Autonomic and brain morphological predictors of stress resilience

Stressful life events are an important cause of psychopathology. Humans exposed to aversive or stressful experiences show considerable inter-individual heterogeneity in their responses. However, the majority does not develop stress-related psychiatric disorders. The dynamic processes encompassing positive and functional adaptation in the face of significant adversity have been broadly defined as resilience. Traditionally, the assessment of resilience has been confined to self-report measures, both within the general community and putative high-risk populations. Although this approach has value, it is highly susceptible to subjective bias and may not capture the dynamic nature of resilience, as underlying construct. Recognizing the obvious benefits of more objective measures of resilience, research in the field has just started investigating the predictive value of several potential biological markers. This review provides an overview of theoretical views and empirical evidence suggesting that individual differences in heart rate variability (HRV), a surrogate index of resting cardiac vagal outflow, may underlie different levels of resilience toward the development of stress-related psychiatric disorders. Following this line of thought, recent studies describing associations between regional brain morphometric characteristics and resting state vagally-mediated HRV are summarized. Existing studies suggest that the structural morphology of the anterior cingulated cortex (ACC), particularly its cortical thickness, is implicated in the expression of individual differences in HRV. These findings are discussed in light of emerging structural neuroimaging research, linking morphological characteristics of the ACC to psychological traits ascribed to a high-resilient profile and abnormal structural integrity of the ACC to the psychophysiological expression of stress-related mental health consequences. We conclude that a multidisciplinary approach integrating brain structural imaging with HRV monitoring could offer novel perspectives about brain-body pathways in resilience and adaptation to psychological stres

Day-to-day variation of salivary cortisol and dehydroepiandrosterone (DHEA) in children from a rural Dominican community

This study examines day-to-day patterns of salivary cortisol and dehydroepiandrosterone (DHEA) under baseline conditions and in response to mild stress among 59 children residing in a rural Caribbean village. Cortisol secretion showed the typical circadian variation with high levels in the morning. Children showed significant increases of cortisol before and during a videotaped interview when compared to routine days. DHEA levels were positively associated with cortisol levels; however, within-day secretion of salivary DHEA was more stable than cortisol and DHEA levels did not change significantly during the day. Average DHEA concentrations were positively associated with age but did not show the sharp increase that is usually observed at the onset of adrenarche. These results highlight both similarities and differences in the secretion of cortisol and DHEA during childhood among rural and industrialized human populations

Can a single low-intensity premature stimulus induce ventricular arrhythmias in the normal heart?

Previously, we observed that a single low-intensity premature ventricular stimulation could occasionally induce spontaneous ectopic beats in normal rat hearts. Possible hypothesis for the arrhythmia is that a premature beat can encounter a zone of conduction block to initiate reentry. However, enhanced dispersion of repolarization, a necessary condition for initiation of reentry, is unlikely to be present in normal myocardium. Thus, the main objective of the present study was to perform detailed pace mapping measurements in normal ventricular myocardium with a view to identify pacing sites and critical coupling intervals which could induce spontaneous ectopic beats and to characterize the reentrant circuits

Decline of cardiomyocyte contractile performance and bioenergetic function in socially stressed male rats

Chronic social stress has been epidemiologically linked to increased risk for cardiovascular disease, yet the underlying pathophysiological mechanisms are still largely elusive. Mitochondrial (dys)function represents a potential intersection point between social stress exposure and (mal)adaptive cardiac responses. In this study, we used a rodent model of social stress to study the extent to which alterations in the cellular mechanical properties of the heart were associated with changes in indexes of mitochondrial function. Male adult rats were exposed to repeated episodes of social defeat stress or left undisturbed (controls). ECG signals were recorded during and after social defeat stress. Twenty-four hours after the last social defeat, cardiomyocytes were isolated for analyses of mechanical properties and intracellular Ca(2+) dynamics, mitochondrial respiration, and ATP content. Results indicated that social defeat stress induced potent cardiac sympathetic activation that lasted well beyond stress exposure. Moreover, cardiomyocytes of stressed rats showed poor contractile performance (e.g., slower contraction and relaxation rates) and intracellular Ca(2+) derangement (e.g., slower Ca(2+) clearing), which were associated with indexes of reduced reserve respiratory capacity and decreased ATP production. In conclusion, this study suggests that repeated social stress provokes impaired cardiomyocyte contractile performance and signs of altered mitochondrial bioenergetics in the rat heart. Future studies are needed to clarify the causal link between cardiac and mitochondrial functional remodeling under conditions of chronic social stress

Elevated miR-34a expression and altered transcriptional profile are associated with adverse electromechanical remodeling in the heart of male rats exposed to social stress.

This study investigated epigenetic risk factors that may contribute to stress-related cardiac disease in a rodent model. Experiment 1 was designed to evaluate the expression of microRNA-34a (miR-34a), a known modulator of both stress responses and cardiac pathophysiology, in the heart of male adult rats exposed to a single or repeated episodes of social defeat stress. Moreover, RNA sequencing was conducted to identify transcriptomic profile changes in the heart of repeatedly stressed rats. Experiment 2 was designed to assess cardiac electromechanical changes induced by repeated social defeat stress that may predispose rats to cardiac dysfunction. Results indicated a larger cardiac miR-34a expression after repeated social defeat stress compared to a control condition. This molecular modification was associated with increased vulnerability to pharmacologically induced arrhythmias and signs of systolic left ventricular dysfunction. Gene expression analysis identified clusters of differentially expressed genes in the heart of repeatedly stressed rats that are mainly associated with morphological and functional properties of the mitochondria and may be directly regulated by miR-34a. These results suggest the presence of an association between miR-34a overexpression and signs of adverse electromechanical remodeling in the heart of rats exposed to repeated social defeat stress, and point to compromised mitochondria efficiency as a potential mediator of this link. This rat model may provide a useful tool for investigating the causal relationship between miR-34a expression, mitochondrial (dys)function, and cardiac alterations under stressful conditions, which could have important implications in the context of stress-related cardiac disease

Arrhythmia susceptibility in senescent rat hearts

Cardiovascular disease increases with age as well as alterations of cardiac electrophysiological properties, but a detailed knowledge about changes in cardiac electrophysiology relevant to arrhythmogenesis in the elderly is relatively lacking. The aim of this study was to determine specific age-related changes in electrophysiological properties of the ventricles which can be related to a structural-functional arrhythmogenic substrate. Multiple epicardial electrograms were recorded on the ventricular surface of in vivo control and aged rats, while arrhythmia vulnerability was investigated by premature stimulation protocols. Single or multiple ectopic beats and sustained ventricular arrhythmias were frequently induced in aged but not in control hearts. Abnormal ventricular activation patterns during sinus rhythm and unchanged conduction velocity during point stimulation in aged hearts suggest the occurrence of impaired impulse conduction through the distal Purkinje system that might create a potential reentry substrate

Psychobiological evidence of the stress resilience fostering properties of a cosmetic routine

Everyday life psychosocial stressors contribute to poor health and disease vulnerabilty. Means alternative to pharmacotherapy that are able to foster stress resilience are more and more under the magnifying glass of biomedical research. The aim of this study was to test stress resilience fostering properties of the self-administration of a cosmetic product enriched with essential oils. On day 0, fourty women, 25-50 years old, self-administered both the enriched cosmetic product (ECP) and a placebo one (PCP). Then, women were randomized for daily self-administration (from day 1 to 28) of either ECP

Autonomic changes induced by provocative motion in rats bred for high (HAB) and low (LAB) anxiety-related behavior: Paradoxical responses in LAB animals.

In humans, associations between anxiety and nausea (including motion-induced) are reported but the underlying mechanisms are not known. Hypothermia is proposed to be an index of nausea in rats. Utilising hypothermia and heart rate as outcome measures we investigated the response to provocative motion in rats selectively bred for high (HAB) and low (LAB) anxiety-related behaviors and in non-selected (NAB) rats to further elucidate the potential relationship between hypothermia and nausea-like state. Core temperature and electrocardiogram were monitored in each group (n=10 per group) using telemetry, with or without circular motion (40min; 0.75Hz) and vehicle or diazepam (2mg/kg, i.p.) pre-treatment. Heart rate and time- and frequency-domain parameters of heart rate variability were derived from the electrocardiogram. There was no baseline difference in core temperature between the three groups (mean 38.0±0.1°C), but HAB animals had a significantly lower resting heart rate (330±7bpm) compared to LAB (402±5bpm) and NAB (401±9bpm). Animals in all groups exhibited hypothermia during motion (HAB: 36.3±0.1°C; NAB: 36.4±0.1°C; LAB: 34.9±0.2°C) with the magnitude (area under the curve, AUC) of the response during 40-min motion being greater in LAB compared to NAB and HAB rats, and this was also the case for the motion-induced bradycardia. Diazepam had minimal effects on baseline temperature and heart rate in all groups, but significantly reduced the hypothermia response (AUC) to motion in all groups by ~30%. Breeding for extremes in anxiety-related behavior unexpectedly selects animals with low trait anxiety that have enhanced bradycardia and hypothermic responses to motion; consequently, this animal model appears to be not suitable for exploring relationships between anxiety and autonomic correlates of nausea. Thermal and cardiovascular responses to motion were little different between HAB and NAB rats indicating that either hypothermia is not an index of a nausea-like state in rats, or that the positive correlation between anxiety and nausea demonstrated in humans does not exist in rats. The mechanism underlying the enhanced physiological responses in LAB requires more detailed study and may provide a novel model to investigate factors modulating motion sensitivity