Stress-induced Negative Affect Research Articles

Childhood adversity and acute stress vulnerability at adulthood: The mediating role of sleep

IntroductionNumerous preclinical and clinical studies established the contribution of childhood adversity to acute stress vulnerability at adulthood. Several different physiological, psychological and behavioral factors have been suggested as putative mediators of this association. Sleep, and more specifically sleep disruption, has emerged as one such promising candidate. First, adverse childhood experiences have been repeatedly associated with adult sleep disorders. Second, individuals that suffer from stress-related psychopathology at adulthood often exhibit sleep disturbances, to the extent that sleep difficulties are diagnostic criteria for many of these disorders. Third, inefficient sleep pre and post exposure to acute stress was shown to increase the likelihood for maladaptive outcome, potently by impairing critical processes that occur during sleep as arousal regulation and memory consolidation.ObjectivesTo date, very few studies integrated these independent lines of research. Also, previous studies mostly assessed sleep via self-reported diary or a single night measurement at laboratory settings. The current study aimed to provide a more ecological and continuous account for sleep patterns, and their putative associations with childhood adversity on the one hand and vulnerability to acute stress at adulthood on the other hand.MethodsNinety-six healthy adult female participants completed the well-established childhood trauma questionnaire (CTQ) before wearing a wearable sensor for seven consecutive days and nights while maintaining their regular life routine. Following that, participants all underwent an acute laboratory stress induction procedure while their psychological and endocrine responses were recorded at multiple time points throughout.ResultsSleep patterns fully mediated the association between childhood adversity and psychological response to acute stress at adulthood (Figure 1). Specifically, elevated levels of childhood trauma were associated with more variation in sleep duration across the recording period, which in turn was associated with higher stress-induced negative affect. Interestingly, this association did not emerge with respect to mean sleep time nor with stress-induced cortisol release.ConclusionsResults imply that childhood trauma may lead to irregular sleep patterns which in turn contribute to exaggerated emotional response to acute stress at adulthood. These findings support the mediating role of sleep in the link between childhood adversity and acute stress vulnerability at adulthood, and highlight sleep as a viable target for early or even preventive intervention.Disclosure of InterestNone Declared

Lifetime stressor exposure, eating expectancy, and acute social stress-related eating behavior: A pre-registered study of the emotional eating cycle

Eating behaviors in response to acute stressors are highly variable: whereas many individuals eat more following stressors, others eat less or show no change in food consumption. Understanding factors that predict individual differences in eating behaviors may help elucidate the psychosocial mechanisms underlying obesity, yet few experimental studies on this topic have been conducted to date. To address this issue, we conducted the present pre-registered study, where we investigated how lifetime stressor exposure moderates the extent to which eating expectancies enhance the learned association between stress-induced negative affect and snack intake. Participants were 44 women (30% non-White) between 18 and 50 years old (M = 27.9), with a mean body mass index of 25.6, who completed assessments of lifetime stressor exposure, eating behaviors, and eating expectancies (eating helps manage negative affect); in a subsequent visit, they were given snacks after an acute social stress task (TSST). The moderated moderation model (PROCESS model 3) yielded a significant three-way interaction. When eating expectancies were high, acute social stress-induced negative affect predicted greater M&M intake for women with very high total lifetime stressor exposure but less M&M intake for women with fewer lifetime stressors. These data thus highlight how lifetime stressor exposure interacts with eating expectancies and acute stress-induced negative affect to predict eating behavior. Replications in larger samples may help explain variability in stress-eating as well as how lifetime stressors contribute to obesity.

Self-beneficial belief updating as a coping mechanism for stress-induced negative affect

Being confronted with social-evaluative stress elicits a physiological and a psychological stress response. This calls for regulatory processes to manage negative affect and maintain self-related optimistic beliefs. The aim of the current study was to investigate the affect-regulating potential of self-related updating of ability beliefs after exposure to social-evaluative stress, in comparison to non-social physical stress or no stress. We assessed self-related belief updating using trial-by-trial performance feedback and described the updating behavior in a mechanistic way using computational modeling. We found that social-evaluative stress was accompanied by an increase in cortisol and negative affect which was related to a positive shift in self-related belief updating. This self-beneficial belief updating, which was absent after physical stress or control, was associated with a better recovery from stress-induced negative affect. This indicates that enhanced integration of positive self-related feedback can act as a coping strategy to deal with social-evaluative stress.

Cooperative synaptic and intrinsic plasticity in a disynaptic limbic circuit drive stress-induced anhedonia and passive coping in mice

Stress promotes negative affective states, which include anhedonia and passive coping. While these features are in part mediated by neuroadaptations in brain reward circuitry, a comprehensive framework of how stress-induced negative affect may be encoded within key nodes of this circuit is lacking. Here, we show in a mouse model for stress-induced anhedonia and passive coping that these phenomena are associated with increased synaptic strength of ventral hippocampus (VH) excitatory synapses onto D1 medium spiny neurons (D1-MSNs) in the nucleus accumbens medial shell (NAcmSh), and with lateral hypothalamus (LH)-projecting D1-MSN hyperexcitability mediated by decreased inwardly rectifying potassium channel (IRK) function. Stress-induced negative affective states are prevented by depotentiation of VH to NAcmSh synapses, restoring Kir2.1 function in D1R-MSNs, or disrupting co-participation of these synaptic and intrinsic adaptations in D1-MSNs. In conclusion, our data provide strong evidence for a disynaptic pathway controlling maladaptive emotional behavior.

Elevated Anandamide, Enhanced Recall of Fear Extinction, and Attenuated Stress Responses Following Inhibition of Fatty Acid Amide Hydrolase: A Randomized, Controlled Experimental Medicine Trial

BackgroundPosttraumatic stress disorder, an area of large unmet medical needs, is characterized by persistence of fear memories and maladaptive stress responses. In rodents, elevation of the endocannabinoid anandamide due to inhibition of fatty acid amide hydrolase (FAAH) facilitates fear extinction and protects against the anxiogenic effects of stress. We recently reported that elevated anandamide levels in people homozygous for a loss-of-function FAAH mutation are associated with a similar phenotype, suggesting a translational validity of the preclinical findings. MethodsIn this double-blind, placebo-controlled experimental medicine study, healthy adults were randomized to an FAAH inhibitor (PF-04457845, 4 mg orally, once daily; n = 16) or placebo (n = 29) for 10 days. On days 9 and 10, participants completed a task battery assessing psychophysiological indices of fear learning, stress reactivity, and stress-induced affective responses. ResultsFAAH inhibition produced a 10-fold increase in baseline anandamide. This was associated with potentiated recall of fear extinction memory when tested 24 hours after extinction training. FAAH inhibition also attenuated autonomic stress reactivity, assessed via electrodermal activity, and protected against stress-induced negative affect, measured via facial electromyography. ConclusionsOur data provide preliminary human evidence that FAAH inhibition can improve the recall of fear extinction memories and attenuate the anxiogenic effects of stress, in a direct translation of rodent findings. The beneficial effects of FAAH inhibition on fear extinction, as well as stress- and affect-related behaviors, provide a strong rationale for developing this drug class as a treatment for posttraumatic stress disorder.

Negative affect is associated with increased stress-eating for women with high perceived life stress

Perceived life stress (PLS) and cognitive restraint are associated with increased comfort food intake under stress and lead to weight gain and obesity, but the mechanisms by which they do so remain unclear. Stress and negative affect (NA) are associated with increased reward-driven comfort food intake as a means to ‘feel better’, particularly for individuals with higher PLS and cognitive restraint. Thus, we propose that PLS and cognitive restraint increase stress-eating by strengthening the relationship between stress-induced NA and comfort food intake. Upon comfort eating, individuals with higher PLS show greater reductions in the negative consequences of stress (e.g. NA). The rewarding effects of this ‘emotional relief’ may promote future stress-induced comfort eating, but this has yet to be examined. Thus, we investigate the pathways by which PLS or cognitive restraint increase snack intake under stress by proposing that 1) stress-induced NA is a stronger predictor of increased snack intake for women with greater PLS and cognitive restraint, and 2) greater PLS will be associated with greater reductions in NA upon snacking under stress (i.e. emotional relief). Forty-three healthy women were given snacks (chips, golden oreos, and M&Ms) to eat after a Trier Social Stress Test or rest period on separate days in counterbalanced order. Following linear regression analyses, we determined that stress-induced NA predicted more snack intake for women with higher PLS, and that higher PLS was associated with heightened emotional relief upon snacking under stress. Future studies are needed to directly assess whether greater emotional relief following stress-eating reinforces the learned association between stress-induced NA and intake, and ultimately explains greater stress-eating and obesity in women with higher PLS. This work may lead clinicians to focus on NA in the treatment of obesity-and stress-related illnesses for women with higher PLS.

The cortisol:C-reactive protein ratio and negative affect reactivity in depressed adults.

We evaluated the effect of the cortisol (CORT) to high sensitivity C-reactive protein (hsCRP) ratio on stress-induced negative affect (NA) reactivity and whether the association was moderated by depressive symptom severity and gender. The CORT/CRP ratio was used to evaluate the integrity of the negative feedback loop between the hypothalamic-pituitary-adrenal axis and inflammatory response system. Basal CORT and hsCRP levels were measured in fasting blood samples from 198 medication-free and nonsmoking healthy men and women. Depressive symptom severity was assessed using the Hamilton Rating Scale for Depression (HAMD). NA ratings were collected at baseline and at the completion of the laboratory stressors, the Anger Recall Interview (ARI) and reading. Adjusting for potential confounders and baseline NA, analysis revealed a significant relationship between CORT/CRP ratio and NA reactivity to ARI as a function of depressive symptom severity. Simple effects revealed that for participants with high HAMD, decreasing CORT/CRP ratio, suggestive of an insufficient CORT release relative to higher hsCRP, predicted increasing stress-induced NA reactivity. For participants with low HAMD, the CORT/CRP ratio failed to predict NA reactivity. Gender did not moderate the joint effect of depressive symptom severity and the CORT/CRP ratio on stress-induced NA reactivity. This is the first study to document that a premorbid dysregulation of the neuro-immune relationship, characterized by an insufficient release of CORT in conjunction with higher CRP, plays a role in stress sensitivity, and specifically NA reactivity, in individuals with elevated levels of depression symptoms. (PsycINFO Database Record

Abstract # 1718 Neuro-immune dysregulation and depressive vulnerability: The Cortisol:C-reactive protein ratio predicts context-dependent negative affect reactivity in men and women with elevated symptoms of depression

We evaluated the predictive effects of the cortisol (CORT) to high sensitivity C-reactive protein (CRP) ratio on stress-induced negative affect (NA) reactivity and whether this association was moderated by depressive symptom severity. Fasting blood samples were collected between 0845 and 0915 and assayed for CORT and CRP in 198 medication-free healthy adults with no history of major depressive disorder (MDD). Depressive symptoms were assessed using the Hamilton Depression (HAMD). NA ratings were collected at baseline and at the completion of two laboratory stressors, a reading task and the Anger Recall Interview (ARI). Adjusting for age, gender, race, and baseline NA, severity of depressive symptoms moderated the relation of CORT/CRP ratio to NA reactivity to ARI ( b = −2.25, p =.03) but not reading. For participants with elevated symptoms of depression, decreasing CORT/CRP ratio ( b = −2.65, p

The Influence of Varied Levels of Received Stress and Support on Negative Emotions and Support Perceptions

The present study assessed the influence of experimentally varied levels of stress and support (received stress and support) on stress-induced negative affect and support perceptions (perceived support). Participants were exposed to either a high or a low level of stress and either received or did not receive support during the experimental session. The results indicated that regardless of the amount of support received, participants exposed to high versus low level of stress reported significantly more stress-induced negative affect. Perceived support, on the other hand, was a function of the interaction between the amount of stress and support received during the experimental task. Under a low level of stress, participants’ support perception remained moderate regardless of the amount of actual support they received; whereas under a high level of stress, participants’ support perception was significantly lower among those who did not receive support compared to those who did. Exploratory analyses indicated that experimentally-induced stress and support predicted negative affect and support judgments above and beyond the influence of individual characteristics (i.e., global self-esteem and dispositional optimism). Taken together, the results suggest that negative emotions were directly influenced by the degree of stress experienced, however the relationship between received and perceived support was moderated by the magnitude of experimentally-induced stress.

A prospective study of stress and alcohol craving in heavy drinkers

Recent work has examined the relationship between stress and relapse to alcohol use in clinical populations. Few prospective studies, however, have examined stress as a precipitant of alcohol problems. The present study is a longitudinal examination of the role of stress reactivity and alcohol craving in the etiology of alcohol problems in a sample of 41 (mean age=20.8), heavy-drinking, young adults. Participants completed a guided imagery exposure to stressful life events, followed by exposure to a neutral imagery control. Following the exposure, participants completed an alcohol cue exposure paradigm. Measures of negative mood (Profile of Mood States (POMS) depression/dejection scale), tension (POMS tension/anxiety scale) and alcohol craving (measured by the Alcohol Urge Questionnaire (AUQ)) were used as indicators of reactivity to stress and to alcohol cues. Polymorphisms of the corticotropin-releasing hormone binding protein (CRH-BP) gene and of the μ-opioid receptor (OPRM1) gene were examined as moderators of this relationship. Results revealed that stress-induced negative mood predicted negative consequences of drinking (scores on the Drinker's Inventory of Consequences (DrInC-2R)), whereas stress and cue-induced alcohol craving did not predict alcohol use or problems. Additionally, the CRH-BP genotype was found to moderate the relationship between stress-induced negative affect and the negative consequences of drinking. The current study supports and extends laboratory research describing phenotypes of stress-induced alcohol craving.

Menstrual cycle‐related changes in amygdala morphology are associated with changes in stress sensitivity

Premenstrual increases in negative mood are thought to arise from changes in gonadal hormone levels, presumably by influencing mood regulation and stress sensitivity. The amygdala plays a major role in this context, and animal studies suggest that gonadal hormones influence its morphology. Here, we investigated whether amygdala morphology changes over the menstrual cycle and whether this change explains differences in stress sensitivity. Twenty-eight young healthy women were investigated once during the premenstrual phase and once during the late follicular phase. T1-weighted anatomical images of the brain were acquired using magnetic resonance imaging and analyzed with optimized voxel-based morphometry. To measure mood regulation and stress sensitivity, negative affect was assessed after viewing strongly aversive as well as neutral movie clips. Our results show increased gray matter volume in the dorsal part of the left amygdala during the premenstrual phase when compared with the late follicular phase. This volume increase was positively correlated with the premenstrual increase in stress-induced negative affect. This is the first study showing structural plasticity of the amygdala in humans at the macroscopic level that is associated with both endogenous gonadal hormone fluctuations and stress sensitivity. These results correspond with animal findings of gonadal hormone-mediated neural plasticity in the amygdala and have implications for understanding the pathogenesis of specific mood disorders associated with hormonal fluctuations.

The psychology of psychiatric genetics: Evidence that positive emotions in females moderate genetic sensitivity to social stress associated with the BDNF Val⁶⁶Met polymorphism.

Previous work indicated protective effects of positive emotions on genetically influenced stress sensitivity. Given the fact that expression of brain-derived-neurotrophic-factor (BDNF) is associated with stress-induced behavioral changes, it was hypothesized that the BDNF Val-sup-6-sup-6Met genotype may mediate genetic effects on stress sensitivity, conditional on the level of concurrent positive emotions. Subjects (n=446) participated in a momentary assessment study, collecting appraisals of stress and affect in the flow of daily life. Multilevel regression analyses examined moderation of daily life stress-induced negative affect (NA) by BDNF genotype, and to what degree this was conditional on concurrent positive emotions. Results showed that heterozygous BDNF "Met" carriers exhibited an increased NA response to social stress compared with "Val/Val" subjects. Positive emotions at the time of the stressor decreased BDNF genetic moderation of the NA response to social stress in a dose-response fashion. This effect was most pronounced in BDNF Met carriers. Thus, the impact of BDNF genotype on stress sensitivity is conditional on the experience of positive emotions. Interdisciplinary research in psychology and psychiatric genetics may lead to the improvement of treatment choices in stress-related disorders.

Genetic risk of depression and stress-induced negative affect in daily life

A bias to develop negative affect in response to daily life stressors may be an important depression endophenotype, but remains difficult to assess. To assess this mood bias endophenotype, uncontaminated by current mood, in the course of daily life. The experience sampling method was used to collect multiple appraisals of daily life event-related stress and negative affect in 279 female twin pairs. Cross-twin, cross-trait associations between dailylife mood bias and DSM-IV depression were conducted. Probands whose co-twins were diagnosed with lifetime depression showed a stronger mood bias to stress than those with co-twins without such a diagnosis, independent of probands' current depressive symptoms and to a greater extent in monozygotic twins than in dizygotic twins. Genetic liability to depression is in part expressed as the tendency to display negative affect in response to minor stressors in daily life. This trait may represent a true depression endophenotype.

Conceptual framework for the etiology of alcoholism: a ?kindling?/stress hypothesis

The rationale for proposing the "kindling"/stress hypothesis is to provide a conceptual basis for the insidious development and maintenance of alcohol abuse. An objective of the hypothesis is to emphasize how continued alcohol abuse is linked to progressive neural adaptation. Work has shown that repeated withdrawals from chronic low levels of alcohol sensitize ("kindle") anxiety-like behavior ("anxiety") in rats, a finding consistent with multiple withdrawal kindling of seizure activity. Additionally, stress substitutes for initial cycles of the multiple withdrawal protocol to sensitize withdrawal-induced anxiety, which is indicative that stress is capable of facilitating neuroadaptive processes related to withdrawal. The persistence of adaptation caused by stress and multiple withdrawals is revealed by the appearance of withdrawal-induced anxiety following a future re-exposure to a single 5-day period of alcohol. This persisting adaptation also permits stress to induce anxiety during a period of abstinence--a response not observed in animals without previous exposure to alcohol. Furthermore, stress interacts with repeated withdrawals to enhance voluntary alcohol drinking. Results of other preclinical and clinical studies reported in the literature are integrated with these investigations in support of the proposed hypothesis. The "kindling"/stress hypothesis is based on the premise that repeated withdrawals from cycles of chronic alcohol exposure contribute to a progressive development of persisting adaptive change that sensitizes withdrawal-induced anxiety and allows stress to evoke symptoms associated with negative affect during abstinence. Thus, these consequences of repeated withdrawals account for the evolution of major characteristics of alcoholism, which include worsened acute withdrawal symptoms and increased stress-induced negative affect during abstinence, both of which enhance the likelihood of relapse--and with relapse an inability to limit an abusive pattern of alcohol intake. The "kindling"/stress hypothesis provides a clear strategy for future studies to explore the advancing neural adaptation proposed to contribute to the pathogenesis of alcoholism.