Microarray analysis of gene expression in the prefrontal cortex in schizophrenia: a preliminar y study Marquis P. Vawter a,b,1 , Jeremy M. Crook c , Thomas M. Hyde c , Joel E. Kleinman c , Daniel R. Weinberger c , Kevin G. Becker d , William J. Freed a, * a Cellular Neurobiology Research Branch, National Institute on Drug Abuse, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA b Psychiatry and Human Behavior, University of California, Irvine, CA 92697-1675, USA c Clinical Brain Disorders Branch, National Institute of Mental Health, 9000 Rockville Pike, Bethesda, MD 20892, USA d DNA Array Unit, Research Resources Branch, National Institute on Aging, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA Received 21 March 2001; received in revised form 4 October 2001; accepted 9 October 2001 Abstract Microarray studies can be used to examine expression levels for large numbers of genes simultaneously and may be applied to identify genes involved in schizophrenia. A microarray with 1127 brain-relevant genes was used to screen relative gene expression in the dorsolateral prefrontal cortex (DLPFC) from three pools of patients with schizophrenia (n = 15) and three matched control pools (n = 15). Pooling of tissue samples was employed as a strategy to detect changes in gene expression that are consistently found across individual cases of schizophrenia. Differences in gene expression were examined by z-ratios in addition to traditional normalized ratios. Three genes that showed consistently decreased expression in schizophrenia by both z- ratio differences and decreased normalized numerical ratios were identified. These were histidine triad nucleotide-binding protein (HINT), ubiquitin conjugating enzyme E2N (UBE2N) and glutamate receptor, ionotropic, AMPA 2 (GRIA2). Moreover, HINT gene expression was decreased to a similar degree in a prior study. In addition, a decrease in AMPA receptor expression is consistent with a decrease in glutamate synaptic function. These results are subject to limitations based on variations inherent to human subjects and tissue samples, possible effects of neuroleptic treatment, and the requirement for verification using independent techniques. Published by Elsevier Science B.V. Keywords: Microarray; Schizophrenia; Genomics; Gene expression; Postmortem; Prefrontal cortex 1. Introduction Differences in gene expression may underlie the pathophysiology of schizophrenia. A number of indi- vidual molecular differences between patients with schizophrenia and controls have been identified by various techniques (Harrison, 1999). Massive parallel screening techniques such as the microarray method- ology employed in this study and other investigations of schizophrenia (Hakak et al., 2001; Mirnics et al., 2000, 2001; Vawter et al., 2001) have been used to simultaneously examine large numbers of genes for differential expression. Through the use of micro- arrays, novel candidate genes can hopefully be iden- 0920-9964/02/$ - see front matter. Published by Elsevier Science B.V. PII:S0920-9964(01)00377-2 * Corresponding author. Tel.: +1-410-550-1405, fax: +1-410- 550-1621. E-mail addresses: wfreed@intra.nida.nih.gov (W.J. Freed), mvawter@uci.edu (M.P. Vawter). 1 Tel.: +1-949-824-9014; fax: +1-949-824-7012. www.elsevier.com/locate/schres Schizophrenia Research 58 (2002) 11 – 20