1. ¹Neuroscience Discovery Research, Wyeth Research, Princeton, NJ, USA
2. ²Molecular Neuropsychiatry Branch, National Institute on Drug Abuse, NIH, DHHS, Baltimore, MD, USA

Correspondence: Dr BP Sokolov, Molecular Neuropsychiatry Branch, National Institute on Drug Abuse, NIH, 5500 Nathan Shock Dr., Baltimore, MD 21224, USA. E-mail: Bsokolov@intra.nida.nih.gov

Received 23 March 2004; Revised 7 June 2004; Accepted 12 July 2004; Published online 10 August 2004.

Abstract

Major depressive disorder is one of the most common and devastating psychiatric disorders. To identify candidate mechanisms for major depressive disorder, we compared gene expression in the temporal cortex from 12 patients with major depressive disorder and 14 matched controls using Affymetrix HgU95A microarrays. Significant expression changes were revealed in families of genes involved in neurodevelopment, signal transduction and cell communication. Among these, the expression of 17 genes related to oligodendrocyte function was significantly (P<0.05, fold change>1.4) decreased in patients with major depressive disorder. Eight of these 17 genes encode structural components of myelin (CNP, MAG, MAL, MOG, MOBP, PMP22, PLLP, PLP1). Five other genes encode enzymes involved in the synthesis of myelin constituents (ASPA, UGT8), or are essential in regulation of myelin formation (ENPP2, EDG2, TF, KLK6). One gene, that is, SOX10, encodes a transcription factor regulating other myelination-related genes. OLIG2 is a transcription factor present exclusively in oligodendrocytes and oligodendrocyte precursors. Another gene, ERBB3, is involved in oligodendrocyte differentiation. In addition to myelination-related genes, there were significant changes in multiple genes involved in axonal growth/synaptic function. These findings suggest that major depressive disorder may be associated with changes in cell communication and signal transduction mechanisms that contribute to abnormalities in oligodendroglia and synaptic function. Taken together with other studies, these findings indicate that major depressive disorder may share common oligodendroglial abnormalities with schizophrenia and bipolar disorder.