Relationship of Psychological Characteristics to Daily Life Ischemia: An Analysis From the National Heart, Lung, and Blood Institute Psychophysiological Investigations in Myocardial Ischemia.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Observation of Complement Protein Gene Expression Before and After Surgery in Opioid-Consuming and Opioid-Naive Patients.

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.

Gene Variants in Hepatic Metabolism, Gamma-Aminobutyric Acid-ergic Reward, and Prostaglandin Pathways in Opioid-Consuming and Opioid-Naïve Patients Presenting for Lower Extremity Total Joint Replacement.

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.

Propofol for Treatment-Resistant Depression: A Pilot Study.

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.

Neural consequences of post-exertion malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

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, p<0.05). Patients and controls had similar physiological responses to exercise (p>0.05). However, patients exercised at significantly lower Watts and reported greater exertion and leg muscle pain (p<0.05). For cognitive performance, a significant Group by Time interaction (p<0.05), 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 (p<0.05) 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 (p<0.05) 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 (p<0.05). 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.

Fatigue sensation and gene expression in trained cyclists following a 40 km time trial in the heat.

PURPOSE: 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. METHODS: 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. RESULTS: 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 (p < 0.05). Increases (p < 0.05) in physical fatigue and pain perception during TTs did not differ between TC and HC (p > 0.30). Both trials resulted in significant post-exercise decreases in metabolite detecting receptors ASIC3, P2X4, TRPV1, and TRPV4; increases in adrenergic receptors α2a, α2c, and ß1; decreases in adrenergic ß2, the immune receptor TLR4, and dopamine (DRD4); and increases in serotonin (HTR1D) and IL-10 (p < 0.05). Post-exercise IL-6 differed between TC and HC, with significantly greater increases observed following HC (p < 0.05). CONCLUSIONS: 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.

It's Complicated: Marital Ambivalence on Ambulatory Blood Pressure and Daily Interpersonal Functioning.

BACKGROUND: 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. PURPOSE: 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). METHODS: Interpersonal functioning and ABP were examined in 94 couples. RESULTS: Spousal and own ambivalent behavior was associated with lower intimacy (ps < .01) and higher systolic ABP (ps < .01). Spousal ambivalent behavior was associated with lower ratings of partner responsiveness (p < .01) and less self- and spousal-disclosure (ps < .05). Mediational analyses indicated that own behavior mediated links between spousal ambivalent behavior and ABP. CONCLUSIONS: Despite the positivity in relationships, individuals whose spouses' or own behavior is ambivalent may not receive cardiovascular protection from this positivity.

Exogenously applied muscle metabolites synergistically evoke sensations of muscle fatigue and pain in human subjects.

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.

The impact of oxytocin administration and maternal love withdrawal on event-related potential (ERP) responses to emotional faces with performance feedback.

This is the first experimental study on the effect of oxytocin administration on the neural processing of facial stimuli conducted with female participants that uses event-related potentials (ERPs). Using a double-blind, placebo-controlled within-subjects design, we studied the effects of 16 IU of intranasal oxytocin on ERPs to pictures combining performance feedback with emotional facial expressions in 48 female undergraduate students. Participants also reported on the amount of love withdrawal they experienced from their mothers. Vertex positive potential (VPP) and late positive potential (LPP) amplitudes were more positive after oxytocin compared to placebo administration. This suggests that oxytocin increased attention to the feedback stimuli (LPP) and enhanced the processing of emotional faces (VPP). Oxytocin heightened processing of the happy and disgusted faces primarily for those reporting less love withdrawal. Significant associations with LPP amplitude suggest that more maternal love withdrawal relates to the allocation of attention toward the motivationally relevant combination of negative feedback with a disgusted face.

Dysregulation of leukocyte gene expression in women with medication-refractory depression versus healthy non-depressed controls.

BACKGROUND: Depressive Disorders (DD) are a great financial and social burden. Females display 70% higher rate of depression than males and more than 30% of these patients do not respond to conventional medications. Thus medication-refractory female patients are a large, under-served, group where new biological targets for intervention are greatly needed. METHODS: We used real-time quantitative polymerase chain reaction (qPCR) to evaluate mRNA gene expression from peripheral blood leukocytes for 27 genes, including immune, HPA-axis, ion channels, and growth and transcription factors. Our sample included 23 females with medication refractory DD: 13 with major depressive disorder (MDD), 10 with bipolar disorder (BPD). Our comparison group was 19 healthy, non-depressed female controls. We examined differences in mRNA expression in DD vs. controls, in MDD vs. BPD, and in patients with greater vs. lesser depression severity. RESULTS: DD patients showed increased expression for IL-10, IL-6, OXTR, P2RX7, P2RY1, and TRPV1. BPD patients showed increased APP, CREB1, NFKB1, NR3C1, and SPARC and decreased TNF expression. Depression severity was related to increased IL-10, P2RY1, P2RX1, and TRPV4 expression. CONCLUSIONS: These results support prior findings of dysregulation in immune genes, and provide preliminary evidence of dysregulation in purinergic and other ion channels in females with medication-refractory depression, and in transcription and growth factors in those with BPD. If replicated in future research examining protein levels as well as mRNA, these pathways could potentially be used to explore biological mechanisms of depression and to develop new drug targets.

Absence of XMRV retrovirus and other murine leukemia virus-related viruses in patients with chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is a multisystem disorder characterized by prolonged and severe fatigue that is not relieved by rest. Attempts to treat CFS have been largely ineffective primarily because the etiology of the disorder is unknown. Recently, CFS has been associated with xenotropic murine leukemia virus-related virus (XMRV) as well as other murine leukemia virus (MLV)-related viruses, though not all studies have found these associations. We collected blood samples from 100 CFS patients and 200 self-reported healthy volunteers from the same geographical area. We analyzed these in a blind manner using molecular, serological, and viral replication assays. We also analyzed samples from patients in the original study that reported XMRV in CFS patients. We did not find XMRV or related MLVs either as viral sequences or infectious viruses, nor did we find antibodies to these viruses in any of the patient samples, including those from the original study. We show that at least some of the discrepancy with previous studies is due to the presence of trace amounts of mouse DNA in the Taq polymerase enzymes used in these previous studies. Our findings do not support an association between CFS and MLV-related viruses, including XMRV, and the off-label use of antiretrovirals for the treatment of CFS does not seem justified at present.

Differences in metabolite-detecting, adrenergic, and immune gene expression after moderate exercise in patients with chronic fatigue syndrome, patients with multiple sclerosis, and healthy controls.

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, ß-1, and ß-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 < .001) and greater mRNA increases in purinergic type 2X4 receptor, transient receptor potential vanilloid type 1, CD14, and all adrenergic receptors than controls (mean ± standard error = 1.3 ± 0.14- to 3.4 ± 0.90-fold increase above baseline, p = .04-.005). Patients with CFS with comorbid fibromyalgia (n = 18) also showed greater increases in acid-sensing ion channel 3 and purinergic type 2X5 receptors (p < .05). Patients with MS had greater postexercise increases than controls in ß-1 and ß-2 adrenergic receptor expressions (1.4 ± 0.27- and 1.3 ± 0.06-fold increases, respectively, p = .02 and p < .001) and greater decreases in TLR4 (p = .02). In MS, IL-10 and TLR4 decreases correlated with higher fatigue scores. 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.

Salivary levels of oxytocin remain elevated for more than two hours after intranasal oxytocin administration.

OBJECTIVE: This is the first study investigating whether levels of oxytocin in saliva remained elevated after intranasal oxytocin administration for the duration of an experiment (in which neurobehavioral effects of oxytocin were observed) taking more than two hours. METHODS: Oxytocin levels were measured in saliva samples collected from 57 female participants right before (T0), approximately 1» h (T1), and approximately 2» h (T2) after intranasal administration of 16 IU of oxytocin or a placebo, using a double-blind, within-subjects design. RESULTS: Average levels of oxytocin did not differ between conditions before use of the nasal spray, markedly increased only after oxytocin administration, and were still elevated after 2» h. CONCLUSION: Salivary levels of oxytocin remained persistently elevated over the course of our experiment, i.e. for more than two hours after intranasal oxytocin administration and over a time-period in which neurobehavioral effects of oxytocin are commonly observed. This suggests that salivary concentrations may be a valuable biomarker for oxytocin, and may help to explain its effects on brain activity, information processing, and behavior.

Early life trauma: An exploratory study of effects on OXTR and NR3C1 gene expression and nurturing self-efficacy in mothers of infants.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Influence of a "warm touch" support enhancement intervention among married couples on ambulatory blood pressure, oxytocin, alpha amylase, and cortisol.

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.

Orthostatic hypotension predicts mortality in middle-aged adults: the Atherosclerosis Risk In Communities (ARIC) Study.

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.

Associations of abdominal fat with perceived racism and passive emotional responses to racism in African American women.

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.

Persistent alterations in biological profiles in women with abuse histories: influence of premenstrual dysphoric disorder.

OBJECTIVE: To examine dysregulation in biological measures associated with histories of abuse in women and whether women with premenstrual dysphoric disorder (PMDD) differ in their dysregulation. DESIGN: Twenty-five women meeting prospective criteria for PMDD and 42 non-PMDD controls underwent structured interview to determine abuse histories and lifetime Axis I diagnoses, excluding those with current Axis I disorders or using medications. MAJOR OUTCOME MEASURES: Plasma cortisol and norepinephrine (NE), heart rate (HR), blood pressure (BP), and vascular resistance index (VRI) were assessed at rest and in response to mental stress. RESULTS: A greater proportion of PMDD women had prior abuse compared with non-PMDD women. Regardless of PMDD status, all abused women had lower plasma NE and higher HRs and tended to have lower plasma cortisol at rest and during stress. Abused women also reported more severe daily emotional and physical symptoms. Greater VRI and BP at rest and during stress were seen only in PMDD women with abuse. CONCLUSION: There is persistent dysregulation in stress-responsive systems in all abused women that cannot be accounted for by current psychiatric illness or medications, and PMDD women may be differentially more vulnerable to the impact of abuse on measures reflecting alpha-adrenergic receptor function.

Patterns of salivary cortisol secretion in pregnancy and implications for assessment protocols.

Cortisol is used in research as a biomarker of psychological stress. Logistical considerations argue for collecting as few samples as possible, balanced against diurnal rhythms and intra-individual variations. 100 pregnant women gave five saliva samples a day for 3 days, at waking, 30 min after waking, and 11:00 a.m., 5:00 p.m., and 9:00 p.m. Timing of collection was confirmed by monitors. Another sample was taken during a clinic visit. Using the 15 measures as the gold standard, correlations and mean area under the curve (AUC) were compared with subsets and the single clinic sample to evaluate alternate collection protocols. Five samples in 1 day, or protocols involving morning and night samples, had the highest correlations with mean AUC (correlation coefficient ranging from 0.82 to 0.88). Standardizing the clinic measurement to a single time of day did not substantially improve correlations with mean AUC. Correlations with measures of reported stress were also not strong.

Correction: Antidepressant and Neurocognitive Effects of Isoflurane Anesthesia versus Electroconvulsive Therapy in Refractory Depression.

[This corrects the article DOI: 10.1371/journal.pone.0069809.].