Stereological approaches to identifying neuropathology in psychosis

The challenges involved in identifying the neuropathological substrates of the clinical syndrome recognized as schizophrenia are well known. Stereological sampling provides a means to obtain accurate and precise quantitative estimates of components of neural circuits and thus offers promise of an enhanced capacity to detect subtle alterations in brain structure associated with schizophrenia. In this review, we 1) consider the importance and rationale for robust quantitative measures of brain abnormalities in postmortem studies of schizophrenia; 2) provide a brief overview of stereological methods for obtaining such measures; 3) discuss the methodological details that should be reported to document the robustness of a stereological study; 4) given the constraints of postmortem human studies, suggest how to approach the limitations of less robust designs; and 5) present an overview of methodologically sound stereological estimates from postmortem studies of schizophrenia.