Autonomic Nervous System Dysregulation Research Articles

Exploring autonomic dysfunction in functional dysphonia: A protocol for a case-control study and a randomized controlled trial.

Although psychological factors have been implicated in patients with functional dysphonia (FD), conventional voice therapy (CVT) typically targets the aberrant voice symptoms exclusively. Yet, CVT is not always successful, and in view of the significant adverse quality of life impact combined with the financial burden on the healthcare system and society, research is needed to elucidate the underlying psychophysiology of FD and improve treatment outcomes. The first objective of this research project is to compare the occurrence and frequency of symptoms and/or disorders related to autonomic nervous system (ANS) dysfunction in patients with FD with gender- and age-matched vocally healthy controls, using a case-control study. The second objective is to compare the effects of a novel therapy for FD based on ANS regulation (i.e., ANS therapy: heart rate variability (HRV) biofeedback) on both autonomic function and voice function versus CVT alone or in combination with ANS therapy (i.e., ANS therapy + CVT), using a randomized controlled trial (RCT). Case-control study: Autonomic (dys)function of patients with FD will becompared with gender- and age-matched vocally healthy controls, using both physiological measures (e.g., HRV, skin conductance level) and psychological patient-reported outcome measures (PROMs, e.g., Neuroception of Psychological Safety Scale, Depression Anxiety and Stress Scale). RCT: The FD group will be randomly assigned to the innovative ANS therapy group, the CVT group or the ANS therapy + CVT group. All patients received 1 month of treatment with 20 min of daily practice. Both the autonomic assessment and the voice assessment will beperformed pretherapy and immediately after therapy by assessors blinded to group allocation and study phase. Higher occurrences of symptoms and/or disorders related to autonomic dysfunction are expected in patients with FD compared with vocally healthy controls. Physiological outcomes: lower HRV, lower cardiac pre-ejection period, higher respiration rate and higher skin conductance level are hypothesized in patients with FD compared with vocally healthy controls. Psychological PROMs: higher self-report of feelings/symptoms related to autonomic dysfunction (e.g., perceived stress, anxiety) is expected in patients with FD compared with vocally healthy controls. The autonomic function is hypothesized to improve more after the ANS therapy and the ANS therapy + CVT compared with the CVT only. Voice function is expected to improve more after the ANS therapy + CVT compared with the ANS therapy and the CVT alone. What is already known on the subject Autonomic dysfunction is well recognized in the field of psychology but remains understudied in the area of voice. Given that the vagus nerve, innervating the larynx, also helps to regulate the ANS, and psychological symptoms commonly observed in patients with FD may reflect ANS dysregulation, research in this area is needed. There is some preliminary evidence that autonomic dysfunction might indeed be associated with FD. However, physiological ANS measures are needed, as well as validated psychological PROMs. What this paper adds to the existing knowledge The first objective of this study is to investigate the occurrence and frequency of symptoms and/or disorders related to autonomic dysfunction in patients with FD as compared with a gender- and age-matched vocally healthy control group. Autonomic (dys)function will be determined by employing both physiological measures (e.g., HRV, skin conductance level) and psychological PROMs (e.g., Neuroception of Psychological Safety Scale, Depression Anxiety and Stress Scale). The second objective is to compare the effects of a novel therapy for FD based on ANS regulation (HRV biofeedback) versus CVT alone or in combination with ANS therapy. What are the potential or actual clinical implications of this work? Success rates of symptomatic CVT for FD are highly variable. This study is expected to lead to innovative results related to the pathogenesis and psychophysiology of FD, a prevalent voice disorder associated with a significant adverse quality of life impact and a substantial financial burden on the healthcare system and society. The results of this study will lead to crucial new insights into both the diagnosis and treatment of FD, contributing to evidence-based practice in the field of voice.

Cardiopulmonary and metabolic responses during a 2-day CPET in myalgic encephalomyelitis/chronic fatigue syndrome: translating reduced oxygen consumption to impairment status to treatment considerations

BackgroundPost-exertional malaise (PEM), the hallmark symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), represents a constellation of abnormal responses to physical, cognitive, and/or emotional exertion including profound fatigue, cognitive dysfunction, and exertion intolerance, among numerous other maladies. Two sequential cardiopulmonary exercise tests (2-d CPET) provide objective evidence of abnormal responses to exertion in ME/CFS but validated only in studies with small sample sizes. Further, translation of results to impairment status and approaches to symptom reduction are lacking.MethodsParticipants with ME/CFS (Canadian Criteria; n = 84) and sedentary controls (CTL; n = 71) completed two CPETs on a cycle ergometer separated by 24 h. Two-way repeated measures ANOVA compared CPET measures at rest, ventilatory/anaerobic threshold (VAT), and peak effort between phenotypes and CPETs. Intraclass correlations described stability of CPET measures across tests, and relevant objective CPET data indicated impairment status. A subset of case–control pairs (n = 55) matched for aerobic capacity, age, and sex, were also analyzed.ResultsUnlike CTL, ME/CFS failed to reproduce CPET-1 measures during CPET-2 with significant declines at peak exertion in work, exercise time, V˙\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\dot{\ ext{V}}$$\\end{document}e, V˙\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\dot{\ ext{V}}$$\\end{document}O2, V˙\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\dot{\ ext{V}}$$\\end{document}CO2, V˙\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\dot{\ ext{V}}$$\\end{document}T, HR, O2pulse, DBP, and RPP. Likewise, CPET-2 declines were observed at VAT for V˙\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\dot{\ ext{V}}$$\\end{document}e/V˙\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\dot{\ ext{V}}$$\\end{document}CO2, PetCO2, O2pulse, work, V˙\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\dot{\ ext{V}}$$\\end{document}O2 and SBP. Perception of effort (RPE) exceeded maximum effort criteria for ME/CFS and CTL on both CPETs. Results were similar in matched pairs. Intraclass correlations revealed greater stability in CPET variables across test days in CTL compared to ME/CFS owing to CPET-2 declines in ME/CFS. Lastly, CPET-2 data signaled more severe impairment status for ME/CFS compared to CPET-1.ConclusionsPresently, this is the largest 2-d CPET study of ME/CFS to substantiate impaired recovery in ME/CFS following an exertional stressor. Abnormal post-exertional CPET responses persisted compared to CTL matched for aerobic capacity, indicating that fitness level does not predispose to exertion intolerance in ME/CFS. Moreover, contributions to exertion intolerance in ME/CFS by disrupted cardiac, pulmonary, and metabolic factors implicates autonomic nervous system dysregulation of blood flow and oxygen delivery for energy metabolism. The observable declines in post-exertional energy metabolism translate notably to a worsening of impairment status. Treatment considerations to address tangible reductions in physiological function are proffered.Trial registration number: ClinicalTrials.gov, retrospectively registered, ID# NCT04026425, date of registration: 2019-07-17.

Increased stress burden and electrodermal reactivity in bladder cancer patients in comparison to healthy controls

The purpose of our study was to assess specific physiological parameters associated with stress responses in bladder cancer (BCa) patients compared to healthy individuals. By examining the transition from a supine to a sitting position, representing a mild physiological load, we investigated the changes in autonomic nervous system (ANS) activity as reflected by alterations in these parameters, indicating shifts in ANS regulation, using non-linear heart rate variability (HRV) parameters (0V%, 2UV%, parasympathetic and sympathetic nervous system – PNS and SNS indices), modified heart rate acceleration (ACmod) and deceleration capacities (DCmod), heart rate (HR), electrodermal activity (EDA), and also their correlations with perceived stress score. Our findings showed that BCa patients (n = 38) exhibited elevated resting HR, heightened SNS index, and increased EDA compared to their healthy counterparts (n = 47), indicating a notable physiological stress burden. The 0V% parameter showed a positive association with the SNS index, ACmod, HR, and EDA parameters, while displaying a negative correlation with the PNS index, DCmod and 2UV%. These non-linear HRV parameters, such as 0V% and 2UV%, offer nuanced insights into the complexities of heartbeat dynamics and autonomic regulation. After the transition from supine to sitting positions, BCa patients displayed higher EDA responses, indicating heightened stress reactivity and ANS sensitivity. These physiological distinctions persisted even when we did not prove differences in the levels of perceived stress between the studied groups. In conclusion, our study emphasizes the significance of identifying cancer patients at risk of ANS dysregulation, paving the way for tailored stress management strategies.

Autonomic nervous system dysregulation in children with monosymptomatic nocturnal enuresis

Autonomic nervous system dysregulation in children with monosymptomatic nocturnal enuresis

Exploration of COVID-19 associated bradycardia using heart rate variability analysis in a case-control study of ARDS patients

BackgroundBradycardia and dysautonomia observed during SARS-Cov2 infection suggests involvement of the autonomic nervous system (ANS). Limited data exists on ANS dysregulation and its association with outcomes in patients with acute respiratory distress syndrome (ARDS) related to COVID-19 (C-ARDS) or other etiologies (NC-ARDS). ObjectivesWe aimed to explore sympathovagal balance, assessed by heart rate variability (HRV), and its clinical prognostic value in C-ARDS compared with NC-ARDS. MethodsA single-center, prospective case-control study was conducted. Consecutive patients meeting ARDS criteria between 2020 and 2022 were included. HRV was assessed using 1-hour electrographic tracing during a stable, daytime period. ResultsTwenty-four patients with C-ARDS and 19 with NC-ARDS were included. Age, sex and ARDS severity were similar between groups. The median heart rate was markedly lower in the C-ARDS group than in the NC-ARDS group (60 [53–72] versus 101 [91–112] bpm, p<.001). Most of HRV parameters were significantly increased in patients with C-ARDS. HRV correlated with heart rate only in patients with C-ARDS. A positive correlation was found between the low-to high-frequency ratio (LF/HF) and length of intensive care unit stay (r = 0.576, p<.001). ConclusionThis study confirmed that C-ARDS was associated with marked bradycardia and severe ANS impairment, suggesting a sympathovagal imbalance with vagal overtone. Poor outcomes appeared to be more related to sympathetic rather than parasympathetic hyperactivation.

690-P: Relationship of Diabetes Distress and Symptoms of Autonomic Nervous System Dysregulation in Type 1 Diabetes Adults

690-P: Relationship of Diabetes Distress and Symptoms of Autonomic Nervous System Dysregulation in Type 1 Diabetes Adults

Obstructive Sleep Apnea and Pulmonary Hypertension: A Chicken-and-Egg Relationship.

Obstructive sleep apnea (OSA) is characterized by repeated episodes of upper airway obstruction during sleep, and it is closely linked to several cardiovascular issues due to intermittent hypoxia, nocturnal hypoxemia, and disrupted sleep patterns. Pulmonary hypertension (PH), identified by elevated pulmonary arterial pressure, shares a complex interplay with OSA, contributing to cardiovascular complications and morbidity. The prevalence of OSA is alarmingly high, with studies indicating rates of 20-30% in males and 10-15% in females, escalating significantly with age and obesity. OSA's impact on cardiovascular health is profound, particularly in exacerbating conditions like systemic hypertension and heart failure. The pivotal role of hypoxemia increases intrathoracic pressure, inflammation, and autonomic nervous system dysregulation in this interplay, which all contribute to PH's pathogenesis. The prevalence of PH among OSA patients varies widely, with studies reporting rates from 15% to 80%, highlighting the variability in diagnostic criteria and methodologies. Conversely, OSA prevalence among PH patients also remains high, often exceeding 25%, stressing the need for careful screening and diagnosis. Treatment strategies like continuous positive airway pressure (CPAP) therapy show promise in mitigating PH progression in OSA patients. However, this review underscores the need for further research into long-term outcomes and the efficacy of these treatments. This review provides comprehensive insights into the epidemiology, pathophysiology, and treatment of the intricate interplay between OSA and PH, calling for integrated, personalized approaches in diagnosis and management. The future landscape of OSA and PH management hinges on continued research, technological advancements, and a holistic approach to improving patient outcomes.

Abstract 2252: Loneliness, quality of life, and physical and mental health among cancer patients: All of US research program

Abstract Background: Loneliness, as a distressing feeling, occurs with a discrepancy between an individual’s social needs and one’s social relationship. Cancer patients, particularly, may feel loneliness, when their expected practical and emotional support from family or friend were not met. Loneliness can impair the capacity to self-regulate lifestyle behaviors and induce systemic inflammation through dysregulation of autonomic nervous system and the hypothalamic-pituitary-adrenal axis. While a growing body of literature has found an association between loneliness and physical or mental health, quality of life, morbidity or mortality, few studies have examined this association among cancer patients and effects of loneliness by sociodemographic characteristics. Method: We used All of US Controlled Tier Dataset v7 (summer 2017-July 1, 2022) which comprised survey and electronic health records data. Study sample included cancer patients aged ≥18 years (N=17,367). Loneliness was measured using the University of California, Los Angeles (UCLA)-3 items loneliness scale, which includes relational connectedness, social connectedness, and self-perceived isolation. Logistic regression models were used to estimate the association between loneliness and self-reported pain, fatigue, fair/poor health physical and mental health status, and quality of life, controlling for various covariates. We stratified the models by age, sex, race/ethnicity, income, education, living arrangement, and marital status. Results: Lonely cancer patients were more likely to have fair or poor quality of life (OR=3.80; 95% CI=3.33-4.34), severe pain (OR=1.55; 95% CI=1.35-1.79), severe or very severe fatigue (OR=2.41; 95% CI=2.07-2.80), fair or poor physical health (OR=2.26; 95% CI=2.05-2.50), and fair or poor mental health (OR=4.22; 95% CI=3.72-4.80) compared to non-lonely cancer patients, controlling for all other covariates. All stratified models generally showed similar results. However, the association between loneliness and severe pain was stronger in the younger group, whereas the association with mental health was stronger in the older group. The effect of loneliness on mental health was stronger among males (OR=5.42; 95% CI=4.30-6.83) than females (OR=3.84; 95% CI=3.29-4.49; p for difference &amp;lt; 0.05). By living arrangements, the relationship between loneliness and severe fatigue was stronger among cancer patients living alone (OR=3.15; 95% CI=2.33-4.25) than those living with others (OR=2.16; 95% CI=1.81-2.59; p for difference &amp;lt; 0.05). Conclusions: In this study, lonely cancer patients were more likely to have poor quality of life, poor mental and physical health, and severe pain and fatigue compared to non-lonely patients. These findings underscore the significance of policy and clinical interventions to alleviate negative effect of loneliness on health outcomes among cancer patients. Citation Format: Hyunjung Lee, Ding Quan Ng, Dongjun Lee, Ahmedin Jemal, Farhad Islami. Loneliness, quality of life, and physical and mental health among cancer patients: All of US research program [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2252.

Mechanisms underlying exercise intolerance in long COVID: An accumulation of multisystem dysfunction.

The pathogenesis of exercise intolerance and persistent fatigue which can follow an infection with the SARS-CoV-2 virus ("long COVID") is not fully understood. Cases were recruited from a long COVID clinic (N = 32; 44 ± 12 years; 10 (31%) men), and age-/sex-matched healthy controls (HC) (N = 19; 40 ± 13 years; 6 (32%) men) from University College London staff and students. We assessed exercise performance, lung and cardiac function, vascular health, skeletal muscle oxidative capacity, and autonomic nervous system (ANS) function. Key outcome measures for each physiological system were compared between groups using potential outcome means (95% confidence intervals) adjusted for potential confounders. Long COVID participant outcomes were compared to normative values. When compared to HC, cases exhibited reduced oxygen uptake efficiency slope (1847 (1679, 2016) vs. 2176 (1978, 2373) mL/min, p = 0.002) and anaerobic threshold (13.2 (12.2, 14.3) vs. 15.6 (14.4, 17.2) mL/kg/min, p < 0.001), and lower oxidative capacity, measured using near infrared spectroscopy (τ: 38.7 (31.9, 45.6) vs. 24.6 (19.1, 30.1) s, p = 0.001). In cases, ANS measures fell below normal limits in 39%. Long COVID is associated with reduced measures of exercise performance and skeletal muscle oxidative capacity in the absence of evidence of microvascular dysfunction, suggesting mitochondrial pathology. There was evidence of attendant ANS dysregulation in a significant proportion. These multisystem factors might contribute to impaired exercise tolerance in long COVID sufferers.

Post-COVID dysautonomias: what we know and (mainly) what we don't know.

Following on from the COVID-19 pandemic is another worldwide public health challenge that is referred to variously as long COVID, post-COVID syndrome or post-acute sequelae of SARS-CoV-2 infection (PASC). PASC comes in many forms and affects all body organs. This heterogeneous presentation suggests involvement of the autonomic nervous system (ANS), which has numerous roles in the maintenance of homeostasis and coordination of responses to various stressors. Thus far, studies of ANS dysregulation in people with PASC have been largely observational and descriptive, based on symptom inventories or objective but indirect measures of cardiovascular function, and have paid little attention to the adrenomedullary, hormonal and enteric nervous components of the ANS. Such investigations do not consider the syndromic nature of autonomic dysfunction. This Review provides an update on the literature relating to ANS abnormalities in people with post-COVID syndrome and presents a theoretical perspective on how the ANS might participate in common features of PASC.

Need to Take Heart? Talk to Your Psychiatrist for 20 Minutes.

A powerful correlation exists between the equilibrium of the sympathetic and parasympathetic nervous systems and heart rate variability (HRV). Thus, HRV is useful as a physiological index of both physical and emotional health; autonomic nervous system dysregulation, with a sympathetic predominance and a low HRV, has been associated with a variety of physical (cardiovascular, neurological) and psychiatric disorders. We used a validated algorithm of measuring the HRV (noninvasive, 2-minute approach) in new psychiatric outpatients in first author's private practice. The subjects had an initial measurement, followed by a 20-minute consultation with minimal supportive psychotherapy, followed by an exit measurement. The initial study spanned the "COVID months"; to control for this variable, an identical study was performed in 2023. There was a highly significant decrease in the sympathetic predominance in the test groups; no such trend was found in the control groups. A short psychiatry consultation may be sufficient to decrease patients' sympathetic hyperactivity and improve their well-being.

An Overview of the Mechanism behind Excessive Volume of Pericardial Fat in Heart Failure.

Heart failure (HF) is a clinical syndrome characterized by myocardial dysfunction leading to inefficient blood filling or ejection. Regardless of the etiology, various mechanisms, including adipokine hypersecretion, proinflammatory cytokines, stem cell proliferation, oxidative stress, hyperglycemic toxicity, and autonomic nervous system dysregulation in the pericardial fat (PCF), contribute to the development of HF. PCF has been directly associated with cardiovascular disease, and an increased PCF volume is associated with HF. The PCF acts as neuroendocrine tissue that is closely linked to myocardial function and acts as an energy reservoir. This review aims to summarize each mechanism associated with PCF in HF.

Evaluation of Anorexia in Cancer and Its Association with Autonomic Nervous System Activity Assessed by Heart Rate Variability

Alterations in the central nervous system in cancer patients are pivotal in determining appetite dysregulation and body weight loss (BWL). Autonomic nervous system activity was tested by measuring heart rate variability (HRV) in cancer patients presenting with anorexia. We considered inpatients with different types of cancer and investigated anorexia using their FAACT scores. HRV was evaluated by a three-channel Holter ECG. The domains of low frequencies (LF, sympathetic activity) and high frequencies (HF, parasympathetic activity) were calculated. Also, SDNN (autonomic activity) and RMSSD (parasympathetic activity) were assessed. We enrolled 56 patients with cancer and 23 controls. In cancer patients, RMSSD and SDNN were lower than in controls (p &lt; 0.001 and p = 0.009). Sympathetic activity (LF nu) was lower in cancer patients than in controls (p = 0.023), including sympathovagal balance (LF/HF nu ratio) (p = 0.025). RMSSD was reduced in anorexic (p &lt; 0.001) and non-anorexic (p = 0.003) cancer patients compared to controls. The SDNN was lower in anorexic cancer patients than in non-anorexic cancer patients (p = 0.025), and it was lower in anorexic cancer patients than in controls (p = 0.001). LF nu was lower in anorexic cancer patients than in controls (p = 0.015), as was LF/HF (p = 0.031). SDNN was negatively correlated with BWL in the cancer group (rho = −0.40; p = 0.007). Our data support the hypothesis that autonomic nervous system dysregulation exists in patients with cancer presenting with anorexia, with implications for its diagnosis and treatment.

Effects of prenatal opioid exposure on infant sympathetic and parasympathetic nervous system activity.

Prenatal opioid exposure has been associated with developmental problems, including autonomic nervous system dysregulation. However, little is known about the effects of prenatal opioid exposure on the autonomic nervous system beyond the first days of life, particularly across both the parasympathetic and sympathetic branches, and when accounting for exposure to other substances. The present study examined the effects of prenatal exposure to opioid agonist therapy (OAT, e.g., methadone) and other opioids on infant autonomic nervous system activity at rest and in response to a social stressor (the Still-Face Paradigm) at six months among 86 infants varying in prenatal opioid and other substance exposure. Results indicated that OAT and other opioids have unique effects on the developing autonomic nervous system that may further depend on subtype (i.e., methadone versus buprenorphine) and timing in gestation. Results are discussed in the context of theoretical models of the developing stress response system.

Overlapping Physiologic Signs of Sepsis and Paroxysmal Sympathetic Hyperactivity After Traumatic Brain Injury: Exploring A Clinical Conundrum.

Paroxysmal sympathetic hyperactivity (PSH) occurs in a subset of patients with traumatic brain injury (TBI) and is associated with worse outcomes. Sepsis is also associated with worse outcomes after TBI and shares several physiologic features with PSH, potentially creating diagnostic confusion and suboptimal management of each. This is the first study to directly investigate the interaction between PSH and infection using robust diagnostic criteria. We performed a retrospective cohort study of patients with TBI admitted to a level I trauma center intensive care unit with hospital length of stay of at least 2weeks. From January 2016 to July 2018, 77 patients diagnosed with PSH were 1:1 matched by age and Glasgow Coma Scale to 77 patients without PSH. Trauma infectious diseases subspecialists prospectively documented assessments corroborating diagnoses of infection. Extracted data including incidence, timing, classification, and anatomical source of infections were compared according to PSH diagnosis. We also evaluated daily PSH clinical feature severity scores and systemic inflammatory response syndrome (SIRS) criteria and compared values for patients with and without confirmed infection, stratified by PSH diagnosis. During the first 2weeks of hospitalization, there were no differences in rates of suspected (62%) nor confirmed (48%) infection between patients with PSH and controls. Specific treatments for PSH were initiated on median hospital day 7 and for confirmed infections on median hospital day 8. SIRS criteria could identify infection only in patients who were not diagnosed with PSH. In the presence of brain injury-induced autonomic nervous system dysregulation, the initiation and continuation of antimicrobial therapy is a challenging clinical decision, as standard physiologic markers of sepsis do not distinguish infected from noninfected patients with PSH, and these entities often present around the same time. Clinicians should be aware that PSH is a potential driver of SIRS, and familiarity with its diagnostic criteria as proposed by the PSH assessment measure is important. Management by a multidisciplinary team attentive to these issues may reduce rates of inappropriate antibiotic usage and misdiagnoses.

The pathophysiology and management of depression in cardiac surgery patients

BackgroundDepression is common in the cardiac surgery population. This contemporary narrative review aims to explore the main pathophysiological disturbances underpinning depression specifically within the cardiac surgery population. The common non-pharmacological and pharmacological management strategies used to manage depression within the cardiac surgery patient population are also explored.MethodsA total of 1291 articles were identified through Ovid Medline and Embase. The findings from 39 studies were included for qualitative analysis in this narrative review.ResultsDepression is associated with several pathophysiological and behavioral factors which increase the likelihood of developing coronary heart disease which may ultimately require surgical intervention. The main pathophysiological factors contributing to depression are well characterized and include autonomic nervous system dysregulation, excessive inflammation and disruption of the hypothalamic–pituitary–adrenal axis. There are also several behavioral factors in depressed patients associated with the development of coronary heart disease including poor diet, insufficient exercise, poor compliance with medications and reduced adherence to cardiac rehabilitation. The common preventative and management modalities used for depression following cardiac surgery include preoperative and peri-operative education, cardiac rehabilitation, cognitive behavioral therapy, religion/prayer/spirituality, biobehavioral feedback, anti-depressant medications, and statins.ConclusionThis contemporary review explores the pathophysiological mechanisms leading to depression following cardiac surgery and the current management modalities. Further studies on the preventative and management strategies for postoperative depression in the cardiac surgery patient population are warranted.

Optimizing Noninvasive Vagus Nerve Stimulation for Systemic Lupus Erythematosus: Protocol for a Multicenter Randomized Controlled Trial.

Systemic lupus erythematosus is a chronic, multisystem, inflammatory disease of autoimmune etiology occurring predominantly in women. A major hurdle to the diagnosis, treatment, and therapeutic advancement of this disease is its heterogeneous nature, which presents as a wide range of symptoms such as fatigue, fever, musculoskeletal involvement, neuropsychiatric disorders, and cardiovascular involvement with varying severity. The current therapeutic approach to this disease includes the administration of immunomodulatory drugs that may produce unfavorable secondary effects. This study explores the known relationship between the autonomic nervous system and inflammatory pathways to improve patient outcomes by treating autonomic nervous system dysregulation in patients via noninvasive vagus nerve stimulation. In this study, data including biomarkers, physiological signals, patient outcomes, and patient quality of life are being collected and analyzed. After completion of the clinical trial, a computer model will be developed to identify the biomarkers and physiological signals related to lupus activity in order to understand how they change with different noninvasive vagus nerve stimulation frequency parameters. Finally, we propose building a decision support system with integrated noninvasive wearable technologies for continuous cardiovascular and peripheral physiological sensing for adaptive, patient-specific optimization of the noninvasive vagus nerve stimulation frequency parameters in real time. The protocol was designed to evaluate the efficacy and safety of transauricular vagus nerve stimulation in patients with systemic lupus erythematosus. This multicenter, national, randomized, double-blind, parallel-group, placebo-controlled study will recruit a minimum of 18 patients diagnosed with this disease. Evaluation and treatment of patients will be conducted in an outpatient clinic and will include 12 visits. Visit 1 consists of a screening session. Subsequent visits up to visit 6 involve mixing treatment and evaluation sessions. Finally, the remaining visits correspond with early and late posttreatment follow-ups. On November 2022, data collection was initiated. Of the 10 participants scheduled for their initial appointment, 8 met the inclusion criteria, and 6 successfully completed the entire protocol. Patient enrollment and data collection are currently underway and are expected to be completed in December 2023. The results of this study will advance patient-tailored vagus nerve stimulation therapies, providing an adjunctive treatment solution for systemic lupus erythematosus that will foster adoption of technology and, thus, expand the population with systemic lupus erythematosus who can benefit from improved autonomic dysregulation, translating into reduced costs and better quality of life. ClinicalTrials.gov NCT05704153; https://clinicaltrials.gov/study/NCT05704153. DERR1-10.2196/48387.

Association and interaction between clinician-rated measures of depression and anxiety with heart rate variability in elderly patients with psychiatric disorders

BackgroundOlder adults are vulnerable to comorbid depression and anxiety symptoms; however, these conditions are widely underrecognized and often untreated. Understanding their combined manifestation using objective measurements, such as clinician-rated scales and heart rate variability (HRV), can help refine the diagnosis and select a treatment strategy for geriatric patients. MethodsThis study included patients over 65 years who were mainly diagnosed with either category of depressive or anxiety disorders from the psychiatric outpatient clinic in a university hospital. A total of 114 patients met eligibility with a completed collection of electrocardiograms, the Hamilton Depression Rating Scale (HDRS; clinician-rated depression), and the Hamilton Anxiety Scale (HAS; clinician-rated anxiety) to assess the severity of symptoms. Both main and interaction effects between HDRS and HAS on HRV parameters were examined. ResultsSignificant interaction effects between clinician-rated depression and anxiety (HDRS × HAS) on HRV reduction in frequency parameters (i.e., nuLF, nuHF, LF/HF ratio) were found, which consistently indicated autonomic nervous system dysregulation. Findings imply that HRV could reflect synergistic effects of comorbid depressive and anxiety symptoms, perhaps due to the amplification of individual symptoms in geriatric patients. ConclusionsThe results imply that using objective measurements can improve diagnostic accuracy, particularly in geriatric patients with comorbid status, and the normalization of the autonomic nervous system might be a candidate target for prevention and treatment.

Reduced heart rate variability during mania in a repeated naturalistic observational study.

Bipolar disorder (BD) is a chronic recurrent mood disorder associated with autonomic nervous system (ANS) dysfunction, indexed by heart rate variability (HRV). Changes in HRV between mood states are sparsely studied longitudinally. We aimed to compare HRV of hospitalized manic individuals with their own euthymic selves in a naturalistic observational study. 34 individuals were included, of which 16 were lost to follow-up. Ultimately 15 patients provided reliable heart rate data in both a manic and euthymic state, using photoplethysmography (PPG) sensor wristbands overnight. We calculated HRV measures Root Mean Square of Successive Differences (RMSSD), High-frequency (HF: 0.15-0.40 Hz), Low-frequency (LF: 0.40-0.15 Hz), Very low-frequency (VLF: 0.0033-0.04 Hz), Total power and Sample Entropy in 5-min night-time resting samples. We compared HRV measures by mood state within individuals using paired t-tests and linear regression to control for age and sex. HRV was lower in the manic state when compared to the euthymic state for all HRV metrics (p ≤ 0.02), with large to medium effect sizes (g = 1.24 to 0.65). HRV changes were not significantly affected by age or sex. This longitudinal study provides evidence of lower HRV in manic states compared to euthymia, indicating an association between ANS dysregulation and changes in bipolar mood state. This corroborates previous cross-sectional studies, although the association may be less clear or reversed in hypomanic states. Further investigation in larger longitudinal samples is warranted.

A History of Suicide Attempt Is Associated with Increased Sympathetic Activation in Bipolar Disorder.

Suicide risk in bipolar disorder (BD) is estimated to be up to 20 times higher than in the general population. While there is a large body of evidence suggesting that increased sympathetic activation is associated with disease and death, there is a paucity of research on the role of autonomic nervous system (ANS) dysfunction in patients with BD who have attempted suicide. Fifty-three participants with BD used a wearable device to assess the association between history of suicide attempt, current suicidal ideation, and ANS dysfunction, including measures of heart rate variability (HRV) and respiratory rate. Data were analyzed in a series of unadjusted and adjusted bivariate models of association controlling for relevant variables. A history of suicide attempts was significantly associated with an increase in respiratory rate (p < 0.01). These results remained significant after adjusting for age, BMI, and current mood state. There was no association between current suicidal ideation and heart rate or respiratory rate. In the frequency domain, HRV parameters suggest reduced parasympathetic (i.e., vagal) activity in participants with a history of suicide attempts and in those with current suicidality, suggesting changes in sympathicovagal balance in BD. Our results suggest that changes in the ANS in patients with BD and a history of suicide attempt are not restricted to pure vagally mediated HRV parameters, but rather signal a general ANS dysregulation. This ANS imbalance may be contributing to illness burden and cardiovascular disease. Further research on the relationship between ANS and suicidality in BD is needed.