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Updated: Jun 26, 2025

Author Spotlight: Exploring Sex-Specific Glial Signatures and Therapeutic Leads for Alzheimer's Disease
Published on: May 20, 2024
Sex affects transcriptional associations with schizophrenia across the dorsolateral prefrontal cortex, hippocampus,
Kynon J M Benjamin1,2,3, Ria Arora4,5, Arthur S Feltrin4
1Lieber Institute for Brain Development, Baltimore, MD, USA. KynonJade.Benjamin@libd.org.
Abstract:
Schizophrenia is a complex neuropsychiatric disorder with sexually dimorphic features, including differential symptomatology, drug responsiveness, and male incidence rate. Prior large-scale transcriptome analyses for sex differences in schizophrenia have focused on the prefrontal cortex. Analyzing BrainSeq Consortium data (caudate nucleus: n = 399, dorsolateral prefrontal cortex: n = 377, and hippocampus: n = 394), we identified 831 unique genes that exhibit sex differences across brain regions, enriched for immune-related pathways. We observed X-chromosome dosage reduction in the hippocampus of male individuals with schizophrenia. Our sex interaction model revealed 148 junctions dysregulated in a sex-specific manner in schizophrenia. Sex-specific schizophrenia analysis identified dozens of differentially expressed genes, notably enriched in immune-related pathways. Finally, our sex-interacting expression quantitative trait loci analysis revealed 704 unique genes, nine associated with schizophrenia risk. These findings emphasize the importance of sex-informed analysis of sexually dimorphic traits, inform personalized therapeutic strategies in schizophrenia, and highlight the need for increased female samples for schizophrenia analyses.
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