ArticleScience advances2019
Drug discovery for psychiatric disorders using high-content single-cell screening of signaling network responses ex vivo.
Article in Science advances, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Neurospecific Molecules Measured in Periphery in Humans: How Do They Correlate with the Brain Levels? A Systematic Review.International journal of molecular sciences · 2022Pooled it
- Functional Mapping of Neurodevelopmental Disease Pathways to Key Neurodevelopmental Processes Represented in the Developmental Neurotoxicity In Vitro Testing Battery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Genomic insights into the tunicamycin-induced endoplasmic reticulum stress response in peripheral blood mononuclear cells: A comprehensive RNA sequencing analysis.Biochemistry and biophysics reports · 2026Article
- Network-based drug repurposing for psychiatric disorders using single-cell genomics.Cell genomics · 2025Article
- Altered PLCβ/IPBiomedicines · 2024Article
- Neuropsychiatric disorders, chronotype and sleep: A narrative review of GWAS findings and the application of Mendelian randomization to investigate causal relationships.Genes, brain, and behavior · 2024Review
- Concordance between the In Vivo Content of Neurospecific Proteins (BDNF, NSE, VILIP-1, S100B) in the Hippocampus and Blood in Patients with Epilepsy.International journal of molecular sciences · 2023Article
- GSK3β and mTORC1 Represent 2 Distinct Signaling Markers in Peripheral Blood Mononuclear Cells of Drug-Naive, First Episode of Psychosis Patients.Schizophrenia bulletin · 2022Article
- Targeting NMDA receptors in neuropsychiatric disorders by drug screening on human neurons derived from pluripotent stem cells.Translational psychiatry · 2022Review
- Systems biological assessment of altered cytokine responses to bacteria and fungi reveals impaired immune functionality in schizophrenia.Molecular psychiatry · 2022Article
- Facing the urgency of therapies for progressive MS - a Progressive MS Alliance proposal.Nature reviews. Neurology · 2021Review
- Functional patient-derived cellular models for neuropsychiatric drug discovery.Translational psychiatry · 2021Review
- MTORC1 signaling as a biomarker in major depressive disorder and its pharmacological modulation by novel rapid-acting antidepressants.Therapeutic advances in psychopharmacology · 2021Review
- Advances toward precision medicine for bipolar disorder: mechanisms & molecules.Molecular psychiatry · 2021Review
- Exploring the neuropsychiatric spectrum using high-content functional analysis of single-cell signaling networks.Molecular psychiatry · 2020Article
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
There is a paucity of efficacious new compounds to treat neuropsychiatric disorders. We present a novel approach to neuropsychiatric drug discovery based on high-content characterization of druggable signaling network responses at the single-cell level in patient-derived lymphocytes ex vivo. Primary T lymphocytes showed functional responses encompassing neuropsychiatric medications and central nervous system ligands at established (e.g., GSK-3β) and emerging (e.g., CrkL) drug targets. Clinical application of the platform to schizophrenia patients over the course of antipsychotic treatment revealed therapeutic targets within the phospholipase Cγ1-calcium signaling pathway. Compound library screening against the target phenotype identified subsets of L-type calcium channel blockers and corticosteroids as novel therapeutically relevant drug classes with corresponding activity in neuronal cells. The screening results were validated by predicting in vivo efficacy in an independent schizophrenia cohort. The approach has the potential to discern new drug targets and accelerate drug discovery and personalized medicine for neuropsychiatric conditions.
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Registered trials
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 OpenQuestion graph.