Details

Autor(en) / Beteiligte

• Ruzicka, W Brad
• Mohammadi, Shahin
• Fullard, John F
• Davila-Velderrain, Jose
• Subburaju, Sivan
• Tso, Daniel Reed
• Hourihan, Makayla
• Jiang, Shan
• Lee, Hao-Chih
• Bendl, Jaroslav
• Voloudakis, Georgios
• Haroutunian, Vahram
• Hoffman, Gabriel E
• Roussos, Panos
• Kellis, Manolis

Titel

Single-cell multi-cohort dissection of the schizophrenia transcriptome

Ist Teil von

• Science (American Association for the Advancement of Science), 2024-05, Vol.384 (6698), p.eadg5136

Ort / Verlag

United States: The American Association for the Advancement of Science

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• The complexity and heterogeneity of schizophrenia have hindered mechanistic elucidation and the development of more effective therapies. Here, we performed single-cell dissection of schizophrenia-associated transcriptomic changes in the human prefrontal cortex across 140 individuals in two independent cohorts. Excitatory neurons were the most affected cell group, with transcriptional changes converging on neurodevelopment and synapse-related molecular pathways. Transcriptional alterations included known genetic risk factors, suggesting convergence of rare and common genomic variants on neuronal population-specific alterations in schizophrenia. Based on the magnitude of schizophrenia-associated transcriptional change, we identified two populations of individuals with schizophrenia marked by expression of specific excitatory and inhibitory neuronal cell states. This single-cell atlas links transcriptomic changes to etiological genetic risk factors, contextualizing established knowledge within the human cortical cytoarchitecture and facilitating mechanistic understanding of schizophrenia pathophysiology and heterogeneity.