Blood and brain gene expression in major psychiatric disorders: A search for biomarkers

Abstract

Microarray investigations in psychiatry have so far implicated a number of genes to be associated with major psychiatric disorders, in particular schizophrenia. In postmortem brain studies, alterations in the expression of transcripts encoding for oligodendrocyte functioning and myelination, mitochondrial-related genes, and energy metabolism, as well as synaptic structure and transmission, have been demonstrated. To a certain extent, these alterations reflect changes in associated mRNAs and proteins previously seen in neuropathological investigations of major psychiatric disorders and hence are of great interest. Assessing gene expression changes in the blood of patients with psychiatric disorders will aid in the characterization of their genetic profile. This, in turn, may eventually allow us to relate these findings to brain-related changes, and hence to potentially identify biomarkers for detection, intervention, and treatment. However, while microarray technology has opened the way for high-throughput gene expression analysis, a significant amount of methodological and technical variability still exists in their application. Therefore, it is necessary that a stringent approach be adopted by researchers in designing such experiments and precaution taken in the final analysis and interpretation of results. The aim of this chapter is to provide a balanced view of microarray investigations in the blood and brain in major psychiatric disorders by highlighting the strengths and weaknesses of such studies in identifying candidate genes. Strategies to overcome these weaknesses will be discussed in the context of advancing and improving future microarray investigations in psychiatry. © Springer Science + Business Media, LLC 2008.