A Microarray Gene Expression Study of Long-term Neuronal Changes Associated with Opioid Administration

Abstract

Statistical methods are applied to a microarray data set arising from an experimental study of opioid dependence. The experiment was designed to investigate how morphine dependence in mice alters gene expression in spinal cord mRNA. The unbalanced design involves two treatments (morphine, placebo) and four time points corresponding to consecutive stages of opioid dependence, classified as tolerance, withdrawal, early abstinence and late abstinence. The aim of the study was to identify genes that characterize the tolerance, withdrawal and two abstinence stages and to describe how gene expression is altered in moving from one stage to the next. This paper first uses a chi- square statistic to identify a small set of genes that exhibit differential expression over one or more treatment combinations. This gene set is then examined further using cluster analysis and inference methods to uncover specific genes and gene clusters that play a role at different stages of opioid dependence and, in particular, a role in the persistence of effect into the late abstinence stage. The latter effect implies that morphine dependence has a long-term genetic impact. The statistical power of the unbalanced study to uncover differentially expressed genes is calculated as a prelude to further investigation.