncovered by our work are glutamatergic synapse for hallucinations, as well as Rap1 signaling for delusions. Some of the biomarkers are targets of existing drugs, of potential utility in pharmacogenomics approaches (matching patients to medications, monitoring response to treatment). The top biomarkers gene expression signatures through bioinformatic analyses suggested a prioritization of existing medications such as clozapine and risperidone, as well as of lithium, fluoxetine, valproate, and the nutraceuticals omega-3 fatty acids and magnesium. Finally, we provide an example of how a personalized laboratory report for doctors would look. Overall, our work provides advances for the improved diagnosis and treatment for schizophrenia and other psychotic disorders.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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