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

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.

Keywords: Microglia; neuroimmunology; neuropsychology.

Figure 1.

Membrane CD45 expression on microglia and CD45/CD200 expression in synaptosomes outcomes when excluding the MDD donors in a euthymic state. (A) CD45 membrane expression on GM and WM microglia was detected by flow cytometry directly after isolation. (B) CD47 and CD200 expression were analyzed by Western blots in cortical synaptosomes. See Scheepstra et al for technical details. Statistics used are one-tailed Mann-Whitney U tests.