Critical factors in gene expression in postmortem human brain: Focus on studies in schizophrenia.

Author(s): Lipska BK, Deep-Soboslay A, Weickert CS, Hyde TM, Martin CE, Herman MM, Kleinman JE

Publication: Bio Psychiatry, 2006, Vol. 60, Page 650

PubMed ID: 16997002 PubMed Review Paper? No

Purpose of Paper

Conclusion of Paper

Studies

1. Study Purpose

   The purpose of this paper was to identify sources of variation in gene expression among patient (diagnosis, age, smoking, agonal state) and postmortem (postmortem interval (PMI), tissue pH) factors and RNA quality for the following genes: PBGD, TBP, GUSB, beta-actin, B2M.

   Summary of Findings:

   Housekeeping gene expression differed among the brain regions examined. PMI, brain pH, and agonal state (rapidity of death) influenced gene expression in a region dependent manner, as PMI and pH were better predictors of expression in the hippocampus while agonal state was inversely proportional to house keeping gene expression in DLPFC white matter. RNA quality, as measured by RNA integrity number (RIN), was a major determinant of gene expression in all brain regions examined. Also RIN was negatively correlated to (a) brain pH in the hippocampus, (b) pH and PMI in DLPFC grey matter, and (c) pH and smoking history in DLPFC white matter. Patient gender did not significantly influence housekeeping gene expression.

   Biospecimens

   • Tissue - Brain

   Preservative Types

   • Frozen

   Diagnoses:

   • Schizophrenia
   • Autopsy
   • Not specified

   Platform:

   Analyte	Technology Platform
   RNA	Spectrophotometry
   RNA	Real-time qRT-PCR
   RNA	Automated electrophoresis/Bioanalyzer

   Pre-analytical Factors:

   Classification	Pre-analytical Factor	Value(s)
   Preaquisition	Patient gender	Female Male
   Preaquisition	Patient age	50.6 +/- 17.6 years for schizophrenic patients 41.7 +/- 14.8 years for non-schizophrenic patients
   Biospecimen Acquisition	Biospecimen location	Hippocampus Dorsolateral prefrontal cortex, gray matter Dorsolateral prefrontal cortex, white matter
   Preaquisition	Diagnosis/ patient condition	No history of psychological problems
   Preaquisition	Rapidity of death	Fast (terminal phase < 10 min.) Not fast (terminal phase >1 h)
   Biospecimen Aliquots and Components	pH	Brain pH 6.42 +/- .32 for schizophrenic patients Brain pH 6.55 +/- .35 for non-schizophrenic pts
   Preaquisition	Diagnosis/ patient condition	Habitual smoker Non-smoker
   Preaquisition	Postmortem interval	39.7 +/- 19.5 h for schizophrenic patients 32.0 +/- 14.3 h for non-schizophrenic patients

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