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1.
Traumatic stress and the autonomic brain-gut connection in development: Polyvagal Theory as an integrative framework for psychosocial and gastrointestinal pathology.
Kolacz, J, Kovacic, KK, Porges, SW
Developmental psychobiology. 2019;(5):796-809
Abstract
A range of psychiatric disorders such as anxiety, depression, and post-traumatic stress disorder frequently co-occur with functional gastrointestinal (GI) disorders. Risk of these pathologies is particularly high in those with a history of trauma, abuse, and chronic stress. These scientific findings and rising awareness within the healthcare profession give rise to a need for an integrative framework to understand the developmental mechanisms that give rise to these observations. In this paper, we introduce a plausible explanatory framework, based on the Polyvagal Theory (Porges, Psychophysiology, 32, 301-318, 1995; Porges, International Journal of Psychophysiology, 42, 123-146, 2001; Porges, Biological Psychology, 74, 116-143, 2007), which describes how evolution impacted the structure and function of the autonomic nervous system (ANS). The Polyvagal Theory provides organizing principles for understanding the development of adaptive diversity in homeostatic, threat-response, and psychosocial functions that contribute to pathology. Using these principles, we outline possible mechanisms that promote and maintain socioemotional and GI dysfunction and review their implications for therapeutic targets.
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2.
Autonomic involvement in hereditary transthyretin amyloidosis (hATTR amyloidosis).
Gonzalez-Duarte, A
Clinical autonomic research : official journal of the Clinical Autonomic Research Society. 2019;(2):245-251
Abstract
PURPOSE Hereditary transthyretin amyloidosis (hATTR amyloidosis) is a progressive disease primarily characterized by adult-onset sensory, motor, and autonomic neuropathy. In this article, we discuss the pathophysiology and principal findings of autonomic neuropathy in hATTR amyloidosis, the most common methods of assessment and progression, and its relation as a predictive risk factor or a measure of progression in the natural history of the disease. METHODS A literature search was performed using the terms "autonomic neuropathy," "dysautonomia," and "autonomic symptoms" in patients with hereditary transthyretin amyloidosis and familial amyloid polyneuropathy. RESULTS Various scales to measure autonomic function have been employed, particularly within the major clinical trials, to assess novel therapies for the disease. Most of the evaluations were taken from diabetic clinical trials. Questionnaires include the COMPASS-31 and Norfolk QOL autonomic nerve function domain, whereas clinical evaluations comprise HRDB and the orthostatic tolerance test. Several treatment options are being employed although only diflunisal and tafamidis have reported improvement in the autonomic abnormalities. CONCLUSIONS Autonomic nerves are often affected before motor nerve impairment, and dysautonomia may support the diagnosis of hATTR amyloidosis when differentiating from other adult-onset progressive neuropathies and from other types of amyloidosis. Most of the progression of autonomic dysfunction is seen in early stages of the disease, commonly before motor impairment or affection of the overall quality of life. Unfortunately, there is no current single standardized approach to evaluate dysautonomia in hATTR amyloidosis.
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Healthy hearts at hectic pace: From daily life stress to abnormal cardiomyocyte function and arrhythmias.
Barbiero, S, Aimo, A, Castiglione, V, Giannoni, A, Vergaro, G, Passino, C, Emdin, M
European journal of preventive cardiology. 2018;(13):1419-1430
Abstract
The hectic pace of contemporary life is a major source of acute and chronic stress, which may have a deleterious impact on body health . In the field of cardiovascular disease, acute emotional stress has been associated with coronary spasm and Takotsubo cardiomyopathy, whereas the manifestations of chronic stress have been overlooked, and most underlying pathophysiology remains to be elucidated. Chronic stress affects the neuronal circuitry composed of cortico-limbic structures and the nuclei regulating autonomic function, eliciting a sympatho-vagal imbalance, characterised by adrenergic activation and vagal withdrawal. Sympathetic terminals are connected to cardiomyocytes in a quasi-synaptic way, producing the so called 'neuro-cardiac junction'. During chronic stress, norepinephrine release is increased, leading to overstimulation of cardiomyocytes via β1-adrenergic receptors, influencing mainly calcium dynamics, and β2-adrenergic receptors, which control housekeeping functions. The circadian rhythm of cardiomyocytes is then impaired, with elongation of the catabolic ('light' phase) over the anabolic ('nocturnal') phase. This leads to a depletion of cell energy storage, and a decreased turnover of cell constituents. Even cell interactions are affected, as coupling between cardiomyocytes decreases while coupling between cardiomyocytes and fibroblasts increases. The ultimate results are changes in the shape and velocity of action potential, fibroblast activation and deposition of extracellular matrix. These alterations may predispose to arrhythmias and may favour the development of a stress-related cardiomyopathy. A better comprehension of this cascade of events may allow us to identify screening protocols and treatment strategies (meditation, yoga, physical activity, psychological assistance, β-blockers) to prevent or relieve ongoing cardiac damage.
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4.
Dysautonomia in the pathogenesis of migraine.
Gazerani, P, Cairns, BE
Expert review of neurotherapeutics. 2018;(2):153-165
Abstract
Migraine is a common complex neurological disorder involving multiple brain areas that regulate autonomic, affective, cognitive, and sensory functions. This review explores autonomic nervous system (ANS) dysfunction in migraine headache sufferers. Areas covered: Reference material for this review was obtained through PubMed searches. Migraine attacks can present with up to 4 phases (premonitory, aura, headache, postdrome) each with distinguishable signs and symptoms. Altered ANS tone can be found from the premonitory through the postdrome phases. Features of the migraine attack that are indicative of altered autonomic function, which include nausea, vomiting, diarrhea, polyuria, eyelid edema, conjunctival injection, lacrimation, nasal congestion, and ptosis, are discussed and putative mechanisms explored. In addition, alteration of ANS function by endogenous and exogenous stressors, such as bright lights, hunger, poor sleep quality, menses, and special dietary components is discussed. The influence of currently employed pharmacological treatments on altered autonomic function during the migraine attack is explored. Expert commentary: Migraine-related alterations in ANS function have a complex pattern, but, in general, an imbalance occurs between sympathetic and parasympathetic tone. Through an improved understanding the role of autonomic changes in pathogenesis of migraine, it may be possible to develop even more effective treatments for migraine sufferers.
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5.
Neural control of sweat secretion: a review.
Hu, Y, Converse, C, Lyons, MC, Hsu, WH
The British journal of dermatology. 2018;(6):1246-1256
Abstract
BACKGROUND Humans have 4 million exocrine sweat glands, which can be classified into two types: eccrine and apocrine glands. Sweat secretion, a constitutive feature, is directly involved in thermoregulation and metabolism, and is regulated by both the central nervous system (CNS) and autonomic nervous system (ANS). OBJECTIVES To explore how sweat secretion is controlled by both the CNS and the ANS and the mechanisms behind the neural control of sweat secretion. METHODS We conducted a literature search on PubMed for reports in English from 1 January 1950 to 31 December 2016. RESULTS AND CONCLUSIONS Acetylcholine acts as a potent stimulator for sweat secretion, which is released by sympathetic nerves. β-adrenoceptors are found in adipocytes as well as apocrine glands, and these receptors may mediate lipid secretion from apocrine glands for sweat secretion. The activation of β-adrenoceptors could increase sweat secretion through opening of Ca2+ channels to elevate intracellular Ca2+ concentration. Ca2+ and cyclic adenosine monophosphate play a part in the secretion of lipids and proteins from apocrine glands for sweat secretion. The translocation of aquaporin 5 plays an important role in sweat secretion from eccrine glands. Dysfunction of the ANS, especially the sympathetic nervous system, may cause sweating disorders, such as hypohidrosis and hyperhidrosis.
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6.
Pathophysiology of essential hypertension: an update.
Saxena, T, Ali, AO, Saxena, M
Expert review of cardiovascular therapy. 2018;(12):879-887
Abstract
Hypertension is caused by increased cardiac output and/or increased peripheral resistance. Areas covered: The various mechanisms affecting cardiac output/peripheral resistance involved in the development of essential hypertension are covered. These include genetics; sympathetic nervous system overactivity; renal mechanisms: excess sodium intake and pressure natriuresis; vascular mechanisms: endothelial cell dysfunction and the nitric oxide pathway; hormonal mechanisms: the renin-angiotensin-aldosterone system (RAAS); obesity, obstructive sleep apnea (OSA); insulin resistance and metabolic syndrome; uric acid; vitamin D; gender differences; racial, ethnic, and environmental factors; increased left ventricular ejection force and hypertension and its association with increased basal sympathetic activity - cortical connections. Expert commentary: Maximum association of hypertension is found with sympathetic overactivity which is directly or indirectly involved in different mechanisms of hypertension including RAAS, OSA, obesity, etc.. It is not overt sympathetic activity but disturbed basal sympathetic tone. Basal sympathetic tone arises from hypothalamus; possibly affected by cortical influences. Therefore, hypertension is not merely a disease of circulatory system alone. Its pathogenesis involves alteration in ANS (autonomic nervous system) and likely in cortical-hypothalamic connections. Assessment of ANS and cortical-hypothalamic connections may be required for better understanding of hypertension.
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7.
Diagnosis of multiple system atrophy.
Palma, JA, Norcliffe-Kaufmann, L, Kaufmann, H
Autonomic neuroscience : basic & clinical. 2018;:15-25
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Abstract
Multiple system atrophy (MSA) may be difficult to distinguish clinically from other disorders, particularly in the early stages of the disease. An autonomic-only presentation can be indistinguishable from pure autonomic failure. Patients presenting with parkinsonism may be misdiagnosed as having Parkinson disease. Patients presenting with the cerebellar phenotype of MSA can mimic other adult-onset ataxias due to alcohol, chemotherapeutic agents, lead, lithium, and toluene, or vitamin E deficiency, as well as paraneoplastic, autoimmune, or genetic ataxias. A careful medical history and meticulous neurological examination remain the cornerstone for the accurate diagnosis of MSA. Ancillary investigations are helpful to support the diagnosis, rule out potential mimics, and define therapeutic strategies. This review summarizes diagnostic investigations useful in the differential diagnosis of patients with suspected MSA. Currently used techniques include structural and functional brain imaging, cardiac sympathetic imaging, cardiovascular autonomic testing, olfactory testing, sleep study, urological evaluation, and dysphagia and cognitive assessments. Despite advances in the diagnostic tools for MSA in recent years and the availability of consensus criteria for clinical diagnosis, the diagnostic accuracy of MSA remains sub-optimal. As other diagnostic tools emerge, including skin biopsy, retinal biomarkers, blood and cerebrospinal fluid biomarkers, and advanced genetic testing, a more accurate and earlier recognition of MSA should be possible, even in the prodromal stages. This has important implications as misdiagnosis can result in inappropriate treatment, patient and family distress, and erroneous eligibility for clinical trials of disease-modifying drugs.
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Monitoring Athletic Training Status Through Autonomic Heart Rate Regulation: A Systematic Review and Meta-Analysis.
Bellenger, CR, Fuller, JT, Thomson, RL, Davison, K, Robertson, EY, Buckley, JD
Sports medicine (Auckland, N.Z.). 2016;(10):1461-86
Abstract
BACKGROUND Autonomic regulation of heart rate (HR) as an indicator of the body's ability to adapt to an exercise stimulus has been evaluated in many studies through HR variability (HRV) and post-exercise HR recovery (HRR). Recently, HR acceleration has also been investigated. OBJECTIVE The aim of this systematic literature review and meta-analysis was to evaluate the effect of negative adaptations to endurance training (i.e., a period of overreaching leading to attenuated performance) and positive adaptations (i.e., training leading to improved performance) on autonomic HR regulation in endurance-trained athletes. METHODS We searched Ovid MEDLINE, Embase, CINAHL, SPORTDiscus, PubMed, and Academic Search Premier databases from inception until April 2015. Included articles examined the effects of endurance training leading to increased or decreased exercise performance on four measures of autonomic HR regulation: resting and post-exercise HRV [vagal-related indices of the root-mean-square difference of successive normal R-R intervals (RMSSD), high frequency power (HFP) and the standard deviation of instantaneous beat-to-beat R-R interval variability (SD1) only], and post-exercise HRR and HR acceleration. RESULTS Of the 5377 records retrieved, 27 studies were included in the systematic review and 24 studies were included in the meta-analysis. Studies inducing increases in performance showed small increases in resting RMSSD [standardised mean difference (SMD) = 0.58; P < 0.001], HFP (SMD = 0.55; P < 0.001) and SD1 (SMD = 0.23; P = 0.16), and moderate increases in post-exercise RMSSD (SMD = 0.60; P < 0.001), HFP (SMD = 0.90; P < 0.04), SD1 (SMD = 1.20; P = 0.04), and post-exercise HRR (SMD = 0.63; P = 0.002). A large increase in HR acceleration (SMD = 1.34) was found in the single study assessing this parameter. Studies inducing decreases in performance showed a small increase in resting RMSSD (SMD = 0.26; P = 0.01), but trivial changes in resting HFP (SMD = 0.04; P = 0.77) and SD1 (SMD = 0.04; P = 0.82). Post-exercise RMSSD (SMD = 0.64; P = 0.04) and HFP (SMD = 0.49; P = 0.18) were increased, as was HRR (SMD = 0.46; P < 0.001), while HR acceleration was decreased (SMD = -0.48; P < 0.001). CONCLUSIONS Increases in vagal-related indices of resting and post-exercise HRV, post-exercise HRR, and HR acceleration are evident when positive adaptation to training has occurred, allowing for increases in performance. However, increases in post-exercise HRV and HRR also occur in response to overreaching, demonstrating that additional measures of training tolerance may be required to determine whether training-induced changes in these parameters are related to positive or negative adaptations. Resting HRV is largely unaffected by overreaching, although this may be the result of methodological issues that warrant further investigation. HR acceleration appears to decrease in response to overreaching training, and thus may be a potential indicator of training-induced fatigue.
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Integrated Cardio-Respiratory Control: Insight in Diabetes.
Bernardi, L, Bianchi, L
Current diabetes reports. 2016;(11):107
Abstract
Autonomic dysfunction is a frequent and relevant complication of diabetes mellitus, as it is associated with increased morbidity and mortality. In addition, it is today considered as predictive of the most severe diabetic complications, like nephropathy and retinopathy. The classical methods of screening are the cardiovascular reflex tests and were originally interpreted as evidence of nerve damage. A more modern approach, based on the integrated control of cardiovascular and respiratory function, reveals that these abnormalities are to a great extent functional, at least in the early stage of the disease, thus suggesting new potential interventions. Therefore, this review aims to go further investigating how the imbalance of the autonomic nervous system is altered and can be influenced in many chronic pathologies through a global view of cardio-respiratory and metabolic interactions and how the same mechanisms are applicable to diabetes.
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Hypothalamic-autonomic control of energy homeostasis.
Seoane-Collazo, P, Fernø, J, Gonzalez, F, Diéguez, C, Leis, R, Nogueiras, R, López, M
Endocrine. 2015;(2):276-91
Abstract
Regulation of energy homeostasis is tightly controlled by the central nervous system (CNS). Several key areas such as the hypothalamus and brainstem receive and integrate signals conveying energy status from the periphery, such as leptin, thyroid hormones, and insulin, ultimately leading to modulation of food intake, energy expenditure (EE), and peripheral metabolism. The autonomic nervous system (ANS) plays a key role in the response to such signals, innervating peripheral metabolic tissues, including brown and white adipose tissue (BAT and WAT), liver, pancreas, and skeletal muscle. The ANS consists of two parts, the sympathetic and parasympathetic nervous systems (SNS and PSNS). The SNS regulates BAT thermogenesis and EE, controlled by central areas such as the preoptic area (POA) and the ventromedial, dorsomedial, and arcuate hypothalamic nuclei (VMH, DMH, and ARC). The SNS also regulates lipid metabolism in WAT, controlled by the lateral hypothalamic area (LHA), VMH, and ARC. Control of hepatic glucose production and pancreatic insulin secretion also involves the LHA, VMH, and ARC as well as the dorsal vagal complex (DVC), via splanchnic sympathetic and the vagal parasympathetic nerves. Muscle glucose uptake is also controlled by the SNS via hypothalamic nuclei such as the VMH. There is recent evidence of novel pathways connecting the CNS and ANS. These include the hypothalamic AMP-activated protein kinase-SNS-BAT axis which has been demonstrated to be a key modulator of thermogenesis. In this review, we summarize current knowledge of the role of the ANS in the modulation of energy balance.