Unraveling the Link between Olfactory Deficits and Neuropsychiatric Disorders

Yang, Kun; Ayala-Grosso, Carlos; Bhattarai, Janardhan P.; Sheriff, Andrew; Takahashi, Tsutomu; Cristino, Alexandre S.; Zelano, Christina; Ma, Minghong

doi:10.1523/jneurosci.1380-23.2023

Cited by 3 publications

(1 citation statement)

References 154 publications

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“…Persistent olfactory impairment (POI) and taste disorder (TD) has been proposed as a marker to identify people with an increased long-term risk of several neurological diseases, such as Alzheimer and Parkinson disease (1)(2)(3)(4)(5)(6)(7). Long-term neuropsychological impairments such as executive, attentional, and memory deficits are consistent with sequalae after mild infection with several classes of viral particles.…”

Section: Introductionmentioning

confidence: 99%

Alzheimer's proteinopathy in olfactory neuroepithelium from persistent olfactory impairment SARS-CoV-2 patients

Grosso,

Pieruzzini,

Rodriguez

et al. 2024

Preprint

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Persistent olfactory impairment (POI) and dysgeusia are lingering symptoms following recovery from Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection. These symptoms, along with neurological changes affecting mood, anxiety, cognitive function, and sleep, have significant public health implications. However, the cause of these symptoms is still unknown. For this reason, we investigated whether the presence of certain proteins, such as amyloid Aβ and α-synuclein in the olfactory mucosa tissue of POI patients, could be associated with neurological changes. We conducted a study where we collected tissue biopsies and cultured cells from patients with normosmic non-cognitive impairment, hyposmic mild cognitive impairment or Alzheimer’s disease, and persistent olfactory impairment (POI) who had been infected with SARS-CoV-2 for 20 months or more. We then examined the expression of amyloid Aβ, α-Synuclein, and tau proteins using immuno-fluorescence and flow cytometry methodology. Our findings revealed that for the first time, amyloid Aβ, α-Synuclein, and tau proteins were detected in olfactory mucosa tissue sections and in cultured olfactory-derived mesenchymal stromal cells from patients with normosmia, hyposmia, and POI post-SARS-CoV-2 with neurological alterations. We also observed that POI occurred in younger post-COVID-19 patients than in those with hyposmia-mild cognitive impairment and normosmia non-cognitive impairment. Immunoreactive positive cells for Aβ, α-syn, and tau proteins were observed in sustentacular-like cells, intermediate cells, and parenchymal sub-lamina propria cells from olfactory mucosa tissue. Our study suggests that the presence of these biomarkers in middle-aged patients may indicate a protein dysmetabolism that could contribute to the progression of a neurodegenerative disorder.

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Section: Introductionmentioning

confidence: 99%

Alzheimer's proteinopathy in olfactory neuroepithelium from persistent olfactory impairment SARS-CoV-2 patients

Grosso,

Pieruzzini,

Rodriguez

et al. 2024

Preprint

View full text Add to dashboard Cite

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Disgust sensitivity and psychopathic behavior: A narrative review

Torres,

Sheikh,

Carpo

et al. 2024

Translational Neuroscience

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Humans live under constant threat from pathogenic microorganisms and minimizing such threat has been a major evolutionary selective force in shaping human behavior and health. A particular adaptive mechanism against the harm caused by parasites and their infectiousness is disgust sensitivity, which has evolved to detect and avoid poisonous foods as well as bodily secretions harboring virulent microorganisms. This ubiquitous and reflexive behavior requires the integration of several internal and external sensory signals between the brain, the autonomic nervous system (ANS), and the gastrointestinal tract. Although the emotional expression of disgust is experienced by almost all individuals, the neural mechanisms of sensory signals underlying disgust sensitivity may differ in certain psychiatric conditions. Psychopathy, for instance, is a personality disorder in which disgust sensitivity to contagious bodily secretions is apparently absent or downregulated from its atypical personality temperament. In this review, we provide convergent behavioral, anatomical, and cellular evidence to suggest that a fractured experience of disgust sensitivity might be an additional feature of psychopathic behavior. First, we discuss the neural networks of certain brain regions mediating the emotional states of disgust and then discuss the intersection of the ANS and gastrointestinal tract in the processing of disgust and its relevance to aberrant antisocial behavior. Together, this work highlights the interconnections between the brain and the bilateral body plan as an integrated cell network that is relevant for understanding common principles underlying function and dysfunction of disgust levels in psychiatric domains.

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Depression, Anxiety, and Neuropsychiatric Symptom Burden in a Longitudinal Cohort with Persistent Psychophysical Post-COVID Olfactory Dysfunction

Saak,

Tervo,

Vilarello

et al. 2024

Brain Sciences

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Background/Objectives: Olfactory dysfunction (OD) is associated with a variety of neurologic deficits and impacts socialization decisions, mood, and overall quality of life. As a common symptom comprising the long COVID condition, persistent COVID-19-associated olfactory dysfunction (C19OD) may further impact the presentations of neuropsychiatric sequelae. Our study aims to characterize the longitudinal burden of depression, anxiety, and neuropsychiatric symptoms in a population with C19OD. Methods: Individuals with perceived C19OD completed a psychophysical screening evaluation of their sense of smell using the comprehensive Sniffin’ Sticks olfactory assessment. Only those with validated psychophysical OD were included in this prospective longitudinal study for baseline and one-year follow-up. Participants also completed PHQ-9, Beck Anxiety Inventory (BAI), and neuropsychiatric symptom questionnaires at each time point. Anxiety, depression, and neuropsychiatric symptom prevalence was calculated and compared between time points with Pearson’s chi-squared, Fisher’s exact, and Wilcoxon rank sum tests. Results: Each neuropsychiatric symptom evaluated in this study was reported by 13–49% of longitudinal cohort participants at both baseline and follow-up, except for seizure (0% at baseline and follow-up) and word-finding difficulty (61–68% at baseline and follow-up). Word-finding and focus difficulties were the most commonly reported symptoms. In total, 41% of participants reported some level of depression at baseline and 38% of participants reported depression at one-year follow-up, while 29% and 27% of participants reported some level of anxiety at respective time points. Conclusions: Individuals with C19OD are at risk for developing persistent neuropsychiatric conditions. These neurologic and psychiatric sequelae are persistent with repeated longitudinal assessment, even at nearly 2.5 years following initial COVID-19 diagnosis.

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Unraveling the Link between Olfactory Deficits and Neuropsychiatric Disorders

Cited by 3 publications

References 154 publications

Alzheimer's proteinopathy in olfactory neuroepithelium from persistent olfactory impairment SARS-CoV-2 patients

Alzheimer's proteinopathy in olfactory neuroepithelium from persistent olfactory impairment SARS-CoV-2 patients

Disgust sensitivity and psychopathic behavior: A narrative review

Depression, Anxiety, and Neuropsychiatric Symptom Burden in a Longitudinal Cohort with Persistent Psychophysical Post-COVID Olfactory Dysfunction

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