Demyelination in Patients with Post-COVID Depression

Abstract

Depression is one of the most severe sequelae of COVID-19, with major depressive disorder often characterized by disruption in white matter (WM) connectivity , stemming from changes in brain myelination. This study aimed to quantitatively assess brain myelination in clinically diagnosed post-COVID depression using recently proposed MRI method, macromolecular proton fraction (MPF) mapping. The study involved 63 recovered COVID-19 patients (52 mild, 11 moderate, 2 severe) at 13.5±10.0 months post-recovery, with matched controls without prior COVID-19 history (n=19). A post-COVID depression group (PCD, n=25) was identified based on psychiatric diagnosis, while a comparison group (noPCD, n=38) included participants with neurological COVID-19 complications, excluding clinical depression. Fast MPF mapping revealed extensive demyelination in PCD patients, particularly in juxtacortical WM (predominantly occipital lobe and medial surface), WM tracts (inferior fronto-occipital fasciculus (IFOF), posterior thalamic radiation, external capsule, sagittal stratum, tapetum), and grey matter (GM) structures (hippocampus, putamen, globus pallidus, and amygdala). The noPCD group also displayed notable demyelination but with less magnitude and propagation. Multiple regression analysis highlighted IFOF demyelination as the primary predictor of PCD presence and severity according to Hamilton scores. The number of post-COVID symptoms was a significant predictor of PCD presence while the number acute of symptoms was a significant predictor of PCD severity. This study, for the first time, reveals extensive demyelination in numerous WM and GM structures in PCD, outlining IFOF demyelination as a key biomarker.

Neurocognitive Changes in Patients with Post-COVID Depression

“…The study showed more extensive brain demyelination in patients with post-COVID depression in comparison to controls and post-COVID patients without clinically diagnosed depression. Moreover, our study identified demyelination of inferior frontooccipital fasciculus (IFOF) as the primary predictor of PCD presence and severity [68]. Anatomically, the IFOF connects early visual processing in the occipital lobe (cuneus and lingual gyri) and the parietal regions with frontal lobe regions [76,77] and also includes the connections between the cingulo-opercular and frontoparietal networks [77,78].…”

“…Since microglial and astroglial reactivation lead to impaired oligodendrocyte functioning and renewal [65][66][67], demyelination or decreased remyelination also might play an important role in cognitive changes in PCD patients. The MRI study performed in the same group of PCD patients supported the hypothesis of brain demyelination after COVID-19 [68]. In that study, we used quantitative macromolecular proton fraction (MPF) mapping [69][70][71] that strongly correlated with myelin content [69,[72][73][74][75].…”

Neurocognitive Changes in Patients with Post-COVID Depression

“…The study showed more extensive brain demyelination in patients with post-COVID depression in comparison to controls and post-COVID patients without clinically diagnosed depression. Moreover, our study identified the demyelination of the inferior fronto-occipital fasciculus (IFOF) as the primary predictor of PCD presence and severity [ 94 ]. Anatomically, the IFOF connects early visual processing in the occipital lobe (cuneus and lingual gyri) and the parietal regions with frontal lobe regions [ 102 , 103 ], and also includes the connections between the cingulo-opercular and frontoparietal networks [ 103 , 104 ].…”

“…Since microglial and astroglial reactivation lead to impaired oligodendrocyte functioning and renewal [91][92][93], demyelination or decreased remyelination might also play important roles in cognitive changes in PCD patients. An MRI study performed on the same group of PCD patients supported the hypothesis of brain demyelination after COVID-19 [94]. In that study, we used quantitative macromolecular proton fraction (MPF) mapping [95][96][97] that strongly correlated with myelin content [95,[98][99][100][101].…”