“This article reviews the steps in a discovery process including the acquisition of high-quality tissue and preparation and use of microarray technology.”

There is currently an international scientific effort to discover the genes associated with mood disorders, including major depressive disorder, bipolar disorder, and schizophrenia. This paper reviews a new methodology for studying thousands of genes in one experiment in contrast to our previous ability to investigate only one gene at a time and thus provides the hope for studying the etiology of these disorders at an entirely new level of complexity. There is increasing recognition that mood disorders constitute major national and international public health problems. Mood disorders are currently ranked at number four out of all diseases on a lifetime disability index by the World Health Organization. These disorders are known to be caused by multiple rather than single gene abnormalities.

This paper describes a novel methodology that is now being used in a large number of areas of neuroscience from cell culture studies to studies in fruit flies, mice, rats, non-human primates, and humans. Microarrays are such a potentially powerful methodology that their use has exploded in basic and clinical research in academia and industry related to a large number of diseases.

This article reviews the steps in a discovery process including the acquisition of high-quality tissue and preparation and use of microarray technology. Identified genes can also be evaluated in terms of their location on chromosomal regions which have been shown to be associated with mood disorders. Microarrays are only the first major step in the process. Further efforts in the investigation involve multiple strategies for studying the function and the potentially abnormal structure of the genes. Microarrays present a method that can identify genes or pathways for potential new targets for developing drugs and eventually could lead to the use of gene therapy and prevention strategies.

Our research represents a truly collaborative investigative program. It was first stimulated by a request for a proposal from the National Institute of Mental Health for the development of research centers. The Principal Investigators on this project include scientists from the University of Michigan (Stan Watson and Huda Akil), University of California, Davis (Ted Jones), Stanford University (Rick Myers, Allan Schatzberg), and University of California, Irvine (William Bunney). Additional collaborators who were on this paper include Blynn G. Bunney, Marquis P. Vawter, Hiroaki Tomita, Jun Li, Simon J. Evans, and Prabhakara V. Choudary. Most of the investigators had a longstanding interest and involvement in research programs concerned with neuroscience studies of the major mental disorders. The group recognized the potential impact of the new microarray technology and built it into a major collaborative effort. Subsequent support for this endeavor came from the Pritzker Family Philanthropic Fund and the William Lion Penzner Foundation. Since this article was written, the investigative team has published a number of papers identifying critical methodological issues in postmortem microarray investigations.