Termination of acute stress response by the endocannabinoid system is regulated through lysine-specific demethylase 1-mediated transcriptional repression of 2-AG hydrolases ABHD6 and MAGL.

Acute environmental stress rarely implies long-lasting neurophysiological and behavioral alterations. On the contrary, chronic stress exerts a potent toxic effect at the glutamatergic synapse whose altered physiology has been recognized as a core trait of neuropsychiatric disorders. The endocannabinoid system (ECS) plays an important role in the homeostatic response to acute stress. In particular, stress induces synthesis of endocannabinoid (eCB) 2-arachidonyl glycerol (2-AG). 2-AG stimulates presynaptic cannabinoid 1 (CB1) receptor contributing to stress response termination through inhibition of glutamate release, restraining thereafter anxiety arousal. We employ mouse models of stress response coupled to gene expression analyses, unravelling that in response to acute psychosocial stress in the mouse hippocampus, ECS-mediated synaptic modulation is enhanced via transcriptional repression of two enzymes involved in 2-AG degradation: α/ß-hydrolase domain containing 6 (ABHD6) and monoacylglycerol lipase (MAGL). Such a process is orchestrated by the epigenetic corepressor LSD1 who directly interacts with promoter regulatory regions of Abhd6 and Magl. Remarkably, negative transcriptional control of Abhd6 and Magl is lost in the hippocampus upon chronic psychosocial stress, possibly contributing to trauma-induced drift of synapse physiology toward uncontrolled glutamate transmission. We previously showed that in mice lysine-specific demethylase 1 (LSD1) increases its hippocampal expression in response to psychosocial stress preventing excessive consolidation of anxiety-related plasticity. In this work, we unravel a nodal epigenetic modulation of eCB turn over, shedding new light on the molecular substrate of converging stress-terminating effects displayed by ECS and LSD1.

Reduced gray matter volume in the left prefrontal, occipital, and temporal regions as predictors for posttraumatic stress disorder: a voxel-based morphometric study.

The concept of acute stress disorder (ASD) was introduced as a diagnostic entity to improve the identification of traumatized people who are likely to develop posttraumatic stress disorder (PTSD). Neuroanatomical models suggest that changes in the prefrontal cortex, amygdala, and hippocampus play a role in the development of PTSD. Using voxel-based morphometry, this study aimed to investigate the predictive power of gray matter volume (GMV) alterations for developing PTSD. The GMVs of ASD patients (n = 21) were compared to those of PTSD patients (n = 17) and healthy controls (n = 18) in whole-brain and region-of-interest analyses. The GMV alterations seen in ASD patients shortly after the traumatic event (T1) were also correlated with PTSD symptom severity and symptom clusters 4 weeks later (T2). Compared with healthy controls, the ASD patients had significantly reduced GMV in the left visual cortex shortly after the traumatic event (T1) and in the left occipital and prefrontal regions 4 weeks later (T2); no significant differences in GMV were seen between the ASD and PTSD patients. Furthermore, a significant negative association was found between the GMV reduction in the left lateral temporal regions seen after the traumatic event (T1) and PTSD hyperarousal symptoms 4 weeks later (T2). Neither amygdala nor hippocampus alterations were predictive for the development of PTSD. These data suggest that gray matter deficiencies in the left hemispheric occipital and temporal regions in ASD patients may predict a liability for developing PTSD.

A core role for cognitive processes in the acute onset and maintenance of post-traumatic stress in children and adolescents.

BACKGROUND: Post-traumatic stress disorder (PTSD) is a common reaction to trauma in children and adolescents. While a significant minority of trauma-exposed youth go on to have persistent PTSD, many youths who initially have a severe traumatic stress response undergo natural recovery. The present study investigated the role of cognitive processes in shaping the early reactions of child and adolescents to traumatic stressors, and the transition to persistent clinically significant post-traumatic stress symptoms (PTSS). METHODS: A prospective longitudinal study of youth aged 8-17 years who had attended a hospital emergency department following single trauma was undertaken, with assessments performed at 2-4 weeks (N = 226) and 2 months (N = 208) post-trauma. Acute stress disorder and PTSD were assessed using a structured interview, while PTSS, depression severity and peritraumatic and post-traumatic cognitive processes were assessed using self-report questionnaires. On the basis of their PTSS scores at each assessment, participants were categorised as being on a resilient, recovery or persistent trajectory. RESULTS: PTSS decreased between the two assessments. Cognitive processes at the 2- to 4-week assessment accounted for the most variance in PTSS at both the initial and follow-up assessment. The onset of post-traumatic stress was associated particularly with peritraumatic subjective threat, data-driven processing and pain. Its maintenance was associated with greater peritraumatic dissociation and panic, and post-traumatic persistent dissociation, trauma memory quality, rumination and negative appraisals. Efforts to deliberately process the trauma were more common in youth who experienced the onset of clinically significant PTSS. Regression modelling indicated that the predictive effect of baseline negative appraisals remained when also accounting for baseline PTSS and depression. CONCLUSIONS: Cognitive processes play an important role in the onset and maintenance of PTSS in children and adolescents exposed to trauma. Trauma-related appraisals play a particular role when considering whether youth make the transition from clinically significant acute PTSS to persistent PTSS.

Posterior and prefrontal contributions to the development posttraumatic stress disorder symptom severity: an fMRI study of symptom provocation in acute stress disorder.

Acute stress disorder (ASD) is predictive of the development of posttraumatic stress disorder (PTSD). In response to symptom provocation, the exposure to trauma-related pictures, ASD patients showed increased activation of the medial posterior areas of precuneus and posterior cingulate cortex as well as of superior prefrontal cortex in a previous study. The current study aimed at investigating which activated areas are predictive of the development of PTSD. Nineteen ASD patients took part in an fMRI study in which they were shown personalized trauma-related and neutral pictures within 4 weeks of the traumatic event. They were assessed for severity of PTSD 4 weeks later. Activation contrasts between trauma-related and neutral pictures were correlated with subsequent PTSD symptom severity. Greater activation in, among others, right medial precuneus, left retrosplenial cortex, precentral and right superior temporal gyrus as well as less activation in lateral, superior prefrontal and left fusiform gyrus was related to subsequently increased PTSD severity. The results are broadly in line with neural areas related to etiological models of PTSD, namely multisensory associative learning recruiting posterior regions on the one hand and failure to reappraise maladaptive cognitions, thought to involve prefrontal areas, on the other.

Acute stress disorder versus chronic posttraumatic stress disorder: inhibition of fear as a function of time since trauma.

BACKGROUND: Previous work has shown that inhibition of fear is impaired in posttraumatic stress disorder (PTSD) resulting from both civilian and combat trauma. The purpose of the present study was to investigate the inhibition of learned fear in traumatized individuals diagnosed with either acute stress disorder (ASD) or PTSD. This is the first study to use a conditioned inhibition paradigm with traumatized individuals within a month of trauma exposure. We hypothesized that impaired fear inhibition would be evident in PTSD, but not ASD. METHOD: Using established translational, psychophysiological methods including fear-potentiated startle, and skin conductance, we examined fear acquisition, stimulus discrimination, and the transfer of learned safety in a Croatian population with ASD or PTSD. This cross-sectional study included three age-matched groups: healthy nontrauma controls (n = 27), a group with chronic PTSD (10 or more years since trauma exposure, n = 24), and a group with ASD (30 days or less since trauma exposure, n = 27). RESULTS: The presence of trauma-related psychopathology, whether acute or chronic, was associated with an impaired ability to transfer learned safety based on fear-potentiated startle measures, while healthy control subjects showed significant fear inhibition in the presence of the safety cue compared to the danger cue, F(1,26) = 12.64, P = .001. CONCLUSIONS: These data expand our previously observed findings of PTSD-associated fear inhibition deficits by demonstrating that trauma-related impairments in safety learning are evident within 30 days of trauma exposure.

Identifying risk of emotional sequelae after critical incidents.

BACKGROUND AND PURPOSE: Ambulance workers could benefit from a method for early identification of incidents likely to result in long-term emotional sequelae. There is evidence that persistence of some measures of anxiety beyond the first week after an incident is associated with sequelae. In this study we test the hypothesis that persistence of self-identifiable components of the acute stress reaction as early as a few days post-incident is associated with sequelae. METHOD: 228 ambulance workers volunteered to complete surveys on occurrence and persistence of physiological, behavioural and emotional responses to an index critical incident in the past, as well as symptoms of depression, post-traumatic stress, somatisation and burnout at the time of the survey. Data were analysed for associations between duration of each reaction and present symptoms. Using cut-off scores for the outcomes, we tested the RR of high scores in each of three situations: occurrence of the reaction, persistence of reaction beyond one night and persistence beyond 1 week. RESULTS: Prolonged duration of all five acute stress reaction components was associated with all four outcomes, with the strongest associations being with post-traumatic stress and depression symptoms. The occurrence of physical symptoms of arousal is an immediate predictor of long-term sequelae. Three other components--disturbed sleep, irritability and social withdrawal--provide potential indicators of long-term emotional sequelae as early as 2 days post-incident. CONCLUSION: Four easily identifiable responses to a critical incident can potentially be used for early self-identification of risk of later emotional difficulties. These findings should be submitted to prospective testing.

Startle reactivity in acute stress disorder and posttraumatic stress disorder.

The aim of this study is to prospectively examine electromyographic (EMG) responses in patients diagnosed with acute stress disorder (ASD) after experiencing a traffic accident or violent attack, within one month after the traumatic event and six months later. Half of the participants met criteria for posttraumatic stress disorder (PTSD) after six months. Psychophysiological parameters can provide a better clarification between ASD and PTSD patients. Heightened startle magnitude in the immediate aftermath of trauma may be a good predictor of PTSD; moreover, a lack of startle habituation appears to be a more stable marker of PTSD, which persists for six months after trauma exposure.

Psychophysiological indicators of acute stress disorder.

AIM: The aim of the current study was to compare basal psychophysiology and startle reflexes in acute stress disorder (ASD) patients and controls. Stress reactions to traumatic event include acute and chronic reactions like ASD and posttraumatic stress disorder (PTSD). They are characterized by prominent psychophysiological symptoms that can give insight into the pathogenesis of PTSD. METHODS: We measured heart-rate (HR), respiratory sinus arrhythmia (RSA), electrodermal activity (EDA) and electromyography (EMG) of musculus orbicularis occuli during an acclimation period and during the presentation of startle stimuli in 29 ASD patients with different traumatic experiences and in 33 healthy controls. RESULTS: ASD subjects had similar habituation to the startle probe as healthy controls. EDA for individuals with ASD after traffic accident was higher then for healthy controls. There were no differences for heart-rate in two compared groups. CONCLUSION: EDA appears to offer the most reliable psychophysiological indices in the ASD following traffic accident.

Do religious habits and coping help in the immediate aftermath of a crisis? Relations with Hurricane Katrina evacuees' acute stress symptoms and functional impairment.

OBJECTIVE: Religious coping has been shown to relate to psychological adjustment in survivors of disasters months or even years afterward. However, because very few studies have assessed coping and well-being during the immediate crisis, little is known about the role of religiousness at this critical time. METHOD: We studied a sample of 132 Hurricane Katrina evacuees (56% male, 74.2% African American, mean age of 43 years) relocated to a Red Cross emergency shelter in Austin, Texas, within 19 days of Hurricane Katrina's landfall. RESULTS: Participants reported high levels of acute stress disorder (ASD) symptoms and functional impairment as well as high resource loss. Belief that God is in control and negative religious coping (perceiving punishment) were positively related to ASD symptoms while negative religious coping (perceiving abandonment) was related to higher functional impairment. The negative religious coping-ASD symptom relationship was moderated by resource loss, such that, for those with lower levels of resource loss, negative religious coping (perceiving punishment) related to even higher levels of ASD symptoms, an effect that diminished with higher resource loss. Neither positive religious coping nor pre-Katrina frequency of service attendance or private prayer related to ASD symptoms or functional impairment. CONCLUSIONS: At least in this sample at the height of disruption following a disaster, little evidence of salutary effects of religiousness were observed. It may be that such effects take time to emerge as people begin their recovery processes or that not all groups find help through their religious coping resources. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Short-term sleep fragmentation enhances anxiety-related behavior: The role of hormonal alterations.

INTRODUCTION: The neuroendocrine background of acute sleep fragmentation in obstructive sleep apnea and sleep fragmentation involvement in psychiatric comorbidities, common in these patients, are still largely unknown. The aim of this study was to determine the effects of short-term experimental sleep fragmentation on anxiety -like behavior and hormonal status in rats. METHODS: Male rats were adapted to treadmill (ON and OFF mode with belt speed set on 0.02m/s and 0.00m/s) and randomized to: 1) treadmill control (TC, only OFF mode); 2) motion, activity control (AC, 10min ON and 30min OFF mode) and 3) sleep fragmentation (SF, 30s ON and 90s OFF mode) group. Six hours later, the animals were tested in the open field, elevated plus maze and light/dark test (n = 8/group). Testosterone, estradiol, progesterone and corticosterone were determined in separate animal cohort immediately upon sleep fragmentation (n = 6/group). RESULTS: SF rats showed decreased rearings number, decreased time spent in the central area and increased thigmotaxic index compared to TC and AC rats in the open field test. Similarly, increased anxiety upon sleep fragmentation was observed in the elevated plus maze and the light/dark test. Significantly lower testosterone, estradiol and progesterone levels were determined in SF in comparison to AC and TC groups, while there was no significant difference in the levels of corticosterone. CONCLUSION: Short term sleep fragmentation enhances anxiety-related behavior in rats, which could be partly mediated by the observed hormonal changes presented in the current study in form of testosterone, estradiol and progesterone depletion.

Psychobiology of posttraumatic stress disorder in pediatric injury patients: a review of the literature.

Research suggests that about a quarter to a third of children with traffic-related injuries develop posttraumatic stress disorder (PTSD). Early symptoms of PTSD have been found to predict poor mental and physical outcome in studies of medically injured children. However, these symptoms are rarely recognized by physicians who provide emergency care for these children. In addition, there is insufficient knowledge about predictors of posttraumatic stress symptoms in this specific pediatric population. Early identification of those children at particular risk is needed to target preventive interventions appropriately. After some introducing remarks on the classification and the nature of posttraumatic stress reactions, current research findings on psychological and biological correlates of PTSD in pediatric injury patients are presented. The particular focus in this paper is on the neurobiological mechanisms that influence psychological responses to extreme stress and the development of PTSD. Continued study of the psychobiology of trauma and PTSD in pediatric injury patients, both in terms of neurobiology and treatment is needed.

Acute stress, but not corticosterone, facilitates acquisition of paired associates learning in rats using touchscreen-equipped operant conditioning chambers.

Acute stress influences learning and memory in humans and rodents, enhancing performance in some tasks while impairing it in others. Typically, subjects preferentially employ striatal-mediated stimulus-response strategies in spatial memory tasks following stress, making use of fewer hippocampal-based strategies which may be more cognitively demanding. Previous research demonstrated that the acquisition of rodent paired associates learning (PAL) relies primarily on the striatum, while task performance after extensive training is impaired by hippocampal disruption. Therefore, we sought to explore whether the acquisition of PAL, an operant conditioning task involving spatial stimuli, could be enhanced by acute stress. Male Long-Evans rats were trained to a predefined criterion in PAL and then subjected to either a single session of restraint stress (30 min) or injection of corticosterone (CORT; 3 mg/kg). Subsequent task performance was monitored for one week. We found that rats subjected to restraint stress, but not those rats injected with CORT, performed with higher accuracy and efficiency, when compared to untreated controls. These results suggest that while acute stress enhances the acquisition of PAL, CORT alone does not. This dissociation may be due to differences between these treatments and their ability to produce sufficient catecholamine release in the amygdala, a requirement for stress effects on memory.

Dysfunctional information processing in individuals with acute exposure to sexual abuse: An ERP study.

Acute stress disorder (ASD) and posttraumatic stress disorder (PTSD) may occur after traumatic event and also cause significant life time impairment. P300 event-related potential (ERP) is a potential biological marker for PTSD and can reflect cognitive impairment in information processing and attention. Despite the usefulness of ERP, there are few attempts to reveal relationships between ASD and P300. In the present study, we aimed to determine if the P300 of the patients who were the victims of sexual abuse reflected the quantitative trait of ASD or if P300 is applicable as a state marker for predicting the risk of PTSD.Fifteen female victims of sexual abuse diagnosed with ASD and 18 healthy controls (HCs) without trauma exposure participated in this study. We investigated the P300 ERPs in patients with ASD to compare them with those of HCs. ERPs were acquired from female adults during an auditory oddball task. Between-group differences in amplitudes or latencies of P300 were investigated using repeated-measures analysis of variance.The ASD groups showed reduced P300 amplitudes at the midline centroparietal site as well as reduced accuracy rates during an auditory oddball task compared with the HCs.These results indicate that ASD have abnormalities in the P300 compared to those in HCs. Moreover, the reduction in P300 could be considered a candidate neurophysiological marker for ASD.

Induced arousal and reexperiencing in acute stress disorder.

This study investigated the relationship of hyperarousal and intrusive symptoms in acute stress disorder (ASD). Civilian trauma survivors with ASD (n = 18) and without ASD (n = 14) completed a hyperventilation provocation test (HVPT) and then completed the Physical Reactions Scale. All participants provided a narrative describing their hyperventilation experience that was audiotaped and independently coded. Individuals with ASD reported greater numbers of intrusive memories and reported greater distress than non-ASD participants. More ASD than non-ASD participants experienced a flashback-type reaction during the hyperventilation. Intrusive symptoms were significantly correlated with elevated arousal following the HVPT. The findings provide evidence that reexperiencing is directly associated with elevated states of arousal.

Acute stress disorder modifies cerebral activity of amygdala and prefrontal cortex.

The diagnosis constraint of acute stress disorder (ASD), consisting of testing individuals in the month following trauma exposure, limits research on the very early and initial stage of the disease. In this regard, this work aims to explore the cerebral mechanism of ASD in a population of fire-fighters before and after trauma exposure. Thirty-six healthy non-traumatized male fire-fighters were explored by an fMRI emotional face-matching task to evaluate the cerebral substrate of emotional recognition. During the two years of the follow-up, two subjects were traumatized, and thus retested, as were 10 non-traumatized subjects among the initial non-exposed ones. In comparison to non-exposed subjects, fire-fighters with ASD had enhanced amygdala, orbitofrontal, and dorsolateral prefrontal BOLD responses to fearful and angry faces (p < .05, FDR-corrected). These results shed new light on the cerebral mechanism associated with ASD. We observed for the first time the existence of an altered fear processing pathway in ASD that is mediated by amygdala and prefrontal cortex hyperactivity, which might be at the core of the disorder.

A tidal ventilation model for oxygenation in respiratory failure.

We develop tidal-ventilation pulmonary gas-exchange equations that allow pulmonary shunt to have different values during expiration and inspiration, in accordance with lung collapse and recruitment during lung dysfunction (Am. J. Respir. Crit. Care Med. 158 (1998) 1636). Their solutions are tested against published animal data from intravascular oxygen tension and saturation sensors. These equations provide one explanation for (i) observed physiological phenomena, such as within-breath fluctuations in arterial oxygen saturation and blood-gas tension; and (ii) conventional (time averaged) blood-gas sample oxygen tensions. We suggest that tidal-ventilation models are needed to describe within-breath fluctuations in arterial oxygen saturation and blood-gas tension in acute respiratory distress syndrome (ARDS) subjects. Both the amplitude of these oxygen saturation and tension fluctuations, and the mean oxygen blood-gas values, are affected by physiological variables such as inspired oxygen concentration, lung volume, and the inspiratory:expiratory (I:E) ratio, as well as by changes in pulmonary shunt during the respiratory cycle.

Brain environment interactions: stress, posttraumatic stress disorder, and the need for a postmortem brain collection.

Stress, especially the extreme stress of traumatic events, can alter both neurobiology and behavior. Such extreme environmental situations provide a useful model for understanding environmental influences on human biology and behavior. This paper will review some of the evidence of brain alterations that occur with exposure to environmental stress. This will include recent studies using neuroimaging and will address the need for histological confirmation of imaging study results. We will review the current scientific approaches to understanding brain environment interactions, and then make the case for the collection and study of postmortem brain tissue for the advancement of our understanding of the effects of environment on the brain. Creating a brain tissue collection specifically for the investigation of the effects of extreme environmental stressors fills a gap in the current research; it will provide another of the important pieces to the puzzle that constitutes the scientific investigation of negative effects of environmental exposures. Such a resource will facilitate new discoveries related to the psychiatric illnesses of acute stress disorder and posttraumatic stress disorder, and can enable scientists to correlate structural and functional imaging findings with tissue abnormalities, which is essential to validate the results of recent imaging studies.

The factor structure of the Autobiographical Memory Test in recent trauma survivors.

The objective of this study was to examine the psychometric properties of the Autobiographical Memory Test (AMT), which is widely used to measure overgeneral autobiographical memory in individuals with depression and a trauma history. Its factor structure and internal consistency have not been explored in a clinical sample. This study examined the psychometric properties of the AMT in a sample of recent trauma survivors (N = 194), who completed the AMT 2 weeks after a trauma. Participants were also assessed with structured clinical interviews for current acute stress disorder and current and past major depressive disorder. Confirmatory factor analysis and item response theory were used to analyze the AMT in the whole sample. The factor structure of the AMT was also compared for (a) individuals with and without lifetime major depressive disorder and (b) individuals with current (posttrauma) major depressive disorder and/or acute stress disorder versus those with neither disorder. In all of these analyses, the AMT with cues of positive and negative valence had a 1-factor structure, which replicates work in nonclinical samples. Based on analyses of the whole sample, scores from the AMT had a reliability estimate of .72, and standard error of measurement was lowest for people who scored low on memory specificity. In conclusion, the AMT measures 1 factor of memory specificity in a clinical sample and can yield reliable scores for memory specificity. More psychometric studies of the AMT are needed to replicate these results with similar and other clinical populations.

Early altered resting-state functional connectivity predicts the severity of post-traumatic stress disorder symptoms in acutely traumatized subjects.

The goal of this study was to investigate the relationship between resting-state functional connectivity and the severity of post-traumatic stress disorder (PTSD) symptoms in 15 people who developed PTSD following recent trauma. Fifteen participants who experienced acute traumatic events underwent a 7.3-min resting functional magnetic resonance imaging scan within 2 days post-event. All the patients were diagnosed with PTSD within 1 to 6 months after trauma. Brain areas in which activity was correlated with that of the posterior cingulate cortex (PCC) were assessed. To assess the relationship between the severity of PTSD symptoms and PCC connectivity, contrast images representing areas positively correlated with the PCC were correlated with the subject's Clinician-Administered PTSD Scale scores (CAPS) when they were diagnosed. Furthermore, the PCC, medial prefrontal cortex and bilateral amygdala were selected to assess the correlation of the strength of functional connectivity with the CAPS. Resting state connectivity with the PCC was negatively correlated with CAPS scores in the left superior temporal gyrus and right hippocampus/amygdala. Furthermore, the strength of connectivity between the PCC and bilateral amygdala, and even between the bilateral amygdala could predict the severity of PTSD symptoms later. These results suggest that early altered resting-state functional connectivity of the PCC with the left superior temporal gyrus, right hippocampus and amygdala could predict the severity of the disease and may be a major risk factor that predisposes patients to develop PTSD.