Imaging transcriptomics identifies gene signatures associated with cortical thinning in schizophrenia

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Schizophrenia is a neuropsychiatric disorder characterized by cortical thinning.
• Structural magnetic resonance imaging (MRI) shows anatomical disturbances.
• The molecular basis of these structural changes is not well understood.

Purpose of the Study:

• To investigate the molecular signatures of cortical thinning in schizophrenia.
• To integrate neuroimaging and transcriptomic data to identify associated genes and pathways.

Main Methods:

• Combined structural MRI from schizophrenia patients and controls with gene expression data.
• Used partial least squares regression to link cortical thickness and gene expression.
• Performed gene ontology enrichment, cell-type deconvolution, and network analysis.

Main Results:

• Identified significant cortical thinning in limbic and paralimbic regions in schizophrenia patients.
• Found associations between cortical alterations and schizophrenia-risk genes (STON2, ANK3, KCNN3).
• Highlighted pathways in stress signaling, calcium homeostasis, and synaptic plasticity, implicating neurons and microglia.

Conclusions:

• Revealed specific molecular correlates of cortical thinning in schizophrenia.
• Identified potential therapeutic targets for neuroanatomical and affective symptoms.
• Advanced understanding of the biological mechanisms underlying structural brain changes in schizophrenia.