Multi-modal responses to the Virtual Reality Trier Social Stress Test: A comparison with standard interpersonal and control conditions.

The Trier Social Stress Test (TSST) is a reliable social-evaluative stressor. To overcome limitations of the in vivo TSST, a standardized virtual reality TSST (VR-TSST) was developed. The present study compares the emotional (anxiety) and physiological (heart period and variability) response to a VR-TSST with an in vivo TSST and a control condition. Participants took part in either an in vivo TSST (N = 106, 64% female), VR-TSST (N = 52, 100% female), or a control TSST (N = 20, 40% female). Mixed linear modeling examined response profile differences related to TSST type. While there was an equivalent anxiety response to the in vivo TSST as the VR-TSST, we found a smaller heart period and heart rate variability response in VR-TSST compared to the in vivo TSST, especially in response to the math part of the test. The present findings demonstrate that social evaluative stress can be successfully induced in a VR setting, producing similar emotional and slightly attenuated cardiovascular responses.

Intranasal oxytocin enhances stress-protective effects of social support in women with negative childhood experiences during a virtual Trier Social Stress Test.

Oxytocin is considered a biological mechanism underlying stress-protective effects of positive social interactions. It is assumed to underlie the women-specific tend-and-befriend response to stress, although few studies have tested this assertion with female samples. The aim of the present study was, therefore, to test whether oxytocin enhances stress-protective effects of social support during stress in women, taking into account the moderating role of childhood adversity. The sample consisted of 180 female undergraduate students who had reported on experiences of childhood abuse and how often their mother used love withdrawal as an insensitive disciplinary strategy. Women participated in a virtual version of the Trier Social Stress Test (TSST) and were randomly assigned to receive 24 IU oxytocin or a placebo and to receive support or no support from a female friend (sub-groups N = 45). Results showed that oxytocin reduced heart rate variability during the TSST in participants who received support, possibly indicating that oxytocin increases attention and stimulates a challenge motivational state in the presence of a friend. In addition, we found that, in the presence of a friend, oxytocin reduced state anxiety levels and cortisol levels after the TSST, but only in women with higher levels of adverse childhood experiences. Our findings may indicate that oxytocin is a neurobiological means to attain and benefit from social support under stressful circumstances, which may be particularly adaptive for women with a history of adversity. Thus, oxytocin may function as motivator for affiliative disposition during stress exposure in women with a history of childhood adversity. Results should be replicated in clinical samples.

Vital exhaustion and cardiovascular prognosis in myocardial infarction and heart failure: predictive power of different trajectories.

BACKGROUND: We examined the different trajectories of vital exhaustion (VE) over a 12-month period and their impact on prognosis in a sample of myocardial infarction (MI) and chronic heart failure (CHF) patients. METHOD: Consecutive MI (n=407) and CHF patients (n=297) were assessed at baseline, and at 3- and 12-month follow-up for symptoms of VE. Latent growth mixture modelling was used to examine the course of VE over time. The combined clinical endpoint was defined as cardiac hospital readmission or death. RESULTS: Four distinct trajectories for VE were found: low VE, decreasing VE, increasing VE, and severe VE. Sex, marital status, left ventricular ejection fraction, psychotropic medication, sample group (CHF v. MI) and depressive symptoms were associated with VE, varying according to classes. The mean follow-up period was 25.3 months in which 34.7% of the patients experienced an event. Multivariate Cox regression showed that, compared with patients in the low VE class, patients in the increasing VE class [hazard ratio (HR)=1.16, 95% confidence interval (CI) 1.58-3.61, p=0.01], and the severe VE class (HR=1.69, 95% CI 1.31-2.64, p=0.02) had an increased risk for adverse cardiovascular events (i.e. cardiovascular hospital readmission or cardiovascular death). Decreasing VE was not related to adverse cardiovascular events (HR=0.97, 95% CI 0.66-1.69, p=0.81). CONCLUSIONS: VE trajectories varied across cardiac patients, and had a differential effect on cardiovascular outcome. Increasing VE and severe VE classes were predictors of poor cardiovascular prognosis. These results suggest that identification of cardiac patients with an increased risk of adverse health outcomes should be based on multiple assessments of VE.

Depression and anxiety as predictors of heart rate variability after myocardial infarction.

BACKGROUND: Reduced heart rate variability (HRV) is a prognostic factor for cardiac mortality. Both depression and anxiety have been associated with increased risk for mortality in cardiac patients. Low HRV may act as an intermediary in this association. The present study examined to what extent depression and anxiety differently predict 24-h HRV indices recorded post-myocardial infarction (MI). METHOD: Ninety-three patients were recruited during hospitalization for MI and assessed on self-reported symptoms of depression and anxiety. Two months post-MI, patients were assessed on clinical diagnoses of lifetime depressive and anxiety disorder. Adequate 24-h ambulatory electrocardiography data were obtained from 82 patients on average 78 days post-MI. RESULTS: In unadjusted analyses, lifetime diagnoses of major depressive disorder was predictive of lower SDNN [standard deviation of all normal-to-normal (NN) intervals; beta=-0.26, p=0.022] and SDANN (standard deviation of all 5-min mean NN intervals; beta=0.25, p=0.023), and lifetime anxiety disorder of lower RMSSD (root mean square of successive differences; beta=-0.23, p=0.039). Depression and anxiety symptoms did not significantly predict HRV. After adjustment for age, sex, cardiac history and multi-vessel disease, lifetime depressive disorder was no longer predictive of HRV. Lifetime anxiety disorder predicted reduced high-frequency spectral power (beta=-0.22, p=0.039) and RMSSD (beta=-0.25, p=0.019), even after additional adjustment of anxiety symptoms. CONCLUSIONS: Clinical anxiety, but not depression, negatively influenced parasympathetic modulation of heart rate in post-MI patients. These findings elucidate the physiological mechanisms underlying anxiety as a risk factor for adverse outcomes, but also raise questions about the potential role of HRV as an intermediary between depression and post-MI prognosis.

A whole-genome scan for 24-hour respiration rate: a major locus at 10q26 influences respiration during sleep.

Identification of genes causing variation in daytime and nighttime respiration rates could advance our understanding of the basic molecular processes of human respiratory rhythmogenesis. This could also serve an important clinical purpose, because dysfunction of such processes has been identified as critically important in sleep disorders. We performed a sib-pair-based linkage analysis on ambulatory respiration rate, using the data from 270 sibling pairs who were genotyped at 374 markers on the autosomes, with an average distance of 9.65 cM. Uni- and multivariate variance-components-based multipoint linkage analyses were performed for respiration rate during three daytime periods (morning, afternoon, and evening) and during nighttime sleep. Evidence of linkage was found at chromosomal locations 3q27, 7p22, 10q26, and 22q12. The strongest evidence of linkage was found for respiration rate during sleep, with LOD scores of 2.36 at 3q27, 3.86 at 10q26, and 1.59 at 22q12. In a simultaneous analysis of these three loci, >50% of the variance in sleep respiration rate could be attributed to a quantitative-trait loci near marker D10S1248 at 10q. Genes in this area (GFRA1, ADORA2L, FGR2, EMX2, and HMX2) can be considered promising positional candidates for genetic association studies of respiratory control during sleep.

Ifosfamide and mesna: effects on the Na/H exchanger activity in renal epithelial cells in culture (LLC-PK1).

Ifosfamide (IF) is an alkylating cytostatic with urotoxic and tubulotoxic side effects which may result in the development of Fanconi syndrome in children. While the urotoxicity of IF is effectively prevented by the uroprotective thiol compound sodium-2-mercaptoethanesulfonate (Mesna), tubulo-toxicity of IF may occur even in the presence of Mesna and in the absence of any signs of urotoxicity. Using the renal tubular cell line LLC-PK1, we investigated whether there is a protective effect of Mesna or of its major dimeric metabolite Dimesna against metabolites of IF with respect to the Na/H exchanger activity. We tested the major IF metabolites 4-hydroperoxy-IF (4-OOH-IF), chloroacetaldehyde (CAA), and acrolein. All metabolites significantly inhibit the Na/H exchanger activity. Half-maximal inhibition of transport occurs at concentrations of 120 mumol/l (4-OOH-IF), 80 (CAA), and 60 mumol/l (acrolein) after 2 h of incubation. The onset of the inhibitory effect of all three metabolites is rapid. Complete inhibition of Na/H exchange by acrolein and CAA is present after a 6-hour exposure to 100 mumol/l of the respective metabolite, while 100 mumol/l 4-OOH-IF causes only 50% inhibition after 24 h of incubation. Dimesna, which the proximal tubular cell has to reduce to Mesna at the expense of intracellular glutathione before it exerts a uroprotective effect, has no protective effect in LLC-PK1 cells. Dimesna (0.3 mmol/l) displaces the dose-response curve for acrolein to the left, indicating an increased toxicity of the combination of acrolein plus Dimesna. Mesna (0.3 mmol/l) has a complete protective effect with respect to acrolein and CAA, while the protective effect versus 100 mumol/l of 4-OOH-IF is incomplete. We conclude that the function of the Na/H exchanger in LLC-PK1 cells is altered by metabolites of IF. The incomplete protection against the toxic effect of 4-OOH-IF by Mesna may explain the pathomechanism by which IF causes tubulotoxicity in the absence of urotoxicity.

Cross-nursing: wet-nursing in a contemporary context.

Cross-nursing, or the breast-feeding of an infant not one's own, appears to be an increasingly popular, if not well reported, practice. The physical and psychologic effects are not well documented, but may be quite different from those of the institutionalized wet-nursing of the past. Three mothers who cross-nurse were interviewed; the practice appears to have had no ill effect on them or their infants. Cross-nursing is a logical and practical extension of the resurgence of breast-feeding and may, in turn, increase the incidence of breast-feeding by making it more attractive to employed mothers. Before the practice can be properly evaluated, however, more data are needed, particularly with regard to possible physical reactions in the infants. In the meantime, pediatricians should be aware that their breast-fed patients may be participating in a cross-nursing situation, and suggest prudent considerations.