Multiomic atlas maps stalled neurogenesis in adult hippocampus of depressed patients
Scientists published a multiomic atlas of the adult human hippocampus in Nature Medicine, the largest study of its kind, to trace molecular dysfunction in major depressive disorder. The team integrated cell-type-specific gene expression, chromatin accessibility, and protein expression data from nonmedicated individuals with the disorder. They identified a neurogenic lineage in the subgranular zone of the hippocampus and found evidence of a stalled neurogenic process tied to stress-related reprogramming and interferon signaling. Excitatory and inhibitory neurons showed dysregulated transcription factor networks. The analysis also revealed cellular stress, excitatory-inhibitory imbalance, impaired synaptic plasticity, reduced metabolic capacity, and immune activation across developmental stages.
The findings provide new understanding of pathogenesis behind hippocampus-dependent cognitive symptoms in major depressive disorder, including negative memory bias. The work maps genetic and epigenetic regulation of gene expression in the disorder and identifies overlapping mechanisms with autoimmune, neurodevelopmental, and neurodegenerative diseases, suggesting potential therapeutic targets.
Written by the Genomes desk from the primary source cited and linked above and checked against it. Research use only; not medical advice. Corrections: editor@genome.news.