Upper cortical layer-driven network impairment in schizophrenia
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Upper cortical layer-driven network impairment in schizophrenia. / 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.
I: Science Advances, Bind 8, Nr. 41, eabn8367, 2022.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Upper cortical layer-driven network impairment in schizophrenia
AU - Batiuk, Mykhailo Y.
AU - Tyler, Teadora
AU - Dragicevic, Katarina
AU - Mei, Shenglin
AU - Rydbirk, Rasmus
AU - Petukhov, Viktor
AU - Deviatiiarov, Ruslan
AU - Sedmak, Dora
AU - Frank, Erzsebet
AU - Feher, Virginia
AU - Habek, Nikola
AU - Hu, Qiwen
AU - Igolkina, Anna
AU - Roszik, Lilla
AU - Pfisterer, Ulrich
AU - Garcia-Gonzalez, Diego
AU - Petanjek, Zdravko
AU - Adorjan, Istvan
AU - Kharchenko, Peter V.
AU - Khodosevich, Konstantin
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
U2 - 10.1126/sciadv.abn8367
DO - 10.1126/sciadv.abn8367
M3 - Journal article
C2 - 36223459
AN - SCOPUS:85139747465
VL - 8
JO - Science advances
JF - Science advances
SN - 2375-2548
IS - 41
M1 - eabn8367
ER -
ID: 323458390