Cholecystokinin-expressing superficial tufted cells modulate odour representation in the olfactory bulb and olfactory behaviours.

In mammals, odour information within the olfactory bulb (OB) is processed by complex neural circuits before being ultimately represented in the action potential activity of mitral/tufted cells (M/Ts). Cholecystokinin-expressing (CCK+) superficial tufted cells (sTCs) are a subset of tufted cells that potentially contribute to olfactory processing in the OB by orchestrating M/T activity. However, the exact role of CCK+ sTCs in modulating odour processing and olfactory function in vivo is largely unknown. Here, we demonstrate that manipulating CCK+ sTCs can generate perception and induce place avoidance. Optogenetic activation/inactivation of CCK+ sTCs exerted strong but differing effects on spontaneous and odour-evoked M/T firing. Furthermore, inactivation of CCK+ sTCs disrupted M/T odour encoding and impaired olfactory detection and odour discrimination. These results establish the role of CCK+ sTCs in odour representation and olfactory behaviours. KEY POINTS: Mice could perceive the activity of CCK+ sTCs and show place avoidance to CCK+ sTC inactivation. Optical activation of CCK+ sTCs increased the percentage of cells with odour response but reduced the odour-evoked response in M/Ts in awake mice. Optical inactivation of CCK+ sTCs greatly decreased spontaneous firing and odour-evoked response in M/Ts. Inactivation of CCK+ sTCs impairs the odour decoding performance of M/Ts and disrupts odour detection and discrimination behaviours in mice. These results indicate that CCK+ sTCs participate in modulating the odour representation and maintaining normal olfactory-related behaviours.

Effects of Radiation on Olfactory Function in Head and Neck Malignancy.

OBJECTIVES: Olfactory dysfunction is an overlooked adverse effect of radiation therapy. This study is designed to find the effect of radiation therapy on olfactory function in head and neck malignancy excluding tumors of nose and nasopharynx and correlate the olfactory changes with the radiotherapy dose. METHOD: This prospective observational study was done over a 2-year period in 34 participants with head and neck malignancies who underwent radiation therapy (RT). The participants olfaction was evaluated subjectively with Italian Nose Obstruction Symptom Evaluation (I-NOSE) scale and objectively by a modified I-Smell test which included an olfactory identification score and an olfactory threshold score at 5 time points. The beginning of RT (T0), at 2 weeks of RT(T1), end of RT (T2), 1 month follow-up (T3), and 3-month follow-up (T4). The near maximum dose to the nasal cavity (D2%) and mean dose to the nasal cavity (Dmean) were calculated for all participants and correlated with olfactory function. RESULTS: A total of 34 patients with head neck malignancy were recruited. The median I-NOSE score reached maximum at the end of radiation and decreased to baseline at 3 months follow-up (P < .001). The olfactory identification score, olfactory threshold score, and median combined olfactory score showed a significant decrease at the end of radiation therapy compared to Pre-radiation therapy values. There was a significant but incomplete recovery in the 3-month follow-up period (P < .001). CONCLUSION: There was a significant deterioration in quality of life for olfaction, olfactory identification, and olfactory threshold at the completion of radiotherapy. At 3 months follow-up, though there was no complete recovery of olfaction, it did not have an adverse effect on the quality of life.

The efficacy of olfactory training in improving olfactory function: a meta-analysis.

PURPOSE: Study the efficacy of olfactory training in smell recovery. METHODS: An extensive search was performed through different databases in order to find articles analyzing the efficacy of olfactory training as a treatment for olfactory dysfunction. Methodological quality of primary studies within the final sample was assessed following PRISMA guidelines. Standardized mean differences in pre-post olfactory training groups, and also in experimental-control and pre-follow up if possible, were computed by Hedges' g effect size statistic. Each effect size was weighted by its inverse variance. RESULTS: Final sample was composed of 36 articles (45 pre-post effect sizes). Contrasts were performed separately for odor identification, odor discrimination, odor threshold and general olfactory function. Moderate to large and heterogeneous effect was obtained for olfactory function (g = 0.755, k = 45, SE = 0.093, CI 95% = [0.572, 0.937]), different moderators had a significant effects, such as, training duration, age and anosmia diagnosis. CONCLUSION: Olfactory training was found to have a positive and significant effect on rehabilitating the olfactory function.

Identification of odorant-binding proteins and functional analysis of antenna-specific BhorOBP28 in Batocera horsfieldi (Hope).

BACKGROUND: The important wood-boring pest Batocera horsfieldi has evolved a sensitive olfactory system to locate host plants. Odorant-binding proteins (OBPs) are thought to play key roles in olfactory recognition. Therefore, exploring the physiological function of OBPs could facilitate a better understanding of insect chemical communications. RESULTS: In this research, 36 BhorOBPs genes were identified via transcriptome sequencing of adults' antennae from B. horsfieldi, and most BhorOBPs were predominantly expressed in chemosensory body parts. Through fluorescence competitive binding and fluorescence quenching assays, the antenna-specific BhorOBP28 was investigated and displayed strong binding affinities forming stable complexes with five volatiles, including (+)-α-Pinene, (+)-Limonene, ß-Pinene, (-)-Limonene, and (+)-Longifolene, which could also elicit conformation changes when they were interacting with BhorOBP28. Batocera horsfieldi females exhibited a preference for (-)-Limonene, and a repellent response to (+)-Longifolene. Feeding dsOBP19 produced by a bacteria-expressed system with a newly constructed vector could lead to the knockdown of BhorOBP28, and could further impair B. horsfieldi attraction to (-)-Limonene and repellent activity of (+)-Longifolene. The analysis of site-directed mutagenesis revealed that Leu7, Leu72, and Phe121 play a vital role in selectively binding properties of BhorOBP28. CONCLUSION: By modeling the molecular mechanism of olfactory recognition, these results demonstrate that BhorOBP28 is involved in the chemoreception of B. horsfieldi. The bacterial-expressed dsRNA delivery system gains new insights into potential population management strategies. Through the olfactory process concluded that discovering novel behavioral regulation and environmentally friendly control options for B. horsfieldi in the future. © 2024 Society of Chemical Industry.

Functional Characterization of the Niemann-Pick C2 Protein BdioNPC2b in the Parasitic Wasp Baryscapus dioryctriae (Chalcidodea: Eulophidae).

Reverse chemical ecology has been widely applied for the functional characterization of olfactory proteins in various arthropods, but few related studies have focused on parasitic wasps. Here, the odorant carrier Niemann-Pick C2 protein of Baryscapus dioryctriae (BdioNPC2b) was studied in vitro and in vivo. Ligand binding analysis revealed that BdioNPC2b most strongly bound to 2-butyl-2-octenal and which compound could elicit an EAG response and attracted B. dioryctriae adults. Moreover, this odorant attractant significantly improved the reproductive efficiency of B. dioryctriae compared to that of the control. Then, the relationship between BdioNPC2b and 2-butyl-2-octenal was validated by RNAi, and site-directed mutagenesis revealed the involvement of three key residues of BdioNPC2b in binding to 2-butyl-2-octenal through hydrogen bonding. Our findings provide not only a deeper understanding of the olfactory function of NPC2 in wasps but also useful information for improving the performance of the parasitoid B. dioryctriae as a biological control agent.

Olfactory threshold as a biomarker of long-term relapse activity in multiple sclerosis.

BACKGROUND: Olfactory threshold (OT) is a marker of short-term inflammatory activity in multiple sclerosis (MS). OBJECTIVE: To investigate whether OT predicts long-term MS clinical disease course. METHODS: This was a 6-year prospective longitudinal study on MS patients at the MS clinic Innsbruck. Clinical visits assessing the occurrence of relapses, Expanded Disability Status Scale (EDSS) scores, and disease-modifying treatment (DMT), were conducted biannually. OT testing was performed at baseline (BL), year 1 (Y1), year 2 (Y2) and year 6 (Y6), using the threshold subscore of the "Sniffin' Sticks" test. Cognitive function was assessed by the Symbol Digit Modalities Test. RESULTS: Of 139 MS patients, 92 were eligible for Y6 follow-up. 68% experienced relapses, 53% EDSS worsening, 29% progression independent of relapse activity (PIRA) and 41% cognitive deterioration. OT scores were lower at BL, Y1 and Y2 in patients requiring DMT escalation. In multivariable analysis, higher OT scores at BL, Y1, Y2 and Y6 were associated with lower risk of relapse (hazard ratio, HR: 0.65-0.92) and EDSS worsening (HR: 0.86-0.89), while no associations were found for PIRA and cognitive deterioration. CONCLUSIONS: OT is a potential surrogate marker for long-term inflammatory disease activity and DMT failure in MS.

Valid olfactory impairment tests can help identify mild cognitive impairment: an updated meta-analysis.

Background: Olfactory testing is emerging as a potentially effective screening method for identifying mild cognitive impairment in the elderly population. Objective: Olfactory impairment is comorbid with mild cognitive impairment (MCI) in older adults but is not well-documented in subdomains of either olfactory or subtypes of cognitive impairments in older adults. This meta-analysis was aimed at synthesizing the differentiated relationships with updated studies. Methods: A systematic search was conducted in seven databases from their availability to April 2023. A total of 38 publications were included, including 3,828 MCI patients and 8,160 healthy older adults. Two investigators independently performed the literature review, quality assessment, and data extraction. The meta-analyses were conducted with Stata to estimate the average effects and causes of the heterogeneity. Results: Compared to normal adults, MCI patients had severe impairments in olfactory function and severe deficits in specific domains of odor identification and discrimination. Olfactory impairment was more severe in patients with amnestic mild cognitive impairment than in patients with non-amnestic MCI. Diverse test instruments of olfactory function caused large heterogeneity in effect sizes. Conclusion: Valid olfactory tests can be complementary tools for accurate screening of MCI in older adults.

Correlation of olfactory function factors with cardiac sympathetic denervation in Parkinson's disease.

BACKGROUND: Hyposmia is a common nonmotor symptom of Parkinson's disease (PD) and reportedly associated with dysautonomia in PD. The smell identification test for measuring olfactory function consists of multiple items to discriminate specific scents. In the present study, factor analysis of the smell identification test was performed, and the correlation of extracted factors with cardiac sympathetic denervation (CSD) in patients with PD was investigated. METHODS: The present study included 183 early PD patients who underwent the Cross-Cultural Smell Identification Test (CC-SIT) and 123I-meta-iodobenzylguanidine (123I-MIBG) myocardial scintigraphy. Factor analysis of 12 items on the CC-SIT was performed using the computed correlation matrix for the binary items, and five smell factors were extracted. Multiple linear regression was performed to determine the correlation of olfactory function with late heart-to-mediastinum (H/M) ratio of 123I-MIBG uptake. RESULTS: The mean CC-SIT score was 6.1 ± 2.6, and 133 patients (72.7%) had CSD. The CC-SIT score and five smell factors were not associated with dopamine transporter uptake or cognitive functions. However, the CC-SIT score significantly correlated with age (P < 0.001) and late H/M ratio (P < 0.001). Factors 1 and 5 showed an increasing trend with larger H/M ratio, although it was not statistically significant (ß = 0.203, P = 0.085 and ß = 0.230, P = 0.085, respectively). Factor 5 significantly correlated with the H/M ratio in PD patients with CSD (ß = 0.676, P = 0.036). DISCUSSION: The results showed olfactory dysfunction to be selectively associated with cardiac sympathetic burden in PD. The correlation of certain factors with CSD indicates the possibility of selective hyposmia in PD patients.

Comparative Olfactory Profiles in Parkinson's Disease and Drug-Induced Parkinsonism.

OBJECTIVE: Drug-induced parkinsonism (DIP) is a frequently encountered diagnostic possibility when considering Parkinson's disease (PD). While olfactory dysfunction is a common clinical feature in PD, the comparison of olfactory function between the two conditions remains insufficient. This study aimed to compare olfactory function, including threshold, discrimination, and identification (TDI) profiles, between PD and DIP. METHODS: Consecutive patients with drug-naïve PD (n = 78) or DIP (n = 31) confirmed through dopamine transporter imaging were enrolled in this study. The YSK olfactory function (YOF) test, composed of TDI domains culturally familiar odorants to Koreans, was administered to all patients. RESULTS: In the study population, patients with DIP were significantly older than patients with PD. Over 70% of patients in each group had hyposmia or anosmia, and there was no significant difference in the occurrence of olfactory dysfunction between the two groups. In addition, there were no differences in the total YOF score and threshold score between the two groups. Meanwhile, the PD group had a significantly lower discrimination and identification score than the DIP group after adjusting for age, sex, the existence of diabetes, disease duration, and cognitive function. CONCLUSION: This study demonstrated that detailed olfactory profiles are different in PD and DIP, even though olfactory dysfunction can be observed in both conditions.

Long-term Recovery Patterns of Olfactory Function after Trans-sphenoidal Approach with Nasoseptal Flap Elevation.

Introduction Nasoseptal flap is widely used in reconstruction of the skull base to prevent cerebrospinal fluid leakage after surgery for skull base lesions. There has been a debate on whether more severe olfactory dysfunction occurs after nasoseptal flap elevation than the conventional trans-sphenoidal approach. Objective To compare the long-term recovery patterns associated with nasoseptal flap and the conventional trans-sphenoidal approach. Methods The subjects were divided into the conventional trans-sphenoidal approach group and the nasoseptal flap elevation group. We followed up self-reported olfactory score using the visual analogue scale and threshold discrimination identification (TDI) score of the Korean Version of the Sniffin Stick test II for 12 months, with olfactory training. Results The study included 31 patients who underwent the trans-sphenoidal approach. Compared with preoperative status, the mean visual analogue scale and TDI scores in the conventional trans-sphenoidal approach group recovered 2 months postoperatively, while in the nasoseptal flap elevation group the visual analogue scale and TDI scores recovered 6 months and 3 months after surgery, respectively. Twelve months after surgery, the visual analogue scale and TDI scores in the conventional trans-sphenoidal approach group were 9.3 ± 0.5 and 28.5 ± 4.3, while those from the nasoseptal flap elevation group were 8.9 ± 1.5 and 27.2 ± 4.7 ( p = 0.326; 0.473). Only one of the patients in the nasoseptal flap elevation group had permanent olfactory dysfunction. Conclusion The olfactory function recovered more gradually in the nasoseptal flap elevation group than in the conventional trans-sphenoidal approach group, but there was no difference between the two groups after 6 months.

Olfactory bulb neurogenesis depending on signaling in the subventricular zone.

Olfaction is a crucial sense that is essential for the well-being and survival of individuals. Olfactory bulb (OB) is the first olfactory relay station, and its function depends on newly generated neurons from the subventricular zone (SVZ). These newly born neurons constantly migrate through the rostral migratory stream to integrate into existing neural networks within the OB, thereby contributing to olfactory information processing. However, the mechanisms underlying the contribution of SVZ adult neurogenesis to OB neurogenesis remain largely elusive. Adult neurogenesis is a finely regulated multistep process involving the proliferation of adult neural stem cells (aNSCs) and neural precursor cells, as well as the migration and differentiation of neuroblasts, and integration of newly generated neurons into preexisting neuronal circuitries. Recently, extensive studies have explored the mechanism of SVZ and OB neurogenesis. This review focused on elucidating various molecules and signaling pathways associated with OB neurogenesis dependent on the SVZ function. A better understanding of the mechanisms underlying the OB neurogenesis on the adult brain is an attractive prospect to induce aNSCs in SVZ to generate new neurons to ameliorate olfactory dysfunction that is involved in various diseases. It will also contribute to developing new strategies for the human aNSCs-based therapies.

Suggestions on the ideal method of conducting community screenings for older adults.

BACKGROUND/OBJECTIVES: Since dementia and frailty lead to a reduced quality of life and risk of needing long-term care in the older adults, we hypothesized that evaluations related to dementia and frailty would be useful and of high interest in screening for the older adults. Therefore, we conducted a community screening incorporating multiple simple evaluations related to dementia and frailty. In addition to various functional evaluations, we investigated interest in tests, thoughts on the disease, and the relationships between subjective (i.e., how one feels about oneself) and objective evaluations (i.e., the results of tests and rating scales). The purpose of this study was to examine the thoughts regarding tests and diseases and the functions that make it difficult to accurately perceive changes by oneself, and to obtain suggestions on the ideal method of community screening for the older adults. SUBJECTS/METHODS: The participants were 86 people aged 65 and over living in Kotoura Town who participated in the community screening, for which we obtained background information and body measurements. We also assessed physical, cognitive and olfactory function, evaluated nutritional status, and we administered a questionnaire (interest in tests, thoughts on dementia and frailty, and a subjective functional evaluation). RESULTS: Regarding interest in tests, the participants answers were highest for physical, cognitive and olfactory function, in that order (68.6%, 60.5%, and 50.0%, respectively). In the survey on thoughts on dementia and frailty, 47.6% of participants felt that people with dementia were viewed with prejudice, and 47.7% did not know about frailty. Regarding the relationship between subjective and objective evaluations, only the assessment of cognitive function did not show a correlation between both evaluations. CONCLUSIONS: From the viewpoint of the participants' degree of interest in and the need for accurate evaluations through objective examination, the findings suggest that the assessment of physical and cognitive function may be beneficial as a screening tool for older adults. Objective evaluation is essential, particularly for assessing cognitive function. However, approximately half the participants believed people with dementia were viewed with prejudice and did not know about frailty, which may lead to barriers to testing and low interest. The importance of increasing the participation rate in community screening through disease-related educational activities was suggested.

Association among Olfactory Function, Lifestyle and BMI in Female and Male Elderly Subjects: A Cross-Sectional Study.

Physical activities seem to counteract the age-related physiological decline of the olfactory function which, influencing the food choices and eating behavior, can affect the body weight of individuals. The main purpose of this cross-sectional study was to evaluate the relationships between olfactory function and BMI in female and male Elderly Subjects (ES), according to the level of their lifestyle activities in physical, cognitive, and social terms. Considering weekly physical activities, the adult elderlies who decided to participate in this study were divided into active ES (n = 65) and non-active ES (n = 68). Assessment of weekly activities and olfactory function were performed by means of face-to-face interviews and the "Sniffin' Sticks" battery test, respectively. The results show that ES who are overweight and with a non-active lifestyle achieved lower TDI olfactory scores than normal weight ES and those classified as active. Hyposmic and non-active ES showed a higher BMI than normosmic and active ES. Sex-related differences, with females performing better than males, were evident in the presence of at least one of the following conditions: non-activity, hyposmia, or overweight. Inverse correlations were found between BMI and TDI olfactory score and between BMI and hours/week spent on physical activities, both when subjects were considered all together and when they were divided into females and males. These findings suggest that a higher BMI is related to the olfactory dysfunction linked to active or non-active lifestyle and the sex-related differences, and the condition of hyposmia is related to the increase in body weight due to lifestyle and sex differences. Given that the relationship between BMI and non-exercise physical activities is comparable to that between BMI and exercise physical activities, and this may be of particular importance for ES with limited mobility.

Gender-Related Differences in the Correlation between Odor Threshold, Discrimination, Identification, and Cognitive Reserve Index in Healthy Subjects.

BACKGROUND: Many studies suggested that olfactory function could be associated with semantic memory, executive function, and verbal fluency. However, the gender-related association between olfactory function and the cognitive domain is not well investigated. The aim of this study was to estimate gender-related differences in the relationship between olfactory function and each specific cognitive domain of the Cognitive Reserve Index (CRI) questionnaire, such as education, working activity, and leisure time in healthy subjects. METHODS: Two hundred and sixty-nine participants were recruited (158 women and 111 men), with a mean age of 48.1 ± 18.6 years. The CRI questionnaire and Sniffin' Sticks test were used to evaluate the cognitive reserve and the olfactory function, respectively. RESULTS: In all subjects, significant associations between the odor threshold versus CRI-Education, between the odor discrimina-tion and identification versus CRI-Working activity and CRI-Leisure Time, were found. In women, odor threshold, discrimination, and identification were associated with CRI-Leisure Time, while in men, only a significant association between odor threshold and CRI-Education was observed. CONCLUSIONS: Our data, showing significant gender-related associations between olfactory function and CRI scores, suggested the use of olfactory evaluation and cognitive reserve as an important screening tool for the early detection of mild cognitive impairment.

Olfactory bulb volume in cochlear implant candidates as compared to age-matched control subjects: A potential marker of cognitive function for auditory information processing.

OBJECTIVE: To evaluate magnetic resonance imaging (MRI)-based olfactory bulb (OB) volumes in cochlear implant (CI) candidates with sensorineural hearing loss as compared to age-matched control subjects with normal hearing. METHODS: A total of 31 pediatric CI candidates (mean ± SD age: 7.0 ± 2.5 years, 51.6% were boys) with sensorineural hearing loss and 35 age-matched control subjects (mean ± SD age: 7.1 ± 2.5 years, 54.3% were boys) with normal hearing were included in this study. Data on demographic characteristics (age, gender) and right and left OB volume (mm3) on MRI using planimetric contouring method were recorded in patients and control groups. RESULTS: Median (min-max) values for right OB volume (80(50-120) vs. 90(50-160) mm3, p = 0.006) and left OB volume (70(50-120) vs. 90(50-170) mm3, p = 0.007) were significantly lower in CI candidates vs. controls, regardless of the gender and age. No significant difference was noted between right and left OB volume in CI candidate and control groups. Hearing loss subgroups of CI candidates including hereditary familial (n = 8), hereditary non-familial (n = 14) and mixed syndromic (9) subgroups were also similar in terms of patient demographics and OB volumes. There was a tendency for having lower left OB volume (60(50-120) vs. 80(60-110) mm3) in girls vs. boys in the CI candidate group, along with a tendency for lower left and right OB volume in candidates vs. controls, particularly at age 11 (median 120 vs. 80 mm3 and 120 vs. 60 mm3, respectively). No significant correlation of age was noted with right and left OB volume overall and in the study groups. CONCLUSION: In conclusion, our findings revealed lower left and right OB volumes in CI candidates compared to control subjects, regardless of age and gender, indicating the presence of baseline olfactory dysfunction in patients with hearing loss planned to undergo CI. Accordingly, MRI-based measurement of OB volume in the pre-surgical workup of CI candidates may serve as a marker of cognitive function enabling auditory information processing that may also correlate with post-operative CI outcomes.

Variations in olfactory function among bipolar disorder patients with different episodes and subtypes.

Purpose: Most studies on olfactory function in individuals with bipolar disorder (BD) have not distinguished between the different subtypes or between the acute phase (mania or depression) and euthymic state. In this study, we compared olfactory function among BD patients with different subtypes and episodes to explore the potential use of olfactory function as a biomarker for the early identification of BD. Patients and methods: The study sample consisted of 117 BD patients who were hospitalized between April 2019 and June 2019, and 47 healthy volunteers as controls. The BD patients were divided into a bipolar I disorder (BD I) (n = 86) and bipolar II disorder (BD II) group (n = 31) according to the different subtypes, and divided into depressive BD (n = 36), manic BD (n = 44), or euthymic BD (n = 37) groups according to the types of episodes they experienced. We assessed olfactory sensitivity (OS) and olfactory identification (OI) via the Sniffin' Sticks test and used the Hamilton Depression Rating Scale (HAMD) and Young Manic Rating Scale (YMRS) to evaluate BD characteristics among all subjects. Results: Compared with controls, the participants with BD showed decreased OS and OI. We found statistically significant differences in OS and OI between the BD I group and controls, as well as differences in OS between the BD I and BD II group. Least-significant difference multiple comparisons revealed statistically significant differences in OS between the depressive BD group, manic BD group and controls and also between the manic BD and euthymic BD group. OI was positively correlated with the YMRS score in the BD I group and OS was negatively correlated with the HAMD score in the BD II group. Conclusion: This may be the first study to compare olfactory function in patients with BD I vs. BD II via pairwise comparisons. Our findings suggest that OS may have potential as a biomarker for distinguishing the different subtypes of BD and as a state-related biomarker for differentiating the acute phase from the euthymic state of BD. However, further prospective research is warranted.

The Association Between Depth of the Olfactory Sulcus, Age, Gender and Olfactory Function: An MRI-based Investigation in More Than 1000 Participants.

OBJECTIVE: The present study aimed to investigate the relationship between olfactory sulcus (OS) depth and olfactory function considering age and gender and to provide normative data on OS depth in a population with normal olfactory function. MATERIALS AND METHODS: OS depth was obtained using T1 magnetic resonance imaging scans. Participants (mean age ± sd = 57 ± 16 years, ranging from 20 to 80 years) were screened for olfactory function using the Sniffin' Sticks Screening 12 test. They were divided into an olfactory dysfunction group (n = 604) and a normosmia group (n = 493). Participants also completed questionnaires measuring depression, anxiety and quality of life. RESULTS: The right OS was deeper than the left side in all age groups. On the left side, women had deeper OS compared with men, exhibiting a higher degree of symmetry in left and right OS depth in women. Variance of olfactory function was largely determined by age, OS depth explained only minor portions of this variance. Normative data for minimum OS depth was 7.55 mm on the left and 8.78 mm on the right for participants aged between 18 and 35 years (n = 144), 6.47 mm on the left and 6.99 mm on the right for those aged 36-55 years (n = 120), and 5.28 mm on the left and 6.19 mm on the right for participants older than 55 years (n = 222). CONCLUSION: Considering the limited resolution of the presently used T1 weighted MR scans and the nature of the olfactory screening test, OS depth explained only minor portions of the variance of olfactory function, which was largely determined by age. Age-related normative data of OS depth are presented as a reference for future work.

Identification of Genes Associated with the Impairment of Olfactory and Gustatory Functions in COVID-19 via Machine-Learning Methods.

The coronavirus disease 2019 (COVID-19), as a severe respiratory disease, affects many parts of the body, and approximately 20-85% of patients exhibit functional impairment of the senses of smell and taste, some of whom even experience the permanent loss of these senses. These symptoms are not life-threatening but severely affect patients' quality of life and increase the risk of depression and anxiety. The pathological mechanisms of these symptoms have not been fully identified. In the current study, we aimed to identify the important biomarkers at the expression level associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-mediated loss of taste or olfactory ability, and we have suggested the potential pathogenetic mechanisms of COVID-19 complications. We designed a machine-learning-based approach to analyze the transcriptome of 577 COVID-19 patient samples, including 84 COVID-19 samples with a decreased ability to taste or smell and 493 COVID-19 samples without impairment. Each sample was represented by 58,929 gene expression levels. The features were analyzed and sorted by three feature selection methods (least absolute shrinkage and selection operator, light gradient boosting machine, and Monte Carlo feature selection). The optimal feature sets were obtained through incremental feature selection using two classification algorithms: decision tree (DT) and random forest (RF). The top genes identified by these multiple methods (H3-5, NUDT5, and AOC1) are involved in olfactory and gustatory impairments. Meanwhile, a high-performance RF classifier was developed in this study, and three sets of quantitative rules that describe the impairment of olfactory and gustatory functions were obtained based on the optimal DT classifiers. In summary, this study provides a new computation analysis and suggests the latent biomarkers (genes and rules) for predicting olfactory and gustatory impairment caused by COVID-19 complications.

Olfactory identification ability among schizophrenia patients, their first-degree relatives and healthy subjects.

OBJECTIVE: Olfactory impairments, including identification, have been reported in patients with schizophrenia, while few studies have examined the olfactory function of unaffected first-degree relatives of patients with schizophrenia, and the sample sizes of first-degree relatives were relatively small. Here, we investigated olfactory identification ability among patients with schizophrenia, first-degree relatives and healthy controls (HCs) using relatively large sample sizes at a single institute. METHODS: To assess olfactory identification ability, the open essence odorant identification test was administered to 172 schizophrenia patients, 75 first-degree relatives and 158 healthy controls. Differences in olfactory identification and correlations between olfactory ability and clinical variables were examined among these participants. RESULTS: We found a significant difference in olfactory identification ability among the diagnostic groups (p = 7.65 × 10-16). Schizophrenia patients displayed lower olfactory identification ability than first-degree relatives (Cohen's d = -0.57, p = 3.13 × 10-6) and healthy controls (d = -1.00, p = 2.19 × 10-16). Furthermore, first-degree relatives had lower olfactory identification ability than healthy controls (d = -0.29, p = 0.039). Olfactory identification ability moderately and negatively correlated with the duration of illness (r = -0.41, p = 1.88 × 10-8) and negative symptoms (r = -0.28, p = 1.99 × 10-4) in schizophrenia patients, although the correlation with the duration of illness was affected by aging (r = -0.24). CONCLUSIONS: Our results demonstrated that schizophrenia patients have impaired olfactory identification ability compared with first-degree relatives and healthy controls, and the impaired olfactory identification ability of first-degree relatives was intermediate between those in schizophrenia patients and healthy controls. Olfactory identification ability was relatively independent of clinical variables. Therefore, olfactory identification ability might be an intermediate phenotype for schizophrenia.