Disentangling these effects will help identify causal genes and improve our neurobiological understanding of SCZ. These results show that APDs may confound SCZ-associated gene expression changes in postmortem brain tissue. In contrast, major cell-type shifts inferred in SCZ were primarily unaffected by APD use. Co-expression modules enriched for synaptic function showed convergent patterns between SCZ and some of the APD effects, while those associated with inflammation and glucose metabolism exhibited predominantly divergent patterns between SCZ and APD effects. Brain transcriptome data from macaques chronically treated with APDs showed that APDs affect the expression of many functionally relevant genes, some of which show expression changes in the same directions as those observed in SCZ. APD exposure was associated with numerous changes in the brain transcriptome, especially among SCZ patients on atypical APDs. We compared differential gene expression in the prefrontal cortex of SCZ patients who tested positive for APDs at the time of death with SCZ patients who did not. However, the extent to which these gene expression changes reflect antipsychotic drug (APD) exposure remains uncertain. Recent postmortem transcriptomic studies of schizophrenia (SCZ) have shown hundreds of differentially expressed genes.

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