ArticlePLoS computational biology2024
Therapeutic dose prediction of α5-GABA receptor modulation from simulated EEG of depression severity.
Article in PLoS computational biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed.
- Linking reduced prefrontal microcircuit inhibition in schizophrenia to EEG biomarkers in silico.PLoS computational biology · 2026Article
- Molecular Mechanisms of Depression: The Interplay Between Genes and Receptors.International journal of molecular sciences · 2025Review
- Decoding the structural and functional diversity of GABAFrontiers in pharmacology · 2025Review
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Authors and funding
5 authors.
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Abstract
Treatment for major depressive disorder (depression) often has partial efficacy and a large portion of patients are treatment resistant. Recent studies implicate reduced somatostatin (SST) interneuron inhibition in depression, and new pharmacology boosting this inhibition via positive allosteric modulators of α5-GABAA receptors (α5-PAM) offers a promising effective treatment. However, testing the effect of α5-PAM on human brain activity is limited, meriting the use of detailed simulations. We utilized our previous detailed computational models of human depression microcircuits with reduced SST interneuron inhibition and α5-PAM effects, to simulate EEG of individual microcircuits across depression severity and α5-PAM doses. We developed machine learning models that predicted optimal dose from EEG with high accuracy and recovered microcircuit activity and EEG. This study provides dose prediction models for α5-PAM administration based on EEG biomarkers of depression severity. Given limitations in doing the above in the living human brain, the results and tools we developed will facilitate translation of α5-PAM treatment to clinical use.
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Registered trials
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