Kamath, V. | bioRxiv Science

bioRxiv2021

Volumetric alteration of olfactory bulb and immune-related molecular changes in olfactory epithelium in first episode psychosis patients

BackgroundOlfactory dysfunction has been reproducibly reported in patients with psychosis, including first episode psychosis (FEP) patients. Consistently, structural abnormalities in the olfactory bulb (OB), a key region of the peripheral olfactory system, have also been reported in psychotic disorders. Meanwhile, 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 located adjacent to the OB and connected via direct neuronal projections. Nevertheless, it is unknown how a disturbance of the OE possibly affects the OB in the pathophysiological context of psychotic disorders. MethodsWe examined the volume of the OB in FEP patients and healthy controls from 3 Tesla magnetic resonance imaging and molecular expression profiles of olfactory neuronal cells (ONCs) enriched from freshly biopsied OE. ResultsWe observed a reduction of the OB volume in FEP patients compared with healthy controls. We also observed a significant alteration in gene expression profiles in the ONCs from FEP patients, supporting the pathological changes in the OE. Among such molecular changes, immune-related molecules and pathways were underscored in association with the OB volume changes in FEP patients. ConclusionsOur data support the OB and OE pathologies in FEP patients. Immune-related molecular changes in the OE can biologically link adverse factors in the nasal cavity, such as air pollution and viral infection, with the OB structural change, both of which have been reported for psychotic disorders.

neuroscience↗

bioRxiv2021

A multimodal study of a first episode psychosis cohort: potential markers of antipsychotic treatment resistance

Treatment resistant (TR) psychosis is considered to be a significant cause of disability and functional impairment. Numerous efforts have been made to identify the clinical predictors of TR. However, the exploration of molecular and biological markers is still at an early stage. To understand the TR condition and identify potential molecular and biological markers, we analyzed demographic information, clinical data, structural brain imaging data, and molecular brain imaging data in 7 Tesla magnetic resonance spectroscopy, from a first episode psychosis cohort that includes 138 patients. Age, gender, race, smoking status, duration of illness, and antipsychotic dosages were controlled in the analyses. We found that TR patients had a younger age at onset, more hospitalizations, more severe negative symptoms, a significant reduction in the volumes of the hippocampus (HP) and superior frontal gyrus (SFG), and a significant reduction in glutathione (GSH) levels in the anterior cingulate cortex (ACC), when compared to non-TR patients. The combination of multiple markers provided a better classification between TR and non-TR patients compared to any individual marker. Our study shows that ACC GSH, HP and SFG volumes, and age at onset could potentially be trait biomarkers for TR diagnosis, while hospitalization and negative symptoms could be used to evaluate the progression of the disease. Multimodal cohorts are essential in obtaining a comprehensive understanding of brain disorders.

neuroscience↗