Hearing Loss in Older People With Schizophrenia: Audiologic Characteristics and Association With Psychosocial Functioning.

OBJECTIVE: The severity and impact of hearing deficits among adults with schizophrenia spectrum disorders may become increasingly relevant with advancing age. This study evaluated hearing ability and associated psychosocial functioning among older adults aged 50-70. DESIGN: Cross-sectional analysis. SETTING: Four outpatient psychiatry clinics in New York City. PARTICIPANTS: Individuals aged 50-70 years with diagnoses of schizophrenia or schizoaffective disorder. MEASUREMENTS: Unaided pure tone air conduction audiometry conducted using a portable audiometry system determined the pure tone average (PTA) hearing threshold across four frequencies: 500, 1k, 2k, and 4k Hz. Better ear PTA defined the hearing threshold. Audiometry data retrieved from the U.S. National Health and Nutrition Examination Survey aided interpretation of sample hearing loss rates. Standard measures evaluated psychiatric symptoms, perceived impact of hearing impairment, loneliness, and quality of life. RESULTS: Among audiometry completers (N = 40), 35% (n = 14) demonstrated subclinical hearing loss (16-25 dB) and 35% (n = 14) had mild or worse hearing loss (≥26 dB). Rates were higher than expected based on age-based population data. Those who perceived hearing handicap rated it moderate (12.2%) or severe (7.3%); those who perceived tinnitus rated the impact as mild to moderate (12.2%) or catastrophic (2.4%). Neither psychiatric symptoms nor interviewer-rated quality of life was associated with hearing ability. Greater loneliness was significantly correlated with worse audiologic performance (r = 0.475, p <0.01) and greater perceived hearing handicap (r = 0.480, p <0.01). CONCLUSION: Identifying the need for hearing loss treatment among aging adults with schizophrenia spectrum disorders is important given the potential implications for social functioning, cognitive, and mental health.

Age-based disparities in hearing loss diagnosis and treatment in the United States population.

OBJECTIVE: To investigate age-related disparities in the diagnosis and treatment of borderline/mild hearing loss (HL) in the United States. STUDY DESIGN: A cross-sectional epidemiologic study. SETTING: The National Health and Nutrition Examination Survey (NHANES). METHODS: Multivariable logistic regressions controlling for hearing level were performed to investigate the association between: (1) age and recent hearing test; (2) age and hearing aid use. Age was grouped into quartiles (<25, 25-49, 50-74, ≥75 years). The first quartile of life was used as a reference group in all odds ratios, controlling for hearing level. RESULTS: Of 2115 participants with borderline/mild HL, 3 % (n = 53) were in age quartile Q1; 7 % (n = 147) were in Q2, 56 % (n = 1190) were in Q3, and 34 % (n = 725) were in Q4. Compared to Q1, those in Q2, Q3, and Q4 had 4.06 times (95 % CI = 2.11-8.02, p < 0.001), 4.51 times (2.56-8.19, p < 0.001), and 4.56 times (2.55-8.39, p < 0.001) lower odds of a hearing test within the past 4 years. Similar, although slightly larger, odds ratios were obtained when the outcome was hearing test within 1 year. Compared to Q1, those in Q2, Q3, and Q4 respectively had 4.38 times (1.47-13.5, p < 0.05), 5.41 times (2.27-11.8, p < 0.001), and 3.95 times (1.65-8.72, p < 0.05) lower odds of using a hearing aid. CONCLUSION: We have characterized a large, unaddressed, and modifiable disparity in the treatment of borderline/mild HL as individuals age out of the first quartile of life. Future studies are needed to explore factors, such as ageism, that may underlie these findings.

Social engagement and depressive symptoms mediate the relationship between age-related hearing loss and cognitive status.

BACKGROUND AND OBJECTIVES: Age-related hearing loss (ARHL) is the third leading cause of years lived with disability. Connections among ARHL, depressive symptoms, social engagement and cognitive status are increasingly reported but the underlying mechanisms leading to these relationships are largely unknown. Exploring these mechanisms is a worthy goal, especially in older adults. This study aimed to examine the mediating effect of social engagement and depressive symptoms on the relationship between ARHL and cognitive status. METHODS: Structural equation modeling (SEM) with path analysis were performed with data from a cross-sectional study conducted in 11 community centers in 2021, which assessed older adults' intrinsic and sensory capacities using the WHO ICOPE framework. Demographic information, health profile, a binary measure of hearing capacity, depressive symptoms, social engagement, and cognitive status of participants were gathered. RESULTS: A total of 304 participants were included. ARHL was positively associated with depressive symptoms (ß = 0.18, p = 0.009) and negatively related to social engagement (ß = -0.13, p = 0.026). Social engagement was positively associated with cognitive status (ß = 0.17, p = 0.005) and negatively associated with depressive symptoms (ß = -0.23, p < 0.001). Greater depressive symptoms were negatively associated with the participants' cognition (ß = -0.13, p = 0.009). Both social engagement (ß = -0.02, p = 0.029) and depressive symptoms (ß = -0.02, p = 0.032) mediated the negative associations between ARHL and cognitive status. CONCLUSIONS: Addressing hearing loss, depressive symptoms, and enhancing social engagement should be investigated as a potential means of minimizing cognitive decline. Well-designed studies are needed to comprehensively inform the clinical practice development, particularly large prospective studies that will facilitate further elucidate possible causal mechanisms behind these observed associations.

Hearing Rehabilitative Treatment for Older Adults With Comorbid Hearing Loss and Depression: Effects on Depressive Symptoms and Executive Function.

OBJECTIVES: Recent research has revealed important neural and psychiatric consequences of hearing loss (HL) in older adults. This pilot study examined the neural effects of HL and the impact of hearing aids on neuropsychiatric outcomes in major depressive disorder (MDD). DESIGN: Twelve-week, double-blind, randomized controlled trial. PARTICIPANTS/INTERVENTION: N = 25 (≥60 years) with MDD and moderate-profound HL were randomized to receive hearing aids (100% gain targets) or sham hearing aids (flat 30 dB HL) in addition to psychiatric treatment-as-usual. MEASUREMENTS: Depressive symptoms (Hamilton Rating Scale for Depression [HRSD]), executive functioning (NIH Toolbox Flanker), integrity of auditory brain areas (structural MRI, diffusion tensor imaging). RESULTS: At baseline, worse speech discrimination was associated with auditory cortical thinning (Left anterior transverse temporal gyrus: r = 0.755, p = 0.012) and lower integrity of the superior longitudinal fasciculus (FA: Left r = 0.772, p = 0.025, Right r = 0.782, p = 0.022). After 12-weeks, hearing aids were effective at improving hearing functioning (Hearing Handicap for the Elderly: active -12.47 versus sham -4.19, t = -2.64, df = 18, p = 0.016) and immediate memory (active +14.9 versus sham +5.7, t = 2.28, df = 16, p = 0.037). Moderate improvement was observed for hearing aids on executive functioning but did not reach statistical significance (Flanker: active +4.8 versus sham -2.4, t = 1.95, df = 15, p = 0.071). No significant effect on depression was found (HRSD: active -5.50 versus sham -7.32, t = 0.75, df = 19, p = 0.46). CONCLUSIONS: HL can affect brain regions important for auditory and cognitive processing, and hearing remediation may have beneficial effects on executive functioning in MDD. Future studies may evaluate whether impairment in cognitive control consequent to HL may be an important risk mechanism for MDD.

A precision medicine tool to understand who responds best to hearing aids in late-life depression.

OBJECTIVES: Accumulating evidence suggests that hearing loss (HL) treatment may benefit depressive symptoms among older adults with Major Depressive Disorder (MDD), but the specific individual characteristics of those who stand to improve most are unknown. METHODS: N = 37 patients ≥60 years with HL and MDD received either active or sham hearing aids in this 12-week double-blind randomized controlled trial. A combined moderator approach was utilized in the analysis in order to examine multiple different pretreatment individual characteristics to determine the specific qualities that predicted the best depressive symptom response to hearing aids. Pretreatment characteristics included: Hearing Handicap Inventory for the Elderly (HHIE-S), pure tone average (PTA), speech reception threshold (SRT), Short Physical Performance Battery (SPPB), cognition (Repeatable Battery for the Assessment of Neuropsychological Status). RESULTS: The analysis revealed a combined moderator, predicting greater improvement with active versus sham hearing aids, that had a larger effect size than any individual moderator (combined effect size [ES] = 0.49 [95% CI: 0.36, 0.76]). Individuals with worse hearing-related disability (HHIE-S: individual ES = -0.16), speech recognition (SRT: individual ES = -0.14), physical performance (SPPB: individual ES = 0.41), and language functioning (individual ES = 0.19) but with relatively less severe audiometric thresholds (PTA: individual ES = 0.17) experienced greater depressive symptom improvement with active hearing aids. CONCLUSIONS: Older adults with relatively worse HL-related, physical, and cognitive functioning may stand to benefit most from hearing aids. Given the large number of older adults experiencing HL and MDD, a non-invasive and scalable means of targeting those most likely to respond to interventions would be valuable.

Subclinical Hearing Loss is Associated With Depressive Symptoms.

OBJECTIVE: To assess whether the relationship between hearing and depressive symptoms is present among older adults classified as normal hearing (≤25 dB). DESIGN: Cross-sectional epidemiologic study (Hispanic Community Health Study). SETTING: US multicentered. PARTICIPANTS: Adults ≥50 years old (n = 5,499) with normal hearing or hearing loss (HL). MEASUREMENTS: The primary exposure was hearing, defined continuously by the 4-frequency pure-tone average threshold (dB) on audiometry. Hearing was additionally categorized into normal hearing (≤25 dB) and HL (>25 dB). The main outcome was depressive symptoms, measured with the Center for Epidemiologic Studies Depression Scale-10 (CESD-10). Depressive symptoms were defined both continuously and binarily (where CESD-10 ≥10 was categorized as clinically significant depressive symptoms). Multivariable linear, logistic, and generalized additive modeling (GAM) regressions were performed. RESULTS: Among those with normal hearing, the CESD-10 score increased by 1.04 points (95% confidence interval [CI]: 0.70, 1.37) for every 10 dB decrease in hearing, adjusting for age, gender, education, cardiovascular disease, and hearing aid use. Among those with HL, the CESD-10 score increased by 0.62 points (95% CI: 0.23, 1.01) for every 10 dB decrease in hearing, adjusting for the same confounders. Similar findings were noted when the outcome was clinically significant depressive symptoms (adjusted odds ratio: 1.28 [1.14, 1.44] in normal hearing versus 1.26 [1.11, 1.44] in HL). In certain sensitivity analyses, the relationship between hearing and depressive symptoms was significantly stronger among those with normal hearing than in those with HL. CONCLUSION: The relationship between hearing and clinically significant depressive symptoms is present among older adults with normal hearing (<25 dB). We introduce the term subclinical HL as imperfect hearing that is classically defined as normal (1-25 dB). The relationship between hearing and late life depressive symptoms may be more sensitive than previously recognized.

A pilot randomized controlled trial of hearing aids to improve mood and cognition in older adults.

OBJECTIVES: Age-related hearing loss (ARHL) is a prevalent condition associated with increased risk for depression and cognitive decline. This 12-week prospective, double-blind pilot randomized controlled trial (RCT) of hearing aids (HAs) for depressed older adults with ARHL evaluated the feasibility of a novel research design. METHODS/DESIGN: N = 13 individuals aged ≥60 years with Major Depressive Disorder or Persistent Depressive Disorder and at least mild hearing loss (pure tone average ≥ 30 dB) were randomized to receive full- (active) vs low-amplification (sham) HAs added to psychiatric treatment as usual. Duration of HA use in hours/day, adverse events frequency, attrition rate, and maintenance of the study blinding were the primary outcome measures. RESULTS: Compliance with HAs was excellent (>9 hours/day for both groups) and rates of adverse events and drop-outs did not differ between groups. Preliminary data demonstrated differential improvement for active vs sham HAs on hearing functioning (Hearing Handicap Inventory for the Elderly [nonparametric effect size (np-ES) = 0.62]), depressive symptoms (Inventory for Depressive Symptomatology [np-ES = 0.31]), cognition (Repeatable Battery for the Assessment of Neuropsychological Status Immediate Memory [np-ES = 0.25]), and general functioning (World Health Organization Disability Assessment Schedule [np-ES = 0.53]). Significantly greater than 50% of both groups correctly guessed their treatment assignment, indicating incomplete concealment of treatment allocation. CONCLUSIONS: This pilot RCT for ARHL and late-life depression was feasible to execute and showed clinical promise, but improved methods of blinding the experimental treatments are needed. Larger studies should investigate whether hearing remediation may be an effective preventative and/or therapeutic strategy for late-life depression and cognitive decline.

Age-related Hearing Loss and Dementia.

Dementia is a devastating disease and global health challenge that is highly prevalent worldwide. A growing body of research has shown an independent association between age-related hearing loss (ARHL) and dementia, identifying ARHL as a compelling potential target in preventive strategies for dementia. However, a causal linkage between ARHL and dementia needs to be investigated before making definitive clinical guidelines and treatment recommendations regarding ARHL as a modifiable risk factor. In this review, we discuss the association between ARHL and dementia, the importance of addressing this finding, as well as common mechanisms (eg, microvascular disease) and causal mechanisms (eg, depletion of cognitive reserve and social isolation) that may explain the nature of this relationship. Future directions for research are also highlighted, including randomized controlled trials, developing high-resolution microvascular imaging, and further refining audiometric testing.

Age-Related Hearing Loss and Its Association with Depression in Later Life.

OBJECTIVES: To evaluate the association between age-related hearing loss (ARHL) and depressive symptoms in older adults over time. METHODS: Data from the Health Aging and Body Composition study (N = 3075, aged 70-79 at baseline) were used previously to conduct a longitudinal latent class analysis to evaluate depression trajectories (Center for Epidemiologic Studies Depression [CES-D] Scale) over 10 years. Restricting to the subset of subjects who had hearing information available (N = 1204), self-reported hearing categories were evaluated over the same period. Association between depression classes and hearing categories were assessed via multinomial logistic regression analyses. Correlation analyses and two-sample t-tests were used to assess cross-sectional associations between depression status and audiometric hearing measures. RESULTS: Low-probability (N = 644), increasing-probability (N = 385), and high-probability (N = 175) trajectories of depressive symptoms were identified for the 10-year period. Impaired/Worsening (N = 182) and Healthy/Improving (N = 1,022) hearing categories were defined using self-reports. With the low-probability depression trajectory as the reference group, subjects reporting Impaired/Worsening hearing had 1.63 times increased odds of having an increasing- (p = 0.0088, 95% CI [1.13, 2.34]) and 1.85 times increased odds of having a high-probability depression trajectory (p = 0.0102, 95% CI [1.16, 2.96]). At Year 5, individuals with depressive symptoms (10CES-D ≥ 10) had impaired hearing ability measured by audiometric threshold for low-frequency (Adjusted mean difference = 2.29 dBHL, p = 0.0005) and mid-frequency sounds (Adjusted mean difference = 2.28 dBHL,p = 0.0049) compared to those with 10CES-D < 10. CONCLUSIONS: ARHL was associated with increased depressive symptoms in older adults. Future studies should investigate whether treatment of ARHL may be an effective prevention and/or therapeutic strategy for depressive symptoms.

Vestibular implantation and longitudinal electrical stimulation of the semicircular canal afferents in human subjects.

Animal experiments and limited data in humans suggest that electrical stimulation of the vestibular end organs could be used to treat loss of vestibular function. In this paper we demonstrate that canal-specific two-dimensionally (2D) measured eye velocities are elicited from intermittent brief 2 s biphasic pulse electrical stimulation in four human subjects implanted with a vestibular prosthesis. The 2D measured direction of the slow phase eye movements changed with the canal stimulated. Increasing pulse current over a 0-400 µA range typically produced a monotonic increase in slow phase eye velocity. The responses decremented or in some cases fluctuated over time in most implanted canals but could be partially restored by changing the return path of the stimulation current. Implantation of the device in Meniere's patients produced hearing and vestibular loss in the implanted ear. Electrical stimulation was well tolerated, producing no sensation of pain, nausea, or auditory percept with stimulation that elicited robust eye movements. There were changes in slow phase eye velocity with current and over time, and changes in electrically evoked compound action potentials produced by stimulation and recorded with the implanted device. Perceived rotation in subjects was consistent with the slow phase eye movements in direction and scaled with stimulation current in magnitude. These results suggest that electrical stimulation of the vestibular end organ in human subjects provided controlled vestibular inputs over time, but in Meniere's patients this apparently came at the cost of hearing and vestibular function in the implanted ear.

Hearing Loss and Reduced Income Growth: A Longitudinal Socioeconomic Analysis.

OBJECTIVE: Hearing loss (HL) has been linked to negative socioeconomic states, including low income. This study examines the relationship between HL and income growth. STUDY DESIGN: Longitudinal observational study. SETTING: Multicentered US epidemiologic study (Hispanic Community Health Study, HCHS). METHODS: Using data from 2 waves of the HCHS, we analyzed the association between HL and income growth in adults ages 18 to 74 years using generalized estimating equations. The exposure was HL, measured by 4-frequency pure-tone average (PTA). The outcome was yearly household income growth, with income graded on a 10-bracket scale from <$10,000 to >$100,000. Models controlled for demographics, hearing aid use, and vascular risk. RESULTS: A total of 1342 participants met inclusion criteria. At visit 1, average age was 47.6 years (SD = 12.2), and average PTA was 13.9 decibels (dB, SD = 9.5). Average follow-up was 5.9 years (SD = 0.6). There was a significant time × HL interaction: with each 10 dB worsening in HL, the odds of belonging to a higher versus a lower income bracket changed by a factor of 0.979 (P < .001) between waves 1 and 2. In other words, the odds of belonging to a higher income group decreased with worsening HL. At 38.6 dB, the odds for income growth became <1, indicating income loss rather than growth. CONCLUSION: Increased HL is associated with reduced income growth, including the possibility of negative growth (ie, income decline). This study emphasizes the value of including socioeconomic measures in randomized controlled trials assessing the impact of HL treatment and the importance of extended follow-up for study participants.

Radiation-Induced Sensorineural Hearing Loss and Potential Management.

The cochlear apparatus is one of the major organs at risk when considering radiation therapy (RT) for brain, head, and neck tumors. Radiation oncologists currently consider mean dose constraints of <35 Gy for conventionally fractioned radiation therapy (RT), <4 Gy for single fraction stereotactic radiosurgery, and <17.1 or 25 Gy for 3- or 5-fraction stereotactic radiosurgery, respectively, as the standard of care. Indeed, dose adjustments are made in the setting of concurrent platinum-based chemotherapy or when prioritizing tumor coverage during treatment planning. Despite guidelines, in many patients, RT to the cochlea may still cause sensorineural hearing loss through progressive degeneration and ossification of the inner ear. There are several audiologic and otolaryngologic interventions for incident RT-induced hearing loss, including hearing aids, cochlear implants, or, in the context of vestibular schwannoma due to neurofibromatosis type 2, auditory brain stem implantation. Cochlear implants are the most effective at restoring hearing and improving quality of life for those with an intact cochlear nerve. An early multidisciplinary approach is essential to optimally manage RT-induced hearing loss, and this topic discussion serves as a guide for radiation oncologists on cochlear dosimetric considerations as well as how to address potential RT-induced adverse effects.

Voice Disorders and Hearing Loss May Be Additive Risk Factors for Depression in a National Cohort.

OBJECTIVES: Hearing loss (HL) (receptive communication impairment) is a known risk factor for depression. However, dysphonia (expressive communication impairment), has received little study. We study HL, self-reported voice disorder, and combined impairment as risk factors for depression in a large national cohort. METHODS: This was a cross-sectional epidemiologic study. Data were analyzed from the Korean National Health and Nutrition Examination Survey (KNHANES) cycles 2008-2012 and 2019-2020. KNHANES uniquely contains both audiometry and voice disorder data. HL (yes/no) was defined as ≥25 dB pure tone average. Voice disorder (yes/no) was defined by self-report. Depression (yes/no) was defined by physician diagnosis. Odds ratios for depression were calculated using multivariable logistic regressions with HL and voice disorder. RESULTS: 8,524 individuals aged 19 to 80 years old had complete data. The mean age was 57.3 years (SD = 13.4) and 64% were women. All regressions were controlled for age and sex. Those with HL, versus those without, had 1.27 times the odds (95% CI = 1.07-1.52, p = 0.007) of depression. Those with self-reported voice disorder, versus those without, had 1.48 times the odds (1.22-1.78, p < 0.001) of depression. Those with HL and self-reported voice disorder, versus those with neither, had 1.79 times the odds (1.27-2.48, p < 0.001) of depression. CONCLUSIONS: This study demonstrates independent relationships between HL and depression and self-reported voice disorder and depression. Combined HL and self-reported voice disorder had nearly 1.8 times the odds of depression. This is likely due to the grossly additive effect of difficulty with incoming and outgoing communication streams. LEVEL OF EVIDENCE: II Laryngoscope, 134:4060-4065, 2024.

National Cohort Data Suggests an Association Between Serious Mental Illness and Audiometric Hearing Loss.

OBJECTIVE: To explore whether there is an association between serious mental illness (SMI) and hearing loss (HL) among US Hispanic adults. STUDY DESIGN AND SETTING: Cross-sectional epidemiological study (Hispanic Community Health Study), including multicentered US volunteers. METHODS: Multivariable linear regressions were conducted to study the association between SMI and HL. Adjustments were made for potential confounders including age, sex, education, vascular disease (hypertension or diabetes mellitus), and cognition. SMI was defined by (1) antipsychotic medication classification and (2) the use of at least 1 antipsychotic medication specifically used to treat SMI in clinical psychiatric practice. HL was measured by pure tone audiometry. RESULTS: A total of 7581 subjects had complete data. The mean age was 55.2 years (SD = 7.5 years) and the mean pure tone average in the better ear was 16.8 dB (SD = 10.7 dB). A total of 194 (2.6%) subjects were taking a HCHS-defined antipsychotic and 98 (1.3%) were taking at least 1 antipsychotic specifically used to treat SMI. On multivariable regression, use of HCHS's classified antipsychotics was associated with 3.75 dB worse hearing (95% confidence interval [CI] = 2.36-5.13, P < .001) and use of antipsychotics specific for SMI was associated with 4.49 dB worse hearing (95% CI = 2.56-6.43, P < .001) compared to those not using antipsychotics. CONCLUSION: SMI, as defined by either the use of HCHS-defined antipsychotics or the use of antipsychotic medication specific for SMI, is associated with worse hearing, controlling for potential confounders. Whether SMI contributes to HL, antipsychotic medication (through ototoxicity) contributes to HL, or whether HL contributes to SMI is unknown and warrants further investigation.

Design and Methods of the Early Age-Related Hearing Loss Investigation Randomized Controlled Trial.

OBJECTIVE: Hearing loss has been identified as a major modifiable risk factor for cognitive decline. The Early Age-Related Hearing Loss Investigation (EARHLI) study will assess the mechanisms linking early age-related hearing loss (ARHL) and cognitive impairment. STUDY DESIGN: Randomized, controlled, single-site, early phase II, superiority trial. SETTING: Tertiary academic medical center. PARTICIPANTS: One hundred fifty participants aged 55 to 75 years with early ARHL (severity defined as borderline to moderate) and amnestic mild cognitive impairment will be included. INTERVENTIONS: Participants will be randomized 1:1 to a best practice hearing intervention or a health education control. MAIN OUTCOME MEASURES: The primary study outcome is cognition measured by the Alzheimer Disease Cooperative Study-Preclinical Alzheimer Cognitive Composite. Secondary outcomes include additional measures of cognition, social engagement, and brain organization/connectivity. RESULTS: Trial enrollment will begin in early 2024. CONCLUSIONS: After its completion in 2028, the EARHLI trial should offer evidence on the effect of hearing treatment versus a health education control on cognitive performance, social engagement, and brain organization/connectivity in 55- to 75-year-old community-dwelling adults with early ARHL and amnestic mild cognitive impairment.

Hair cell replacement in adult mouse utricles after targeted ablation of hair cells with diphtheria toxin.

We developed a transgenic mouse to permit conditional and selective ablation of hair cells in the adult mouse utricle by inserting the human diphtheria toxin receptor (DTR) gene into the Pou4f3 gene, which encodes a hair cell-specific transcription factor. In adult wild-type mice, administration of diphtheria toxin (DT) caused no significant hair cell loss. In adult Pou4f3(+/DTR) mice, DT treatment reduced hair cell numbers to 6% of normal by 14 days post-DT. Remaining hair cells were located primarily in the lateral extrastriola. Over time, hair cell numbers increased in these regions, reaching 17% of untreated Pou4f3(+/DTR) mice by 60 days post-DT. Replacement hair cells were morphologically distinct, with multiple cytoplasmic processes, and displayed evidence for active mechanotransduction channels and synapses characteristic of type II hair cells. Three lines of evidence suggest replacement hair cells were derived via direct (nonmitotic) transdifferentiation of supporting cells: new hair cells did not incorporate BrdU, supporting cells upregulated the pro-hair cell gene Atoh1, and supporting cell numbers decreased over time. This study introduces a new method for efficient conditional hair cell ablation in adult mouse utricles and demonstrates that hair cells are spontaneously regenerated in vivo in regions where there may be ongoing hair cell turnover.

Correlates of hearing loss among adults with schizophrenia.

BACKGROUND: Hearing loss (HL) is associated with adverse cognitive, mental, and physical health outcomes. There is evidence that across age groups HL is more prevalent in people with schizophrenia than the general population. Given that people with schizophrenia may already be vulnerable to cognitive and psychosocial disability, we sought to examine how hearing ability relates to concurrent levels of cognitive, mental and daily functioning. METHODS: Community-dwelling adults with schizophrenia (N = 84) ages 22-50 completed pure tone audiometry assessments. Hearing threshold (in decibels) was defined as the lowest detectable pure tone at 1000 Hz. Pearson correlation was used to test the hypothesis that higher hearing thresholds (worse hearing) would be significantly associated with poorer performance on the Brief Assessment of Cognition in Schizophrenia (BACS). Additional analyses explored the relationships between audiometric threshold and functional capacity measured with the Virtual Reality Functional Capacity Assessment Tool (VRFCAT) and symptoms severity rated on the Positive and Negative Syndrome Scale (PANSS). RESULTS: Hearing threshold was inversely and significantly correlated with the BACS composite score (r = -0.27, p = 0.017). This relationship was reduced but remained significant after controlling for age (r = -0.23, p = 0.04). Hearing threshold was not associated with VRFCAT or psychiatric symptom measures. CONCLUSIONS: While schizophrenia and HL are independently associated with cognitive impairment, the magnitude of impairment in this sample was greater among those with poorer hearing. Findings warrant further mechanistic study of the relationship between hearing impairment and cognition and have implications for addressing modifiable health risk factors for higher morbidity and mortality in this vulnerable population.

Prevalence of Subclinical Hearing Loss in the United States.

OBJECTIVE: Current definitions of hearing loss (HL) may be insufficiently strict, as subclinical hearing loss (SCHL; >0 and ≤25 dB hearing level) has been associated with deleterious age-related conditions. SCHL prevalence and mean age of HL onset in the United States has not been characterized. STUDY DESIGN: A cross-sectional epidemiologic prevalence study. SETTING: US Community. METHODS: We analyzed cross-sectional audiometric data in the US National Health and Nutrition Examination Survey (2005-2012, 2015-2018, n = 15,649). Results were scaled to the current population using weighting. RESULTS: 79.6% of participants (227.32 million Americans) had SCHL. The mean age of HL onset at thresholds of 25, 20, and 15 dB was 74, 66, and 55 years, respectively, for the 4-frequency pure-tone average, and 48, 44, and 35 years for the high-frequency pure-tone average. CONCLUSION: We present SCHL prevalence and define HL onset by various sensitive definitions. These results inform ongoing public health efforts to increase hearing aid utilization, particularly given the arrival of over-the-counter hearing aids.

Assessing the Accuracy of Otomatch.com Data for Individuals Applying to Otolaryngology Residency.

OBJECTIVES: Otomatch.com is an online forum for residency applicants to discuss the otolaryngology match process including academic metrics. The purpose of this study is to assess the accuracy of self-reported match data on Otomatch relative to official data reported by the National Residency Match Program (NRMP) and the Association of American Medical Colleges (AAMC). METHODS: Data was collected from publicly editable Otomatch forums (2017-2018, 2018-2019, 2019-2020) and curated Otomatch survey responses (2018-2019, 2019-2020) whose results are released after Match Day. Aggregated data was collected from the NRMP 2018 and 2020 Charting Outcomes in the Match and AAMC Report on Residents (2017-2018, 2018-2019). Measures of interest included Step 1 scores, Step 2 CK scores, publications, number of interview invitations, number of interviews attended, and AOA status. ANOVA and 2 tailed T tests were performed to compare variables within each match year. RESULTS: Average Step 2 CK score was significantly higher on publicly editable Otomatch forums than AAMC in 2017-2018 (257vs 253, P < .05) and 2018-2019 (258vs 252, P < .05). Interviews attended were significantly higher on Otomatch survey responses than the publicly editable forum in 2019-2020 (13vs 9, P-value < .05). Step 1 scores, interview invitations, and AOA status were not statistically significantly different when data was available. CONCLUSION: Applicant statistics from online forums, online surveys, NRMP, and AAMC are consistent, except for Step 2 CK scores. Self-reported data on the Otomatch forum is an accurate estimate of academic metrics of otolaryngology residency applicants.

Inhibition of Notch activity promotes nonmitotic regeneration of hair cells in the adult mouse utricles.

The capacity of adult mammals to regenerate sensory hair cells is not well defined. To explore early steps in this process, we examined reactivation of a transiently expressed developmental gene, Atoh1, in adult mouse utricles after neomycin-induced hair cell death in culture. Using an adenoviral reporter for Atoh1 enhancer, we found that Atoh1 transcription is activated in some hair cell progenitors (supporting cells) 3 d after neomycin treatment. By 18 d after neomycin, the number of cells with Atoh1 transcriptional activity increased significantly, but few cells acquired hair cell features (i.e., accumulated ATOH1 or myosin VIIa protein or developed stereocilia). Treatment with DAPT, an inhibitor of γ-secretase, reduced notch pathway activity, enhanced Atoh1 transcriptional activity, and dramatically increased the number of Atoh1-expressing cells with hair cell features, but only in the striolar/juxtastriolar region. Similar effects were seen with TAPI-1, an inhibitor of another enzyme required for notch activity (TACE). Division of supporting cells was rare in any control or DAPT-treated utricles. This study shows that mature mammals have a natural capacity to initiate vestibular hair cell regeneration and suggests that regional notch activity is a significant inhibitor of direct transdifferentiation of supporting cells into hair cells following damage.