Cue-induced cocaine craving enhances psychosocial stress and vice versa in chronic cocaine users

There is evidence that stress and craving contribute to the development, maintenance, and relapse in cocaine use disorder. Previous research has shown altered physiological responses to psychosocial stress as well as increased vegetative responding to substance-related cues in chronic cocaine users (CU). However, how psychosocial stress and cue-induced craving interact in relation to the physiological response of CU is largely unknown. Therefore, we investigated the interaction between acute psychosocial stress and cocaine-cue-related reactivity in 47 CU and 38 controls. Participants were randomly exposed first to a video-based cocaine-cue paradigm and second to the Trier Social Stress Test (TSST) or vice versa in a crossed and balanced design to investigate possible mutually augmenting effects of both stressors on the physiological stress response. Plasma cortisol, ACTH, and noradrenaline as well as subjective stress and craving were assessed repeatedly over the course of the experimental procedure. Growth models and discontinuous growth models were used to estimate the responses during the cocaine-cue paradigm and TSST. Overall, both groups did not differ in their endocrinological responses to the TSST but CU displayed lower ACTH levels at baseline. The TSST did not elevate craving in CU. However, if the cocaine-cue video was shown first, CU displayed an enhanced cortisol response to the subsequent TSST. Cocaine-cues robustly evoked craving in CU but no stress response, while cue-induced craving was intensified after the TSST. Taken together, CU did not show an altered acute stress response during the TSST but stress and craving together seem to have mutually augmenting effects on their stress response.

Stress system dysfunction revealed by integrating reactivity of stress pathways to psychological stress in lean and overweight/obese men

While the patterns of response within the sympatho-adrenal medullary (SAM) system and hypothalamo-pituitary adrenal (HPA) axis are interesting and important in their own accord, the overall response to acute psychological stress involves reactivity of both pathways We tested the hypothesis that consideration of the integrated response of these pathways may reveal dysregulation of the stress systems that is not evident when considering either system alone. Age matched lean and overweight/obese men were subjected to a Trier Social Stress Test and reactivity of the SAM system (salivary alpha amylase, systolic blood pressure, diastolic blood pressure and heart rate) and the HPA axis (salivary cortisol) were measured. Relative reactivity of SAM system and HPA axis was calculated as the ratio between the measures from each pathway. While analysis of reactivity of individual stress pathways showed no evidence of dysfunction in overweight/obese compared with lean men, analysis of HPA/SAM reactivity revealed significantly lower cortisol over systolic blood pressure (CoSBP) and cortisol over diastolic blood pressure (CoDBP) reactivity in overweight/obese compared with lean men. Other measures of HPA/SAM reactivity and all measures of SAM/HPA reactivity were unaltered in overweight/obese compared with lean men. These findings suggest that the cortisol response per unit of blood pressure response is blunted in men with elevated adiposity. Further, these findings support a notion of a coordinated overall approach to activation of the stress pathways with the degree of activation in one pathway being related to the degree of activation of the other.

An Evaluation of Speech-Based Recognition of Emotional and Physiological Markers of Stress

Life in modern societies is fast-paced and full of stress-inducing demands. The development of stress monitoring methods is a growing area of research due to the personal and economic advantages that timely detection provides. Studies have shown that speech-based features can be utilised to robustly predict several physiological markers of stress, including emotional state, continuous heart rate, and the stress hormone, cortisol. In this contribution, we extend previous works by the authors, utilising three German language corpora including more than 100 subjects undergoing a Trier Social Stress Test protocol. We present cross-corpus and transfer learning results which explore the efficacy of the speech signal to predict three physiological markers of stress—sequentially measured saliva-based cortisol, continuous heart rate as beats per minute (BPM), and continuous respiration. For this, we extract several features from audio as well as video and apply various machine learning architectures, including a temporal context-based Long Short-Term Memory Recurrent Neural Network (LSTM-RNN). For the task of predicting cortisol levels from speech, deep learning improves on results obtained by conventional support vector regression—yielding a Spearman correlation coefficient (ρ) of 0.770 and 0.698 for cortisol measurements taken 10 and 20 min after the stress period for the two corpora applicable—showing that audio features alone are sufficient for predicting cortisol, with audiovisual fusion to an extent improving such results. We also obtain a Root Mean Square Error (RMSE) of 38 and 22 BPM for continuous heart rate prediction on the two corpora where this information is available, and a normalised RMSE (NRMSE) of 0.120 for respiration prediction (−10: 10). Both of these continuous physiological signals show to be highly effective markers of stress (based on cortisol grouping analysis), both when available as ground truth and when predicted using speech. This contribution opens up new avenues for future exploration of these signals as proxies for stress in naturalistic settings.

Rapid volumetric brain changes after acute psychosocial stress

Rapid structural brain plasticity after acute stress has been shown in animals. It is unknown whether such stress-related brain changes also occur in humans, in which they have been found, using structural magnetic resonance imaging (MRI), after motor learning and visual stimulation. We here investigated grey matter volume (GMV) changes after acute stress in humans and tested their relation to psychophysiological stress measures. Sixty-seven healthy men (25.8 +/- 2.7 years) completed a standardized psychosocial laboratory stressor (Trier Social Stress Test) or a control version while blood, saliva, heart rate, and psychometrics were sampled. T1-weighted MP2RAGE images at 3T MRI were acquired 45 min before and 90 min after intervention onset. GMV changes were analysed using voxel-based morphometry. Associations with endocrine, autonomic, and subjective stress measures were tested with linear models. We found significant group-by-time interactions in several brain clusters including anterior/mid-cingulate cortices and bilateral insula: GMV was increased in the stress group relative to the control group, in which several clusters showed a GMV decrease. We found no significant group-by-time interaction for other MRI parameters, including cerebral blood flow, but a significant association of GMV changes with state anxiety and heart rate variability changes. In summary, we show rapid GMV changes following acute psychosocial stress in humans. The results suggest that endogenous circadian brain changes are counteracted by acute stress and generally emphasize the influence of stress on the brain.

Evidence of Delayed, Recursive Benefits of Self-Affirmation on Anxiety in Socially Anxious University Students

Introduction: Persons with social anxiety disorder (SAD) often experience social interactions as threatening and commonly avoid them or perform poorly in them (Asher et al., 2017). Self-affirmation is an intervention shown to help individuals engage effectively in situations they perceive as threatening (Sherman & Hartson, 2011). We hypothesized that self-affirmation would allow socially anxious individuals to participate in more social activities, do so more effectively, and with less stress and anxiety. Methods: Following completion of baseline measures, 75 socially anxious university students were randomly assigned to complete a self-affirming or control writing task. They subsequently completed the Trier Social Stress Test for Groups (TSST-G), and received SAD psychoeducation designed to promote social engagement over the coming month, after which they were reassessed on baseline measures of social anxiety. Results Self-affirmation demonstrated no benefit at the time of engagement in the TSST-G. However, at follow-up, self-affirmed students reported significantly less discomfort, anxiety, and distress related to a variety of social behaviors as well as more engagement in those behaviors, relative to baseline, compared with non-affirmed students. Moreover, significantly more affirmed than non-affirmed participants reported clinically significant reductions in symptoms of SAD at follow-up. Discussion These results help to broaden our conceptualization of self-affirmation and provide support for its potential utility in treatment for those with SAD.

Cortisol and C-Reactive Protein Vary During Sleep Loss and Recovery but Are Not Markers of Neurobehavioral Resilience

Cortisol and C-reactive protein (CRP) typically change during total sleep deprivation (TSD) and psychological stress; however, it remains unknown whether these biological markers can differentiate robust individual differences in neurobehavioral performance and self-rated sleepiness resulting from these stressors. Additionally, little is known about cortisol and CRP recovery after TSD. In our study, 32 healthy adults (ages 27–53; mean ± SD, 35.1 ± 7.1 years; 14 females) participated in a highly controlled 5-day experiment in the Human Exploration Research Analog (HERA), a high-fidelity National Aeronautics and Space Administration (NASA) space analog isolation facility, consisting of two baseline nights, 39 h TSD, and two recovery nights. Psychological stress was induced by a modified Trier Social Stress Test (TSST) on the afternoon of TSD. Salivary cortisol and plasma CRP were obtained at six time points, before (pre-study), during [baseline, the morning of TSD (TSD AM), the afternoon of TSD (TSD PM), and recovery], and after (post-study) the experiment. A neurobehavioral test battery, including measures of behavioral attention and cognitive throughput, and a self-report measure of sleepiness, was administered 11 times. Resilient and vulnerable groups were defined by a median split on the average TSD performance or sleepiness score. Low and high pre-study cortisol and CRP were defined by a median split on respective values at pre-study. Cortisol and CRP both changed significantly across the study, with cortisol, but not CRP, increasing during TSD. During recovery, cortisol levels did not return to pre-TSD levels, whereas CRP levels did not differ from baseline. When sex was added as a between-subject factor, the time × sex interaction was significant for cortisol. Resilient and vulnerable groups did not differ in cortisol and CRP, and low and high pre-study cortisol/CRP groups did not differ on performance tasks or self-reported sleepiness. Thus, both cortisol and CRP reliably changed in a normal, healthy population as a result of sleep loss; however, cortisol and CRP were not markers of neurobehavioral resilience to TSD and stress in this study.

Protocol for a cross-sectional study: Effects of a Multiple Sclerosis Relapse Therapy with Methylprednisolone on Offspring Neurocognitive Development and Behaviour (MS-Children)

Introduction: Multiple Sclerosis (MS) is the most common neuroimmunological disease in women of childbearing age. Current MS therapy consists of immunomodulatory relapse prevention with disease-modifying therapies (DMTs) and acute relapse therapy with the synthetic glucocorticoid (GC) methylprednisolone (MP). As most DMTs are not approved for use during pregnancy, treatment is usually discontinued, increasing the risk for relapses. While MP therapy during pregnancy is considered relatively save for the foetus, it may be detrimental for later cognitive and neuropsychiatric function. The underlying mechanism is thought to be an epigenetically mediated desensitisation of GC receptors, the subsequent increase in stress sensitivity, and a GC-mediated impairment of brain development. The aim of this study is to investigate the associations of foetal MP exposure in the context of MS relapse therapy with later cognitive function, brain development, stress sensitivity, and behaviour. Methods and analysis: 80 children aged 8 to 18 years of mothers with MS will be recruited. 40 children, exposed to GC in utero will be compared to 40 children without foetal GC exposure. The intelligence quotient will serve as primary outcome. Secondary outcomes will include attention, motor development, emotional excitability, Attention-Deficit Hyperactivity Disorder-related symptoms, and behavioural difficulties. The Trier Social Stress Test will test stress sensitivity, EEG and MRI will assess functional and structural brain development. To determine underlying mechanisms, DNA methylation of the GC receptor gene and the H19/IGF2 locus and changes in the microbiome and the metabolome will be investigated. Primary and secondary outcomes will be analysed using linear regression models. Time-variant outcomes of the stress test will be analysed in two mixed linear models exploring overall activity and change from baseline. Ethics and dissemination: This study was approved by the participating institutions' ethics committees and results will be presented in accordance with the STROBE 2007 Statement. Trial registration: https://clinicaltrials.gov/ct2/show/NCT04832269?id=ZKSJ0130

Effects of Music Intervention on Stress in Concussed and Non-Concussed Athletes

Sport-related concussion is a serious public health issue affecting millions of individuals each year. Among the many negative side effects, emotional symptoms, such as stress, are some of the most common. Stress management is repeatedly cited by expert groups as an important intervention for this population. It was shown that music has relaxing effects, reducing stress through the activation of brain areas involved in emotions and pleasure. The objective of this study was to explore the effects of a music-listening intervention compared with silence on experimentally induced stress in concussed and non-concussed athletes. To this aim, four groups of athletes (non-concussed music, non-concussed silence, concussed music, and concussed silence) performed the Trier Social Stress Test, for which both physiological (skin conductance level) and self-reported stress measurements were taken. No significant difference was found in the pattern of stress recovery for self-reported measurements. However, the skin conductance results showed greater and faster post-stress recovery after listening to music compared with silence for concussed athletes only. Taken together, these results suggest that music could be an efficient stress management tool to implement in the everyday life of concussed athletes to help them prevent stress accumulation.