Considering hearing loss as a modifiable risk factor for dementia.

INTRODUCTION: Accumulating evidence links hearing loss to impaired cognitive performance and increased risk for dementia. Hearing loss can lead to deafferentation-induced atrophy of frontotemporal brain regions and dysregulation of cognitive control networks from increased listening effort. Hearing loss is also associated with reduced social engagement, loneliness, and depression, which are independently associated with poor cognitive function. AREAS COVERED: We summarize the evidence and postulated mechanisms linking hearing loss to dementia in older adults and synthesize the available literature demonstrating beneficial effects of hearing remediation on brain structure and function. EXPERT OPINION: : Further research is needed to evaluate whether treatment of hearing loss may reduce risk of cognitive decline and improve neural consequences of hearing loss. Studies may investigate the pathologic mechanisms linking these late-life disorders and identify individuals vulnerable to dementia, and future clinical trials may evaluate whether hearing treatment may reduce the risk for dementia.

Evidence suggests that hearing loss is associated with impaired cognitive performance, increased risk for dementia, and poor brain health in older adults. Fortunately, preliminary studies have shown positive effects of hearing treatment on cognitive outcomes and reversal of adverse neural effects of hearing loss. In the following, we review the available evidence providing support for hearing loss as a modifiable risk factor for dementia. However, there are important limitations to such findings, and further research is needed to definitively evaluate whether hearing treatment may protect cognitive and brain health in older adults. If future studies demonstrate that hearing treatment has beneficial effects on cognitive and neural outcomes, such results may take advantage of the recent widespread efforts to improve access to hearing treatment in the United States.

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.

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.

Hearing loss and risk of depressive symptoms in older adults in the Health ABC study.

Objective: Hearing loss (HL) is highly prevalent among older adults and may lead to increased risk of depressive symptoms. In both cross-sectional and longitudinal analysis, we quantified the association between HL and depressive symptoms, incorporating the variable nature of depressive symptoms and characterizing by race and gender. Methods: Data were from the Health, Aging, and Body Composition study. Depressive symptoms were measured using the Center for Epidemiologic Study Depression Scale short form (CES-D 10), defined as CES-D 10 score ≥10 or treatment for depression. Hearing was defined via four-frequency pure-tone average (PTA) decibel hearing level (dB HL), categorized as normal hearing (PTA ≤25 dB HL), mild HL (PTA26-40 dB HL), and ≥moderate HL (PTA > 40 dB HL). Associations at baseline were quantified using logistic regression, incident depressive symptoms using Cox proportional hazard models, and change in depressive symptoms over time using growth mixture models and multinomial logistic regression. Results: Among 2,089 older adults (1,082 women, 793 Black; mean age 74.0 SD: 2.8), moderate or greater HL was associated with greater odds of concurrent [Odds Ratio (OR):2.45, 95% CI:1.33, 4.51] and incident depressive symptoms [Hazard Ratio (HR):1.26, 95% CI:1.00, 1.58]. Three depressive symptom trajectory patterns were identified from growth mixture models: low, moderate increasing, and borderline high depressive symptom levels. Those with moderate or greater HL were more likely to be in the borderline high depressive-symptom trajectory class than the low trajectory class [Relative Risk Ratio (RRR):1.16, 95% CI:1.01, 1.32]. Conclusions: HL was associated with greater depressive symptoms. Although findings were not statistically significantly different by gender and race, estimates were generally stronger for women and Black participants. Investigation of psychosocial factors and amelioration by hearing aid use could have significant benefit for older adults' quality of life.

Age-Related Hearing Loss, Neuropsychological Performance, and Incident Dementia in Older Adults.

BACKGROUND: Age-related hearing loss (HL) has been associated with dementia, though the neurocognitive profile of individuals with HL is poorly understood. OBJECTIVE: To characterize the neurocognitive profile of HL. METHODS: N = 8,529 participants from the National Alzheimer's Coordinating Center ≥60 years and free of cognitive impairment who were characterized as Untreated-, Treated-, or No HL. Outcomes included executive function (Trail Making Test [TMT] Part B), episodic memory (Immediate/Delayed Recall), language fluency (Vegetables, Boston Naming Test), and conversion to dementia. Regression models were fit to examine associations between HL and neurocognitive performance at baseline. Cox proportional hazards models examined the links between HL, neurocognitive scores, and development of dementia over follow-up. RESULTS: At baseline, those with Untreated HL (versus No HL) had worse neurocognitive performance per standardized difference on executive function (TMT Part B [mean difference = 0.05 (95% CI 0.00, 0.10)]) and language fluency (Vegetables [mean difference = -0.07 (95% CI -0.14, -0.01)], Boston Naming Test [mean difference = -0.07 (95% CI -0.13, -0.01)]). No differences in these neurocognitive performance scores were demonstrated between Treated HL and No HL groups other than MMSE [mean difference = -0.06 (95% CI -0.12, 0.00)]. Through follow-up, executive dysfunction differed by hearing group (χ2(2) = 46.08, p < 0.0001) and was present among 39.12% in No HL, 44.85% in Untreated HL, and 49.40% in Treated HL. Worse performance across all cognitive domains predicted incident dementia. CONCLUSION: The observed association between Untreated HL and lower cognitive ability that improved when hearing aids were worn may reflect an inability to hear the test instructions. Future studies using cognitive assessments validated for use in HL are needed to evaluate the neuropsychological profile of HL and identify individuals at risk for dementia.

Neural circuits and behavioral pathways linking hearing loss to affective dysregulation in older adults.

Substantial evidence now links age-related hearing loss to incident major depressive disorder in older adults. However, research examining the neural circuits and behavioral mechanisms by which age-related hearing loss leads to depression is at an early phase. It is known that hearing loss has adverse structural and functional brain consequences, is associated with reduced social engagement and loneliness, and often results in tinnitus, which can independently affect cognitive control and emotion processing circuits. While pathways leading from these sequelae of hearing loss to affective dysregulation and depression are intuitive to hypothesize, few studies have yet been designed to provide conclusive evidence for specific pathophysiological mechanisms. Here we review the neurobiological and behavioral consequences of age-related hearing loss, present a model linking them to increased risk for major depressive disorder and suggest how future studies may facilitate the development of rationally designed therapeutic interventions for older adults with impaired hearing to reduce risk for depression and/or ameliorate depressive symptoms.

Age-Related Hearing Loss, Late-Life Depression, and Risk for Incident Dementia in Older Adults.

BACKGROUND: Hearing loss (HL), late-life depression, and dementia are 3 prevalent and disabling conditions in older adults, but the interrelationships between these disorders remain poorly understood. METHODS: N = 8529 participants ≥60 years who were free of cognitive impairment at baseline were analyzed from National Alzheimer's Coordinating Center Uniform Data Set. Participants had either No HL, Untreated HL, or Treated HL. Primary outcomes included depression (15-item Geriatric Depression Scale ≥5) and conversion to dementia. A longitudinal logistic model was fit to examine the association between HL and changes in depressive symptoms across time. Two Cox proportional hazards models were used to examine HL and the development of dementia: Model A included only baseline variables and Model B included time-varying depression to evaluate for the direct effect of changes in depression on dementia over time. RESULTS: Treated HL (vs no HL) had increased risk for depression (odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.04-1.54, p = .02) and conversion to dementia (hazard ratio [HR] = 1.29, 95% CI = 1.03-1.62, p = .03). Baseline depression was a strong independent predictor of conversion to dementia (HR = 2.32, 95% CI = 1.77-3.05, p < .0001). Development/persistence of depression over time was also associated with dementia (HR = 1.89, 95% CI = 1.47-2.42, p < .0001), but only accounted for 6% of the direct hearing-dementia relationship (Model A logHR = 0.26 [SE = 0.12] to Model B logHR = 0.24 [SE = 0.12]) suggesting no significant mediation effect of depression. CONCLUSIONS: Both HL and depression are independent risk factors for eventual conversion to dementia. Further understanding the mechanisms linking these later-life disorders may identify targets for early interventions to alter the clinical trajectories of at-risk individuals.

Association of Hearing Loss With Psychological Distress and Utilization of Mental Health Services Among Adults in the United States.

Importance: Psychological distress affects health and health care utilization. Hearing loss (HL) is highly prevalent and undertreated, and it may be a potentially modifiable risk factor for psychological distress. Objective: To investigate the association between HL, psychological distress, and mental health care utilization among adults in the United States. Design, Setting, and Participants: This cross-sectional study included 25 665 individuals aged 18 years and older who participated in the 2017 National Health Interview Survey, a home-based nationally representative cross-sectional survey of noninstitutionalized US adults conducted by trained interviewers. Exposures: Self-reported hearing and hearing aid use. Main Outcomes and Measures: Kessler psychological distress scale (scores ≥5 indicating moderate distress), self-reported use of medication to treat depression or anxiety symptoms, and use of mental health services in the past year. Results: A total of 25 665 adults (mean [SD] age 47.0 [18.1] years, 51.7% [95% CI, 51.0%-52.5%] women, weighted to be representative of the US adult population) were included in the analysis. Compared with 11 558 participants (49.3%; 95% CI, 48.2%-50.5%) with no HL, the 9390 (35.3%; 95% CI, 34.4%-36.2%) with mild HL and 4717 (15.4%; 95% CI, 14.8%-16.0%) with moderate or worse HL had increased odds of moderate psychological distress (mild HL: odds ratio [OR], 1.49; 95% CI, 1.35-1.62; moderate HL: OR, 2.12; 95% CI, 1.87-2.41) and were more likely to report antidepressant medication use (mild HL: OR, 1.39; 95% CI, 1.17-1.67; moderate HL: OR, 2.07; 95% CI, 1.70-2.57), and antianxiety medication use (mild HL: OR, 1.39; 95% CI, 1.16-1.67; moderate HL: OR, 1.94; 95% CI, 1.57-2.39). Moderate HL was associated with increased odds of use of mental health services (moderate HL: OR, 1.53; 95% CI, 1.30-1.79). Among individuals with moderate HL, those with hearing aids (1066 [22.6%]) were less likely to experience psychological distress than those without hearing aids (3651 [77.4%]; OR, 0.66; 95% CI, 0.53-0.83). Conclusions and Relevance: In a large nationally representative sample of US adults, self-reported HL was associated with both greater psychological distress and increased rates of antidepressant and antianxiety medication use and utilization of mental health services. Further research is needed to investigate whether HL may be a modifiable risk factor for these outcomes.

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.

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.

Association of Audiometric Age-Related Hearing Loss With Depressive Symptoms Among Hispanic Individuals.

Importance: Age-related hearing loss is highly prevalent and has recently been associated with numerous morbid conditions of aging. Late-life depression is also prevalent and can be resistant to available treatments. Preliminary studies examining the association between hearing loss and late-life depression have been limited by subjective hearing measures, small sample sizes, and primarily white populations. Objective: To assess whether a cross-sectional association exists between objective audiometric hearing loss and depressive symptoms in older Hispanic adults. Design, Setting, and Participants: This cross-sectional study uses 2008-2011 Hispanic Community Health Study/Study of Latinos data collected in Miami, Florida, San Diego, California, Chicago, Illinois, or the Bronx, New York, from 5328 Hispanic adults 50 years or older who had exposure, outcome, and covariate data. Data analyses were conducted from March 2018 to September 2018. Exposure: Audiometric hearing loss (pure-tone average). Main Outcomes and Measures: Center for Epidemiologic Studies Depression Scale, 10-item version (CESD-10) score of 10 or higher, which indicates clinically significant depressive symptoms. Results: The median age (interquartile range) of the 5328 participants was 58 (53-63) years, and 3283 participants (61.6%) were female. The mean (SD) CESD-10 score was 7.7 (6.4). Of the 5328 included participants, 1751 (32.9%) had clinically significant depressive symptoms. The odds of having these symptoms increased 1.44 (95% CI, 1.27-1.63) times for every 20 dB of hearing loss, adjusting for hearing aid use, age, sex, educational level, study site, geographic background, cardiovascular disease, and antidepressant use. Compared with those for individuals with normal hearing (0 dB), the odds of having clinically significant depressive symptoms was 1.81 (95% CI, 1.48-2.22) times as high in individuals with mild hearing loss (median threshold, 32.5 dB), 2.38 (95% CI, 1.77-3.20) times as high in individuals with moderate hearing loss (median threshold, 47.5 dB), and 4.30 (95% CI, 2.61-7.09) times as high in individuals with severe hearing loss (median threshold, 80 dB). Conclusions and Relevance: Objective hearing loss appears to be associated with clinically significant depressive symptoms in older Hispanic people, with greater hearing loss seemingly associated with greater odds of having depressive symptoms. Given the high prevalence of untreated hearing loss in older adults, hearing loss may be a potentially modifiable risk factor for late-life depression.

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.

Sensation and Psychiatry: Linking Age-Related Hearing Loss to Late-Life Depression and Cognitive Decline.

Recent research has linked age-related hearing loss to impaired performance across cognitive domains and increased risk for dementia diagnosis. The data linking hearing impairment to incident late-life depression are more mixed but suggest that diminished hearing does increase risk for depression. Behavioral mechanisms may explain these associations, such as the withdrawal of older adults from situations in which they may have difficulty hearing and communicating, which may contribute to the development of social isolation, loneliness, and consequent cognitive decline and depression. At a neural level, chronic hearing loss leads to reduced activation in central auditory pathways, resulting in compensatory increased activation in the cognitive control network, dysfunctional auditory-limbic connectivity, and deafferentation-induced atrophy in frontal brain regions. These pathologic changes decrease cognitive performance and increase depression risk by reducing cognitive reserve, increasing executive dysfunction, and disrupting normative emotion reactivity and regulation. Based on the available data and informed by this model, evidence-based suggestions are proposed for clinicians treating older adults, and a research agenda is advanced to facilitate the development of rationally designed and age-appropriate psychiatric treatments for older adults with age-related hearing loss. First and foremost, treating hearing loss should be investigated as a means of improving cognitive and depressive outcomes in well-designed studies incorporating comprehensive psychiatric assessments, randomization, objective documentation of compliance, and analyses of treatment mediators that will facilitate further therapeutic development. Multimodal neuroimaging studies integrating audiometric, neuropsychological, and clinical assessments also are needed to further evaluate the model proposed. [AJP at 175: Remembering Our Past As We Envision Our Future April 1995: Effect of Hearing Enhancement on Medical Status Ratings Twenty-one elderly psychiatric patients had lower levels of psychopathology when assessed while wearing hearing aids. (Am J Psychiatry 1995; 152:629-631 )].

Somatic and neuroendocrine responses to standard and biologically salient acoustic startle stimuli in monkeys.

The startle response, a simple defensive response to a sudden stimulus signaling proximal threat, has been well studied in rodents and humans, but has been rarely examined in monkeys. The first goal of the present studies was to develop a minimally immobilizing startle measurement paradigm and validate its usefulness by testing two core features of the startle response (habituation and graded responsivity) in squirrel monkey subjects. Two different types of startle stimuli were used: standard broad-band noise bursts, and species-specific alarm vocalizations ("yaps") which are elicited in response to threat in both wild and captive animals. The second goal of the present studies was to test whether yaps produce enhanced startle responsivity due to their increased biological salience compared to simple, non-biologically relevant noise bursts. The third goal of the present studies was to evaluate the hypothalamic-pituitary-adrenal (HPA) axis response to startle stimuli, as little is known about the stress-activating role of startle stimuli in any species. These experiments determined that the whole-body startle response in relatively unrestrained squirrel monkeys habituates across repeated stimulus presentations and is proportional to stimulus intensity. In addition, differential habituation was observed across biologically salient vs. standard acoustic startle stimuli. Responses to "yaps" were larger initially but attenuated more rapidly over trials. Responses to "yaps" were also larger in the early subepochs of the response window but then achieved a lower level than responses to noise bursts in the later subepochs. Finally, adrenocorticotropic hormone and cortisol concentrations were significantly elevated above baseline after startle stimuli presentation, though monkeys did not exhibit differential HPA axis responses to the two types of startle stimuli. The development of monkey startle methodology may further enhance the utility of this paradigm in translational studies of human stress-related psychiatric disorders.