The present study focuses on the evaluation of autonomic nervous function, which is increasingly being used as an objective measure of fatigue state. It has recently been reported that autonomic nervous activity, which is expressed as total heart rate variability (HRV) power, is associated with, and can be used as an objective measure of, mental and physical fatigue. Total HRV power (log (LF + HF)) has been shown to decline with ageing, and thus cannot be utilized as a fatigue index in populations with a different age composition. In the present study, we devised standard scores (deviation value) for autonomic nervous activity corrected for individual age calculated from the distribution of such activity in individual age cohorts. This allowed us to accurately evaluate an individual's autonomic nervous activity, even when that individual was part of a group with members of different ages. Standard scores were quantified using autonomic nervous function data gathered from 1,969 healthy individuals (age range 20–77 years).The efficacy of this method in mental health screening was investigated by evaluating both autonomic nervous function and subjective levels of fatigue among corporate workers. Based on results from the Brief Job Stress Questionnaire recommended by the research team of the Ministry of Health, Labour and Welfare, 103 participants were divided into two groups (a high-stress group [n = 17] and a non–high-stress group [n = 86]). Visual analog scale (VAS) scores for all fatigue-related symptoms were significantly higher among the high-stress than among the non–high-stress group (p < 0.01).The mean standard score for autonomic nervous activity was 56.3 for the non–high-stress group. The score for the high-stress group was significantly lower, at 47.9 (p < 0.01), indicating that autonomic nervous function was reduced among participants who experienced high stress. According to an analysis of raw and standard scores in each domain, autonomic nervous activity did not significantly correlate with stress-causing factors (e.g., overwork) or other factors affecting stress responses (e.g., support from supervisors and colleagues), but did exhibit a significant positive correlation with physical and mental responses to stress (r = 0.334, p < 0.01). Lower raw scores for mental and physical responses to stress represent stronger subjective symptoms. Moreover, greater stress responses were found to be associated with lower standard scores for autonomic nervous activity.In terms of fatigue-related symptoms rated using the VAS, autonomic nervous activity negatively correlated with mental stress, physical stress, fatigue/malaise, depressed mood, anxiety/fear, tension, irritation/anger, cognitive decline, and muscle/joint/general pain, and positively correlated with motivation/vitality. Reduced autonomic nervous activity was observed with high stress, confirming that standard scores for autonomic nervous activity are associated with mental and physical responses to stress and subjective fatigue-related symptoms.These res...

Objective: Although psychological and/or physiological stress has been well documented to influence immune responses, the precise mechanism for immunomodulation remains to be elucidated. The present work describes the role of the hypothalamic-pituitary-adrenal (HPA) axis in the mechanism of stress-mediated enhanced-resistance to lethality after lipopolysaccharide (LPS) injection. Methods/Results: Preconditioning with restraint stress (RS) resulted in enhanced activation of the HPA axis in response to LPS injection and suppressed LPS-induced release of proinflammatory cytokines and nitric oxide metabolites. Melanocortin 2 receptor-deficient mice (MC2R^-/-) failed to increase plasma levels of glucocorticoids in response to LPS injection, and exhibited high sensitivity to LPS-induced lethality with enhanced release of proinflammatory cytokines as compared with MC2R^+/- mice. Real-time PCR analysis revealed that RS induced upregulation of uncoupling protein-2 (UCP2) in macrophages in the lung and the liver of MC2R^+/-, but not of MC2R^-/-, mice. In addition, RS increased UCP2-dependent uncoupling activity of isolated mitochondria from the liver of MC2R^+/-, but not of MC2R^-/-, mice. In vitro study revealed that corticosterone and dexamethasone directly increased UCP2 expression in mouse RAW 264.7 macrophages and suppressed the generation of LPS-induced mitochondrial reactive oxygen species (ROS) and TNF-α production. Knockdown of UCP2 by small interfering RNA blunted the dexamethasone action for suppressing LPS-induced mitochondrial ROS and TNF-α production. Conclusion: The present work suggests that RS enhances activation of the HPA axis to release glucocorticoids and upregulation of UCP2 in macrophages, thereby increasing the resistance to endotoxin-induced systemic inflammation and death.

Major depressive disorder (MDD) and chronic fatigue syndrome (CFS) have overlapping symptoms, and differentiation is important to administer the proper treatment. The present study aimed to assess the usefulness of heart rate variability (HRV) indices. Frequency-domain HRV indices, including high-frequency (HF) and low-frequency (LF) components, their sum (LF+HF), and their ratio (LF/HF), were measured in a three-behavioral-state paradigm composed of initial rest (Rest), task load (Task), and post-task rest (After) periods to examine autonomic regulation. It was found that HF was low at Rest in both disorders, but was lower in MDD than in CFS. LF and LF+HF at Rest were low only in MDD. Attenuated responses of LF, HF, LF+HF, and LF/HF to task load and an excessive increase in HF at After were found in both disorders. The results indicate that an overall HRV reduction at Rest may support a diagnosis of MDD. HF reduction was found in CFS, but with a lesser severity. Response disturbances of HRV to Task were observed in both disorders, and would suggest the presence of CFS when the baseline HRV has not been reduced. Linear discriminant analysis using HRV indices was able to differentiate MDD from CFS, with a sensitivity and specificity of 91.8% and 100%, respectively. HRV indices in MDD and CFS show both common and different profiles, and can be useful for the differential diagnosis.

Fatigue is a common sense caused by crushing labor, stressful social events and various illnesses. It is usually judged by their subjective symptoms, but it should be evaluated in an objective perspective. Here we show that the decrease of working efficiency and sympathetic hyperactivity are associated with mental fatigue state caused by prolonged mental workload. Recently we made a new mental fatigue model of healthy volunteers caused by long-term computerized Kraepelin test (CKT) workload. CKT is our new software for automatically checking the calculation capability, with which it is easy to determine the reaction time (RT), coefficient of variance of reaction time (CV), and accuracy of the answers (AC) during tasks. We put 24 healthy volunteers into the fatigue state by subjecting them to 120 minutes' CKT workload, and then studied the changes in fatigue sensation, RT, CV, and AC before and after the CKT workload. The fatigue sensation, RT, and CV were clearly increased by the fatigue-inducing task and recovered during the resting period. We also studied the changes in autonomic nerve activity by using heart rate variability analysis. The low/high frequency component ratio (LF/HF) was significantly increased by the fatigue-inducing task and decreased by resting, suggesting that mental stress causes a relatively sympathetic nerve activity-dominant state. Therefore, our new fatigue model involveing a long-term CKT workload is a good mental fatigue model to provide much information about the fatigue state simultaneously, and the increase of RT, CV, and proportion of sympathetic activity (LF/HF) are associated with mental fatigue state. These might be useful objective biomarkers or evaluating a mental fatigue state.

Background Enhanced oxidative stress is involved with fatigue in hemodialysis (HD) patients. Molecular hydrogen (H2) could improve the redox status. Thus, the study examines whether HD solution rendered by electrolyzed water containing H2 (E-HD) could impact the fatigue and autonomic balance of patients. Methods This single-arm, prospective observational study examined 95 patients on chronic HD (54 males; mean age and HD duration; 71.4 years and 10.6 years). Fatigue status on HD and HD-free days was compared between control HD (CHD) and 8 weeks after commencement of E-HD, using a visual analog scale (VAS) and an original scale. Autonomic balance was analyzed with the degree of activities of the sympathetic and parasympathetic nervous system via frequency analysis of a continuous beat interval. Results Patients were classified into three groups according to the presence of subjective fatigue during the period of CHD: Group A (40.0%), fatigue only on HD days; Group B (11.6%), presence of fatigue on both HD and HD-free days; and Group C (48.4%), freedom from fatigue. During the 8-week observation period of E-HD, VAS scores were significantly decreased on HD days in Group A, while Group B showed no significant changes in VAS on HD days, but significant decreases on HD-free days. No consistent changes were found in Group C. Significant increases in percentages of patients who reported absence of fatigue were seen in Group A on HD days and in Group B on HD-free days in week 8. Regarding changes in autonomic balance parameters after E-HD commencement, a positive correlation was identified between changes in VAS and autonomic balance in Group A. Conclusion E-HD may ameliorate fatigue in patients with subjective symptoms on HD and HD-free days. The influence of autonomic balance by E-HD and its impact on fatigue needs to be elucidated.