86 Conclusions Postmortem studies in schizophrenia have contributed significantly to the considerable, albeit partial, progress which has been made towards understanding the Dinaciclib in vitro neuropathological (Tables I to III) and neurochemical (Table IV) characteristics of the disorder. Although imaging modalities provide

an increasingly powerful and diverse technical armamentarium, in several key areas, there is no substitute for direct, examination of the brain. For instance, it is not (yet) possible to measure neuronal size, synaptic terminals, or neuronal Inhibitors,research,lifescience,medical gene expression in any other way. The important thing is to apply each method judiciously and to choose the appropriate range of techniques to allow integration of in vivo with postmortem data. Table IV. Key postmortem findings concerning the major transmitter Inhibitors,research,lifescience,medical systems implicated in schizophrenia. AMPA: amino-3-hydroxy-5-methyl-4-isQxazole propionic acid; DA: dopamine; FC: frontal cortex; GABA: γ-aminobutyric acid; HC: hippocampus; 5-HT: serotonin; … Beyond Inhibitors,research,lifescience,medical these simple issues of robustness and convergence, contemporary postmortem studies of schizophrenia are attempting to answer several questions (Table V). First, what is the core

neuropathology of schizophrenia and in what sense is it specific? Features such as decreased cortical volume and cytoarchitectural abnormalities are certainly not unique to schizophrenia, overlapping with those observed in a range of other conditions.50 There could be a diagnostic lesion characteristic of schizophrenia, still going unrecognized, though this is increasingly implausible. Or, it could be the precise combination of alterations, and their location and timing, which produce schizophrenia. Some clarification will emerge as other idiopathic Inhibitors,research,lifescience,medical and putatively neurodevelopmental conditions, such as bipolar disorder87 and autism,88 are investigated. A complete answer, however, will also likely require identification of the causative genes

Inhibitors,research,lifescience,medical and a better understanding of the pathogenesis, not just, the pathology, of schizophrenia. At this point, one reencounters the circular problem: the goal of the research is to find a valid endophenotype, yet without one the goal may be unattainable. Table V Some questions for postmortem studies else of schizophrenia. A second area to highlight concerns the relationship between the structural abnormalities and the pathophysiology of the disorder. Functional imaging and neuropsychological data, have led to the view that aberrant, functional connectivity between brain regions underlies schizophrenia.89,90 The question is whether the neuropathological features represent its structural and molecular basis,6 since such dysconnectivity docs not necessarily require an anatomical substrate.91 A related question concerns which aspect, of the clinical syndrome is most related to the neuropathology.