Elsevier

Biological Psychiatry

Volume 69, Issue 2, 15 January 2011, Pages 127-133
Biological Psychiatry

Review
Novel Approaches to the Study of Postmortem Brain in Psychiatric Illness: Old Limitations and New Challenges

https://doi.org/10.1016/j.biopsych.2010.09.035Get rights and content

Biological psychiatry has made significant advances through the development of postmortem studies, animal models, and studies with living humans. Although these approaches each have advantages and disadvantages, the postmortem field is undergoing a significant shift toward more complex and informative methodologies. In the first part of this review, we summarize the long-standing methodologic challenges facing this field. In the second part of the article, we discuss the innovative approaches being used for postmortem studies, including laser capture microdissection and subcellular fractionization. These techniques will permit scientists working in the postmortem field to ask and answer the largest possible questions, providing new targets for drug discovery and improved treatments for severe mental illness.

Section snippets

Long-Standing Challenges

The selection of samples for postmortem brain studies includes consideration of manner of death, age, sex, tissue pH, mRNA integrity (RIN), postmortem interval (PMI), diagnostic certainty, comorbid substance use, and prior medication treatment status. Despite attempts to rigorously characterize samples, studies of a particular illness often find inconsistent results for the same dependent variable. For example, postmortem studies of the NR1 subunit of the N-methyl-D-aspartate glutamate receptor

Summary

Although there have been important advances in the field of mental health research, a full accounting of the etiologies of severe mental illnesses such as schizophrenia and the mood disorders remains to be achieved. Postmortem studies have a critical role, along with animal models and studies of living patients, in the search for causes and cures for these diseases. Promising innovative methodologies combined with increasingly bigger and better characterized subjects cohorts have the postmortem

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