Search

Cardiac ischemia during daily life is associated with an increased risk of adverse outcomes. Mental stress is known to provoke cardiac ischemia and is related to psychological variables. In this multicenter cohort study, we assessed whether psychological characteristics were associated with ischemia in daily life.This study examined patients with clinically stable coronary artery disease (CAD) with documented cardiac ischemia during treadmill exercise (n = 196, mean [standard deviation] age = 62.64 [8.31] years; 13% women). Daily life ischemia (DLI) was assessed by 48-hour ambulatory electrocardiophic monitoring. Psychological characteristics were assessed using validated instruments to identify characteristics associated with ischemia occurring in daily life stress.High scores on anger and hostility were common in this sample of patients with CAD, and DLI was documented in 83 (42%) patients. However, the presence of DLI was associated with lower anger scores (odds ratio [OR] = 2.03; 95% confidence interval [CI] = 1.12-3.69), reduced anger expressiveness (OR = 2.04; 95% CI = 1.10-3.75), and increased ratio of anger control to total anger (OR = 2.33; 95% CI = 1.27-4.17). Increased risk of DLI was also associated with lower hostile attribution (OR = 2.22; 95% CI = 1.21-4.09), hostile affect (OR = 1.92; 95% CI = 1.03-3.58), and aggressive responding (OR = 2.26; 95% CI = 1.25-4.08). We observed weak inverse correlations between DLI episode frequency and anger expressiveness, total anger, and hostility scores. DLI was not associated with depression or anxiety measures. The combination of the constructs low anger expressiveness and low hostile attribution was independently associated with DLI (OR = = 2.59; 95% CI = 1.42-4.72).In clinically stable patients with CAD, the tendency to suppress angry and hostile feelings, particularly openly aggressive behavior, was associated with DLI. These findings warrant a study in larger cohorts, and intervention studies are needed to ascertain whether management strategies that modify these psychological characteristics improve outcomes.

Gene variants may contribute to individual differences in the experience of pain and the efficacy and reward of treatments. We explored gene variation in opioid-naïve and opioid-consuming patients undergoing elective lower extremity total joint replacement. We focused on 3 gene pathways including prostaglandin, gamma-aminobutyric acid (GABA)-ergic reward, and hepatic metabolism pathways. We report that for genes with possible or probable deleterious impact in these 3 pathways, opioid consumers had more gene variants than opioid-naïve patients (median 3 vs 1, P = .0092). We conclude that chronic opiate users may have genetic susceptibility to altered responses in reward/dependency and pain/inflammation pathways.

Background We hypothesized that propofol, a unique general anesthetic that engages N-methyl-D-aspartate and gamma-aminobutyric acid receptors, has antidepressant properties. This open-label trial was designed to collect preliminary data regarding the feasibility, tolerability, and efficacy of deep propofol anesthesia for treatment-resistant depression. Methods Ten participants with moderate-to-severe medication-resistant depression (age 18–45 years and otherwise healthy) each received a series of 10 propofol infusions. Propofol was dosed to strongly suppress electroencephalographic activity for 15 minutes. The primary depression outcome was the 24-item Hamilton Depression Rating Scale. Self-rated depression scores were compared with a group of 20 patients who received electroconvulsive therapy. Results Propofol treatments were well tolerated by all subjects. No serious adverse events occurred. Montreal Cognitive Assessment scores remained stable. Hamilton scores decreased by a mean of 20 points (range 0–45 points), corresponding to a mean 58% improvement from baseline (range 0–100%). Six of the 10 subjects met the criteria for response (>50% improvement). Self-rated depression improved similarly in the propofol group and electroconvulsive therapy group. Five of the 6 propofol responders remained well for at least 3 months. In posthoc analyses, electroencephalographic measures predicted clinical response to propofol. Conclusions These findings demonstrate that high-dose propofol treatment is feasible and well tolerated by individuals with treatment-resistant depression who are otherwise healthy. Propofol may trigger rapid, durable antidepressant effects similar to electroconvulsive therapy but with fewer side effects. Controlled studies are warranted to further evaluate propofol’s antidepressant efficacy and mechanisms of action. ClinicalTrials.gov: NCT02935647.

Opioids may influence inflammation. We compared genes associated with pain and inflammation in patients who consumed opioids (3-120 mg of oral morphine equivalents per day) with those who did not for differential expression. White blood cells were assayed in 20 patients presenting for total lower extremity joint replacement. We focused on messenger ribonucleic acid expression of complement proteins. We report that the expression of a complement inhibitor, complement 4 binding protein A, was reduced, and the expression of a complement activator, complement factor D, was increased in opioid-consuming patients. We conclude that opioid consumption may influence expression of complement activators and inhibitors.

Post exertion malaise is one of the most debilitating aspects of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, yet the neurobiological consequences are largely unexplored. The objective of the study was to determine the neural consequences of acute exercise using functional brain imaging. Fifteen female Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients and 15 healthy female controls completed 30min of submaximal exercise (70% of peak heart rate) on a cycle ergometer. Symptom assessments (e.g. fatigue, pain, mood) and brain imaging data were collected one week prior to and 24h following exercise. Functional brain images were obtained during performance of: 1) a fatiguing cognitive task - the Paced Auditory Serial Addition Task, 2) a non-fatiguing cognitive task - simple number recognition, and 3) a non-fatiguing motor task - finger tapping. Symptom and exercise data were analyzed using independent samples t-tests. Cognitive performance data were analyzed using mixed-model analysis of variance with repeated measures. Brain responses to fatiguing and non-fatiguing tasks were analyzed using linear mixed effects with cluster-wise (101-voxels) alpha of 0.05. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients reported large symptom changes compared to controls (effect size ≥0.8, p0.05). Patients and controls had similar physiological responses to exercise (p0.05). However, patients exercised at significantly lower Watts and reported greater exertion and leg muscle pain (p0.05). For cognitive performance, a significant Group by Time interaction (p0.05), demonstrated pre- to post-exercise improvements for controls and worsening for patients. Brain responses to finger tapping did not differ between groups at either time point. During number recognition, controls exhibited greater brain activity (p0.05) in the posterior cingulate cortex, but only for the pre-exercise scan. For the Paced Serial Auditory Addition Task, there was a significant Group by Time interaction (p0.05) with patients exhibiting increased brain activity from pre- to post-exercise compared to controls bilaterally for inferior and superior parietal and cingulate cortices. Changes in brain activity were significantly related to symptoms for patients (p0.05). Acute exercise exacerbated symptoms, impaired cognitive performance and affected brain function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients. These converging results, linking symptom exacerbation with brain function, provide objective evidence of the detrimental neurophysiological effects of post-exertion malaise.

Most interventions on relationships and health have focused on altering positive aspects of relationship such as social support. Given the separability of positive and negative aspects of relationships it is less clear if such interventions can also influence relationship negativity. This pilot study of 9 individuals tested the influence of a novel 6-week loving-kindness meditation (LKM) intervention on changes over time in social support, social negativity, depression, and life satisfaction. Consistent with past work, LKM participants showed increases in perceived support and decreases in depression. Extending prior work, LKM participants also showed decreases in social negativity, which was more closely linked to changes in depression compared to social support. These data suggest the feasibility of using LKM to increase relationship positivity, decrease relationship negativity, and enhance psychological well-being.

Pregabalin, an approved treatment for fibromyalgia (FM), has been shown to decrease sympathetic nervous system (SNS) activity and inhibit sympathetically maintained pain, but its effects on exercise responses have not been reported. Methods. Using a randomized double-blind crossover design, we assessed the effect of 5 weeks of pregabalin (versus placebo) on acute cardiovascular and subjective responses to moderate exercise in 19 FM patients. Blood pressure (BP), heart rate (HR), and ratings of perceived exertion (RPE) during exercise and ratings of pain, physical fatigue, and mental fatigue before, during, and for 48 hours after exercise were compared in patients on pregabalin versus placebo and also versus 18 healthy controls. Results. On placebo, exercise RPE and BP were significantly higher in FM patients than controls (p<0.04). Pregabalin responders (n=12, defined by patient satisfaction and symptom changes) had significantly lower exercise BP, HR, and RPE on pregabalin versus placebo (p<0.03) and no longer differed from controls (p>0.26). Cardiovascular responses of nonresponders (n=7) were not altered by pregabalin. In responders, pregabalin improved ratings of fatigue and pain (p<0.04), but negative effects on pain and fatigue were seen in nonresponders. Conclusions. These preliminary findings suggest that pregabalin may normalize cardiovascular and subjective responses to exercise in many FM patients.

Objective To determine if independent candidate genes can be grouped into meaningful biologic factors, and whether these factors are associated with the diagnosis of chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FMS), while controlling for comorbid depression, sex, and age. Methods We included leukocyte messenger RNA gene expression from a total of 261 individuals, including healthy controls (n = 61), patients with FMS only (n = 15), with CFS only (n = 33), with comorbid CFS and FMS (n = 79), and with medication-resistant (n = 42) or medication-responsive (n = 31) depression. We used exploratory factor analysis (EFA) on 34 candidate genes to determine factor scores and regression analysis to examine whether these factors were associated with specific diagnoses. Results EFA resulted in 4 independent factors with minimal overlap of genes between factors, explaining 51% of the variance. We labeled these factors by function as 1) purinergic and cellular modulators, 2) neuronal growth and immune function, 3) nociception and stress mediators, and 4) energy and mitochondrial function. Regression analysis predicting these biologic factors using FMS, CFS, depression severity, age, and sex revealed that greater expression in factors 1 and 3 was positively associated with CFS and negatively associated with depression severity (Quick Inventory for Depression Symptomatology score), but not associated with FMS. Conclusion Expression of candidate genes can be grouped into meaningful clusters, and CFS and depression are associated with the same 2 clusters, but in opposite directions, when controlling for comorbid FMS. Given high comorbid disease and interrelationships between biomarkers, EFA may help determine patient subgroups in this population based on gene expression.

Marriage decreases cardiovascular morbidity although relationship quality matters. While some marriages contain highly positive aspects (supportive), marriages may also simultaneously contain both positive and negative aspects (ambivalent). Individuals whose spouses or own behavior is ambivalent may not experience the same cardiovascular-protective benefits of marriage. The purpose of this study is to elucidate the physiological pathways by which marital quality may influence long-term health and examine ambivalent behavior on interpersonal-functioning and ambulatory blood pressure (ABP). Interpersonal functioning and ABP were examined in 94 couples. Spousal and own ambivalent behavior was associated with lower intimacy (ps

In animals, adverse early experience alters oxytocinergic and glucocorticoid activity and maternal behavior in adulthood. This preliminary study explored associations among childhood trauma (loss of a parent or sexual abuse in childhood), maternal self-efficacy, and leukocyte gene expression (mRNA) of oxytocin and glucocorticoid receptors (OXTR and NR3C1) in mothers of infants.62 mothers (20 with early life trauma) with healthy 3-month old infants reported maternal self-efficacy, depression, infant temperament, and overall social support; the effects of early trauma on these measures were assessed. Of these, 35 mothers (14 with early trauma) underwent blood draws after 2 infant feeding times; their OXTR and NR3C1 mRNA was compared to a control group of 25 no-infant women without early trauma, and also was examined for associations with self-efficacy.OXTR mRNA was increased in mothers of infants versus no-infant controls (p 0.0003), and mothers with greatest prior maternal experience had higher OXTR than those with less experience (0-2 vs. 3+ older children, p 0.033). Mothers with early trauma and less maternal experience had lower OXTR mRNA than no-trauma mothers (p 0.029) and lower NR3C1 mRNA than controls (p 0.004). Mothers with depression also had lower NR3C1 than other mothers (p 0.003) but did not differ in OXTR. Mothers with early trauma also reported their support network to be less helpful and more upsetting and unpredictable than other mothers (p 0.035-p 0.005). Regarding maternal behavior, in mothers with early trauma, helpful support networks increased self-reported nurturing self-efficacy when babies were not fussy but decreased it with fussy babies (p 0.05). Support was unrelated to self-efficacy in no-trauma mothers. Similarly, among mothers with low OXTR or NR3C1 (-1SD, most having early trauma and lower maternal experience), greater support was associated with lower self-efficacy (p 0.05), while mothers with high OXTR or NR3C1 (+1SD) tended to have higher self-efficacy with greater support.These preliminary findings need confirmation in a larger sample but suggest that childhood trauma influences maternal behavior and both OXTR and NR3C1 pathways in mothers of infants, and that both depression and prior maternal experience may be other important factors. Effects on maternal behavior appear to require more complex modeling.

Prior studies report that couples with higher relationship quality show higher oxytocin (OT) levels, yet other studies report those with higher distress have increased OT. This study investigated these competing predictions in the context of a support enhancement intervention among 34 young married couples ( N = 68). Preintervention marital quality (Dyadic Adjustment Scale) was examined for associations with plasma and salivary OT levels 4 weeks apart and for changes between these time points within the intervention group. High relationship quality, not distress, was associated with higher OT in both saliva and plasma at both time points. No significant interaction was found between marital quality and intervention condition; relationship quality and support intervention were both independently associated with higher postintervention OT levels.

depression is associated with lower relationship quality, but this association could overlap with effects of other affective characteristics correlated with depression, specifically anger and hostility. We examined actor and partner associations of depressive symptoms and anger/hostility with relationship quality in 152 Caucasian and 42 african american young married or cohabitating couples. in significant actor and partner effects, higher levels of depressive symptoms and anger/hostility were independently associated with lower overall relationship quality, though they were associated with differing aspects of relationship quality. although findings were generally similar across ethnic groups, partners’ depression was significantly more closely related to relationship quality for Caucasian than african american couples. hence, models of emotional adjustment and relationship quality should be expanded beyond depression to include anger/hostility, and preliminary evidence suggests potential ethnic similarities and differences.

Study objectives To examine whether subjective sleep quality and sleep duration moderate the association between age and telomere length (TL). Design Participants completed a demographic and sleep quality questionnaire, followed by a blood draw. Setting Social Neuroscience Laboratory. Participants 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. Interventions N/A. Measurements and results 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. Conclusions 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.

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 if this combination could activate sensations, and if so determined how these 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 (APB). Infusion of individual metabolites at maximum amounts evoked no fatigue or pain. Metabolite combinations found in resting muscles (pH 7.4+300nM ATP+1mM lactate) also evoked no sensation. The infusion of a metabolite-combination found in muscle during moderate endurance-exercise (pH 7.3+400nM ATP+5 mM lactate) produced significant fatigue sensations. Infusion of a metabolite-combination associated with vigorous exercise (pH 7.2+500nM ATP+10mM lactate) produced stronger sensations of fatigue and some ache. Higher levels of metabolites (as found with ischemic 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.

Objectives: Although perceiving one’s social ties as sources of ambivalence has been linked to negative health outcomes, the more specific contexts by which such relationships influence health remain less studied. We thus examined if perceived spousal relationship quality in three theoretically important contexts (i.e., support, capitalization, everyday life) predicted inflammation. Method: Ninety-four married couples completed measures of perceived spousal positivity and negativity in support, capitalization, and everyday contexts. These scores were used to derive an index of relationship ambivalence whereby interactions were rated as containing both positive and negative aspects. Serum levels of IL-6, fibrinogen, and CRP were assessed from plasma. Results: Perceiving ambivalence toward one’s spouse in a support context was linked to greater inflammation even when considering health behaviors, relationship-specific romantic attachment style, spouse negativity/positivity ratings, and overall marital satisfaction. Perceiving ambivalence toward a spouse during capitalization predicted higher fibrinogen levels only, whereas no links were found with perceived spousal ambivalence in everyday life contexts. Conclusion: Perceptions of ambivalence during support may be a particularly important relational context in which marital ties influence health. (PsycINFO Database Record (c) 2013 APA, all rights reserved)

Objective Chronic fatigue syndrome (CFS) and multiple sclerosis (MS) are characterized by debilitating fatigue, yet evaluation of this symptom is subjective. We examined metabolite-detecting, adrenergic, and immune gene expression (messenger ribonucleic acid [mRNA]) in patients with CFS (n = 22) versus patients with MS (n = 20) versus healthy controls (n = 23) and determined their relationship to fatigue and pain before and after exercise. Methods Blood samples and fatigue and pain ratings were obtained at baseline and 0.5, 8, 24, and 48 hours after sustained moderate exercise. Leukocyte mRNA of four metabolite-detecting receptors (acid-sensing ion channel 3, purinergic type 2X4 and 2X5 receptors, and transient receptor potential vanilloid type 1) and four adrenergic (α-2a, β-1, and β-2 receptors and catechol-O-methyltransferase) and five immune markers (CD14, toll-like receptor 4 [TLR4], interleukin [IL] 6, IL-10, and lymphotoxin α) was examined using quantitative polymerase chain reaction. Results Patients with CFS had greater postexercise increases in fatigue and pain (10-29 points above baseline, p Conclusions Postexercise mRNA increases in metabolite-detecting receptors were unique to patients with CFS, whereas both patients with MS and patients with CFS showed abnormal increases in adrenergic receptors. Among patients with MS, greater fatigue was correlated with blunted immune marker expression.

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.

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.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by recurring abdominal pain associated with altered bowel habits in patients who do not show signs or symptoms of an alternative disease to explain these symptoms.1 Many IBS patients have been found to be hypersensitive to balloon distension of the colon and rectum.2–4 Although not all IBS patients demonstrate this hypersensitivity, visceral hyperalgesia is so common in IBS patients that it is often considered to be a biologic marker for IBS.4,5 Contrary to earlier reports, which found evidence of visceral but not somatic hyperalgesia, most recent investigations have also demonstrated somatic hyperalgesia in IBS patients.6–9 These new data suggest the possibility that IBS patients may have a dysregulation in central pain processing similar to that seen in other chronic pain disorders such as fibromyalgia syndrome (FMS) and temporomandibular disorders (TMD).10 Investigations to explore central pain dysregulation in these and other chronic pain disorders have focused on two aspects, namely (1) exaggerations in temporal summation that facilitates ascending pain signals, and (2) deficits in diffuse noxious inhibitory controls (DNIC) that provide tonic descending anti-nociceptive signals. Research consistently shows enhanced temporal summation of afferent pain signals as well as deficits in DNIC in FMS11–13 and TMD patients14–17 compared to healthy controls (HCs), supporting the view that central alteration in pain signaling is an important contributor to the onset or worsening of chronic pain symptoms.10,18–21 According to Lautenbacher and Rollman, the nature of FMS, or any chronic pain condition, points to a deficient DNIC process reflecting decrements in endogenous analgesic systems.11 The counterirritation phenomenon known as DNIC occurs when pain perception from one nociceptive stimulus is substantially inhibited by a second nociceptive stimulus administered somewhere else in the body.22 This inhibition is potent, affecting all of the activities of the wide dynamic range neurons in the dorsal horn. DNIC mechanisms act like a barrier to prevent the spread of pain and keep it bearable by providing a tonic inhibitory influence.21 Deficits in DNIC are believed to play an important role in geriatric and chronic pain.10,18–21,23 Testing DNIC requires administering a phasic, noxious test stimulus (TS), before and concurrent with a tonic noxious conditioning stimulus (CS), typically, ischemic, cold pressure, or noxious heat pain, heteroptopically.11,13,23–25 The difference between the pain that is experienced with the first phasic pain stimulus, without the CS, compared with the second phasic stimulus of identical intensity and duration during the concurrent tonic pain is described as the DNIC effect. Wilder-Smith and colleagues in 200426 reported deficits in DNIC in IBS patients compared with controls using a visceral TS of painful intrarectal distensions during application of a somatic CS (placing the foot in ice-water).26 Although these investigators report group differences in the activity of magnetic resonance imaging in pain regulatory centers of the brain during the DNIC procedure, the choice of rectal distensions as the TS and noxious cold applied to the foot as the CS present several questions that need to be addressed. (1) It cannot be determined if the reduction in median pain scores for the TS during concurrent noxious CS was due to distraction from the CS, which is known to effect DNIC measures11,13,18 or (2) whether the lack of DNIC in IBS patients was due to hypervigilance to the TS of rectal distensions.27 Using painful gut distensions for IBS patients as the TS may complicate the evaluation of DNIC. (3) Peripheral sensitization of gut afferent fibers due to a history of chronic abdominal pain may interfere with the assessment of the central pain regulatory process of DNIC on rectal pain perception. Peripheral sensitization occurs when polymodal C-fiber nociceptors and A-fiber mechanonociceptors increase their sensitivity after repeated noxious stimulation, which is unique to the nociceptive system. According to Bouin and colleagues,28 dysregulation in the neurobiology of visceral (gut) afferents and pain sensitivity control is believed to explain IBS symptoms. (4) Convergence of nociceptive afferent signals from rectal distension and from cold pain at the foot that share transmission pathways in lumbar dorsal horn neurons may further complicate the assessment of the effect of the CS on the TS. Also, Wilder-Smith et al did not control for psychologic factors29–34 or cardiovascular reactivity,35,36 which have been shown to influence pain measurements. The aim of the present investigation was to assess group differences in central analgesic mechanisms by comparing DNIC in IBS patients and HCs using a somatic TS and a somatic CS, while controlling for nonspecific effects on pain perception, such as distraction from the CS, psychologic symptoms, and cardiovascular reactivity.

Objective 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. Methods 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. Results 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. Conclusion Increasing warm touch among couples has a beneficial influence on multiple stress-sensitive systems.

Objectives. An excess in abdominal fat may predispose African American women to chronic health conditions such as diabetes and cardiovascular disease. Because stress may increase body fat in the center-body region, we used the waist-to-hip ratio (WHR) to examine associations between excess abdominal fat and perceived racism (a chronic stressor) and daily stress. Passive emotional responses to perceived racism, hypothesized to have particularly adverse effects, were also examined. Methods. We controlled for body mass index in multiple logistic regression models among 447 African American women who completed a telephone interview on perceived racism. Results. Passive emotional responses were not related to WHR (odds ratio [OR]=1.4; 95% confidence interval [CI]=0.8, 2.4). High perceived racism was associated with a low WHR in this population (OR=0.4; 95% CI=0.3, 0.8). However, high daily stress was related to a high WHR (OR=2.7; 95% CI=1.1, 6.7). Conclusions. Findings support an association between daily stress and WHR but do not support our hypothesis that passive emotional responses to perceived racism increase abdominal fat. Further study of the stress physiology of perceived racism in African American women is warranted.

We examined the effect of race-effort cycling exercise with and without heat stress on post-exercise perceptions of fatigue and pain, as well as mRNA expression in genes related to exercise responses.Trained cyclists (n = 20) completed 40 km time trials during temperate (TC, 21 °C) and hot (HC, 35 °C) conditions. Blood lactates were measured 1 and 5 min post-exercise. Venous blood samples and ratings of fatigue and pain perceptions were obtained at baseline and at 0.5, 8, 24, and 48 h post-exercise. Leukocyte mRNA expression was performed for metabolite detecting, adrenergic, monoamine, and immune receptors using qPCR.Significantly lower mean power (157 ± 32.3 vs 187 ± 40 W) and lactates (6.4 ± 1.7 vs 8.8 ± 3.2 and 4.2 ± 1.5 vs 6.6 ± 2.7 mmol L(-1) at 1- and 5-min post-exercise) were observed for HC versus TC, respectively (p0.05). Increases (p0.05) in physical fatigue and pain perception during TTs did not differ between TC and HC (p0.30). Both trials resulted in significant post-exercise decreases in metabolite detecting receptors ASIC3, P2X4, TRPV1, and TRPV4; increases in adrenergic receptors α2a, α2c, and β1; decreases in adrenergic β2, the immune receptor TLR4, and dopamine (DRD4); and increases in serotonin (HTR1D) and IL-10 (p0.05). Post-exercise IL-6 differed between TC and HC, with significantly greater increases observed following HC (p0.05).Both TT performances appeared to be regulated around a specific sensory perception of fatigue and pain. Heat stress may have compensated for lower lactate during HC, thereby matching changes in metabolite detecting and other mRNAs across conditions.

To determine if independent candidate genes can be grouped into meaningful biologic factors, and whether these factors are associated with the diagnosis of chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FMS), while controlling for comorbid depression, sex, and age.We included leukocyte messenger RNA gene expression from a total of 261 individuals, including healthy controls (n = 61), patients with FMS only (n = 15), with CFS only (n = 33), with comorbid CFS and FMS (n = 79), and with medication-resistant (n = 42) or medication-responsive (n = 31) depression. We used exploratory factor analysis (EFA) on 34 candidate genes to determine factor scores and regression analysis to examine whether these factors were associated with specific diagnoses.EFA resulted in 4 independent factors with minimal overlap of genes between factors, explaining 51% of the variance. We labeled these factors by function as 1) purinergic and cellular modulators, 2) neuronal growth and immune function, 3) nociception and stress mediators, and 4) energy and mitochondrial function. Regression analysis predicting these biologic factors using FMS, CFS, depression severity, age, and sex revealed that greater expression in factors 1 and 3 was positively associated with CFS and negatively associated with depression severity (Quick Inventory for Depression Symptomatology score), but not associated with FMS.Expression of candidate genes can be grouped into meaningful clusters, and CFS and depression are associated with the same 2 clusters, but in opposite directions, when controlling for comorbid FMS. Given high comorbid disease and interrelationships between biomarkers, EFA may help determine patient subgroups in this population based on gene expression.

Background— An association between orthostatic hypotension (OH) and mortality has been reported, but studies are limited to older adults or high-risk populations. Methods and Results— We investigated the association between OH (a decrease of 20 mm Hg in systolic blood pressure or a decrease of 10 mm Hg in diastolic blood pressure on standing) and 13-year mortality among middle-aged black and white men and women from the Atherosclerosis Risk in Communities Study (1987–1989). At baseline, 674 participants (5%) had OH. All-cause mortality was higher among those with (13.7%) than without (4.2%) OH. After we controlled for ethnicity, gender, and age, the hazard ratio (HR) for OH for all-cause mortality was 2.4 (95% confidence interval [CI], 2.1 to 2.8). Adjustment for risk factors for cardiovascular disease and mortality and selected health conditions at baseline attenuated but did not completely explain this association (HR=1.7; 95% CI, 1.4 to 2.0). This association persisted among subsets that (1) excluded those who died within the first 2 years of follow-up and (2) were limited to those without coronary heart disease, cancer, stroke, diabetes, hypertension, or fair/poor perceived health status at baseline. In analyses by causes of death, a significant increased hazard of death among those with versus without OH persisted after adjustment for risk factors for cardiovascular disease (HR=2.0; 95% CI, 1.6 to 2.7) and other deaths (HR=2.1; 95% CI, 1.6 to 2.8) but not for cancer (odds ratio=1.1; 95% CI, 0.8 to 1.6). Conclusions— OH predicts mortality in middle-aged adults. This association is only partly explained by traditional risk factors for cardiovascular disease and overall mortality.

The neuroactive steroid allopregnanolone (ALLO) is stress sensitive, negatively modulates the HPA axis, and has been implicated in mood disorders. We examined ethnic differences in plasma ALLO at rest and following mental stress in African American (AA) men (n = 21) and women (n = 24) and non-Hispanic White men (n = 24) and women (n = 25). Overall, AA women had lower ALLO concentrations than non-Hispanic White women (p < .05), especially following mental stress (p < .01). Only 20% of AA women showed the expected stress-induced increase in ALLO compared with 59% of non-Hispanic White women (p < .01). No ethnic differences were seen in men. For both ethnic groups, poststress ALLO was negatively correlated with poststress cortisol (p < .05). Results are interpreted to reflect dysregulation in ALLO mechanisms in AA women and may have implications for ethnic differences in mood disorders.

This study examined the relations of one’s own total trait hostility and one’s spouse’s hostility as influences on cardiovascular (CV) responses to couple interactions (including conflict discussions) in 45 married couples aged 24—50. Systolic blood pressure and cardiac index (CI) reactivity to conflict discussion and recovery after conflict was greater in low hostile males if they were interacting with high hostile wives (p < .02). Vascular resistance index (VRI) reactivity to interactions was greater in high hostile husbands with high hostile wives (p < .05). Women showed no adverse CV effects of having a hostile spouse when their own hostility was low. Instead, seeming to anticipate the subsequent couple interactions, wives from duos in which both partners were high in hostility had higher baseline VRI levels and lower baseline CI compared to wives from duos in which both were low in hostility (ps < .05), and they simply maintained these group differences with no greater CV reactivity during the interactions. Findings suggest that CV responses before, during, and after marital discussions, particularly those characterized by conflict, may be influenced not only by one’s own hostility but by the hostility of one’s partner as well.

Prospective studies link marriage to better cardiovascular health, but marital dissatisfaction and discord predict increased rates of hypertension, higher blood pressure (BP), greater reactivity to stress, and left ventricular mass.To determine and compare effects of partner status and relationship quality on 24-h BP, urinary norepinephrine and cortisol, and self-reported stress and negative affect.Ambulatory BP (ABP) and 24-h urine collections were obtained during a typical work day in 325 adults, including 139 African Americans (AAs). Participants cohabiting with a spouse or partner were classified into high, intermediate and low relationship quality (RQ) groups and compared to those without partners (Alone).Mean ABP was nearly identical in participants with versus without partners (125.7/76.9 versus 125.9/76.7 mmHg). High RQ subjects had lower mean waking ABP than intermediate/low RQ and Alone groups [systolic blood pressure (SBP), F=3.45; diastolic blood pressure (DBP), F=3.38, P-values0.05]. High RQ was related to lower SBP and DBP in African Americans, and to lower SBP in Whites. High RQ was also linked to lower SBP and DBP in men, and to lower SBP in women. High RQ subjects reported less negative affect and stress than all other groups (P0.05). Norepinephrine was lower in partnered versus Alone women regardless of RQ status.Relationship quality is a better predictor of daily BP, affect and stress than partner status. High RQ is linked to lower ABP across race and gender. This reduced ABP may be due, in part, to the stress buffering effects of better RQ and/or the stress enhancing effects of poor RQ.

In animals, ventral stroking for >5 days increases oxytocin (OT) activity and decreases blood pressure (BP), but related human studies are few. Thus, relationships between self-reported frequency of partner hugs, plasma OT and BP levels were examined in 59 premenopausal women before and after warm contact with their husbands/partners ending with hugs. Higher baseline OT before partner contact was associated with lower BP and heart rate, and met criteria to be a partial mediator of the lower resting BP shown by women reporting more frequent hugs (P < 0.05). OT levels during post-contact stress were unrelated to hugs or BP. Menstrual cycle phase did not influence any OT measure. Thus, frequent hugs between spouses/partners are associated with lower BP and higher OT levels in premenopausal women; OT-mediated reduction in central adrenergic activity and peripheral effects of OT on the heart and vasculature are pathways to examine in future research.

This study examined gender differences in smoking-related analgesia and stress-induced analgesia (SIA), as a function of pain modality. Forty men (20 smokers, 20 nonsmokers) and 37 women (17 smokers) were tested twice for pain sensitivity to tourniquet ischemia, thermal heat, and cold pressor tests; once following mental stress and once following rest control, counterbalancing order. Cardiovascular and neuroendocrine responses to mental stress were also examined. While expected gender differences in pain sensitivity were observed, women smokers had greater threshold and tolerance times to ischemic pain than women nonsmokers (P

Ghrelin, a gut-brain peptide that signals hunger, is normally suppressed after meals. Subnormal suppression of postprandial ghrelin, previously noted in obese, insulin-resistant individuals, may contribute to increased food intake. Given the ethnic disparities in obesity and obesity-related cardiovascular morbidity in the United States, the present study compared a single postprandial ghrelin measure in 43 women (22 white, 21 black). Each completed a rigorously controlled 4-d dietary intervention designed to maintain weight and constant daily sodium and potassium intake (220 mEq Na, 40 mEq K). Two hours after consuming a test meal of identical content, blood samples were drawn to assess postprandial ghrelin, leptin, and norepinephrine; resting cardiovascular function was measured; and a 24-h urinary cortisol sample was obtained. Independent of body mass index, postprandial ghrelin was significantly higher in black vs. white women, and higher ghrelin was associated with higher cortisol in blacks, who failed to show the expected inverse relation between ghrelin and central obesity seen in whites. Higher ghrelin was correlated with higher blood pressure but lower norepinephrine in obese women. These findings suggest subnormal postprandial ghrelin suppression (or faster ghrelin rebound) in black women, especially the obese, that might play a role in their increased prevalence of obesity and cardiovascular disorders.

OBJECTIVE: This study investigated whether women with premenstrual dysphoric disorder (PMDD) who also had histories of sexual abuse differed from women with PMDD with no previous sexual abuse and from women without PMDD in hypothalamic-pituitary-thyroid (axis measures). METHODS: Ten sexually abused women with PMDD were compared with 18 nonabused women with PMDD and 22 nonabused women without PMDD for hypothalamic-pituitary-thyroid axis hormone concentrations during the follicular and luteal phases of confirmed ovulatory cycles. RESULTS: Compared with the women without PMDD, only the group of women with PMDD with sexual abuse showed greater variance in both cycle phases in thyroid-stimulating hormone concentrations and greater luteal phase variance in free and total thyroxine (T4) and reverse tri-iodothyronine (T3). In the group of nonabused women with PMDD, there was greater variance in follicular phase thyroxine-binding globulin concentrations compared with the group without PMDD. Women with PMDD with abuse had greater mean concentrations of total T3 and thyroxine-binding globulin, greater total T3/free T4 and free T3/free T4 ratios, and lower ratios of free T3/total T3 and free T4/total T4 than either of the other 2 nonabused groups. Greater total T3 concentrations and histories of major depression independently predicted premenstrual symptoms in all women with PMDD, together accounting for 31% to 38% of the variance in anxiety, anger, and depression ratings. CONCLUSIONS: These results suggest increased conversion of T4 to T3 and increased binding of thyroid hormones in women with PMDD with previous sexual abuse. Abnormal total T3 concentrations may have pathophysiological significance in PMDD. Language: en

In response to post-Women's Health Initiative dialog regarding individualized hormone replacement therapy (HRT), this study evaluates cardiovascular and neuroendocrine effects of HRT versus placebo in postmenopausal women grouped according to time since menopause.Resting and stress blood pressure (BP), hemodynamic, plasma catecholamine, and cholesterol levels were obtained in 69 women randomly assigned to placebo or active HRT in a 6-month double-blind study. Analyses evaluated if treatment effects differed among those postmenopausal less than 5 years versus 5 years or more.Compared with the placebo-treated and HRTor =5 groups, the HRT5 group showed reduced BP (P.0007) and trends toward reduced vascular resistance and norepinephrine (P.07). HRTor =5 group generally did not differ from placebo.Reduced BP and sympathetic tone are evident in some HRT users, with diminishing benefit after the initial postmenopausal years. Time since menopause may be an important consideration in making individualized patient treatment decisions.

To test the hypothesis that, in postmenopausal smokers, transdermal estrogen would be more effective than oral estrogen in reducing blood pressure (BP) and vascular and norepinephrine responses to stress and in increasing endothelial function and vascular beta2-adrenoceptor responsivity.By using a randomized, double-blind, placebo-controlled design, 82 healthy postmenopausal smokers were tested before and after 6 months of therapy with transdermal estrogen (0.05 mg/d) plus a progestin (2.5 mg/d; n = 31), oral conjugated equine estrogen (0.625 mg/d) plus a progestin (2.5 mg/d; n = 30), or placebo (n = 21). Dependent measures included resting and stress-induced increases in BP, total peripheral resistance, and plasma norepinephrine, as well as endothelial function and beta-adrenoceptor responsivity.When compared with placebo, the transdermal estrogen group showed more consistent reductions in total peripheral resistance at rest and in response to mental stress than the oral estrogen group. Only the transdermal group showed treatment-related reductions in behavioral stress norepinephrine, baseline rest, and behavioral stress BP levels, and increases in vascular beta2-adrenoceptor responsivity and endothelium-dependent vasodilation. Posttreatment concentrations of serum estradiol and estrone were lower and the serum estradiol/estrone ratio closer to pre-menopausal values in the group receiving transdermal estrogen compared with oral estrogen.Six months of transdermal estrogen therapy is associated with greater reductions in measures reflecting vascular sympathetic tone than oral estrogen therapy in healthy postmenopausal smokers. Thus, transdermal estrogen may be associated with a more favorable risk/ benefit ratio in postmenopausal smokers, a group at high risk of osteoporosis and cardiovascular disease.

OBJECTIVE: To examine the biological correlates associated with histories of sexual or physical abuse in women meeting DSM criteria for premenstrual dysphoric disorder (PMDD) and in healthy, non-PMDD controls. METHODS: Twenty-eight women with prospectively confirmed PMDD were compared with 28 non-PMDD women for cardiovascular and neuroendocrine measures at rest and in response to mental stressors, and for beta-adrenergic receptor responsivity, during both the follicular and luteal phase of the menstrual cycle. Structured interview was used to assess psychiatric history and prior sexual and physical abuse experiences. All subjects were free of current psychiatric comorbidity and medication use. RESULTS: More PMDD women had prior sexual and physical abuse experiences than controls (20 vs. 10, respectively). Relative to nonabused PMDD women, PMDD women with prior abuse (sexual or physical) exhibited significantly lower resting norepinephrine (NE) levels and significantly greater beta1- and beta2-adrenoceptor responsivity and greater luteal phase NE reactivity to mental stress. For non-PMDD control women, abuse was associated with blunted cortisol, cardiac output, and heart rate reactivity to mental stress relative to nonabused controls. CONCLUSIONS: The results of this initial study suggest that a history of prior abuse is associated with alterations in physiological reactivity to subsequent mental stress in women, but that the biological correlates of abuse may be different for PMDD vs. non-PMDD women. Language: en

BROWNLEY, K. A., A. L. HINDERLITER, S. G. WEST, S. S. GIRDLER, A. SHERWOOD, and K. C. LIGHT. Sympathoadrenergic Mechanisms in Reduced Hemodynamic Stress Responses after Exercise. Med. Sci. Sports Exerc., Vol. 35, No. 6, pp. 978 –986, 2003. Purpose: This study examines the acute effects of moderate aerobic exercise on 1) hemodynamic and sympathetic activity during behavioral stress and 2) -adrenergic receptor responsivity in a biracial sample of 24 sedentary adults. Methods: Before and after exercise, blood pressure (BP), impedance-derived cardiovascular measures, and plasma norepinephrine (NE) and epinephrine (EPI) were assessed during mental arithmetic and active speech tasks, and -adrenergic receptor responsivity was assessed using a standard isoproterenol challenge procedure. Results: After exercise, BP, NE, and EPI responses to stress were reduced (0.0001 P 0.08), preejection period (PEP) was elongated (P 0.0001), and 1- and 2-receptor responsivity (P 0.02) was enhanced. Approximately 65% of the prepost exercise mean arterial pressure response difference could be accounted for by changes in sympathetic factors, with change in NE and PEP being the single best predictors. Conclusions: Reduced BP responses to stress after acute exercise are strongly linked to a decrease in sympathetic drive, as evidenced by reduced NE responses and elongation of the PEP. Coincident with this overall dampening of the hemodynamic response to stress, increases in cardiac and vascular -adrenergic receptor responsivity occur. These findings may have important implications for future translational studies that seek to articulate the mechanisms through which regular aerobic exercise reduces the risks of hypertensive and coronary heart disease. Key Words: BLOOD PRESSURE, STRESS REACTIVITY, SYMPATHETIC NERVOUS SYSTEM, BETA-ADRENERGIC RECEPTOR, CATECHOLAMINE

The association between the blood pressure response to a change from the supine to the standing position and the 6-year incidence of hypertension was studied in a bi-ethnic, middle-aged cohort of 6951 normotensive men and women free of coronary heart disease at baseline. Postural change in systolic blood pressure (SBP) was categorized into deciles, and the middle four deciles served as the referent (no change) group. In unadjusted analyses, the incidence of hypertension was higher among both those with SBP increases and decreases relative to those in the referent group. Associations were modestly attenuated after controlling for age, ethnicity, and gender and cardiovascular disease risk factors. However, after adjustment for baseline, seated SBP, a modest association with incident hypertension persisted only for SBP decreases. Orthostatic hypotension (upon standing) was associated with incident hypertension and isolated systolic hypertension and, unexpectedly, this increased risk was highest among those with the lowest levels of baseline, resting SBP.

To evaluate the cardiovascular changes associated with menopause, we studied hemodynamics at rest, ambulatory blood pressure, and left ventricular structure in a biracial cohort of pre- and postmenopausal women of similar age, race, weight, and blood pressure. Despite similar levels of blood pressure, postmenopausal women had a higher indexed peripheral resistance (2,722 +/- 757 vs 2,262 +/- 661 dynes.s.m(2)/cm(5), p

This study examined pain sensitivity and pain modularity mechanisms (e.g., beta-endorphin levels, blood pressure) in women with premenstrual dysphoric disorder (PMDD; n = 27) and healthy controls (n = 27) during the follicular and luteal phases of the menstrual cycle. Physiological measures were taken during rest and ischemic pain testing. In both cycle phases, PMDD women (a) displayed lower resting cortisol and beta-endorphin levels and (b) exhibited shorter pain threshold and tolerance times and greater pain unpleasantness ratings during pain. PMDD women also reported greater pain unpleasantness and intensity and had lower beta-endorphin levels in their luteal phase and tended to display higher blood pressure levels at rest and during pain testing. Results suggest that endogenous opioids may be pathophysiologically relevant to PMDD and that the hypothalamic-pituitary-gonadal axis may modulate pain sensitivity in PMDD.

Older cancer survivors are a vulnerable population due to an increased risk for chronic diseases (e.g., cardiovascular disease) compounded with treatment late-effects and declines in physical functioning. Therefore, interventions that reduce chronic disease risk factors (i.e., blood pressure, chronic inflammation, and cortisol) are important in this population. Tai chi chih (TCC) is a mind-body exercise associated with reductions in chronic disease risk factors, but has not been examined with older cancer survivors. In a feasibility randomized controlled trial of TCC, we examined secondary outcomes of blood pressure, salivary cortisol, and inflammatory cytokines (interleukin (IL)-6, IL-12, tumor necrosis factor-α, IL-10, IL-4) due to their implications in chronic diseases.Sixty-three senior female cancer survivors (M age = 67 years, SD = 7.15) with physical functioning limitations (SF-12 physical functioning ≤80 or role-physical ≤72) were randomized to 12-weeks (60-min, three times a week) of TCC or Health Education control (HEC) classes. Resting blood pressure, 1-day salivary cortisol samples, and fasting plasma samples for cytokine multiplex assays were collected at baseline and 1-week post-intervention.Controlling for baseline values, the TCC group had significantly lower systolic blood pressure (SBP, p = 0.002) and cortisol area-under-curve (AUC, p = 0.02) at post-intervention than the HEC group. There was no intervention effect on inflammatory cytokines (p's 0.05).This TCC feasibility trial was associated with significant reductions in SBP and cortisol AUC in senior female cancer survivors. Larger, definitive trials are needed to confirm these findings.Senior survivors' have an increased risk for chronic diseases; however, TCC interventions may help reduce associated risk factors.

Objective. To evaluate leukocyte gene expression for 9 selected genes (mRNAs) as biological markers in patients with medication refractory depression before and after treatment with ECT or isoflurane anesthesia (ISO).Methods. In a substudy of a nonrandomized open-label trial comparing effects of ECT to ISO therapy, blood samples were obtained before and after treatment from 22 patients with refractory depression, and leukocyte mRNA was assessed by quantitative PCR. Patients’ mRNAs were also compared to 17 healthy controls.Results. Relative to controls, patients before treatment showed significantly higher IL10 and DBI and lower ADRA2A and ASIC3 mRNA (P<0.025). Both ECT and ISO induced significant decreases after treatment in 4 genes: IL10, NR3C1, DRD4, and Sult1A1. After treatment, patients’ DBI, ASIC3, and ADRA2A mRNA remained dysregulated.Conclusion. Significant differences from controls and/or significant changes after ECT or ISO treatment were observed for 7 of the 9 mRNAs studied. Decreased expression of 4 genes after effective treatment with either ECT or ISO suggests possible overlap of underlying mechanisms. Three genes showing dysregulation before and after treatment may be trait-like biomarkers of medication refractory depression. Gene expression for these patients has the potential to facilitate diagnosis, clarify pathophysiology, and identify potential biomarkers for treatment effects.

Sex differences in the pathophysiologic course of coronary artery disease (CAD) are widely recognized, yet accurate diagnosis of coronary artery disease in women remains challenging.To determine sex differences in the clinical manifestation of CAD, we studied chest pain reported during daily activities, exercise, and mental stress in 170 men and 26 women. All patients had documented CAD (50% narrowing in at least 1 major coronary artery or prior myocardial infarction) and all had 1-mm ST-segment depression on treadmill exercise. We collected psychologic test results, serum samples (potassium, epinephrine, norepinephrine, cortisol, b-endorphin, and glucose), and cardiac function, sensory threshold, and autonomic function data at specified times before, during, or after exercise and mental stress tests to assess measures of depression, anxiety, and neurohormonal and thermal pain perception.Women reported chest pain more often than men during daily activities (P =.04) and during laboratory mental stressors (P =.01) but not during exercise. Men had lower scores than women on measures of depression, trait anxiety, harm avoidance, and reward dependence (P.05 for all). Women had significantly lower plasma b-endorphin levels at rest (4.2 +/- 3.9 vs 5.0 +/- 2.5 pmol/L for men, P =.005) and at maximal mental stress (6.4 +/- 5.1 vs 7.4 +/- 3.5 pmol/L for men, P.01). A higher proportion of women than men had marked pain sensitivity to graded heat stimuli applied to skin (hot pain threshold41 degrees C, 33% vs 10%, P =.001).Our results reflect sex differences in the affective and discriminative aspects of pain perception and may help explain sex-related differences in clinical presentations.

Objective: Our aim was to compare the effects of transdermal versus oral estrogens on vascular resistance index, mean arterial pressure, serum lipid concentrations, norepinephrine, and left ventricular structure. Study Design: Ten postmenopausal women received transdermal estradiol (0.05 mg/d) plus cyclic oral progesterone for 6 months. Responses were compared with those of 23 women receiving oral conjugated estrogens (0.625 mg/d) plus cyclic progesterone and with those of 9 subjects receiving placebo in a concurrent randomized trial. We assessed the vascular resistance index and the mean arterial pressure at rest and during behavioral stressors. Results: Oral and transdermal estrogen significantly decreased the vascular resistance index, mean arterial pressure, norepinephrine, and total and low-density lipoprotein cholesterol to a similar extent. Changes in the vascular resistance index and mean arterial pressure were equally evident at rest and during stress. Although both treatments reduced left ventricular mass (–4% to –6%) and relative wall thickness (–3% to –5%), these changes were not statistically significant. Conclusions: Equivalent reductions in vascular resistance index, norepinephrine, mean arterial pressure, and cholesterol were observed with transdermal and oral estrogens. Future studies comparing novel hormone regimens with oral hormone replacement therapy should include multiple risk markers to allow better assessment of their potential impact on coronary artery health. (Am J Obstet Gynecol 2001;184:926-33.)

Using a randomized, placebo-controlled design, this study assessed the effects of estrogen alone (ES) or in combination with cyclic progesterone (EP) on daily ratings of mood and physical symptoms before and after 6 months of daily hormone treatment. Fifty-four postmenopausal women were recruited from the community at large and specifically selected as being asymptomatic at the time of enrollment and without significant psychiatric history. Ratings were obtained every day for 30 days prior to treatment and again every day during the last 30 days of treatment. Results revealed that when compared with pretreatment levels, women randomized to EP (n = 16) exhibited statistically significant increases in daily depression, cramping, and breast tenderness and a marginally significant increase in daily anxiety. However, these increases were mild, not clinically significant, and did not interfere with normal functioning. Women randomized to ES (n = 20) showed no significant change in daily mood measures, although they did experience an increase in breast tenderness with estrogen. A significant placebo (n = 18) effect was observed, as there was a reliable reduction in daily irritability ratings (p < 0.05) with placebo. These findings suggest that for most postmenopausal women, the use of hormones will not be associated with clinically significant changes in mood or physical symptoms, which weighs favorably into the cost-benefit ratio for women considering hormone replacement therapy.