Biology subjects

Kamath, V.

Publications and source records attributed to Kamath, V..

3 recordsLinked to original sources

bioRxiv2022

Immune-related molecular changes in the olfactory epithelium, structural alteration in the olfactory bulb, and psychosis

Smell deficits and neurobiological changes in the olfactory bulb (OB) and olfactory epithelium (OE) have been observed in schizophrenia and related disorders. The OE is the most peripheral olfactory system located outside the cranium, and is connected with the brain via direct neuronal projections to the OB. Nevertheless, it is unknown whether and how a disturbance of the OE affects the OB in schizophrenia and related disorders. Addressing this gap would be the first step in studying the impact of OE pathology in the disease pathophysiology in the brain. In this cross-species study, we observed that chronic, local OE inflammation with a set of upregulated genes in an inducible olfactory inflammation (IOI) mouse model led to a volume reduction, layer structure changes, and alterations of neuron functionality in the OB. Furthermore, IOI model also displayed behavioral deficits relevant to negative symptoms (avolition) in parallel to smell deficits. In first episode psychosis (FEP) patients, we observed a significant alteration in immune/inflammation-related molecular signatures in olfactory neuronal cells (ONCs) enriched from biopsied OE and a significant reduction in the OB volume, compared with those of healthy controls (HC). The increased expression of immune/inflammation-related molecules in ONCs was significantly correlated to the OB volume reduction in FEP patients, but no correlation was found in HCs. Moreover, the increased expression of human orthologues of the IOI genes in ONCs was significantly correlated with the OB volume reduction in FEP, but not in HCs. Together, our study implies a potential mechanism of the OE-OB pathology in patients with psychotic disorders (schizophrenia and related disorders). We hope that this mechanism may have a cross-disease implication, including COVID-19-elicited mental conditions that include smell deficits.

molecular biology↗

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↗