Figure 2. Subtraction image at two different brain levels (40 mm and 50 mm above the anterior commissure-posterior commissure [AC-PC] line) of schizophrenic

volunteers (SZ) performing a task. The regional cerebral blood flow (rCBF) of the schizophrenic volunteers … Some of our functional imaging studies have focused on the hippocampus. Because statistical parametric mapping (SPM) analytic techniques rely on group average data and because the hippocampus is both small Inhibitors,research,lifescience,medical and variably located in humans, magnetic resonance-guided hand sampling producing volumes of interest (VOIs) is necessary to adequately represent. the structure. We used magnetic resonance-guided individual VOI image sampling and made several interesting observations about, hippocampal function. First, in a practiced, overlearned auditor}’ recognition task, the hippocampus remains uninvolved with task performance with respect to changes in rCBF, in both normal volunteers and those with schizophrenia. This confirms that novelty and/or learning is necessary for hippocampal Inhibitors,research,lifescience,medical activation. Inhibitors,research,lifescience,medical Second, rCBF in

the schizophrenic hippocampus is greater than in the normal hippocampus bilaterally, and across different task conditions. Third, the noncompetitive JV-methyl-D-aspartate (NM’DA) antagonist, ketamine reduces rCBF in the schizophrenic hippocampus, but not in the normal hippocampus, over a 30-min time course. This last observation suggests that the affected hippocampus, which already evidences elevated rCBF in the medication-free state, is more sensitive Inhibitors,research,lifescience,medical to glutamatergic inhibition. This observation is consistent with some of our other postmortem findings showing reduced

NM’DA receptor NR, subunits in schizophrenia, and hence potential reductions in the number of functional N.M.DA receptors. Theories of schizophrenia Dopamine Hypotheses to explain the manifestations of schizophrenia have been NVP-BEZ235 order posited for centuries. The finding a half century ago that antipsychotic drugs block dopamine receptors in brain82 and thereby reduce psychotic symptoms strongly Inhibitors,research,lifescience,medical supported the idea that an overactive dopaminergic system causes schizophrenia. Many years and many experiments later, evidence to support, this idea has now been generated using modern imaging tools.83 Yet. while increased dopamine release may be associated with the psychotic Mannose-binding protein-associated serine protease manifestations of schizophrenia, there is slim evidence that dopaminergic abnormalities may be more broadly influential in cognitive or negative manifestations or in a broader schizophrenia process. Neural systems As knowledge of normal brain function has revealed intricate and complexly interacting neural systems, so these ideas have also been applied to schizophrenia. The work of DeLong84 has suggested that there are longtract pathways between the frontal cortex and subcortical areas through which the basal ganglia and thalamus influence the function of the frontal cortex.