Chronic Stress最新文献

Background: Posttraumatic stress disorder (PTSD) is a significant burden among combat Veterans returning from the wars in Iraq and Afghanistan. While empirically supported treatments have demonstrated reductions in PTSD symptomatology, there remains a need to improve treatment effectiveness. Functional magnetic resonance imaging (fMRI) neurofeedback has emerged as a possible treatment to ameliorate PTSD symptom severity. Virtual reality (VR) approaches have also shown promise in increasing treatment compliance and outcomes. To facilitate fMRI neurofeedback-associated therapies, it would be advantageous to accurately classify internal brain stress levels while Veterans are exposed to trauma-associated VR imagery. Methods: Across 2 sessions, we used fMRI to collect neural responses to trauma-associated VR-like stimuli among male combat Veterans with PTSD symptoms (N = 8). Veterans reported their self-perceived stress level on a scale from 1 to 8 every 15 s throughout the fMRI sessions. In our proposed framework, we precisely sample the fMRI data on cortical gray matter, blurring the data along the gray-matter manifold to reduce noise and dimensionality while preserving maximum neural information. Then, we independently applied 3 machine learning (ML) algorithms to this fMRI data collected across 2 sessions, separately for each Veteran, to build individualized ML models that predicted their internal brain states (self-reported stress responses). Results: We accurately classified the 8-class self-reported stress responses with a mean (± standard error) root mean square error of 0.6 (± 0.1) across all Veterans using the best ML approach. Conclusions: The findings demonstrate the predictive ability of ML algorithms applied to whole-brain cortical fMRI data collected during individual Veteran sessions. The framework we have developed to preprocess whole-brain cortical fMRI data and train ML models across sessions would provide a valuable tool to enable individualized real-time fMRI neurofeedback during VR-like exposure therapy for PTSD.

For many marginalized people, coping with discrimination is not a temporary condition. Rather it is endemic to living in a discriminatory society and a source of ongoing stress. In this paper, we explore the need to provide people struggling to cope with the skills to tackle not just the personal consequences of discrimination, but also to understand and address the root causes of their pain, and specifically the ones that lie outside of themselves. We propose using the concept of social capital to bring greater awareness among clients, clinicians, and society in general about the need to pair the treatment of personal distress with concurrent practices to understand and tackle larger systemic issues impacting their mental health. People with marginalized identities are often expected to find ways to cope with oppression and then sent back into a broken world, perhaps with stronger coping skills, but often ones which do not address the root cause or source of the pain, which is social injustice. We propose that it is therapeutically important to problematize, pathologize and address the systems and narratives that discriminate and cause people to need to cope, instead of focusing therapeutic interventions only on the internal resources of the person doing the coping.

Suicidal ideation and behavior are among the most severe psychiatric presentations, warranting emergency room visits and psychiatric admission for higher levels of care. In the United States, suicide rates continue to climb, especially in younger patients, and the continued psychosocial stressors of the COVID-19 pandemic may further exacerbate this crisis. Suicidal ideation and behavior are core features of a major depressive episode, but there are limited treatment options to rapidly redress these life-threatening symptoms. Racemic ketamine and its S-enantiomer, esketamine, are N-methyl-D-aspartate receptor antagonists and glutamate modulators that have robust antidepressant efficacy in treatment-resistant major depressive disorder and bipolar depression. Additionally, both ketamine and esketamine have demonstrated rapid-acting antisuicidal efficacy in major mood disorders. In August 2020, this culminated in a first-in-class approval of Spravato® (intranasal esketamine) for the treatment of major depressive disorder with acute suicidal ideation and behavior. In this article, we review the literature in support of the antisuicidal efficacy of ketamine and esketamine.

A stressor-related disorder wherein traumatic experience precipitates protracted disruptions to mood and cognition, post-traumatic stress disorder (PTSD) is associated with wide-ranging abnormalities across the body. While various methods have investigated these deviations, only proton magnetic resonance spectroscopy (¹H MRS) enables noninvasive measurement of small-molecule metabolites in the living human. ¹H MRS has correspondingly been employed to test hypotheses about the composition and function of multiple brain regions putatively involved in PTSD. Here we systematically review methodological considerations and reported findings, both positive and negative, of the current ¹H-MRS literature in PTSD (N = 32 studies) to communicate the brain regional metabolite alterations heretofore observed, providing random-effects model meta-analyses for those most extensively studied. Our review suggests significant PTSD-associated decreases in N-acetyl aspartate in bilateral hippocampus and anterior cingulate cortex with less evident effect in other metabolites and regions. Model heterogeneities diverged widely by analysis (I² < 0.01% to 90.1%) and suggested regional dependence on quantification reference (creatine or otherwise). While observed variabilities in methods and reported findings suggest that ¹H-MRS explorations of PTSD could benefit from methodological standardization, informing this standardization by quantitative assessment of the existing literature is currently hampered by its small size and limited scope.

Background: Most preclinical research on the effects of stress has been done on male subjects, even though women are more prone than men to experience stress-related problems. Chronic social defeat stress (CSDS) is a rodent model of psychosocial stress. However, this model has been challenged in female mouse studies since neither male nor female resident mice attack intruder females. A female-to-female CSDS model is needed to investigate the physiological and behavioral aspects.

Methods: The intruders were either male or female C57BL/6J mice, whereas the residents were male or ovariectomized (OVX) female CD-1 mice. The CD-1 aggressor mice had direct physical contact with the C57BL/6J mice for 10 min before initiating sensory contact with them for 24 h. Jump escape and freezing were evaluated during the social defeat of days 1 and 12. Experimental C57BL/6J mice underwent a social interaction test after suffering social defeat for 12 days.

Results: We found that the number of attack bites and attack latency had a significant negative correlation during the selection of aggressors. In the single-housed OVX mice, 34% of mice met the criterion of the selection of aggressors. However, single-housed OVX mice did not show sustained aggressive behavior (eg, attack bites) through the 12-day CSDS. As a result, we did not find susceptible mice during the social interaction test. In contrast, during the selection of aggressors, 42% of OVX mice housed with partners satisfied the criterion and displayed consistently aggressive behavior. CSDS produced susceptible (50%) and resilient (50%) phenotypes during the social interaction test. Notably, male and OVX female CD-1 mice housed with partners had similar amounts of attack bites and attack rates over the 12-day CSDS. Finally, we found that chronically socially defeated male and female mice displayed different coping behaviors (eg, active vs passive) with social defeat.

Conclusions: Our study demonstrates that OVX CD-1 mice housed with mates exhibited territorial aggression toward female intruders, producing susceptibility and resilience to social avoidance. Additionally, socially defeated male and female mice displayed different behavioral susceptibility to social defeat.

Background: Stress and cortisol dysregulation are linked to NCDs. Moreover, stress favours unhealthy lifestyle patterns, which increase the risk for NCDs. The role of the Cortisol Awakening Response (CAR) and the effect of lifestyle interventions on the same remain unclear. Methods: The impact of the intensive 8-week phase of the Healthy Lifestyle Community Programme (HLCP, cohort 1) on parameters of the CAR, ie cortisol values 0 (sample [S]1), 30), 45 and 60 minutes post-awakening, average peak, S1-peak delta and area under the increase curve (AUC_I), and perceived stress levels (PSL) was evaluated in a non-randomized, controlled trial. Covariates of the CAR (eg sleep measures) and irregularities in sampling were assessed. The intervention focussed on stress management, a healthy diet, regular exercise, and social support. Participants were recruited from the general population. Multiple linear regression analyses were conducted. Results: 97 participants (age: 56 ± 10 years; 71% female), with 68 in the intervention group (IG; age: 55 ± 8, 77% female) and 29 participants in the control group (CG; age: 59 ± 12, 59% female), were included in the analysis. The baseline characteristics of both groups were comparable, except participants of IG were younger. On average, the PSL at baseline was low in both groups (IG: 9.7 ± 5.4 points; CG: 8.5 ± 6.9 points; p = .165), but 22% (n = 15) in the IG and 20% (n = 6) in the CG reported a high PSL. Most participants reported irregularities in CAR sampling, eg interruption of sleep (IG: 80% CG: 81%). After 8 weeks, most CAR parameters and the PSL decreased in the IG and CG, resulting in no differences of change between the groups. In the IG only, a decrease of PSL was linked to an increase of CAR parameters, eg AUC_I (correlation coefficient = -0.307; p = .017). Conclusion: The HLCP may potentially reduce PSL and change the CAR, but results cannot be clearly attributed to the programme. Methodological challenges and multiple confounders, limit suitability of the CAR in the context of lifestyle interventions. Other measures (eg hair-cortisol) may give further insights. Trial registration: German Clinical Trials Register (DRKS); DRKS00018821; www.drks.de.

Background: Individuals who report sexual identity-uncertainty are at-risk for heavy alcohol consumption and alcohol use disorder symptomology. The current study examined the impact of states of aversive self-focus on subsequent consumption of ostensibly alcohol-containing beverages among a sample of women in early adulthood with varying levels of sexual identity-uncertainty (N = 75).

Methods: Utilizing a 2 (self-focus: negative vs. neutral) × 2 (attribution for any psychological discomfort: external vs. none given) between-subjects design with 3 within-person assessments of salivary cortisol, both a moderation model and mixed-effects general linear model were tested.

Results: States of aversive self-focus caused increases in overall consumption among women higher in sexual identity-uncertainty. Findings suggested consumption of ostensibly alcohol-containing beverages was more likely among women higher in sexual identity-uncertainty who also reported consuming beverages to cope with distress. Among women who reported higher levels of sexual identity-uncertainty and drinking-to-cope motives, salivary cortisol concentrations dampened more quickly over time, as they supposedly consumed alcohol.

Conclusion: Findings demonstrate that, among women reporting sexual identity-uncertainty who are motivated to consume alcohol to forget about troubles or worries, situations which evoke states of aversive self-focus may contribute to differences in alcohol consumption in early adulthood.

Background: A robust literature supports the role of the metabotropic glutamate receptor type 5 (mGluR5) in cognitive functioning. mGluR5 is also implicated in the pathophysiology of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD), which are characterized by cognitive alterations. However, the relationship between mGluR5 and cognition in MDD and PTSD has not yet been directly investigated. To address this gap, we examined the relationship between in vivo mGluR5 availability and cognition in PTSD, MDD, and matched healthy adults (HA).

Methods: Individuals with PTSD (N = 28) and MDD (N = 21), and HA (N = 28) were matched for age, gender, and smoking status. Participants completed ¹⁸F-FPEB positron emission tomography (PET) scan, psychiatric and cognitive assessments.

Results: Across models examining the relationship between mGluR5 availability and different domains of cognition across diagnostic groups, only the interaction of diagnosis*attention was significant (F _4,64 = 3.011, P = .024). Higher mGluR5 availability was associated with poorer attention in PTSD in 4 frontolimbic regions of interests (ROI's: OFC (r = -.441, P = .016), vmPFC (r = -.408, P = .028), dlPFC (r = -.421, P = .023), hippocampus (r = -.422, P = .025). By contrast, mGluR5 availability in the MDD group was positively related to Attention (ATTN) in the OFC (r = .590, P = .006), vmPFC (r = .653, P = .002), and dlPFC (r = .620, P = .004). Findings in the hippocampus for MDD followed the same pattern but did not survive correction for multiple comparisons (r = .480, P = .036). ATTN and mGluR5 availability were not significantly related in the HA group. Of note, in MANOVA analyses group*ATTN interaction results in the OFC did not survive multiple comparisons (P = .046). All other findings survived correction for multiple comparisons and remained significant when covarying for potential confounds (eg, depressed mood).

Conclusions: We observed a significant relationship between frontolimbic mGluR5 availability and performance on tests of attention in individuals with MDD and PTSD. This finding aligns with animal work showing dysregulation in mGluR5 in cognitive functioning, and differed as a function of diagnosis. Results suggest interventions targeting mGluR5 may help bolster cognitive difficulties, highlighting the importance of employing different mGluR5 directed treatment strategies in MDD and PTSD.

Preliminary evidence supports the use of psychedelics for major depressive disorder (MDD). However, less attention has been given to the neural mechanisms behind their effects. We conducted a systematic review examining the neuroimaging correlates of antidepressant response following psychedelic interventions for MDD. Through MEDLINE, Embase, and APA PsycINFO, 187 records were identified and 42 articles were screened. Six published studies and one conference abstract were included. Five ongoing trials were included from subjective outcomesTrials.gov. Our search covered several psychedelics, though included studies were specific to psilocybin, ayahuasca, and lysergic acid diethylamide. Three psilocybin studies noted amygdala activity and functional connectivity (FC) alterations that correlated with treatment response. Two psilocybin studies reported that FC changes in the medial and ventromedial prefrontal cortices correlated with treatment response. Two trials from a single study reported global decreases in brain network modularity which correlated with antidepressant response. One ayahuasca study reported increased activity in the limbic regions following treatment. Preliminary evidence suggests that the default mode and limbic networks may be a target for future research on the neural mechanisms of psychedelics. More data is required to corroborate these initial findings as the evidence summarized in this review is based on four datasets.

Background: Many of the conditions of the COVID-19 pandemic were consistent with factors shown to be predictive of parental stress and burnout. The purpose of the current study was to use a retrospective pretest method to gain an understanding of the effects of the COVID-19 pandemic on levels of parental burnout and on parenting practices.

Method: A brief survey was conducted using a retrospective pretest method to examine parental burnout (The Parental Burnout Assessment, Roskam et al, 2018) and parenting practices (The Alabama Parenting Questionnaire, Frick, 1991). The survey asked parent participants to answer questions about their experiences before and during the pandemic.

Results: Findings indicated that the pandemic had a significant impact on parents, increasing overall levels of parental burnout and impacting parenting practices by reducing use of positive parenting strategies and increasing use of inconsistent discipline and corporal punishment. These changes in parenting practices were even more pronounced for parents whose levels of parental burnout moved from "normal" levels before the pandemic to clinical levels during the pandemic.

Conclusion: The findings of the current study suggest that the COVID-19 pandemic has had a negative impact on levels of parental burnout and parenting practices. Although additional research is needed, the results suggest that there is a need for clinicians to understand the effects that the pandemic may have had on parents and families with an understanding that families may be at ongoing risk despite a relaxation of COVID-19 restrictions.