Gene Expression Changes and Potential Impact of Endophenotypes in Major Psychiatric Disorders

Abstract

Gene expression investigations within psychiatry have implicated a number of different genes that are associated with major psychiatric disorders, with the majority of these studies carried out in brains from patients with schizophrenia. In post-mortem brain studies, alterations in the expression of genes involved in oligodendrocyte functioning and myelination, mitochondrial-related functions and energy metabolism as well as synaptic structure and transmission have been identified. To an extent these alterations reflect changes in mRNAs and proteins previously reported in neuropathological investigations of psychiatric disorders. The advent of assessing gene expression changes in the blood of patients with psychiatric disorders may allow us to correlate 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 number of methodological and technical questions still exist with their application. It is therefore necessary that a stringent approach be adopted by researchers when designing gene expression studies and precaution taken as to the final analysis and interpretation of the data generated. 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 benefits and pitfalls of such studies in identifying candidate genes. The relationship between these alterations and endophenotypes in identifying such biomarkers will be discussed as well as potential strategies to overcome weaknesses within studies and how to improve future investigations.