Investigations of the neurobiology of schizophrenia and other psychiatric disorders have become increasingly dependent upon approaches that require the availability of postmortem human brain specimens. Indeed, a major rationale for the Center’s work is based on the widely replicated postmortem findings of alterations in cortical GABA neurons in individuals with schizophrenia. This growing interest in the postmortem human brain had been driven by a number of factors including 1) The opportunity to ask questions regarding the molecular and neural circuitry bases of schizophrenia that cannot currently, and are not likely to be in the foreseeable future, addressable through other approaches; 2) An improved ability to incorporate in postmortem studies the types of experimental designs and controls for potential confounds that characterize other areas of empirical study; 3) The availability of novel technologies and more rigorous quantitative methods for assessing the pathology of schizophrenia; and 4) The potential to identify and validate molecular targets for new therapeutic interventions. These types of studies now offer the promise of advances on a number of fronts, from the molecular phenotyping of schizophrenia into more homogeneous categories, to the delineation of pathophysiological cascades, and to the identification of novel targets for therapeutic interventions. Thus, studies of the postmortem human brain represent a critical and complementary approach to in vivo human studies, as well as an essential interface between clinical investigations and studies in animal models.
For our studies of schizophrenia which typically has its onset in early to mid- adulthood, we have sought to acquire postmortem human brain specimens from a cohort of young and middle-aged adults who lived in the community and died suddenly outside of a hospital setting. Because our studies focus on understanding pathogenetic and pathophysiological processes, we have sought to minimize the potential complications introduced by aging, associated medical illnesses and interventions, and factors such as antemortem hypoxia. Although our approach precludes the antemortem diagnostic assessment of subjects, we have developed methods for acquiring this information based on structured interviews with surviving relatives and other sources of information. Postmortem human brain specimens are obtained from autopsies conducted at the Allegheny County Medical Examiner’s Office located in downtown Pittsburgh, several miles from the University of Pittsburgh.
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Corrie Long