For any gene expression study, the quality of the starting material significantly impacts the ability to detect biologically relevant changes in gene expression. Multiple studies have established that high-quality RNA can be obtained from human postmortem brain6–10, even in cases with long postmortem intervals or with low brain pH. Ensuring a consistent and high level of RNA integrity has therefore become a standard quality control step prior to transcriptional analysis. Other potential confounding factors, such as agonal state/brain pH, age, gender, ethnicity, and smoking history, may differentially influence ante-mortem gene expression of individual transcripts and of specific groups of transcripts, and have to be addressed for each case-control comparison. Consideration of agonal state/brain pH is particularly important to ensure that reliable gene expression data can be extracted. The duration and extent of the agonal state appears to be inversely related to brain pH11, and a lower brain pH, indicating a protracted agonal state, has been associated with significant changes in transcriptional profile12, in particular of apoptotic, reactive oxygen stress, mitochondrial, chaperone and proteasome pathways.13 Furthermore, variations in respiratory stress in
