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Transcriptional Regulation in Schizophrenia 107regions coincide to disrupt cell signaling and synaptic plasticity in a developmentallyprogressive manner resulting in schizophrenic symptomology.The temporal lobe, including the hippocampus and entorhinal cortex (EC), is aprimary brain region associated with schizophrenia. The EC is integral to the activityof the hippocampus, regulating the interaction of the hippocampus with otherbrain regions. Functionally, the EC is involved in declarative memory (Squire &Zola-Morgan, 1991; Squire & Zola, 1996). Specifically, the EC along with otherregions of the temporal lobe, mediates episodic (time, place and associated emotions)and semantic (facts and concepts) memory. Bilateral lesions of the EC producesignificant memory (Baxter & Murray, 2001; Leonard et al., 1995) andcognitive deficits (Chavoix et al., 2002). Moreover, functional imaging studiesindicate that the EC is activated in the associative aspects of memory (Klingberget al., 1994) and that activity modulation in the EC is involved in the encodingphase of declarative memory (Fernandez et al., 1999).Schizophrenic patients (SCZ) exhibit diffuse cognitive impairment throughoutthe course of the illness that is associated with dysregulation of the temporal lobe.Neuropsychological studies attribute differential deficits in verbal and visual declarativememory to hippocampal dysfunction (Gruzelier et al., 1988; Saykinet al., 1991). Moreover, such deficits persist after more florid psychotic symptomsresolve or improve with treatment (Gur et al., 2003), perhaps indicating aneuroanatomical abnormality in the ventromedial temporal lobe.Functional imaging studies report significant deficits in temporal lobe functionin SCZ (Gur, 1995; Gur et al., 1995; Nordahl et al., 1996; Russell et al.,1997; Tamminga et al., 1992). Structural imaging studies indicate a slight, butsignificant, volume reduction in temporal lobe structures including the EC inSCZ (Altshuler et al., 2000; Bogerts et al., 1993; Gur et al., 2000; Lee et al.,2004; Shenton et al., 1992; B. Turetsky et al., 1995; B. I. Turetsky et al., 2003),although other studies fail to observe these differences (Buchanan et al., 1993).Normally, the human hippocampus increases in volume throughout adolescence(Saitoh et al., 2001), and this change is more pronounced in males versus females(Suzuki et al., 2005). Following young adulthood, there is a gradual declinein EC and HIPP volumes albeit at a slightly different rates (Pruessneret al., 2001; Raz et al., 2004). In contrast to individuals without schizophrenia,hippocampal volume is decreased in individuals diagnosed with childhoodonsetschizophrenia (Giedd et al., 1999; Jacobsen et al., 1998) and adolescents/young adults designated as high risk show significant reductions in temporallobe volumes (Lawrie et al., 2002). Interestingly, there is a relative paucity ofneurodegeneration, cell death, or gliosis observed in the brains of SCZ (Arnoldet al., 1998; Falkai et al., 1999), suggesting that there are alterations in the neuralcircuitry in SCZ.The human cortex has a laminar structure consisting of six “layers.” In normalhuman cortex, the different cell types are distributed in a specific laminar pattern.