Postmortem study identifies claustrum gene-expression changes in schizophrenia

The case-control study analyzed RNA-sequencing data from postmortem dorsal claustrum (dCLA) samples from 47 people with schizophrenia and 49 unaffected comparison participants. The primary outcome was gene-expression differences between groups; the researchers also assessed gene-set enrichment and compared findings with the anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (dlPFC), putamen, and caudate.

The analysis identified 1,717 differentially expressed genes in the dCLA, of which 1,149 (66.9%) were upregulated in schizophrenia. Upregulated genes were often associated with immune responses or transcription regulation, while downregulated genes were often related to mitochondrial activity or oxidative phosphorylation. The dCLA had more detected differentially expressed genes than the ACC (289) or dlPFC (102), although threshold-free analyses showed a shared pattern of expression changes across these three regions.

The findings point to the dCLA as a site of molecular alterations associated with schizophrenia, but do not establish whether these changes cause illness or indicate a treatment target. The study used postmortem tissue, and the authors note that connectivity, intrinsic circuitry, or cell-type composition could contribute to the observed pattern. The results do not by themselves support a change in clinical care.