Upper cortical layer-driven network impairment in schizophrenia.
IF: 14.957
Cited by: 18


Schizophrenia is one of the most widespread and complex mental disorders. To characterize the impact of schizophrenia, we performed single-nucleus RNA sequencing (snRNA-seq) of >220,000 neurons from the dorsolateral prefrontal cortex of patients with schizophrenia and matched controls. In addition, >115,000 neurons were analyzed topographically by immunohistochemistry. Compositional analysis of snRNA-seq data revealed a reduction in abundance of GABAergic neurons and a concomitant increase in principal neurons, most pronounced for upper cortical layer subtypes, which was substantiated by histological analysis. Many neuronal subtypes showed extensive transcriptomic changes, the most marked in upper-layer GABAergic neurons, including down-regulation in energy metabolism and up-regulation in neurotransmission. Transcription factor network analysis demonstrated a developmental origin of transcriptomic changes. Last, Visium spatial transcriptomics further corroborated upper-layer neuron vulnerability in schizophrenia. Overall, our results point toward general network impairment within upper cortical layers as a core substrate associated with schizophrenia symptomatology.


Spatial Transcriptomics

MeSH terms

GABAergic Neurons
Prefrontal Cortex
RNA, Small Nuclear
Transcription Factors


Batiuk, Mykhailo Y
Tyler, Teadora
Dragicevic, Katarina
Mei, Shenglin
Rydbirk, Rasmus
Petukhov, Viktor
Deviatiiarov, Ruslan
Sedmak, Dora
Frank, Erzsebet
Feher, Virginia
Habek, Nikola
Hu, Qiwen
Igolkina, Anna
Roszik, Lilla
Pfisterer, Ulrich
Garcia-Gonzalez, Diego
Petanjek, Zdravko
Adorjan, Istvan
Kharchenko, Peter V
Khodosevich, Konstantin