Psychoneuroendocrinology最新文献

Difficulties in fear regulation can sometimes result in maladaptive fear responses. To better understand how to improve fear regulation, it is important to determine how known factors, such as sex hormone status and stress, might interact to influence fear memory. Research has shown that women with high estradiol levels (mid-cycle) and men exhibit better extinction retention compared to women with low estradiol levels (women in the early follicular cycle or using oral contraceptives). Stress has also been demonstrated to affect both the learning and retention of extinction. Despite documented interactions between stress and sex hormones, their combined effects have not been thoroughly studied. This study aims to examine the impact of stress as a function of sex hormone status on extinction learning and retention.

A total of 168 non-clinical participants were studied, including men (n = 46), women using oral contraceptives (n = 38), women in the early follicular phase (n = 40), and women in mid-cycle (n = 44). On Day 1, fear acquisition training was performed. On day 2, prior to extinction training, half of the participants were exposed to a psychosocial stressor, while the other half performed a non-stressful control task. On day 3, extinction retention was tested. Fear was quantified using skin conductance responses, while stress hormones were quantified through saliva samples.

Exposure to stress prior to extinction training did not affect extinction learning, regardless of sex hormone status. In contrast, pre-extinction stress exposure had different effects on extinction retention depending on hormone status. Stressed men showed impairment in extinction retention compared to controls, while the experimental condition had no effect on naturally cycling women. Regardless of stress exposure, early follicular women exhibited a deficit in fear regulation, while mid-cycle women showed effective fear regulation. Among women using oral contraceptives, the stress group demonstrated better extinction retention compared to the control group.

These results demonstrate the importance of considering sex hormone status and stress exposure during extinction learning, as both components may modulate extinction retention. These results could help identifying hormonal conditions that may enhance the effectiveness of extinction-based psychological therapies used in the treatment of fear-related disorders.

Stress-related disorders are commonly associated with abnormalities in hypothalamic-pituitary-adrenal (HPA) axis activity. Preliminary studies with cortisol administration in the aftermath of trauma suggest that this HPA axis hormone can potentially prevent maladaptive behavioral and biological stress responses. However, the efficacy of glucocorticoid administration during the peripuberty period has not been tested yet, although this lifetime is a critical time window in brain development and is highly sensitive to the harmful effects of stress. To further examine the short and long-lasting impact of glucocorticoids treatment given during the post-peripubertal stress period, the present study utilized a rat model of peripubertal stress-induced psychopathology and animals were subjected to a battery of tests to assess anxiety-like behaviors, exploratory behavior and reactivity to novelty at late adolescence and sociability, anhedonia and stress coping behaviors at adulthood. All the experiments were performed in males and females to evaluate the potential behavioral sex differences. Overall, our results demonstrated that rats exposed to peripubertal stress show decreased sociability in adulthood without differences in anxiety and depression-like behaviors. Moreover, this study shows that the administration of corticosterone after stress exposure at peripuberty does not prevent stress-induced behavioral alterations. However, we observed that some stress-induced behavioural alterations and corticosterone responses are sex-specific. Thus, the data obtained highlight that delineating sex differences in stress-related studies may ultimately contribute to the development of effective therapeutic interventions for each sex.

Objective

Emerging work suggests that affect regulation strategies (e.g., active coping, anger expression) predict disease and mortality risk, with sometimes divergent estimates by sex or education levels. However, few studies have examined potential underlying biological mechanisms. This study assessed the longitudinal association of affect regulation with future allostatic load.

Method

In 2004–2006, 574 participants from the Midlife in the United States study completed validated scales assessing use of nine general and emotion-specific regulatory strategies (e.g., denial, anger expression). As a proxy for how flexibly participants regulate their affect, variability in the use of regulatory strategies was operationalized using a standard deviation-based algorithm and considered categorically (i.e., lower, moderate, greater variability) to assess non-linear effects. Participants also provided data on relevant covariates and 24 allostatic load biomarkers (e.g., cortisol, blood pressure). In 2017–2021, these biomarkers were again collected. Linear regressions modeled betas (β) and 95 % confidence intervals (CI) examining associations of affect regulatory constructs with future allostatic load.

Results

In fully-adjusted models including initial allostatic load, general regulatory strategies were unrelated to future allostatic load. Yet, greater versus moderate affect regulation variability levels predicted lower allostatic load (β=−0.14; 95 %CI: −0.27, −0.01). Only among more educated participants, greater use of anger expression predicted lower allostatic load, while the reverse was noted with anger control (β_expression=−0.12; 95 %CI: −0.20, −0.05; β_control=0.14; 95 %CI: 0.05, 0.24).

Conclusions

While general regulatory strategies appeared unrelated to allostatic load, greater variability in their use and anger-related strategies showed predictive value. Subsequent studies should examine these associations in larger, more diverse samples.

Armed conflict and forced migration (ACFM) represent a set of extreme environments that are increasingly common for children and adolescents to experience. Adolescence may constitute a sensitive period (puberty and psychoneurological maturation) through which ACFM adversity leaves a lasting mark. Adolescence has become a focal point for analysis and intervention as it relates to the effects of early life adversity on puberty, linear growth, and mental health. Research in public health and psychological science suggests early life adversity (ELA) may accelerate puberty, heightening risks for mental health disorders. However, it is not well substantiated whether ACFM-derived adversities accelerate or delay relative pubertal timing. Secondly, ACFM provides salient context through which to probe the relationships between nutritional, psychosocial, and demographic changes and their respective impact on puberty and mental health. We conducted a narrative review which 1) examined constructions of early life adversity and their proposed influence on puberty 2) reviewed empirical findings (n = 29 studies, n = 36 samples) concerning effects of ACFM ELA on age at menarche and 3) discussed proposed relationships between early life adversity, puberty, and mental ill-health. Contrary to prior research, we found war-derived early life adversity was more consistently associated with pubertal delay than acceleration and may exert counterintuitive effects on mental health. We show that ELA cannot be operationalized in the same way across contexts and populations, especially in the presence of extreme forms of human stress and resilience. We further discuss the ethics of puberty research among conflict-affected youth.

A key component of stress management and biofeedback training is the use of relaxation exercises, such as slow/deep breathing (6 breaths/minute) in heart coherence exercises (HCEs). Breathing exercises are also increasingly being integrated into smartphones as part of health apps, though their effectiveness in adolescents after acute stress has rarely been validated scientifically. The aim of the current study was to investigate the effectiveness of an app-guided HCE (n = 36) after an acute stress situation (Trier Social Stress Test) compared with natural relaxation (n = 37), among healthy adolescents (aged 11–17 years). Endocrine, autonomic, and psychological stress parameters (cortisol, alpha-amylase, heart rate, heart rate variability, mood) were examined in 73 adolescents (46 female, 27 male; M_age = 13.86, SD_age = 1.87). Significant group differences were found in heart rate variability, with higher values in the low frequency band and low-to-high frequency ratio for the HCE condition, possibly indicating improved physiological functions through the stimulation of vagal tone and baroreflex. The use of a general breathing technique (natural and app-guided) also resulted in stronger relaxation reactions in cortisol when controlling for the previous stronger stress reactivity. On the other hand, app-guided slow breathing without a long training may be experienced as more uncomfortable during relaxation. The integration of breathing exercises in health apps for adolescents appears to be useful, offering a helpful and low-threshold coping/relaxation strategy during acute stress situations. Further studies should examine the benefits of app-guided breathing exercises in both psychiatric samples and the general population across a wide age range.

Posttraumatic stress disorder (PTSD) is a pervasive issue within military populations, with approximately 29 % of post-9/11 service members experience PTSD at some point in their lifetime. One potentially important factor in PTSD development and treatment response is dysregulation of the stress response system stemming from exposure to multiple traumas and sustained operational stress associated with military training and deployment. In particular, the end-product of the hypothalamic-pituitary-adrenal (HPA) axis, cortisol, is of particular interest to researchers examining physiological stress response in the context of mental health. Research exploring cortisol has been ongoing for decades, both to further understand its pathways and mechanisms, and to develop potential novel PTSD treatments. This paper provides a narrative review of some of the published literature examining cortisol’s role in PTSD as a potential factor in development, maintenance, and treatment augmentation, with emphasis on military populations. The results of this review highlight the importance of exploring alterations to the stress response system, and cortisol in particular, for the evaluation and treatment of PTSD in the military, the need for more comprehensive work towards understanding development of these alterations through military training and service, and its impact on long-term PTSD outcomes.

The social functions of oxytocin are diverse, and the specific aspects of information processing involved in emotional contagion remain unclear. We compared some fear-related behaviors among oxytocin receptor knockout mice and oxytocin-receptor-reduced mice with that of wild-type mice. In the observational fear assay, which reflects fear emotional contagion, mice that observed other individuals receiving electric shocks exhibited vicarious freezing. Mice with reduced or knockout oxytocin receptor expression showed reduced vicarious freezing. In the emotional discrimination assay, which reflects the ability to perceive others’ emotional cues, we compared approach and scent-sniffing behaviors toward fear and emotionally neutral individuals. While wild-type mice were able to detect the fear emotion of others, mice with reduced or knocked-out oxytocin receptors showed reduced discrimination ability. In the fear behavior assays, which do not present social cues, we did not find these differences in oxytocin receptor expression in the brain. These findings indicate that oxytocin plays a role in emotional contagion by perceiving the emotions of others.

Background

Depression is a multifaceted disorder that represents one of the most common causes of disability. The risk for developing depression is increased in women and among individuals with chronic diseases. For example, individuals in the United States with diabetes mellitus (DM) are at a twofold increased risk of developing depression compared to the general population and approximately one-quarter of women with diabetes have comorbid depression. The neurobiological mechanisms underlying this association between diabetes and depression is not fully understood and is particularly under-investigated in female models. We sought to explore the role of neuroinflammation in diabetes-induced depression in a female mouse model of hyperglycemia.

Methods

To this end, we utilized female C57BL/6 J mice to (1) characterize the depressive-like symptoms in response to 75 mg/kg/day dose of streptozotocin (STZ) over 5 days, a dose reported to induce hyperglycemia in female mice (n=20), (2) determine if female hyperglycemic mice are sensitized to unpredictable chronic mild stress (UCMS)-induced depressive-like behavior and neuroinflammation (n=28), and (3) investigate if female hyperglycemic mice are primed to respond to a subthreshold dose of lipopolysaccharide (LPS), an acute inflammatory challenge (n=21).

Results

Our results demonstrate that female mice exhibit robust hyperglycemia but limited evidence of depressive-like behavior in response to 75 mg/kg STZ. Additionally, we observe that healthy female mice have limited response to our stress protocol; however, hyperglycemic mice display increased stress-sensitivity as indicated by increased immobility in the forced swim test. While STZ mice show evidence of mild neuroinflammation, this effect was blunted by stress. Further, STZ mice failed to display a sensitization to inflammation-induced depressive-like behavior.

Conclusion

We interpret this data to indicate that while STZ-induced hyperglycemia does increase vulnerability to stress-induced depressive-like behavior, this effect is not a consequence of neuroinflammatory priming. Future studies will seek to better understand the mechanisms underlying this sensitization.

Stress is associated with increased vulnerability to psychosis, yet the mechanisms that contribute to these effects are poorly understood. Substantial literature has linked reduced hippocampal volume to both psychosis risk and early life stress. However, less work has explored the direct and indirect effects of stress on psychosis through the hippocampus in preclinical samples- when vulnerability for psychosis is accumulating. The current paper leverages the Adolescent Brain Cognitive Development (ABCD) Study sample to examine whether objective psychosocial stressors, specifically adverse childhood experiences (ACE), are linked to vulnerability for psychosis, measured by psychotic-like experiences (PLE) severity, in late childhood and early adolescence, both directly and indirectly through the deleterious effects of stress on the hippocampus. Baseline data from 11,728 individuals included previously examined and validated items to assess ACE exposure, hippocampal volume, and PLE severity – a developmentally appropriate metric of risk for psychosis. Objective psychosocial stress exposure in childhood was associated with elevated PLE severity during the transition from childhood to adolescence. Hippocampal volume was significantly reduced in individuals with greater PLE severity and greater childhood stress exposure compared to peers with low symptoms or low stress exposure. These findings are consistent with a hippocampal vulnerability model of psychosis risk. Stress exposure may cumulatively impact hippocampal volume and may also reflect a direct pathway of psychosis risk. Objective psychosocial stress should be considered as a treatment target that may impact neurodevelopment and psychosis risk.