Prior Stress Exposure Research Articles

Stress-induced impairment of fear extinction recall is associated with changes in neuronal activity patterns in PVT

Treatment resistance of anxiety-related disorders often arises from an inappropriate fear expression, impairment in fear extinction, and spontaneous return of fear. Stress exposure is considered a high risk factor for neuropsychiatric disorders, but understanding of the long-term consequences of stress is limited, particularly when it comes to treatment outcome. Therefore, studying the consequences of acute stress would provide critical information on the role of stress in psychopathology. In the present study, we investigated the effect of acute immobilization stress on anxiety-like behavior and on conditioned fear memory. Our results demonstrate that prior stress exposure had no effect on anxiety-related behavior, fear acquisition, as well as fear extinction compared to non-stressed controls, but resulted in significantly higher rates of freezing during recall of extinction, indicating a consolidation failure. Further, immunohistochemical analysis of the expression of the immediate early gene c-Fos after recall of extinction revealed increased neuronal activity in the posterior paraventricular nucleus of the thalamus (PVT) in previously stressed animals compared to non-stressed controls. These results indicate, firstly, that acute stress affects long-term fear memory even after successful extinction training, and secondly, a strong involvement of the PVT in maladaptive fear responses induced by prior stress. Thus, stress-induced changes in PVT neuronal activity might be of importance for the pathophysiology of stress-sensitive anxiety-related psychiatric disorders, since exposure to an earlier acute stressor could counteract the success of therapy.

Sex- and stress-dependent effects of a single injection of ketamine on open field and forced swim behavior

Ketamine has emerged as a novel treatment for common psychiatric conditions such as Major Depressive Disorder (MDD) and anxiety disorders, many of which can be initiated and exacerbated by psychological stress. Sex differences in the frequency of both anxiety and depressive disorders are well known and could be due to sex differences in neuroendocrine responses to stress. Ketamine is known to modulate the hormonal response to stress, specifically corticosterone. It is not clear if the acute effect of ketamine on corticosterone differs by sex, or what role this could play in subsequent behavior. Here we test whether a single injection of (R,S)-ketamine (30 mg/kg, i.p.), administered either with or without unpredictable chronic stress (UCS), has different sustained effects on open field test (OFT), elevated zero maze (EZM) or forced swim test (FST) behavior in female versus male C57BL/6J mice. In the OFT (24 h post-injection), ketamine increased center square exploration in males but not females. In contrast, in the FST (72 h post-injection), females showed a trend toward a decrease in immobility after ketamine whereas males were not strongly modulated. These behavioral effects of ketamine were stronger in the presence of UCS than in unstressed animals. UCS animals also showed lower corticosterone after injection than unstressed animals, and in the presence of UCS ketamine increased corticosterone; these effects were similar in both sexes. Corticosterone post-injection did not predict subsequent behavior. These findings complement a growing preclinical literature suggesting both stress-dependency and sex differences in OFT and FST behavioral responses to ketamine. LAY SUMMARY In humans, it is known that major depression and anxiety disorders, which can be caused or made worse by exposure to psychological stress, occur roughly twice as frequently in women than in men, but the underpinnings of these effects are not well characterized. In the current study, we explored how sex interacts with stress and ketamine (a rapidly acting antidepressant) by assessing both open field and forced swim behavior in mice after chronic mild stress. We report the novel finding that male mice exhibit greater exploration of the aversive center square in the open field after ketamine, whereas females trended toward lower immobility (often interpreted as an antidepressant-like effect) in the forced swim test after this drug, and these effects were amplified by prior stress exposure.

Unexpected role of stress as a possible resilience mechanism upon mild traumatic brain injury (mTBI) in mice

IntroductionMild traumatic brain injury (mTBI) is common and associated with cognitive impairment. Stress and mTBI are known to modulate the neural function. The present study aims at exploring the effect of prior stress exposure on cognitive function following mTBI. MethodsEight weeks old male ICR mice were subjected to either stress induced by forced swimming stress alone, stress followed by an immediate mTBI, or stress followed by 30 min break and then mTBI. We had two control groups: SHAM group - a control group which was not exposed to stress nor to mTBI and control mTBI group - a control group which was exposed only to TBI with no stress. Mice were weighed prior and at 12, 24 h and 1 week following interventions. Motor evaluation was conducted by rotarod. Behavioral changes were evaluated using open field, Y maze, elevated plus maze and staircase tests, at 12 h and 1 week following interventions. Brain levels of NMDAR subunits (R1, R2A, R2B), GABABR1, glucocorticoid and mineralocorticoid receptors (GR, MR) were evaluated using western blot. ResultsStress alone, mTBI alone, and stress followed by immediate mTBI resulted in a significant weight loss compared to control (p < 0.05). Stress 30 min prior to mTBI had a protective effect on weight (p = 0.14 compared to control). The stress and mTBI alone groups showed reduced time at the center of the open field arena 1 week after intervention (p < 0.05 for both). Time in the novel arm of the Y maze was significantly shorter in the mTBI and stress followed by delayed mTBI (p = 0.02). Immediate stress prior to mTBI had normalized times in the novel arm (p = 0.95 compared to control). Combination of stress and mTBI significantly modified NMDAR subunits levels (increased NMDAR1, p < 0.008, decreased NMDAR2A p = 0.02) as well as increased MR levels (p = 0.04). ConclusionExposure to stress prior to mTBI may improve the cognitive consequences of mTBI. These data may point towards a novel, unexpected role of stress as a possible resilience mechanism in the setting of mTBI.

Chronic stress in adolescence differentially affects cocaine vulnerability in adulthood in a selectively bred rat model of individual differences: role of accumbal dopamine signaling

Stress during adolescence has profound effects on the onset and severity of substance use later in life. However, not everyone with adverse experiences during this period will go on to develop a substance use disorder in adulthood, and the factors that alter susceptibility to substance use remain unknown. Here, we investigated individual differences in response to stress and drugs of abuse using our selectively bred high-responder (bHR) and low-responder (bLR) rats. These animals model extremes of temperamental tendencies and differ dramatically in both stress responsiveness and addiction-related traits. The present study investigated how environmental interventions in the form of a chronic variable stress (CVS) regimen in early adolescence interact with the bHR/bLR phenotype to alter behavioral sensitization to cocaine in adulthood. We also determined whether accumbal dopamine signaling is involved in the interaction of stress history and cocaine by assessing the mRNA levels of dopamine D1 (D1R) and D2 (D2R) receptors. Our results showed that CVS history alone had enduring and phenotype-specific effects on accumbal dopamine signaling. Importantly, adolescent stress had opposing effects in the two lines- decreasing the locomotor response to cocaine challenge in bHRs but increasing this measure in bLRs. Moreover, these opposing effects on cocaine sensitivity following adolescent CVS were accompanied by parallel effects in the accumbal dopamine system, with prior stress and cocaine exposure interacting to decrease D2R mRNA in bHRs but increase it in bLRs. Overall, these findings indicate that environmental challenges encountered in adolescence interact with genetic background to alter vulnerability to cocaine later in life. Lay Summary Stress experienced during adolescence affects the onset and severity of drug dependence later in life. However, not everyone with adverse experiences during this period will go on to develop SUD in adulthood. Using a rat model of innate differences in emotional reactivity, this study shows that the interplay between individual temperament and previous experience of adolescent stress/trauma determines whether an individual will be vulnerable or resilient to develop SUDs later in life. In addition, the present study shows that the dopamine D2 receptor in the brain’s reward center, nucleus accumbens, may be implicated in this interplay.

The Moderating Role of Coping Style on Chronic Stress Exposure and Cardiovascular Reactivity Among African American Emerging Adults.

Chronic stress exposure may contribute to dysregulation of cardiovascular functions and increase CVD risk among African Americans. This study investigated the direct and interactive effects of chronic stress exposure and coping styles on cardiovascular reactivity to acute stress. A sample of African American emerging adults (n = 277) completed a battery of self-report assessments and underwent the Trier Social Stress Test (TSST) across two time points. Prior chronic stress exposure was negatively associated with heart rate (HR) reactivity among females at 1-month follow-up. Task-oriented coping was positively associated with HR reactivity, while avoidance-oriented coping showed a negative association. Higher use of emotion-oriented coping moderated the relationship between chronic stress exposure and HR reactivity, resulting in more robust reactivity. Among females, but not males, lower use of avoidance-oriented coping moderated the relationship between prior chronic stress exposure and HR reactivity, also resulting in more robust reactivity. Prior chronic stress exposure and the use of maladaptive coping strategies may confer negative impacts on cardiovascular reactivity, particularly among African American females. Using adaptive coping styles may mitigate these effects and improve cardiovascular reactivity. These findings provide preliminary support for psychosocial determinants of health within a controlled laboratory experiment and highlight important gender differences to consider in prevention efforts for African American cardiovascular health disparities.

Community rescue in experimental phytoplankton communities facing severe herbicide pollution.

Community rescue occurs when ecological or evolutionary processes restore positive growth in a highly stressful environment that was lethal to the community in its ancestral form, thus averting biomass collapse in a deteriorating environment. Laboratory evidence suggests that community rescue is most likely in high-biomass communities that have previously experienced moderate doses of sublethal stress. We assessed this result under more natural conditions, in a mesocosm experiment with phytoplankton communities exposed to the ubiquitous herbicide glyphosate. We tested whether community biomass and prior herbicide exposure would facilitate community rescue after severe contamination. We found that prior exposure to glyphosate was a very strong predictor of the rescue outcome, while high community biomass was not. Furthermore, although glyphosate had negative effects on diversity, it did not influence community composition significantly, suggesting a modest role for genus sorting in this rescue process. Our results expand the scope of community rescue theory to complex ecosystems and confirm that prior stress exposure is a key predictor of rescue.

Evidence for impaired extinction learning in humans after distal stress exposure.

Stressful or traumatic events can be risk factors for anxiety or trauma- and stressor-related disorders. In this regard, it has been shown that stress affects aversive learning and memory processes. In rodents, stress exposure 10days prior to fear acquisition impairs fear extinction. However, in humans the effect of distal stress on fear conditioning is sparse. Therefore, we examined the influence of distal stress on fear memory in humans in two studies. In Study 1, participants underwent either socially evaluated cold-pressor test (SECPT) or sham procedure 10days or 40min before a fear conditioning paradigm (four groups, N=78). In Study 2, context effects were examined by conducting SECPT and sham procedures 10days prior conditioning either in the later fear conditioning context or in another context (three groups, N=69). During acquisition phase, one geometrical shape (conditioned stimulus, CS+) was paired with painful electric shocks (unconditioned stimulus, US), but never a second shape (CS-). Extinction phase was identical to acquisition, but without US delivery. Importantly, for Study 1 these phases were conducted on one day, while for Study 2 on two separated days. Successful fear acquisition was indicated by aversive ratings and startle potentiation to CS+ versus CS- in both studies. Interestingly, participants stressed 10days earlier showed impaired extinction on the implicit level (startle potentiation to CS+ vs. CS-) in Study 1 and only in the acquisition context on the explicit level (aversive ratings for CS+ vs. CS-) in Study 2. In sum, distal stress may strengthen later acquired fear memories and thereby impair fear extinction. This finding could have clinical implications, showing that prior stress exposure sensitizes later aversive processing and impairs therapy.

Pattern of dopamine signaling during aversive events predicts active avoidance learning

Learning to avoid aversive outcomes is an adaptive strategy to limit one's future exposure to stressful events. However, there is considerable variance in active avoidance learning across a population. The mesolimbic dopamine system contributes to behaviors elicited by aversive stimuli, although it is unclear if the heterogeneity in active avoidance learning is explained by differences in dopamine transmission. Furthermore, it is not known how dopamine signals evolve throughout active avoidance learning. To address these questions, we performed voltammetry recordings of dopamine release in the ventral medial striatum throughout training on inescapable footshock and signaled active avoidance tasks. This approach revealed differences in the pattern of dopamine signaling during the aversive cue and the safety period that corresponded to subsequent task performance. Dopamine transmission throughout the footshock bout did not predict performance but rather was modulated by the prior stress exposure. Additionally, we demonstrate that dopamine encodes a safety prediction error signal, which illustrates that ventral medial striatal dopamine release conveys a learning signal during both appetitive and aversive conditions.

Cold treatment enhances low‐temperature flight performance in false codling moth, Thaumatotibia leucotreta (Lepidoptera: Tortricidae)

Abstract In sterile insect technique programmes, temperatures experienced by insects during rearing and handling, along with cool temperatures after release, can negatively affect performance and activity levels. Phenotypic plasticity (trait modifications caused by prior stress exposure) can offset these effects but is poorly understood in many species and traits. We investigated the effects of a cold treatment (2 °C for 16 h) on flight performance in adult false codling moth, Thaumatotibia leucotreta. Using diverse methods, flight performance was tested using flight assays in the laboratory and in the field under varying environmental conditions. The flight performance of T. leucotreta in the laboratory was affected by cold treatment (relative to a 25 °C control group), test temperature and their interaction. Field recapture of released moths was significantly affected by the interaction between cold treatment and environmental conditions. Field recapture counts depended on the ambient temperature upon release. For example, under warmer conditions (&gt;17 °C), the recapture count of cold‐treated moths was lower than that of the untreated control group, whereas the recapture count of cold‐treated moths at cooler temperatures was significantly higher. Our results suggest a temperature‐dependent interaction between acute cold exposure and flight performance in adult T. leucotreta, which may be used to enhance the efficacy of the sterile insect technique under cooler environmental conditions.

Effects of Trauma in Adulthood and Adolescence on Fear Extinction and Extinction Retention: Advancing Animal Models of Posttraumatic Stress Disorder.

Evidence for and against adolescent vulnerability to posttraumatic stress disorder (PTSD) is mounting, but this evidence is largely qualitative, retrospective, or complicated by variation in prior stress exposure and trauma context. Here, we examine the effects of development on trauma vulnerability using adult post-natal (PN) day 61, early adolescent (PN23) and mid adolescence (PN34) rats and two types of trauma: an established animal model of PTSD, single prolonged stress (SPS), and a novel composite model—SPS predation (SPSp) version. We demonstrate that early and mid adolescent rats are capable of fear conditioning and fear extinction, as well as extinction retention. Our results also demonstrate that both types of trauma induced a deficit in the retention of fear extinction in adulthood, a hallmark of PTSD, but not after early or mid adolescence trauma, suggesting that adolescence might convey resilience to SPS and SPSp traumas. Across all three life stages, the effects of SPS exposure and a novel predation trauma model, SPSp, had similar effects on behavior suggesting that trauma type did not affect the likelihood of developing PTSD-like symptoms, and that SPSp is a predation-based trauma model worth exploring.

Life stress as a risk factor for sustained anxiety and cortisol dysregulation during the first year of survivorship in ovarian cancer

Patients with ovarian cancer often report elevated anxiety at diagnosis that decreases posttreatment. However, a minority of patients experience sustained anxiety. Few studies have examined risk factors for persistent anxiety or its physiologic sequelae in ovarian cancer. Therefore, the authors investigated associations between prior life events, anxiety, inflammation (plasma levels of interleukin-6), and diurnal cortisol profiles in patients with ovarian cancer during the first year postdiagnosis. Participants (n = 337) completed surveys and had blood and salivary sampling prediagnosis, postchemotherapy (6 months), and 12 months after diagnosis. The Life Events and Difficulties Schedule was administered to a patient subset (n = 127) within 1 month of diagnosis. Linear mixed-effects models were used to analyze relations between anxiety and biologic variables over time. Linear regression models assessed whether anxiety trajectories mediated associations between prior stress exposure and biologic variables. Age, chemotherapy at 1 year, and cancer stage were covariates. Decreased anxiety was associated with a more normalized cortisol slope over time (β = 0.092; P = .047). Early life adversity was related to flatter cortisol slopes over time (β = -0.763; P = .002); this relation was partially mediated by anxiety trajectory (P = .046). More danger-related events prediagnosis were associated with sustained anxiety (β = 0.537; P = .019) and flatter cortisol slopes over time (β = -0.243; P = .047); anxiety partially mediated the relation between danger and cortisol slope (P = .037). Neither anxiety nor prior stress exposure was related to levels of interleukin-6. Because dysregulated cortisol has been related to fatigue, poorer quality of life, and shorter survival in patients with ovarian cancer, those who have prior life events and chronic anxiety during the first year postdiagnosis may be at risk for more negative outcomes. Cancer 2018. © 2018 American Cancer Society.

Effects of acute psychological stress on athletic performance in elite male swimmers.

While physical activity has been shown to affect psychological as well as physiological stress responses, less research has explored the effects of acute stress on athletic performance. The current study hence aimed to investigate the effect of an acute psychological stress (APS) provocation on performance and plasma lactate concentration during a following 200-m swim race among elite male swimmers. Furthermore, associations between physiological stress responses (salivary cortisol and testosterone), and outcome measures (speed and lactate) were explored. Twenty-three elite male swimmers participated in an experimental counterbalanced within-group repeated measures design consisting of an APS provocation followed by a 200-m race and, on a separate day, a control race without prior stress exposure. Salivary cortisol and testosterone were collected prior to each race. Race time was recorded, and serum lactate was collected immediately following, and five min after completed race. Race speed was significantly slower (1.53 [95% CI: 0.08-2.79] seconds) following the APS provocation than under control conditions. Prerace cortisol levels were positively associated with lactate response when preceding stress exposure was present (rho =0.483 immediately, and rho=0.429 five minutes post race, P<0.05). Under control conditions however, both increased testosterone (rho =-657, P=0.001) and cortisol (rho =-0.491, P=0.020) levels were associated with faster race times. The results indicated a negative impact of APS exposure on athletic performance. Further, potential beneficial effects on performance from physiological stress responses (as reflected by salivary cortisol and testosterone) may be diminished during performance following an APS provocation, compared with a regular non-provoked performance situation.

High Salt Intake Enhances Stress Coping Behaviors: Role for Vasopressin Signaling from PVN to Amygdala

Responsivity to an acute stressor can vary depending on prior or concurrent stress exposure. High dietary sodium chloride (salt) is an osmotic stressor that increases the risk and severity of multiple stress‐related disease modalities, notably hypertension. Given that Americans consume more than twice the recommended daily salt allowance, we explored the possibility that high salt intake could enhance responsivity to a psychogenic stress. Mice underwent chronic salt loading (SL) by drinking 4% saline for 1 week. SL increased serum osmolality (P&lt;0.01) and corticosterone (P&lt;0.01), suggesting osmotic dehydration activated the hypothalamic‐pituitary‐adrenal stress axis. To determine if osmotic stress enhances behavioral responsivity to a psychogenic stress, salt loaded mice underwent a forced swim test (FST) for five minutes. SL increased time swimming (P&lt;0.01) and time grooming thereafter (P&lt;0.01), indicating enhanced active stress coping or responsivity. Furthermore, SL enhanced FST induction of c‐Fos in the hypothalamic paraventricular nucleus (PVN) (P&lt;0.05) and the central (P&lt;0.05) and basolateral (P&lt;0.01) nuclei of the amygdala, which are synaptically connected and which modulate cardiovascular and behavioral responsivity to stress. Immunostaining for the stress‐related neuropeptide arginine vasopressin (VP) showed SL and FST each increased VP positive neurons in the PVN (P&lt;0.05, P&lt;0.05) with the greatest increase in mice exposed to both SL and FST stress (P&lt; 0.05). This observed neurochemical plasticity raises the intriguing possibility that future stressors could elicit exaggerated circuit activation and hence exaggerated behavioral and cardiovascular responses due to a greater available VP reservoir. Indeed, co‐labeling for c‐Fos/VP showed SL drove activation of PVN‐VP cells (P&lt;0.01). VP type 1 receptors (V1R) in the amygdala are a major synaptic target of PVN inputs, and nanoinjections of a V1R antagonist bilaterally into the amygdala attenuated the enhancing effect of SL on active coping (time spent mobile) in the FST. Of note, V1R antagonist reduced time spent mobile during the FST both in salt loaded and control mice (P&lt;0.05, P&lt;0.05). Data indicate that neuronal and behavioral responses to an acute psychogenic stressor is potentiated by high salt intake. This enhancing effect appears to involve activation of a PVN‐amygdala VPergic neural pathway. Ongoing retrograde labeling experiments will determine if SL and/or swim stress recruit and activate PVN‐VP neurons that project to the amygdala and to sympathoexcitatory regions including the rostroventral lateral medulla and spinal cord that drive sympathetic outflow in support of blood pressure. Future studies will utilize in situ hybridization to determine if recruitment of VP positive neurons occurs due to stress‐induced production of VP‐mRNA from VP output neurons. These data would provide mechanistic insight into how stress exposure sensitizes behavioral and cardiovascular responses to future heterotypic stressors.Support or Funding InformationSupport: NIH T32‐HL007446, and by HL088052 and AHA 25710176 (GMT)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Repeated Stress Exaggerates Lipopolysaccharide-Induced Inflammatory Response in the Rat Spleen.

Spleen is an immune organ innervated with sympathetic nerves which together with adrenomedullary system control splenic immune functions. However, the mechanism by which prior stress exposure modulates the immune response induced by immunogenic challenge is not sufficiently clarified. Thus, the aim of this study was to investigate the effect of asingle (2h) and repeated (2h daily for 7days) immobilization stress (IMO) on the innate immune response in the spleen induced by lipopolysaccharide (LPS, 100µg/kg). LPS elevated splenic levels of norepinephrine and epinephrine, while prior IMO prevented this response. LPS did not alter de novo production of catecholamines, however, prior IMO attenuated phenylethanolamine N-methyltransferase gene expression. Particularly repeated IMO exacerbated LPS-induced down-regulation of α1B- and β1-adrenergic receptors (ARs), while enhanced α2A- and β2-AR mRNAs. Elevated expression of inflammatory mediators (iNOS2, IL-1β, IL-6, TNF-α, IL-10) was observed following LPS and repeated IMO againpotentiated this effect. These changes were associated with enhanced Ly6C gene expression, a monocyte marker, and elevated MCP-1, GM-CSF, and CXCL1 mRNAs suggesting an increased recruitment of monocytes and neutrophils into the spleen. Additionally, we observed increased Bax/Bcl-1 mRNA ratio together with reduced B cell numbersin rats exposed to repeated IMOand treated with LPSbut not inacutely stressed rats. Altogether, these data indicate that repeated stress via changes in CA levels and specific α- and β-AR subtypes exaggerates the inflammatory response likely by recruiting peripheral monocytes and neutrophils to the spleen, resulting in the induction of apoptosis within this tissue, particularly in B cells. These changes may alter the splenic immune functions with potentially pathological consequences.

Distress, Worry, and Functioning Following a Global Health Crisis: A National Study of Americans’ Responses to Ebola

The 2014 Ebola crisis received unprecedented media attention in the United States, despite low risk of transmission. We examined theoretically derived correlates of psychological response to the crisis, including Ebola-related media exposure, prior mental health history, and stress response to a recent prior collective trauma (the 2013 Boston Marathon bombing, BMB). A national probability sample completed a survey 2–4 weeks post-BMB; 18 months later, the same sample reported responses to the Ebola crisis ( N = 3,447). History of mental health diagnoses, acute stress response to the BMB, and Ebola-related media exposure were associated with greater psychological distress and functional impairment. Prior acute stress and Ebola-related media exposure were also associated with Ebola-related worry; individuals with higher BMB-related acute stress who consumed more Ebola-related media were more worried about contracting Ebola. Media coverage of the Ebola public health crisis was associated with negative psychological outcomes, even among individuals at low risk for contracting the disease.

Repeated daily restraint stress induces adaptive behavioural changes in both adult and juvenile mice

Chronic stress is known to be a risk factor for the development of depression and anxiety, disorders which often begin during adolescence. Restraint stress is a commonly used stressor in adult rodents, however the effects of repeated restraint stress in juvenile mice have not been well characterised. Here we have shown for the first time the behavioural and hormonal effects of repeated restraint stress in both adult and juvenile BALB/c and C57BL/6 mice. Repeated daily restraint stress (2h/day for 3, 7 or 14days) provoked a robust physiological response evident as increased corticosterone levels and decreased body weight after 14days. However, habituation of the stress-response was evident during repeated exposure to the stressor in both adult and juvenile mice. The behavioural changes seen in response to repeated restraint stress were complex. In juvenile mice, repeated restraint stress evoked an increase in exploratory behaviours in the elevated plus maze, a decrease in time spent immobile in the forced swim test and a decrease in sucrose preference. In adult mice fewer behavioural changes were seen. Interestingly BALB/c and C57BL/6 mice showed qualitatively similar response to 3days repeated restraint stress. The behavioural changes we observed, as a result of prior stress exposure, may represent an adaptive stress-coping response or resilience. Both the hormonal and behavioural effects of stress were more pronounced in juvenile mice than in adults. This wider range of behavioural responses seen in juvenile mice might reflect a greater ability to engage in adaptive stress-coping strategies that likely have beneficial effects evident in future stress challenges.

Post-traumatic stress disorder associated with natural and human-made disasters in the World Mental Health Surveys.

Research on post-traumatic stress disorder (PTSD) following natural and human-made disasters has been undertaken for more than three decades. Although PTSD prevalence estimates vary widely, most are in the 20-40% range in disaster-focused studies but considerably lower (3-5%) in the few general population epidemiological surveys that evaluated disaster-related PTSD as part of a broader clinical assessment. The World Mental Health (WMH) Surveys provide an opportunity to examine disaster-related PTSD in representative general population surveys across a much wider range of sites than in previous studies. Although disaster-related PTSD was evaluated in 18 WMH surveys, only six in high-income countries had enough respondents for a risk factor analysis. Predictors considered were socio-demographics, disaster characteristics, and pre-disaster vulnerability factors (childhood family adversities, prior traumatic experiences, and prior mental disorders). Disaster-related PTSD prevalence was 0.0-3.8% among adult (ages 18+) WMH respondents and was significantly related to high education, serious injury or death of someone close, forced displacement from home, and pre-existing vulnerabilities (prior childhood family adversities, other traumas, and mental disorders). Of PTSD cases 44.5% were among the 5% of respondents classified by the model as having highest PTSD risk. Disaster-related PTSD is uncommon in high-income WMH countries. Risk factors are consistent with prior research: severity of exposure, history of prior stress exposure, and pre-existing mental disorders. The high concentration of PTSD among respondents with high predicted risk in our model supports the focus of screening assessments that identify disaster survivors most in need of preventive interventions.

Prior stressor exposure delays the recovery of surgery-induced cognitive impairment and prolongs neuroinflammation in aged rats

Increasing evidence indicates that stress potentiates pro-inflammatory response to a subsequent peripheral immune challenge. The present study investigated if prior exposure to inescapable tailshock (IS) delayed the recovery of surgery-induced spatial learning and memory impairment and prolonged hippocampus interleukin (IL)-1β and IL-6 expression. MethodsA total of 192 aged rats were trained with Morris water-maze (MWM) for 6 consecutive days. A single session of inescapable tailshock was performed on day 6 after training. Then, the rats subjected to partial hepatectomy. Hippocampal-dependent spatial learning and memory were assessed on postoperative days 1, 3 and 7. The cytokines IL-1β and IL-6 and ionized calcium binding adaptor protein (Iba)-1 were measured at each time point. Cluster of differentiation 200 (CD200) was also measured to explore potential mechanisms of glial cell activation. ResultsExposure of IS alone failed to affect the latency to platform and increase hippocampal cytokine levels at each time point. However, IS alone significantly increased the expression levels of Iba-1. A prolonged latency and additional significant increase in hippocampal levels of IL-1β and IL-6 were observed when partial hepatectomy was performed in aged rats exposed to IS 24h later. The combination of IS and surgical trauma dramatically upregulated the levels of Iba-1 and significantly decreased the expression of CD200. ConclusionIS alone failed to induce cognitive deficits and increase pro-inflammatory cytokines expression. However, IS delayed the recovery of surgery-induced spatial learning and memory impairment and prolonged pro-inflammatory response to the subsequent surgery challenge.

Hormone levels in neonatal hair reflect prior maternal stress exposure during pregnancy

Hormones present in hair provide summative information about endocrine activity while the hair was growing. Therefore, it can be collected from an infant after birth and still provide retrospective information about hormone exposure during prenatal development. We employed this approach to determine whether a delimited period of maternal stress during pregnancy affected the concentrations of glucocorticoids and gonadal hormones in the hair of neonatal rhesus monkeys. Hair from 22 infant monkeys exposed to 5 weeks of gestational disturbance was compared to specimens from 13 infants from undisturbed control pregnancies. Using an LC/MS/MS based technique, which permitted seven steroid hormones to be quantified simultaneously, we found 2 hormones were significantly different in infants from disturbed pregnancies. Cortisol and testosterone levels were lower in the hair of both male and female neonates. Maternal hair hormone levels collected on the same day after delivery no longer showed effects of the disturbance earlier during pregnancy. This study documents that a period of acute stress, lasting for 20% of gestation, has sustained effects on the hormones to which a developing fetus is exposed.

Prior stress exposure increases pain behaviors in a rat model of full thickness thermal injury

Thermal burns among individuals working in highly stressful environments, such as firefighters and military Service Members, are common. Evidence suggests that pre-injury stress may exaggerate pain following thermal injury; however current animal models of burn have not evaluated the potential influence of pre-burn stress. This sham-controlled study evaluated the influence of prior stress exposure on post-burn thermal and mechanical sensitivity in male Sprague-Dawley rats. Rats were exposed to 20min of inescapable swim stress or sham stress once per day for three days. Exposure to inescapable swim stress (1) increased the intensity and duration of thermal hyperalgesia after subsequent burn and (2) accelerated the onset of thermal hyperalgesia and mechanical allodynia after subsequent burn. This stress-induced exacerbation of pain sensitivity was reversed by pretreatment and concurrent treatment with the serotonin-norepinephrine reuptake inhibitor (SNRI) duloxetine. These data suggest a better understanding of mechanisms by which prior stress augments pain after thermal burn may lead to improved pain treatments for burn survivors.