Towards precision medicine for anxiety disorders: objective assessment, risk prediction, pharmacogenomics, and repurposed drugs

Title	Towards precision medicine for anxiety disorders: objective assessment, risk prediction, pharmacogenomics, and repurposed drugs
Authors	K. Roseberry, H. Le-Niculescu, D. F. Levey, R. Bhagar, K. Soe, J. Rogers, S. Palkowitz, N. Pina, W. A. Anastasiadis, S. S. Gill, S. M. Kurian, A. Shekhar, A. B. Niculescu
Magazine	Molecular Psychiatry
Date	03/07/2023
DOI	10.1038/s41380-023-01998-0
Introduction	Anxiety disorders are increasingly common, impacting individuals' functional abilities and diminishing quality of life. The absence of objective diagnostic tools often leads to underdiagnosis and suboptimal treatment, contributing to adverse life events or addictions. This study aimed to identify blood biomarkers for anxiety through a four-step methodology. Initially, a longitudinal within-subject design was employed in individuals with psychiatric disorders to pinpoint blood gene expression alterations between self-reported low and high anxiety states. Subsequently, candidate biomarkers were prioritised using a Convergent Functional Genomics approach, integrating existing field evidence. The top biomarkers derived from this initial identification and ranking were then validated in an independent cohort of psychiatric subjects experiencing clinically severe anxiety. Finally, these candidate biomarkers were evaluated for their clinical utility, specifically their capacity to predict anxiety severity and future clinical deterioration (e.g., hospitalisations where anxiety was a contributing factor), within another independent cohort of psychiatric subjects. The research demonstrated enhanced accuracy of individual biomarkers through a personalised strategy, stratified by gender and diagnosis, particularly evident in women. GAD1, NTRK3, ADRA2A, FZD10, GRK4, and SLC6A4 emerged as the biomarkers with the strongest overall evidence. Furthermore, the study determined which biomarkers are targets of existing therapeutic agents (such as valproate, omega-3 fatty acids, fluoxetine, lithium, sertraline, benzodiazepines, and ketamine), indicating their potential for guiding patient-medication matching and treatment response monitoring. The biomarker gene expression signature also facilitated the identification of drugs suitable for repurposing in anxiety treatment, including estradiol, pirenperone, loperamide, and disopyramide. Given the adverse consequences of unmanaged anxiety, the current scarcity of objective treatment guidance, and the addictive potential of current benzodiazepine-based anxiety medications, there is a critical need for the precise and personalised approaches developed in this research.
Quote	K. Roseberry, H. Le-Niculescu and D. F. Levey et al. Towards precision medicine for anxiety disorders: objective assessment, risk prediction, pharmacogenomics, and repurposed drugs. Mol. Psychiatry. 2023. Vol. 28(7):2894-2912. DOI: 10.1038/s41380-023-01998-0
Element	Lithium (Li)
Industry	Pharmaceutical Industry , Chemical & Pharmacy , Research & Laboratory , Medical Devices