To investigate whether a support intervention (warm touch enhancement) influences physiological stress systems that are linked to important health outcomes. Growing evidence points to a protective ...effect of social and emotional support on both morbidity and mortality.
In this study, 34 healthy married couples (n = 68), aged 20 to 39 years (mean = 25.2 years), were randomly assigned to a "behavior monitoring" control group or participated in a 4-week intervention study in which clinic levels of plasma oxytocin, 24-hour ambulatory blood pressure, and salivary cortisol and alpha amylase were obtained pre and post intervention, at the same time salivary oxytocin was taken at home during weeks 1 and 4.
Salivary oxytocin was enhanced both early and late in the intervention group and alpha amylase was reduced at post treatment in intervention group husbands and wives relative to controls. Husbands in the intervention group had significantly lower post treatment 24-hour systolic blood pressure than the control group.
Increasing warm touch among couples has a beneficial influence on multiple stress-sensitive systems.
New Findings
What is the central question of this study?
Can physiological concentrations of metabolite combinations evoke sensations of fatigue and pain when injected into skeletal muscle? If so, ...what sensations are evoked?
What is the main finding and its importance?
Low concentrations of protons, lactate and ATP evoked sensations related to fatigue. Higher concentrations of these metabolites evoked pain. Single metabolites evoked no sensations. This suggests that the combination of an ASIC receptor and a purinergic P2X receptor is required for signalling fatigue and pain. The results also suggest that two types of sensory neurons encode metabolites; one detects low concentrations of metabolites and signals sensations of fatigue, whereas the other detects higher levels of metabolites and signals ache and hot.
The perception of fatigue is common in many disease states; however, the mechanisms of sensory muscle fatigue are not understood. In mice, rats and cats, muscle afferents signal metabolite production in skeletal muscle using a complex of ASIC, P2X and TRPV1 receptors. Endogenous muscle agonists for these receptors are combinations of protons, lactate and ATP. Here we applied physiological concentrations of these agonists to muscle interstitium in human subjects to determine whether this combination could activate sensations and, if so, to determine how the subjects described these sensations. Ten volunteers received infusions (0.2 ml over 30 s) containing protons, lactate and ATP under the fascia of a thumb muscle, abductor pollicis brevis. Infusion of individual metabolites at maximal amounts evoked no fatigue or pain. Metabolite combinations found in resting muscles (pH 7.4 + 300 nm ATP + 1 mm lactate) also evoked no sensation. The infusion of a metabolite combination found in muscle during moderate endurance exercise (pH 7.3 + 400 nm ATP + 5 mm lactate) produced significant fatigue sensations. Infusion of a metabolite combination associated with vigorous exercise (pH 7.2 + 500 nm ATP + 10 mm lactate) produced stronger sensations of fatigue and some ache. Higher levels of metabolites (as found with ischaemic exercise) caused more ache but no additional fatigue sensation. Thus, in a dose‐dependent manner, intramuscular infusion of combinations of protons, lactate and ATP leads to fatigue sensation and eventually pain, probably through activation of ASIC, P2X and TRPV1 receptors. This is the first demonstration in humans that metabolites normally produced by exercise act in combination to activate sensory neurons that signal sensations of fatigue and muscle pain.
Many patients have serious depression that is nonresponsive to medications, but refuse electroconvulsive therapy (ECT). Early research suggested that isoflurane anesthesia may be an effective ...alternative to ECT. Subsequent studies altered drug, dose or number of treatments, and failed to replicate this success, halting research on isoflurane's antidepressant effects for a decade. Our aim was to re-examine whether isoflurane has antidepressant effects comparable to ECT, with less adverse effects on cognition.
Patients with medication-refractory depression received an average of 10 treatments of bifrontal ECT (n = 20) or isoflurane (n = 8) over 3 weeks. Depression severity (Hamilton Rating Scale for Depression-24) and neurocognitive responses (anterograde and retrograde memory, processing speed and verbal fluency) were assessed at Pretreatment, Post all treatments and 4-week Follow-up.
Both treatments produced significant reductions in depression scores at Post-treatment and 4-week Follow-up; however, ECT had modestly better antidepressant effect at follow-up in severity-matched patients. Immediately Post-treatment, ECT (but not isoflurane) patients showed declines in memory, fluency, and processing speed. At Follow-up, only autobiographical memory remained below Pretreatment level for ECT patients, but isoflurane patients had greater test-retest neurocognitive score improvement.
Our data reconfirm that isoflurane has an antidepressant effect approaching ECT with less adverse neurocognitive effects, and reinforce the need for a larger clinical trial.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Oxytocin (OT) is a peptide increasingly studied in relation to human social interactions, affiliation, and clinical disorders. Studies are constrained by use of invasive blood draws and would benefit ...from a reliable salivary OT assay. Our goals were to examine feasibility of salivary OT measurement, compare salivary to plasma OT responses in 12 breast‐ and 8 formula‐feeding mothers, and assess the degree of correlation between plasma and salivary OT. Using a commercial EIA kit, we measured OT in 5 saliva and 7 plasma samples in a protocol designed to elicit changes in OT (Rest, Infant Interaction, Stress, Feeding). Breast‐feeders had higher OT levels than formula‐feeders across all conditions in plasma (+36%) and saliva (+23%). OT levels and ranges were similar in saliva and plasma, with slightly greater variance in saliva. Concurrently sampled plasma and salivary OT were correlated at end of Baseline Rest (r=+.59, p=.022) and Post‐Stress Recovery (r=+.59, p=.025). These data suggest that salivary OT assay is feasible, and will be of value where plasma samples are not possible. Validation with larger samples is needed.
Summary Oxytocin (OT) activity increases in response to stress as well as to warm social contact. Subclinical depression is associated with higher stress but less reward from social contacts. The ...present investigation was intended to examine whether husbands and wives with high depressive symptomatology scores have increased plasma and salivary OT that may be mediated partly by higher perceived stress, and also to assess whether an intervention to convey partner support through “warm touch” may reduce effects of depressive symptoms on OT. In this study, 34 healthy married couples ( n = 68) ages 20–39 provided self reports of depressive symptoms (CESD) and stress (Perceived Stress Scale) before being randomly assigned to a 4-week intervention study enhancing partner support through “warm touch”, or to a “behavior monitoring” control group. Plasma oxytocin levels were obtained pre- and post-intervention, while salivary oxytocin was taken at home during week 1 and week 4. Results revealed that subjects with higher depressive symptoms scores had higher plasma OT levels at pre-intervention, and higher salivary OT levels at home during week 1 ( p < .05). Plasma OT results were moderated by gender such that plasma OT levels were highest among females high in depressive symptomology. Higher perceived stress was also linked to both higher depressive symptomatology ( r = + 65, p < .0001) and plasma OT ( p < .05) and a significant mediator. During the intervention, salivary OT remained elevated among subjects high in depressive symptomatology in the control group but not the intervention group. At post-intervention, plasma OT levels in subjects with vs. without depressive symptomatology no longer differed. Results indicate that subclinical depression is associated with elevated plasma and salivary OT levels, which may be mediated in part by increased stress. OT differences linked to subclinical depression were minimized by the warm touch intervention.
. Light AR, Bateman L, Jo D, Hughen RW, VanHaitsma TA, White AT, Light KC (University of Utah, Salt Lake City, UT, USA). Gene expression alterations at baseline and following moderate exercise in ...patients with Chronic Fatigue Syndrome and Fibromyalgia Syndrome. J Intern Med 2012; 271: 64–81.
Objectives. To determine mRNA expression differences in genes involved in signalling and modulating sensory fatigue, and muscle pain in patients with chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FM) at baseline, and following moderate exercise.
Design. Forty‐eight patients with CFS only, or CFS with comorbid FM, 18 patients with FM that did not meet criteria for CFS, and 49 healthy controls underwent moderate exercise (25 min at 70% maximum age‐predicted heart rate). Visual‐analogue measures of fatigue and pain were taken before, during and after exercise. Blood samples were taken before and 0.5, 8, 24 and 48 h after exercise. Leucocytes were immediately isolated from blood, number coded for blind processing and analyses and flash frozen. Using real‐time, quantitative PCR, the amount of mRNA for 13 genes (relative to control genes) involved in sensory, adrenergic and immune functions was compared between groups at baseline and following exercise. Changes in amounts of mRNA were correlated with behavioural measures and functional clinical assessments.
Results. No gene expression changes occurred following exercise in controls. In 71% of patients with CFS, moderate exercise increased most sensory and adrenergic receptor’s and one cytokine gene’s transcription for 48 h. These postexercise increases correlated with behavioural measures of fatigue and pain. In contrast, for the other 29% of patients with CFS, adrenergic α‐2A receptor’s transcription was decreased at all time‐points after exercise; other genes were not altered. History of orthostatic intolerance was significantly more common in the α‐2A decrease subgroup. FM‐only patients showed no postexercise alterations in gene expression, but their pre‐exercise baseline mRNA for two sensory ion channels and one cytokine were significantly higher than controls.
Conclusions. At least two subgroups of patients with CFS can be identified by gene expression changes following exercise. The larger subgroup showed increases in mRNA for sensory and adrenergic receptors and a cytokine. The smaller subgroup contained most of the patients with CFS with orthostatic intolerance, showed no postexercise increases in any gene and was defined by decreases in mRNA for α‐2A. FM‐only patients can be identified by baseline increases in three genes. Postexercise increases for four genes meet published criteria as an objective biomarker for CFS and could be useful in guiding treatment selection for different subgroups.
► Greater plasma oxytocin is related to greater vasodilation in response to behavioral stress. ► Greater oxytocin is related to reduced heart rate and greater cardiac stroke volume response to ...stress. ► Greater plasma oxytocin is related to lower plasma norepinephrine.
In addition to known reproductive and social affiliation functions, oxytocin (OT) has been identified as a cardiovascular hormone. OT synthesis and receptors are found in cardiac and vascular tissue. Animal studies suggest that OT activates an ‘anti-stress’ response that reduces cardiovascular and neuroendocrine stress reactivity. We tested 28 early postpartum mothers, obtaining multiple blood samples for OT, the sympathetic marker, norepinephrine (NE), and the lactation hormone, prolactin, while monitoring their cardiovascular responses to two stressors: public speaking and forehead cold pressor. Although plasma OT did not increase reliably from pre-stress levels during stressors, greater overall OT level was related to greater vasodilation and cardiac stroke volume responses to both tasks, to reduction in heart rate to the cold pressor, as well as to lower plasma NE and higher prolactin levels. In contrast, higher NE was linked to increases in heart rate and decreases in stroke volume. These data support a cardioprotective role for OT, which may influence the magnitude and hemodynamic determinants of cardiovascular stress responses.
We examined whether the magnitude of plasma oxytocin (OT), norepinephrine (NE), cortisol, and blood pressure (BP) responses before and after a brief episode of warm contact (WC) with the ...spouse/partner may be related to the strength of perceived partner support.
Subjects were 38 cohabiting couples (38 men, 38 women) aged 20 to 49 years. All underwent 10 minutes of resting baseline alone, 10 minutes of WC together with their partner, and 10 minutes of postcontact rest alone.
Greater partner support (based on self-report) was related to higher plasma oxytocin in men and women across the protocol before and after WC. In women, higher partner support was correlated with lower systolic blood pressure (SBP) during solitary rest after WC but not before. Also, higher OT in women was linked to lower BP at baseline and to lower NE at all 4 measurements.
Greater partner support is linked to higher OT for both men and women; however, the importance of OT and its potentially cardioprotective effects on sympathetic activity and BP may be greater for women.
To examine whether subjective sleep quality and sleep duration moderate the association between age and telomere length (TL).
Participants completed a demographic and sleep quality questionnaire, ...followed by a blood draw.
Social Neuroscience Laboratory.
One hundred fifty-four middle-aged to older adults (age 45-77 y) participated. Participants were excluded if they were on immunosuppressive treatment and/or had a disease with a clear immunologic (e.g., cancer) component.
N/A.
Subjective sleep quality and sleep duration were assessed using the Pittsburgh Sleep Quality Index (PSQI) and TL was determined using peripheral blood mononuclear cells (PBMCs). There was a significant first-order negative association between age and TL. Age was also negatively associated with the self-reported sleep quality item and sleep duration component of the PSQI. A significant age × self-reported sleep quality interaction revealed that age was more strongly related to TL among poor sleepers, and that good sleep quality attenuated the association between age and TL. Moreover, adequate subjective sleep duration among older adults (i.e. greater than 7 h per night) was associated with TL comparable to that in middle-aged adults, whereas sleep duration was unrelated to TL for the middle-aged adults in our study.
The current study provides evidence for an association between sleep quality, sleep duration, and cellular aging. Among older adults, better subjective sleep quality was associated with the extent of cellular aging, suggesting that sleep duration and sleep quality may be added to a growing list of modifiable behaviors associated with the adverse effects of aging.
Background
Multiple sclerosis (MS) patients experience fatigue as a chronic symptom that decreases quality of life. Commonly, fatigue in MS patients is manifested as decreased motor function during ...or after physical activity and is associated with changes in brain metabolism.
Objective
To determine brain activation patterns in MS patients and healthy controls during a simple motor task before and after fatiguing hand-grip exercise.
Methods
Functional magnetic resonance imaging (fMRI) scans were conducted on 10 MS patients and 13 healthy controls during 4-finger flexion and extension in rested and fatigued states.
Results
Before the fatigue protocol, MS patients had greater activation in the contralateral primary motor cortex, insula, and cingulate gyrus than controls. Following fatiguing exercise, controls showed increased activation of precentral gyrus and insula while patients did not show any activation increases and actually decreased activity to the insula.
Conclusion
Results indicate that before fatiguing exercise, MS patients marshaled more brain activation compared to controls, which may represent functionally adaptive changes in response to demyelination. This increased activation may suggest that patients require more effort to perform even simple motor tasks, possibly because peripheral or central signals for fatigue are chronically enhanced. When fatigued further by muscle contraction, brain activation cannot be further increased.