ИСТИНА

Inflammatory processes may contribute to psychiatric disorders and suicide. Earlier, we reported greater densities of perivascular phagocytes in dorsal prefrontal white matter (DPFWM) in suicide than in non-suicide deaths. To distinguish between greater vascularity and greater coverage of vessels by perivascular phagocytes, and to determine whether the excess of perivascular phagocytes is derived from microglia or from non-parenchymal immune cells, we made stereological estimates of vascular surface area density (A VTOTAL ) by staining for glucose transporter Glut-1, and the fraction of vascular surface area (AF) immunoreactive (IR) for CD163 (CD163 AF) in dorsal and ventral prefrontal white and gray matter. Manner of death or psychiatric diagnosis showed no association with CD163 AF in any region. Suicide was associated with a lower A VTOTAL compared with non-suicides in DPFWM (p = 0.018) but not with A VTOTAL in the three other regions of interest. Thus, the earlier observation of increased density of perivascular phagocytes in DPFWM after suicide cannot be attributed to infiltration by peripheral monocytes or to increased vascularity. Greater A VTOTAL ventrally than dorsally (p = 0.002) was unique to suicide and white matter. Using postmortem toxicology on the brain, we also found effects of medications. Lower A VTOTAL detected in DPFWM of suicides is independent of the presence of benzodiazepines or other medications. However, benzodiazepines and other medications were linked to a greater density of Iba-1-IR phagocytes in DPFWM in suicide. To better understand the biological mechanisms linking maladaptive behavior, altered immune response and BBB changes in suicide, we are performing molecular and neuroanatomical assessments of BBB integrity in suicide, including quantification of transcriptional and protein expression changes in brain microvessels and stereological evaluation of plasma protein extravasation in completed suicide.