Inflammation-related pathology in the olfactory epithelium: its impact on the olfactory system in psychotic disorders

Abstract

Olfactory dysfunction has been reproducibly reported in patients with psychosis. Consistently, some studies have reported structural abnormalities in the olfactory bulb (OB) in psychotic disorders with modest sample size. Air pollution and viral infections in the upper respiratory tract, including those of SARS-CoV-2, are reportedly risk factors for brain dysfunction and mental disorders. These risk factors can disturb the olfactory epithelium (OE) that is connected with the OB via direct neuronal projections. Nevertheless, it is unknown whether and how a disturbance of the OE could possibly affect the structure of OB in the pathophysiological context of psychotic disorders. To address this knowledge gap, we first utilized an inducible OE inflammation mouse model (IOI model) and found that OE inflammation could induce a significant reduction in the OB volume, shrinkage of the glomerular layer and the external plexiform layer of OB, and decrease in the immunoreactivity of OMP (olfactory sensory neuron marker), Vglut2 (glutamatergic presynaptic marker), CCK8 (tufted cell marker), and PGP9.5 (mitral cell marker) in the glomerular layer of OB in IOI mice compared to control mice. We then analyzed 3 Tesla magnetic resonance imaging and molecular expression profiles of olfactory neuronal cells (ONCs) biopsied from living human subjects. Interestingly, we also observed a significant reduction in the OB volume, as well as alterations in the expression profiles in ONCs in first episode psychosis (FEP) patients compared to healthy controls. Higher expression levels of IOI immune genes (genes coding immune-related transcription factors up-regulated in IOI mice) in ONCs was significantly associated with smaller volumes of the OB in FEP patients. The subgroup of FEP patients with an up-regulation of IOI immune genes had significantly smaller OB volumes than other FEP patients. Together, our study implied the existence and connections between OE and OB pathologies in psychotic disorders.

Human olfactory neuronal cells through nasal biopsy: molecular characterization and utility in brain science

“…We also conducted a pathway analysis and identified 12 significant pathways between TR and non-TR patients, which included immune/inflammatory pathways (Table 4). These pathways have also been highlighted when we compared the entire patients (including both TR and non-TR patients) and healthy subjects in our past publications (Yang et al, 2021(Yang et al, , 2022a.…”