Reporting Psychiatric Disease Characteristics in Post-Mortem- and Biological Research

Author:

Scheepstra Karel123ORCID,Mizee Mark2,Wever Dennis12ORCID,Hsiao Cheng-Chih12,Zhang Lin4,Swaab Dick14,Hamann Jörg15,Huitinga Inge126

Affiliation:

1. Neuroimmunology research group, Netherlands Institute for Neuroscience, Amsterdam, The Netherlands

2. Psychiatric Program of the Netherlands Brain Bank, Netherlands Institute for Neuroscience, Amsterdam, The Netherlands

3. Adult Psychiatry, Amsterdam Neuroscience, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands

4. Neuropsychiatric Disorders Lab, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, the Netherlands

5. Department of Experimental Immunology, Amsterdam institute for Infection and Immunity, Amsterdam University Medical Center, Amsterdam, The Netherlands

6. Center for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands

Abstract

Inflammation is a prominent hypothesis in the neurobiology of depression. In our transcriptomic profiling study of microglia in chronic major depressive disorder (MDD), we revealed a distinct disease-associated microglia (DAM) transcriptomic profile exclusively found in cortical gray matter, that we have designated DepDAM. These DepDAM revealed an immune-suppressed state, with a possible upstream mechanism for microglial suppression, by upregulation of CD200 and CD47 (“don’t eat me signals”) located on synapses. We extensively report on disease characteristics, such as cause of death, reason for euthanasia, and psychiatric state when deceased. When excluding MDD donors in a euthymic state, the trend of lower CD45 membrane expression on white matter microglia became significant, and the difference in gray matter microglia became larger. For Western blot analysis of CD47 and CD200, both means of the definitely depressed donor groups (MDD-D) increased. This underscores the utmost importance of reporting on patient and episode characteristics, such as severity, episode traits, (type of) suicidality, mode of decease, and state of illness at death in post-mortem- and biological psychiatric research. For psychiatric post-mortem research, we suggest using well-characterized donors (eg, after “psychological autopsy”) selected by an experienced clinician.

Funder

Netherlands Organization for Scientific Research

Publisher

SAGE Publications

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