Original articleCritical Factors in Gene Expression in Postmortem Human Brain: Focus on Studies in Schizophrenia
Section snippets
Subjects
Human brain specimens were collected in the Section on Neuropathology of the Clinical Brain Disorders Branch at the National Institute of Mental Health (NIMH) through the Offices of the Chief Medical Examiner of the District of Columbia and of Northern Virginia, after autopsy, and through tissue donations via funeral homes. Informed consent to study brain tissue was obtained from the surviving next-of-kin for all cases, according to Protocol #90-M-0142 approved by the NIMH/National Institutes
Subject Selection
Fifty-three subjects with a documented history of schizophrenia and 90 control subjects were identified as suitable for further studies after excluding individuals having: 1) a primary psychiatric diagnosis other than schizophrenia, such as a mood disorder, substance abuse, or anxiety disorder; 2) clinical history and/or neuropathological abnormalities consistent with a primary neurological disorder such as Alzheimer’s disease, Parkinson’s disease, or diffuse Lewy Body disease; 3) a positive
Discussion
In this study, we report the results of a series of analyses aimed at parsing variance in gene expression in postmortem brain tissue. We also estimated a fold of between-group differences in gene expression that could be resolved with these brain tissue samples. We confirmed the often-reported observations that RNA quality, pH, PMI, and age result in changes in gene expression and that patients with schizophrenia as a sample population tend to have more extreme values in these confounders than
Summary
We have identified and/or validated factors that should be considered when assembling a cohort of postmortem brains for the investigation of gene expression. We found that the most important factor affecting expression levels of housekeeping genes, regardless of the diagnosis or brain tissue type, was total RNA quality. Accurate and reliable assessment of RNA quality should thus be an essential step in gene expression studies. Other factors to be considered include pH, PMI, age, agonal state,
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