Linking GWAS risk genes to transcriptional features of major depressive disorder via in vivo Perturb-seq - PubMed
3 hours ago
- #Perturb-seq
- #Oxytocin Signaling
- #Major Depressive Disorder
- Developed an in vivo AAV-Perturb-seq system for parallel loss-of-function screening of major depressive disorder (MDD) risk genes in the mouse brain.
- Identified a cluster of risk genes whose loss downregulates oxytocin signaling in neurons, a feature also observed in MDD patients.
- Demonstrated that neuron-specific downregulation of Dennd1a impairs the oxytocin receptor-ERK pathway and induces depressive-like behaviors in mice.
- Showed that pharmacological enhancement of the oxytocin signaling pathway alleviates depressive-like phenotypes in Dennd1a-deficient mice and restores signaling in human neurons.
- Highlights the importance of patient stratification for targeted treatments in complex psychiatric disorders like MDD.