OMICS A Journal of Integrative Biology Volume 10, Number 4, 2006 © Mary Ann Liebert, Inc. Genome Wide Gene Expression Studies in Mood Disorders ADOLFO SEQUEIRA and GUSTAVO TURECKI ABSTRACT Microarrays offer the possibility of screening in parallel virtually all genes expressed in a given tissue or to study the molecular signature associated with available treatments. As such, this technology has been increasingly used to investigate multifactorial and polygenic complex traits such as psychiatric disorders, in particular, schizophrenia and mood disor- ders. This review focuses on microarray studies investigating mood disorders. Study designs, methodologic approaches and limitations, subsequent follow-up strategies, and confirmation of results are discussed. Despite the apparent disparate and not always concordant results, it appears evident that this technology is a powerful and inevitable approach for the study of mood disorders, especially when phenotype-specific confounders are properly accounted for. Thus, alterations of mitochondrial, oligodendrocyte, and myelin related genes in bipo- lar disorder, of signaling and olidendroglial related genes in depression, and of GABA-glu- tamate related genes in depression and suicide have been observed and have confirmed new avenues for the study and the treatment of these complex disorders. INTRODUCTION M OOD DISORDERS, also known as affective disorders, are common conditions characterized by mood dysregulation and neurovegetative dysfunction, the most severe variants of which are bipolar disor- der and major depressive disorder. Major depressive disorder may be recurrent (known as unipolar de- pression) or not. Bipolar disorder, classically referred to as manic-depressive illness, differs from major de- pression by presentation of periods of mania during which mood is elated, in addition to depressive episodes. One-year prevalence estimates are approximately 1.3% for bipolar disorder and range between 6.4 and 10.1% for major depression. As a consequence, mood disorders are among the most significant causes of disability. The greatest loss to society, however, is the mortality associated with suicide, which is a com- plication of mood disorders. Between 50 and 70% of suicide completers die during an episode of major de- pression (Arsenault-Lapierre et al., 2004; Cavanagh et al., 2003), and prospective follow-up studies in ma- jor depression suggest that between 7 and 15% of patients will die by suicide (Angst et al., 1992, 1999, 2002; Blair-West, et al., 1999). The investigation of the neurobiological basis of mood disorder began in the late 1950s with the advent of the first efficient pharmacological interventions. Since then, there have been increasing efforts to un- derstand the biological basis of these conditions. Bipolar disorder and major depression are intrinsically re- McGill Group for Suicide Studies, Douglas Hospital, McGill University, Verdun, Quebec, Canada. 444