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

Yang, Kun; Hua, Jun; Etyemez, Semra; Paez, Adrian; Prasad, Neal; Ishizuka, Koko; Sawa, Akira; Kamath, Vidyulata

doi:10.1016/j.schres.2021.07.016

Cited by 11 publications

(13 citation statements)

References 86 publications

(119 reference statements)

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“…The potential associations between nasal inflammation and OB have been suggested by preclinical studies [53][54][55] . On the other hand, our group has reported preliminary observations of a reduction of the OB volume derived from T1-weighted images at 3 Tesla in FEP patients (n=16) compared with healthy controls (n=22) 56 .…”

Section: Introductionmentioning

confidence: 93%

“…The potential associations between nasal inflammation and OB have been suggested by preclinical studies 53–55 . On the other hand, our group has reported preliminary observations of a reduction of the OB volume derived from T1-weighted images at 3 Tesla in FEP patients (n=16) compared with healthy controls (n=22) 56 . Based on this background, we hypothesize that stress response in the OE may affect the structure of OB in the pathophysiological context of psychotic disorders.…”

Section: Introductionmentioning

confidence: 93%

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

Yang

Hasegawa

Hua

et al. 2022

Preprint

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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.

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Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 93%

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

Yang

Hasegawa

Hua

et al. 2022

Preprint

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“…All these observations suggest that, although the mechanism of the association between nasal viral infections and schizophrenia remains unknown, nasal inflammation caused by infections may contribute to olfactory disturbances in psychopathology of schizophrenia. In this line, a recent molecular study based on RNA sequencing has shown that certain molecular pathways involved in the immune/inflammatory system, such as the NF- κB signalling pathways, are altered in the ONs in the OE, and that these changes correlate with the volume of OB in patients with the first episode of psychosis [ 109 ••].…”

Section: Pathophysiological Mechanisms Involved In Loss Of Smell In M...mentioning

confidence: 99%

Olfactory Dysfunction in Mental Illness

Marı́n

Alobid

Fuentes

et al. 2023

Curr Allergy Asthma Rep

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Purpose of Review Olfactory dysfunction contributes to the psychopathology of mental illness. In this review, we describe the neurobiology of olfaction, and the most common olfactory alterations in several mental illnesses. We also highlight the role, hitherto underestimated, that the olfactory pathways play in the regulation of higher brain functions and its involvement in the pathophysiology of psychiatric disorders, as well as the effect of inflammation on neurogenesis as a possible mechanism involved in olfactory dysfunction in psychiatric conditions. Recent Findings The olfactory deficits present in anxiety, depression, schizophrenia or bipolar disorder consist of specific alterations of different components of the sense of smell, mainly the identification of odours, as well as the qualifications of their hedonic valence (pleasant or unpleasant). Epidemiological findings have shown that both environmental factors, such as air pollutants, and inflammatory disease of the upper respiratory tract, can contribute to an increased risk of mental illness, at least in part, due to peripheral inflammatory mechanisms of the olfactory system. Summary In this review, we describe the neurobiology of olfaction, and the most common olfactory function alterations in several psychiatric conditions and its role as a useful symptom for the differential diagnosis. We also highlight the effect of inflammation on neurogenesis as a possible mechanism involved in olfactory dysfunction in these psychiatric conditions.

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“…To demonstrate the validity and utility of ONCs as surrogate neuronal cells, in the present study, we used clinical data and biospecimens collected from study participants recruited by clinical cohorts [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] established at Johns Hopkins Schizophrenia Center under approval of the Johns Hopkins Medicine Institutional Review Boards. All study participants provided written informed consent.…”

Section: Study Participantsmentioning

confidence: 99%

“…The present study used clinical data and biospecimens collected from study participants recruited by clinical cohorts established at the Johns Hopkins Schizophrenia Center (Kano et al, 2013;Mor et al, 2013;Kamath et al, 2018Kamath et al, , 2019Posporelis et al, 2018;Faria et al, 2019Faria et al, , 2021Nucifora et al, 2019;Wang et al, 2019Wang et al, , 2023Avigdor et al, 2021;Coughlin et al, 2021;Narita et al, 2021;Yang et al, 2021Yang et al, , 2022bEtyemez et al, 2022bEtyemez et al, , 2022a. This study was conducted with the approval of the Johns Hopkins Medicine Institutional Review Boards.…”

Section: Human Subjects Who Contributed To the Nasal Biopsymentioning

confidence: 99%

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

Yang

Ishizuka

Lane

et al. 2022

Preprint

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Biopsy is an essential procedure of clinical medicine in which we obtain tissues and cells that are supposed to directly reflect pathological changes of each disease. Biopsy from the brain is difficult at both practical and ethical levels. Nasal biopsy that captures tissues with olfactory neurons has been considered as an alternative method of obtaining neurons from living patients with brain disorders. However, insufficient characterization of biopsied cells/tissues has hampered a wider use of nasal tissues as surrogate resources for the brain. By conducting single cell and bulk RNA-sequence analysis of olfactory neuronal cells (ONCs) enriched from nasal biopsied tissues and using multiple pubic datasets in comparison, we now report precise characterization of ONCs at the molecular levels. These cells are easily and reproducibly prepared and have two major strengths. They are homogeneous and neuronal, resembling excitatory neurons in the dorsolateral prefrontal cortex and anterior cingulate cortex in molecular signatures.

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

Cited by 11 publications

References 86 publications

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

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

Olfactory Dysfunction in Mental Illness

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

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