Psychosocial Stress Responses Research Articles

Effects of Arginine-vasopressin in the Brain on Social Behavior and Communication in a Psychosocial Stress Animal Model

Psychosocial stressors (e.g., anxiety, personality traits, social isolation) are risk factors for negative health outcomes, including cardiovascular disease and neuropsychiatric disorders. However, there is a knowledge gap regarding the biological mechanisms that underlie these risk-outcome relationships. To address this gap, our team uses the Syrian hamster ( Mesocricetus auratus) as an animal model for investigating psychosocial behaviors and stress responses. Our previous findings and work reported by others indicate that the neuropeptide arginine-vasopressin (AVP) acts in the brain to regulate the expression of social behavior and communication. In the present study, stereotaxic surgeries were used to cannulate six adult hamsters (1 female, 5 males) with cannulae aimed at different forebrain regions, mostly focusing on hypothalamic areas. Cannulated animals were microinjected with 200 nl of a 9 μM AVP solution and saline in counterbalanced order with a 4-day inter-test interval. Three of the six animals displayed a type of social communication behavior called flank marking in response to AVP, whereas none of the animals flank marked in response to saline; these group differences were statistically significant (χ2 (1, N=6)= 4.0, p< 0.05). Previous research groups confirmed the anterior hypothalamic area (AHA) as a site of action for the effects of AVP on social behaviors. Our results suggest that, in addition to the AHA, the dorsomedial hypothalamic nucleus (DM) and posterior hypothalamic area (PH) may also be sites of action for AVP. We are currently testing the behavioral effects of AVP when microinjected into the midbrain. The preliminary findings reported here will help us identify areas of the brain that are part of a larger neural network that is involved in the regulation of social behavior and stress responses by AVP. Our long-term goal is to develop a psychosocial stress model to test the hypothesis that AVP may have therapeutic potential for psychosocial stress-associated conditions, including cardiovascular disease and neuropsychiatric disorders. This research is supported by NIH grant #5K01HL145339-03 (PI: M. Gil). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Neural Mechanisms Underlying the Impact of Psychological Resilience on Psychosocial Stress Responses

Background: High psychological resilience (HR) could protect individuals from psychosocial stress and thereby make individuals less vulnerable to depression and anxiety; however, the underlying neural mechanism remains to be investigated.Methods: The Montreal Imaging Stress Task (MIST) was administered to participants of 59 healthy individuals with HR and 56 individuals with low psychological resilience (LR) during functional magnetic resonance imaging (fMRI) scanning. Cortisol concentrations and subjective stress levels were collected across the MIST. Repeated measures analyses of variance were conducted to measure the group differences in subjective and cortisol stress responses. Two‐sample t‐tests were conducted to detect the group differences in stress‐related brain activation and functional connectivity (FC).Results: The LR group exhibited an increase in cortisol concentration after the MIST, whereas the HR group exhibited a decrease in cortisol concentration after the MIST. The LR group exhibited higher activation in the left anterior insula and lower FC between the left orbitofrontal cortex (OFC) and the right temporal pole (TP) (all pFWE < 0.05). Mediation analyses revealed that the left anterior insula mediates the relationship between psychological resilience and depression and the left OFC–right TP FC mediates the relationship between psychological resilience and anxiety.Conclusions: Findings highlight that the anterior insula and OFC–TP FC could be the critical neural mechanism underlying the interaction between psychological resilience and psychosocial stress. Moreover, higher anterior insula activation and lower OFC–TP FC could be the crucial neural mechanism of individuals with low psychological resilience developing into depression/anxiety when experiencing daily psychosocial stressors.

The intestinal γδ T cells: functions in the gut and in the distant organs.

Located in the frontline against the largest population of microbiota, the intestinal mucosa of mammals has evolved to become an effective immune system. γδ T cells, a unique T cell subpopulation, are rare in circulation blood and lymphoid tissues, but rich in the intestinal mucosa, particularly in the epithelium. Via rapid production of cytokines and growth factors, intestinal γδ T cells are key contributors to epithelial homeostasis and immune surveillance of infection. Intriguingly, recent studies have revealed that the intestinal γδ T cells may play novel exciting functions ranging from epithelial plasticity and remodeling in response to carbohydrate diets to the recovery of ischemic stroke. In this review article, we update regulatory molecules newly defined in lymphopoiesis of the intestinal γδ T cells and their novel functions locally in the intestinal mucosa, such as epithelial remodeling, and distantly in pathological setting, e.g., ischemic brain injury repair, psychosocial stress responses, and fracture repair. The challenges and potential revenues in intestinal γδ T cell studies are discussed.

Dectin-1 signaling on colonic γδ T cells promotes psychosocial stress responses.

The intestinal immune system interacts with commensal microbiota to maintain gut homeostasis. Furthermore, stress alters the microbiome composition, leading to impaired brain function; yet how the intestinal immune system mediates these effects remains elusive. Here we report that colonic γδ T cells modulate behavioral vulnerability to chronic social stress via dectin-1 signaling. We show that reduction in specific Lactobacillus species, which are involved in T cell differentiation to protect the host immune system, contributes to stress-induced social-avoidance behavior, consistent with our observations in patients with depression. Stress-susceptible behaviors derive from increased differentiation in colonic interleukin (IL)-17-producing γδ T cells (γδ17 T cells) and their meningeal accumulation. These stress-susceptible cellular and behavioral phenotypes are causally mediated by dectin-1, an innate immune receptor expressed in γδ T cells. Our results highlight the previously unrecognized role of intestinal γδ17 T cells in the modulation of psychological stress responses and the importance of dectin-1 as a potential therapeutic target for the treatment of stress-induced behaviors.

Vagus activation by Cold Face Test reduces acute psychosocial stress responses

Chronic stress is linked to dysregulations of the two major stress pathways—the sympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis, which could for example result from maladaptive responses to repeated acute stress. Improving recovery from acute stress could therefore help to prevent this dysregulation. One possibility of physiologically interfering with an acute stress reaction might be provided by applying a cold stimulus to the face (Cold Face Test, CFT) which activates the parasympathetic nervous system (PNS), leading to immediate heart rate decreases. Therefore, we investigated the use of the CFT protocol as an intervention to reduce acute stress responses. Twenty-eight healthy participants were exposed to acute psychosocial stress via the Montreal Imaging Stress Task (MIST) in a randomized between-subjects design while heart rate (HR), heart rate variability (HRV), and salivary cortisol were assessed. While both groups were equally stressed during the procedure, participants with CFT intervention showed better recovery, indicated by significant (p<0.05) differences in HR(V). We additionally found a significantly (p<0.05) lower cortisol response to the MIST and less overall cortisol secretion in the CFT condition. Both findings indicate that the CFT can successfully stimulate the PNS and inhibit the HPA axis. To the best of our knowledge, our experiment is the first to successfully use the CFT as a simple and easy-to-apply method to modify biological responses to acute stress.

Abstract 14955: The Biological Bases of Psychosocial Stress-Associated Cardiovascular Disease: Investigating the Cardioprotective Properties of Central Arginine-Vasopressin

Psychosocial stressors (e.g., anxiety, personality traits, social isolation) are risk factors for cardiovascular events and heart disease. However, there is a lack of knowledge regarding the biological mechanisms that underlie this risk-outcome relationship. To address this knowledge gap, our team uses two non-traditional animal models, the Syrian hamster ( Mesocricetus auratus ) and gray short-tailed opossum ( Monodelphis domestica ). We previously reported that social isolation-induced aggression, a type of psychosocial stress experience, leads to increased neural activation in the ventral tegmental area (VTA) of the midbrain. The VTA contains tyrosine hydroxylase (TH)-producing (putative dopamine, DA) neurons and is innervated by vasopressin (AVP) fibers. DA and AVP play a role in social behavior, and we investigated whether these two systems interact when an individual experiences psychosocial stress-induced aggression. Here we report that social interactions increased Fos, the protein product of the immediate early gene c-fos that serves as a marker of neuronal activation, in non-TH cells in an area of the VTA called the interfascicular nucleus (IF) of male subjects. Previous social experience increased the number of TH-positive cells in the IF but had no effect on the number of AVP-ir fibers. Conversely, levels of aggressive and social dominance behaviors were positively correlated with the number of AVP-ir fibers in the IF, whereas there was no relationship between these behaviors and the number of TH-positive cells. In socially naïve males, AVP microinjected into the VTA inhibited the duration of aggressive behavior. We are currently investigating the impact of our psychosocial stress paradigms on myocardial injury in both males and females. Our results suggest a complex interaction between AVP and DA systems in the brain in psychosocial stress responses. Our long-term goal is to build on these preliminary findings to determine whether AVP in the VTA may reduce psychosocial stress-induced myocardial injury, a first step in exploring heart-brain interactions that may link psychosocial stress with negative cardiovascular disease outcomes.

Early life stress moderated the influence of reward anticipation on acute psychosocial stress responses.

Recent studies suggest that reward anticipation decreases individuals' acute stress responses. However, individuals who have experienced early life stress (ELS) may have a blunted capacity for reward anticipation, which reduces its buffering effect on psychosocial stress responses. To investigate this phenomenon, 66 young adults completed the Trier Social Stress Test following a reward anticipation task, and their ELS levels were measured using the Childhood Trauma Questionnaire (CTQ). Meanwhile, the current study collected biological and psychological measures of stress by analysing cortisol levels, heart rates, heart rate variability (HRV) as well as subjective stress levels, in response to the Trier Social Stress test. Results showed that reward anticipation successfully decreased acute stress responses in general, and it also improved participants' HRV. However, this effect was more evident in individuals with low ELS than those with high ELS. These findings help us deepen understandingof the role of reward anticipation in fostering resilience under stress and the potentially important implications for individuals who have been exposed to ELS are also discussed.

Alzheimer's pathogenic mechanisms and underlying sex difference.

AD is a neurodegenerative disease, and its frequency is often reported to be higher for women than men: almost two-thirds of patients with AD are women. One prevailing view is that women live longer than men on average of 4.5years, plus there are more women aged 85years or older than men in most global subpopulations; and older age is the greatest risk factor for AD. However, the differences in the actual risk of developing AD for men and women of the same age is difficult to assess, and the findings have been mixed. An increasing body of evidence from preclinical and clinical studies as well as the complications in estimating incidence support the sex-specific biological mechanisms in diverging AD risk as an important adjunct explanation to the epidemiologic perspective. Although some of the sex differences in AD prevalence are due to differences in longevity, other distinct biological mechanisms increase the risk and progression of AD in women. These risk factors include (1) deviations in brain structure and biomarkers, (2) psychosocial stress responses, (3) pregnancy, menopause, and sex hormones, (4) genetic background (i.e., APOE), (5) inflammation, gliosis, and immune module (i.e., TREM2), and (6) vascular disorders. More studies focusing on the underlying biological mechanisms for this phenomenon are needed to better understand AD. This review presents the most recent data in sex differences in AD-the gateway to precision medicine, therefore, shaping expert perspectives, inspiring researchers to go in new directions, and driving development of future diagnostic tools and treatments for AD in a more customized way.

Recurring sequences of multimodal non-verbal and verbal communication during a human psycho-social stress test: A temporal pattern analysis

BackgroundThe Trier Social Stress Test (TSST) is a widely used protocol to study human psycho-social stress responses. Quantitative reports of non-verbal behaviors have been carried out by means of the Ethological Coding System for Interviews (ECSI). However, no data have described whether and how non-verbal and verbal behaviors take part in the composition of multimodal sequences of communication during the test. MethodFive non-verbal ECSI categories and four verbal behaviors related with communication were included in the Ethogram. A focal sampling was employed to ensure a high temporal resolution of the behavioral annotation. T-Pattern Analysis was employed to detect statistically-grounded behavioral sequences. ResultsAs a first step, frequency, overall duration and mean time length were reported for each component of the Ethogram. Besides, T-Pattern Analysis revealed that communication during TSST is organized according to a complex temporal patterning. We found 51 different sequences (T-patterns): 8 T-patterns included exclusively non-verbal behaviors; 17 T-patterns included verbal behaviors and 26 T-patterns encompassed mixed non-verbal and verbal behaviors. T-patterns were discussed depending on their putative functional meaning since non-verbal behaviors almost did not overlap within patterns. ConclusionsThe implementation of an Ethogram including non-verbal and verbal components highlights the multimodal human communication in TSST. T-Pattern Analysis unveils the real-time interplay among these components. In this study results are discussed according to Jakobson's six constitutive factors of communication.

A major psychosocial stress circuit

Neuroscience Psychological stress induces various physiological responses by activating the sympathetic nervous system. The brain circuits involved in these functions are still not completely understood. In a rat model, Kataoka et al. combined anatomical tracing, immediate early gene expression analysis, pharmacology, optogenetics, electrophysiology, and genetic cell ablation to provide evidence for the prominent role of a ventral part of the medial prefrontal cortex in sympathetic responses to social defeat stress. This brain region sends excitatory projections to the dorsomedial hypothalamus as a central coordinator of the psychosocial stress responses. This pathway is crucial for understanding how psychosocial stress influences a variety of body functions. Science , this issue p. [1105][1] [1]: /lookup/doi/10.1126/science.aaz4639

A central master driver of psychosocial stress responses in the rat.

The mechanism by which psychological stress elicits various physiological responses is unknown. We discovered a central master neural pathway in rats that drives autonomic and behavioral stress responses by connecting the corticolimbic stress circuits to the hypothalamus. Psychosocial stress signals from emotion-related forebrain regions activated a VGLUT1-positive glutamatergic pathway from the dorsal peduncular cortex and dorsal tenia tecta (DP/DTT), an unexplored prefrontal cortical area, to the dorsomedial hypothalamus (DMH), a hypothalamic autonomic center. Genetic ablation and optogenetics revealed that the DP/DTT→DMH pathway drives thermogenic, hyperthermic, and cardiovascular sympathetic responses to psychosocial stress without contributing to basal homeostasis. This pathway also mediates avoidance behavior from psychosocial stressors. Given the variety of stress responses driven by the DP/DTT→DMH pathway, the DP/DTT can be a potential target for treating psychosomatic disorders.

Non-medical prescription opioid users exhibit dysfunctional physiological stress responses to social rejection

Non-medical prescription opioid use (NMPOU) recently increased dramatically, especially in the U.S. Although chronic opioid use is commonly accompanied by deficits in social functioning and dysregulation of the hypothalamic-pituitary adrenergic (HPA) stress axis, little is known about the impact of NMPOU on psychosocial stress responses. Therefore, we measured physiological responses of the autonomic nervous system and the HPA axis to social rejection using the Cyberball paradigm. We compared 23 individuals with NMPOU, objectively confirmed by hair and urine analyses, with 29 opioid-naïve, healthy controls. As expected, heart rate variability (HRV), an index of parasympathetic activity, increased significantly during exclusion within controls, while in the NMPOU group only a trend in the same direction was found. However, increased HRV was robustly moderated by opioid craving indicating worse emotion regulation to social exclusion specifically in individuals with high opioid craving. Greater levels of the adrenocorticotropic hormone and cortisol responses to social rejection were found in the NMPOU group indicating hyperreactivity of the HPA axis to social exclusion. Self-ratings suggest that opioid users were aware of rejection, but less emotionally affected by exclusion. Furthermore, controls showed greater negative mood after the Cyberball confirming the task’s validity. Moreover, NMPOU individuals reported a smaller social network size compared to controls. Present findings suggest that chronic NMPOU is associated with dysfunctional physiological responses to psychosocial stressors such as social rejection. In sum, NMPOU was associated with poorer regulation of the parasympathetic nervous system, especially under opioid craving highlighting its potential importance in relapse prevention.

Sexual dimorphism in predisposition to Alzheimer's disease.

Clinical studies indicate that Alzheimer's disease (AD) disproportionately affects women in both disease prevalence and rate of symptom progression, but the mechanisms underlying this sexual divergence are unknown. Although some have suggested this difference in risk is a reflection of the known differences in longevity between men and women, mounting clinical and preclinical evidence supports women also having intrinsic susceptibilities toward the disease. Although a number of potential risk factors have been hypothesized to mediate these differences, none have been definitively verified. In this review, we first summarize the epidemiologic studies of prevalence and incidence of AD among the sexes. Next, we discuss the most likely risk factors to date that interact with biological sex, including (1) genetic factors, (2) sex hormones (3) deviations in brain structure, (4) inflammation and microglia, and (5) and psychosocial stress responses. Overall, though differences in life span are likely to account for part of the divide between the sexes in AD prevalence, the abundance of preclinical and clinical evidence presented here suggests an increase in intrinsic AD risk for women. Therefore, future studies focusing on the underlying biological mechanisms for this phenomenon are needed to better understand AD pathogenesis in both sexes, with the eventual goal of sex-specific prevention and treatment strategies.

The effect of superstitious thinking on psychosocial stress responses and perceived task performance

Previous research on superstitious belief, a subset of paranormal belief (Irwin, ), has suggested that people tend to invoke luck‐related superstitions in stressful situations as an attempt to gain an illusion of control over outcomes. Based on this, the current study examined whether luck‐related superstition, in the form of a “lucky” pen, could influence the psychological response to a psychosocial stressor. Participants (N = 114), aged between 17 and 59 years (M = 22.98, SD = 4.57) from James Cook University Singapore, were randomly assigned to one of four conditions: (a) no‐stress with no lucky pen; (b) no‐stress with a lucky pen; (c) stress with no lucky pen or; (d) stress with a lucky pen. The results revealed that participants provided with a lucky pen experienced lower state anxiety when exposed to the stressor. Further, participants provided with a lucky pen perceived their performance to be better than those without it. However, superstitious belief did not significantly change following exposure to stress. Taken together, the present findings add some support to the suggestion that belief in transferable luck may facilitate coping with a stressor. However, further research is needed to fully understand the mechanisms behind the potential benefits of superstitious belief.

The impact of long working hours on psychosocial stress response among white-collar workers.

This study examined the association between long working hours and psychosocial stress responses. In total, 1,122 white-collar workers from a company in Korea completed self-administered questionnaires following a lecture about the study aim, procedures, and confidentiality. Psychosocial stress responses were evaluated using the Psychosocial Well-being Index - Short Form (PWI-SF), and psychosocial working conditions were evaluated with the Korean Occupational Stress Scale - Short Form (KOSS-SF). Multivariate logistic regression analysis was performed after adjusting for demographic variables and psychosocial working conditions to examine associations between long working hours and psychosocial stress responses. In comparison with the reference group, which worked 40–44 hours per week, the crude odds ratio (OR) of the respondents who worked 60 or more hours was 4.56 (95% confidence interval (CI), 2.55–8.15) in terms of psychosocial stress responses. After adjusting for demographic variables, the adjusted OR of those working ≥60 hours was 5.61 (95% CI, 3.01–10.47). After adjusting for both demographic variables and psychosocial working conditions, the adjusted OR of those working ≥60 hours was 3.25 (95% CI, 1.56–6.79). This study found that long working hours are significantly related to psychosocial stress responses among white-collar workers in one Korean company.

Cortisol Stress Response Variability in Early Adolescence: Attachment, Affect and Sex.

Attachment, affect, and sex shape responsivity to psychosocial stress. Concurrent social contexts influence cortisol secretion, a stress hormone and biological marker of hypothalamic-pituitary-adrenal axis activity. Patterns of attachment, emotion status, and sex were hypothesized to relate to bifurcated, that is, accentuated and attenuated, cortisol reactivity. The theoretical framework for this study posits that multiple individual differences mediate a cortisol stress response. The effects of two psychosocial stress interventions, a modified Trier Social Stress Test for Teens and the Frustration Social Stressor for Adolescents were developed and investigated with early adolescents. Both of these protocols induced a significant stress reaction and evoked predicted bifurcation in cortisol responses; an increase or decrease from baseline to reactivity. In Study I, 120 predominantly middle-class, Euro-Canadian early adolescents with a mean age of 13.43years were studied. The girls' attenuated cortisol reactivity to the public performance stressor related significantly to their self-reported lower maternal-attachment and higher trait-anger. In Study II, a community sample of 146 predominantly Euro-Canadian middle-class youth, with an average age of 14.5years participated. Their self-reports of higher trait-anger and trait-anxiety, and lower parental attachment by both sexes related differentially to accentuated and attenuated cortisol reactivity to the frustration stressor. Thus, attachment, affect, sex, and the stressor contextual factors were associated with the adrenal-cortical responses of these adolescents through complex interactions. Further studies of individual differences in physiological responses to stress are called for in order to clarify the identities of concurrent protective and risk factors in the psychosocial stress and physiological stress responses of early adolescents.

Effectiveness of a Comprehensive Stress Management Program to Reduce Work-Related Stress in a Medium-Sized Enterprise

ObjectivesTo assess the effectiveness of a comprehensive workplace stress management program consisting of participatory action-oriented training (PAOT) and individual management.MethodsA comprehensive workplace stress management program was conducted in a medium-sized enterprise. The baseline survey was conducted in September 2011, using the Korean Occupational Stress Scale (KOSS) and Worker’s Stress Response Inventory (WSRI). After implementing both organizational and individual level interventions, the follow up evaluation was conducted in November 2011.ResultsMost of the workers participated in the organizational level PAOT and made Team-based improvement plans. Based on the stress survey, 24 workers were interviewed by a researcher. After the organizational and individual level interventions, there was a reduction of several adverse psychosocial factors and stress responses. In the case of blue-collar workers, psychosocial factors such as the physical environment, job demands, organizational system, lack of rewards, and occupational climate were significantly improved; in the case of white-collar workers, the occupational climate was improved.ConclusionsIn light of these results, we concluded that the comprehensive stress management program was effective in reducing work-related stress in a short-term period. A persistent long-term follow up is necessary to determine whether the observed effects are maintained over time. Both team-based improvement activities and individual interviews have to be sustainable and complementary to each other under the long-term plan.

Transcranial electrical stimulation modifies the neuronal response to psychosocial stress exposure

Stress is a constant characteristic of everyday life in our society, playing a role in triggering several chronic disorders. Therefore, there is an ongoing need to develop new methods in order to manage stress reactions. The regulatory function of right medial-prefrontal cortex (mPFC) is frequently reported by imaging studies during psychosocial stress situations. Here, we examined the effects of inhibitory and excitatory preconditioning stimulation via cathodal and anodal transcranial direct current stimulation (tDCS) on psychosocial stress related behavioral indicators and physiological factors, including the cortisol level in the saliva and changes in brain perfusion. Twenty minutes real or sham tDCS was applied over the right mPFC of healthy subjects before the performance of the Trier Social Stress Test (TSST). Regional cerebral blood flow (rCBF) was measured during stimulation and after TSST, using pseudo-continuous arterial spin labeling (pCASL). Comparing the effect of the different stimulation conditions, during anodal stimulation we found higher rCBF in the right mPFC, compared to the sham and in the right amygdala, superior PFC compared to the cathodal condition. Salivary cortisol levels showed a decrease in the anodal and increase in cathodal groups after completion of the TSST. The behavioral stress indicators indicated the increase of stress level, however, did not show any significant differences among groups. In this study we provide the first insights into the neuronal mechanisms mediating psychosocial stress responses by prefrontal tDCS.

Effects of panel sex composition on the physiological stress responses to psychosocial stress in healthy young men and women

Men and women differ in regard to psychosocial stress responses. Biological and contextual factors are known to mediate these differences; however, few studies investigated their interaction. In the present study, we examined contributions of both contextual and biological factors to the stress response of young healthy adults. Men and women were exposed to a modified version of Trier Social Stress Test. The participants gave a speech in front of a panel of judges, composed of either male or female panelists. Both men, and women presented a cortisol increase only when exposed to opposite sex panelists. Interestingly, this effect was only observed in women in their follicular phase. This finding showed that the induction of a psychosocial stress response does not strictly rely on direct social evaluation, but also depends on the sex composition of the panel. Implications for future studies are discussed.

Current Research in Preterm Birth

Preterm birth is one of the leading causes of infant mortality and the leading cause of infant morbidity in the United States. It accounts for >70% of neonatal deaths and almost half of long-term neurological disabilities. The Centers for Disease Control and Prevention (CDC) is collaborating with state health departments, universities, communities, and healthcare providers to understand why preterm births occur and how to address preterm birth risk factors. These collaborations include identification of genetic and other biological markers for the early detection of women at high risk of preterm birth; improving understanding of the relationships among psychosocial stress, immune and inflammatory responses, and preterm risk; and designing community strategies to improve the health of pregnant women. By conducting public health research activities that explore the genetic, biological, clinical, behavioral, social, and community determinants of preterm birth, CDC will continue to elucidate the complex interactions of these factors and how they influence preterm birth.