A number of recent studies have found a schizophrenia-associated loss of cells or volume in the human thalamus. Unfortunately, these previous studies did not have the resolution necessary to precisely localize the abnormalities.
The specific aims of the proposed research are to use efficient stereological methods to: 1) Survey the entire thalamus for schizophrenia-related loss of volume or cellularity, 2) Localize any detected abnormalities to particular cytoarchitectonic divisions, and 3) Investigate the specificity of any detected abnormalities to schizophrenia. The investigator will use well-characterized postmortem material from the Mount Sinai Medical Center/Bronx Veteran's Affairs Hospital Schizophrenia Brain Bank to test the following primary hypotheses: 1) Previously reported schizophrenia-associated abnormalities in the mediodorsal thalamic nucleus will primarily involve its parvocellular and caudal divisions which, in man, have a prefrontal cortical dependence. The magnocellular division which does not degenerate following prefrontal ablations may be relatively spared in schizophrenia. 2) Schizophrenia-associated loss of cells and volume will not be restricted to the mediodorsal nucleus. Other nuclei where abnormalities are likely to occur include those with predominately temporolimbic connections and those with patterns of connections suggesting the potential for a role in arousal or in gating signals to and from cortex. The more specific sensory and motor relay nuclei are likely to be spared. 3) The schizophrenia-associated thalamic abnormalities are not common to all chronic mental illnesses and will not be seen in subjects with affective disorders. The studies of the present proposal will lay the groundwork for more definitive future explorations that will more fully assess the main and interactive effects of age, chronic institutionalization, neuroleptic exposure, and gender on the anatomy of thalamic nuclei where schizophrenia-associated abnormalities are found.
