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Transcriptional Regulation in Schizophrenia 109The DLPFC is one brain region that has been implicated in the pathophysiologyof schizophrenia. Significant decreases in prefrontal cortical volume in adolescentSCZ (James et al., 2004) and in first episode SCZ (Bagary et al., 2003)have been observed. Glutamate serves as the primary chemical transmitter in corticalregions and serves to integrate and coordinate information within the DLPFCand between other cortical regions (Levitt et al., 1993). Changes in glutamate transmissionin the DLPFC are believed to underlie cognitive functions that are disturbedin schizophrenia (Lewis & Gonzalez-Burgos, 2000), and pathophysiologicalevidence in SCZ supports this: decreased cell size of neurons that utilize glutamateas their primary transmitter (Pierri et al., 2001), decreased inputs to these neurons(Glantz & Lewis, 2000), and crowding of these glutamate neurons (Selemonet al., 1998) in the DLPFC. In addition to glutamate, studies using postmortembrain tissue from SCZ reveal changes in another important cell type in the DLPFC–GABA utilizing cells (Hashimoto et al., 2003; Lewis et al., 1999; Pierri et al., 1999;Woo et al., 1997; Woo et al., 1998). Despite evidence for the involvement of thesecell populations in schizophrenia, specific molecular changes underlying thiscellular dysfunction are not well characterized in SCZ.Synaptic Proteins and SchizophreniaSeveral possible mechanisms of neuronal dysfunction underlie schizophrenia,including alterations in synaptic function (Aston et al., 2004). Synapses are comprisedof several types of proteins and are known to be involved in thepathogenesis of schizophrenia (Eastwood, 2004), but two groups that have receivedconsiderable attention include synaptic vesicle proteins (e.g., syntaxin,synpatophysin, synaptotagmin), which assist in neurotransmitter release, andsynaptic plasma membrane proteins (e.g., SNAP23 and SNAP25), which play acritical role in synaptogenesis. Two approaches have been taken to further understandthe influence of the genes encoding synaptic proteins on the manifestationof schizophrenia. Mutational/polymorphic analysis has revealed asignificant association of a nonsense mutation (an alteration in sequence thatresults in premature cessation of translation, producing a truncated protein thatis usually not functional) in synaptogyrin 1 with schizophrenia (Verma et al.,2004), whereas another study did not find an association of polymorphisms insynapsin III, even though the gene encoding the transcript maps to a schizophreniasusceptibility region (Imai et al., 2001; Ohmori et al., 2000; Ohtsukiet al., 2000; Tsai et al., 2002). A greater number of studies have examined levelsof mRNA and/or protein in specific brain regions to determine their relationshipto the pathophysiology of schizophrenia. For example, synaptophysinmRNA is significantly decreased in the hippocampus (Eastwood et al., 1995a;Eastwood & Harrison, 1999; Webster et al., 2001) and mRNA and protein levelsare decreased in the temporal lobe of SCZ (Eastwood & Harrison, 1995).Decreases in additional synaptic proteins are reported in the temporal lobe of