Chronic Stress最新文献

Background: Previous research showed acute psychedelic effects were associated with decreases in racial trauma (RT) symptoms among black, indigenous, and people of color (BIPOC). Among samples comprised primarily of white participants, positive outcomes of psychedelic experiences have been mediated by increases in psychological flexibility. Therefore, we examined whether changes in psychological flexibility from before to after a psychedelic experience mediated the relationship between acute psychedelic effects and changes in RT symptoms among BIPOC.

Methods: This cross-sectional online survey study included 313 BIPOC (mean age = 33.1; SD = 11.2; female = 57%). A multiple linear regression analysis was used to examine the association between acute psychedelic effects and decreases in RT symptoms in a nonclinical setting; a path analysis was used to explore whether changes in psychological flexibility mediated this relationship.

Results: Acute insight and challenging effects were significantly (p < .001) associated with decreases in RT symptoms following a psychedelic experience. Increases in psychological flexibility partially mediated relationships between greater intensity of psychological insight and less intensity of challenging experiences and decreases in RT symptoms (ps<.001).

Conclusion: This research suggests psychedelics confer potential benefits in decreasing RT symptoms among BIPOC and psychological flexibility may be an important mediator of these effects. Future research should test this hypothesis in a longitudinal clinical trial among BIPOC.

Background: Child maltreatment negatively affects the formation of internal schemata of self and other during development, leading to negative adaptations in self-concept and social cognition. Clinical reports suggest the efficacy of psychedelics in treating the psychopathological sequelae of child maltreatment. Altering maladaptive schemata of self and other implicated in negative self-concept and impaired social cognition may be a central mechanism for reducing posttraumatic stress symptoms.

Aims: This study aims to assess whether psychedelic use moderates the relationships between child maltreatment and self-concept, social cognition, and posttraumatic stress symptoms.

Method: An online survey was completed by 166 participants and included measures of maltreatment exposure and severity, history of intentional therapeutic psychedelic use, posttraumatic stress symptoms, internalized shame, and facial emotion recognition.

Results: Child maltreatment significantly correlated with posttraumatic stress symptoms (r = .26 and r = .20, p < .01) and internalized shame (r = .18, p < .05). Of all maltreatment subtypes, emotional abuse and neglect most strongly correlated with complex trauma symptoms (r = .32, p < .001) and internalized shame (r = .31, p < .001). Participants with a history of intentional therapeutic psychedelic use reported significantly lower complex trauma symptoms (d = 0.33, p < .05) and internalized shame (d = 0.35, p < .05) despite similar histories of maltreatment. Differences in complex trauma symptoms (d = 0.66, p < .01) and internalized shame (d = 0.80, p < .001) were largest for participants with a history of more than 5 occasions of intentional therapeutic psychedelic use. A history of more than 5 occasions of intentional therapeutic psychedelic use significantly moderated the relationship between emotional abuse and neglect and complex trauma symptoms (p < .01). No associations were found between maltreatment or psychedelic use and facial emotion recognition.

Conclusion: These findings demonstrate that using psychedelic drugs with therapeutic intent is associated with lower levels of complex trauma symptoms and internalized shame in individuals with histories of child maltreatment. Psychedelic use may have therapeutic benefit in treating the posttraumatic sequelae of child maltreatment.

Background: Autonomic dysregulation may lead to blunted sympathetic reactivity in chronic pain states. Autonomic responses are controlled by the central autonomic network (CAN). Little research has examined sympathetic reactivity and associations with brain CAN structures in the presence of chronic pain; thus, the present study aims to investigate how chronic pain influences sympathetic reactivity and associations with CAN brain region volumes.

Methods: Sympathetic reactivity was measured as change in skin conductance level (ΔSCL) between a resting reference period and walking periods for typical and complex walking tasks (obstacle and dual-task). Participants included 31 people with (n = 19) and without (n = 12) chronic musculoskeletal pain. Structural 3 T MRI was used to determine gray matter volume associations with ΔSCL in regions of the CAN (i.e., brainstem, amygdala, insula, and anterior cingulate cortex).

Results: ΔSCL varied across walking tasks (main effect p = 0.036), with lower ΔSCL in chronic pain participants compared to controls across trials 2 and 3 under the obstacle walking condition. ΔSCL during typical walking was associated with multiple CAN gray matter volumes, including brainstem, bilateral insula, amygdala, and right caudal anterior cingulate cortex (p's < 0.05). The difference in ΔSCL from typical-to-obstacle walking were associated with volumes of the midbrain segment of the brainstem and anterior segment of the circular sulcus of the insula (p's < 0.05), with no other significant associations. The difference in ΔSCL from typical-to-dual task walking was associated with the bilateral caudal anterior cingulate cortex, and left rostral cingulate cortex (p's < 0.05).

Conclusions: Sympathetic reactivity is blunted during typical and complex walking tasks in persons with chronic pain. Additionally, blunted sympathetic reactivity is associated with CAN brain structure, with direction of association dependent on brain region. These results support the idea that chronic pain may negatively impact typical autonomic responses needed for walking performance via its potential impact on the brain.

Mood disorders represent a pressing public health issue and significant source of disability throughout the world. The classical monoamine hypothesis, while useful in developing improved understanding and clinical treatments, has not fully captured the complex nature underlying mood disorders. Despite these shortcomings, the monoamine hypothesis continues to dominate the conceptual framework when approaching mood disorders. However, recent advances in basic and clinical research have led to a greater appreciation for the role that amino acid neurotransmitters play in the pathophysiology of mood disorders and as potential targets for novel therapies. In this article we review progress of compounds that focus on these systems. We cover both glutamate-targeting drugs such as: esketamine, AVP-786, REL-1017, AXS-05, rapastinel (GLYX-13), AV-101, NRX-101; as well as GABA-targeting drugs such as: brexanolone (SAGE-547), ganaxolone, zuranolone (SAGE-217), and PRAX-114. We focus the review on phase-II and phase-III clinical trials and evaluate the extant data and progress of these compounds.

Major depressive disorder (MDD) is one of the leading causes of morbidity and all-cause mortality (including suicide) worldwide, and, unfortunately, first-line monoaminergic antidepressants and evidence-based psychotherapies are not effective for all patients. Subanesthetic doses of the N-methyl-D-aspartate receptor antagonists and glutamate modulators ketamine and S-ketamine have rapid and robust antidepressant efficacy in such treatment-resistant depressed patients (TRD). Yet, as with all antidepressant treatments including electroconvulsive therapy (ECT), not all TRD patients adequately respond, and we are presently unable to a priori predict who will respond or not respond to ketamine. Therefore, antidepressant treatment response biomarkers to ketamine have been a major focus of research for over a decade. In this article, we review the evidence in support of treatment response biomarkers, with a particular focus on genetics, functional magnetic resonance imaging, and neurophysiological studies, i.e. electroencephalography and magnetoencephalography. The studies outlined here lay the groundwork for replication and dissemination.

A cardinal feature of Post-traumatic stress-related disorder (PTSD) is a paradoxical memory alteration including both intrusive emotional hypermnesia and declarative/contextual amnesia. Most preclinical, but also numerous clinical, studies focus almost exclusively on the emotional hypermnesia aiming at suppressing this recurrent and highly debilitating symptom either by reducing fear and anxiety or with the ethically questionable idea of a rather radical erasure of traumatic memory. Of very mixed efficacy, often associated with a resurgence of symptoms after a while, these approaches focus on PTSD-related symptom while neglecting the potential cause of this symptom: traumatic amnesia. Two of our preclinical studies have recently demonstrated that treating contextual amnesia durably prevents, and even treats, PTSD-related hypermnesia. Specifically, promoting the contextual memory of the trauma, either by a cognitivo-behavioral, optogenetic or pharmacological approach enhancing a hippocampus-dependent memory processing of the trauma normalizes the fear memory by inducing a long-lasting suppression of the erratic traumatic hypermnesia.

Background: Accumulating evidence implicates the endocannabinoid system, including variants in the cannabinoid-1 receptor gene (CNR1), in the pathophysiology of posttraumatic stress disorder (PTSD). The synonymous G1359A variant (rs1049353) in the CNR1 gene has been linked to PTSD in individuals exposed to childhood abuse. In this study, the effects of the rs1049353 genotype and childhood abuse on overall PTSD symptoms, as well as PTSD symptom clusters were examined in order to examine how this interaction relates to the phenotypic expression of this disorder.

Method: Data were analyzed from 1,372 Caucasian U.S. veterans who participated in the National Health and Resilience in Veterans Study. Multivariable analyses were conducted to evaluate the association between rs1049353 genotype, childhood abuse, and their interaction in relation to PTSD symptoms.

Results: A significant interaction between rs1049353 genotype and childhood abuse was observed, with A allele carriers with histories of childhood abuse reporting greater severity of PTSD symptoms, most notably anxious arousal, relative to G/G homozygotes. Significant main effects of childhood abuse on overall PTSD symptoms, and re-experiencing, emotional numbing, and dysphoric arousal symptom clusters, as well as of A allele carrier status on anxious arousal symptoms were observed.

Conclusions: Results of this study replicate prior work and suggest that the rs1049353-by-childhood abuse interaction is particularly associated with the manifestation of anxious arousal symptoms of PTSD. Taken together, these findings underscore the importance of considering the phenotypic heterogeneity of PTSD in gene-environment studies of this multifaceted disorder.

Depression and anxiety disrupt daily function and their effects can be long-lasting and devastating, yet there are no established physiological indicators that can be used to predict onset, diagnose, or target treatments. In this review, we conceptualize depression and anxiety as maladaptive responses to repetitive stress. We provide an overview of the role of chronic stress in depression and anxiety and a review of current knowledge on objective stress indicators of depression and anxiety. We focused on cortisol, heart rate variability and skin conductance that have been well studied in depression and anxiety and implicated in clinical emotional states. A targeted PubMed search was undertaken prioritizing meta-analyses that have linked depression and anxiety to cortisol, heart rate variability and skin conductance. Consistent findings include reduced heart rate variability across depression and anxiety, reduced tonic and phasic skin conductance in depression, and elevated cortisol at different times of day and across the day in depression. We then provide a brief overview of neural circuit disruptions that characterize particular types of depression and anxiety. We also include an illustrative analysis using predictive models to determine how stress markers contribute to specific subgroups of symptoms and how neural circuits add meaningfully to this prediction. For this, we implemented a tree-based multi-class classification model with physiological markers of heart rate variability as predictors and four symptom subtypes, including normative mood, as target variables. We achieved 40% accuracy on the validation set. We then added the neural circuit measures into our predictor set to identify the combination of neural circuit dysfunctions and physiological markers that accurately predict each symptom subtype. Achieving 54% accuracy suggested a strong relationship between those neural-physiological predictors and the mental states that characterize each subtype. Further work to elucidate the complex relationships between physiological markers, neural circuit dysfunction and resulting symptoms would advance our understanding of the pathophysiological pathways underlying depression and anxiety.

Background: Prolonged intermittent theta-burst stimulation (piTBS) and repetitive transcranial magnetic stimulation (rTMS) are effective antidepressant interventions for major depressive disorder (MDD). Cognition-modulated frontal theta (frontalθ) activity had been identified to predict the antidepressant response to 10-Hz left prefrontal rTMS. However, whether this marker also predicts that of piTBS needs further investigation.

Methods: The present double-blind randomized trial recruited 105 patients with MDD who showed no response to at least one adequate antidepressant treatment in the current episode. The recruited patients were randomly assigned to one of three groups: group A received piTBS monotherapy; group B received rTMS monotherapy; and group C received sham stimulation. Before a 2-week acute treatment period, electroencephalopgraphy (EEG) and cognition-modulated frontal theta changes (Δfrontalθ) were measured. Depression scores were evaluated at baseline, 1 week, and 2 weeks after the initiation of treatment.

Results: The Δfrontalθ at baseline was significantly correlated with depression score changes at week 1 (r = -0.383, p = 0.025) and at week 2 for rTMS group (r = -0.419, p = 0.014), but not for the piTBS and sham groups. The area under the receiver operating characteristic curve for Δfrontalθ was 0.800 for the rTMS group (p = 0.003) and was 0.549 for the piTBS group (p = 0.619).

Conclusion: The predictive value of higher baseline Δfrontalθ for antidepressant efficacy for rTMS not only replicates previous results but also implies that the antidepressant responses to rTMS could be predicted reliably at baseline and both piTBS and rTMS could be effective through different neurobiological mechanisms.

Post-traumatic stress disorder (PTSD) is a highly prevalent disorder and a highly debilitating condition. Although anhedonia is an important construct of the disorder, the relationship between PTSD and reward functioning is still under-researched. To date, the majority of research on PTSD has focused on fear: fear learning, maintenance, and extinction. Here we review the relevant literature-including clinical observations, self-report data, neuroimaging research, and animal studies-in order to examine the potential effects of post-traumatic stress disorder on the reward system. Our current lack of sufficient insight into how trauma affects the reward system is one possible hindrance to clinical progress. The current review highlights the need for further investigation into the complex relationship between exposure to trauma and the reward system to further our understandings of the ethology of PTSD.