Psychologically traumatic stress inducing redox - inflammation interplay; which comes first?

Evidence suggests the involvement of redox and inflammation fields under conditions of psychological trauma. Factors from immunity, Hypothalamic-Adrenal-Pituitary axis, Kynurenine pathway, Dysglycemia, Glutamatergic systems as well as elements from redox mechanisms participate in a highly complex neurobiological process. Yet, little is known about their interplay. There is evidence suggesting a psychologically traumatic stress induced redox-originated inflammatory activation and vice versa. A holistic approach would suggest a parallel activation of the involved mechanisms with highly tight interdependency. The present report aims at collecting the evidence supporting either directionality of the involved mechanisms, finally suggesting a diagram depicting a synthesis of this interplay.

Associations of trauma and posttraumatic stress disorder with aldosterone in women.

BACKGROUND: Posttraumatic stress disorder (PTSD) has been associated with increased cardiovascular risk, however, underlying mechanisms have not been fully specified. PTSD is associated with stress-related hormones, including dysregulated glucocorticoid activity. Dysregulation of aldosterone, a mineralocorticoid activated by psychological stress and implicated in cardiovascular damage, may be a relevant pathway linking PTSD and cardiovascular risk. Few studies to date have evaluated the association between PTSD and aldosterone, none with repeated measures of aldosterone. We examined if trauma and PTSD were associated with altered aldosterone levels relative to women unexposed to trauma. METHODS: The association of trauma exposure and chronic PTSD with plasma aldosterone levels was investigated in 521 middle-aged women in the Nurses' Health Study II. Aldosterone was assessed at two time points, 10-16 years apart, and trauma exposure and PTSD were also ascertained for both time points. Regarding exposure assessment, women were characterized based on a structured diagnostic interview as: having chronic PTSD (PTSD at both time points; n = 174); being trauma-exposed (trauma exposure at first time point but no PTSD; n = 174); and being unexposed (no trauma exposure at either time point; reference group for all analyses; n = 173). Linear mixed models examined associations of trauma and PTSD status with log-transformed aldosterone levels, adjusting for covariates and health-related variables that may confound or lie on the pathway between PTSD and altered aldosterone levels. RESULTS: Across the sample, mean aldosterone concentration decreased over time. Adjusting for covariates, women with chronic PTSD had significantly lower aldosterone levels averaged over time, compared to women unexposed to trauma (ß = - 0.08, p = 0.04). Interactions between trauma/PTSD group and time were not significant, indicating change in aldosterone over time did not differ by trauma/PTSD status. Post-hoc exploratory analyses suggested that menopausal status partially mediated the relationship between chronic PTSD status and aldosterone level, such that postmenopausal status explained 7% of the effect of PTSD on aldosterone. CONCLUSIONS: These findings indicate that PTSD is associated with lower levels of aldosterone. Further work is needed to understand implications of this type of dysregulation in a key biological stress system for cardiovascular and other health outcomes previously linked with PTSD.

The Interplay Between Postsynaptic Striatal D2/3 Receptor Availability, Adversity Exposure and Odd Beliefs: A [11C]-Raclopride PET Study.

BACKGROUND: Between unaffected mental health and diagnosable psychiatric disorders, there is a vast continuum of functioning. The hypothesized link between striatal dopamine signaling and psychosis has guided a prolific body of research. However, it has been understudied in the context of multiple interacting factors, subclinical phenotypes, and pre-postsynaptic dynamics. METHOD: This work investigated psychotic-like experiences and D2/3 dopamine postsynaptic receptor availability in the dorsal striatum, quantified by in vivo [11C]-raclopride positron emission tomography, in a sample of 24 healthy male individuals. Additional mediation and moderation effects with childhood trauma and key dopamine-regulating genes were examined. RESULTS: An inverse relationship between nondisplaceable binding potential and subclinical symptoms was identified. D2/3 receptor availability in the left putamen fully mediated the association between traumatic childhood experiences and odd beliefs, that is, inclinations to see meaning in randomness and unfounded interpretations. Moreover, the effect of early adversity was moderated by a DRD2 functional variant (rs1076560). The results link environmental and neurobiological influences in the striatum to the origination of psychosis spectrum symptomology, consistent with the social defeat and diathesis-stress models. CONCLUSIONS: Adversity exposure may affect the dopamine system as in association with biases in probabilistic reasoning, attributional style, and salience processing. The inverse relationship between D2/3 availability and symptomology may be explained by endogenous dopamine occupying the receptor, postsynaptic compensatory mechanisms, and/or altered receptor sensitivity. This may also reflect a cognitively stabilizing mechanism in non-help-seeking individuals. Future research should comprehensively characterize molecular parameters of dopamine neurotransmission along the psychosis spectrum and according to subtype profiling.

Alcohol Use Disorder Masks the Effects of Childhood Adversity, Lifetime Trauma, and Chronic Stress on Hypothalamic-Pituitary-Adrenal Axis Reactivity.

BACKGROUND: Individuals with alcohol use disorder (AUD) and those who have experienced traumas or chronic stress exhibit dysregulated hypothalamic-pituitary-adrenal (HPA) axis reactivity. Whether and how trauma and stress histories interact with AUD to affect HPA axis reactivity has not been assessed. METHODS: In the present study, 26 healthy male controls and 70 abstinent men with AUD were administered a pharmacologic probe [ovine corticotropin-releasing hormone (oCRH)] and psychosocial stressor to assess HPA axis reactivity. Plasma adrenocorticotropin hormone (ACTH) and cortisol were assessed every 10-20 minutes. Hierarchical clustering of multiple measures of trauma and stress identified 3 distinct clusters: childhood adversity, lifetime trauma, and chronic stress. General linear model procedures were used to examine main effects of group (AUD/control) and interaction effects of the 3 clusters upon net-integrated ACTH and cortisol response. RESULTS: We found that higher levels of childhood adversity, lifetime trauma, and chronic stress were each associated with blunted oCRH-induced ACTH reactivity in controls, but not in the AUD group. Recent chronic stress within the prior 6 months had the strongest influence upon ACTH reactivity in the control group, and lifetime trauma, the least. CONCLUSIONS: Childhood adversity, lifetime trauma, and chronic stress likely exert persistent, measurable effects upon HPA axis functioning in healthy controls. This association appears to be masked in individuals with AUD, potentially confounding studies examining the effects of stress, adversity, and/or trauma upon the HPA axis in this population during the protracted withdrawal phase of recovery. Future work targeting stress exposure and reactivity should consider the heightened effect of previous alcohol use relative to past adversity and trauma.

Salivary oxytocin after oxytocin administration: Examining the moderating role of childhood trauma.

Although oxytocin administration influences behavior, its effects on peripheral oxytocin concentrations are mixed and derived from studies on healthy subjects. Additionally, trauma attenuates the behavioral effects of oxytocin, but it is unknown whether it also influences its effect on peripheral circulation. This study examined whether salivary oxytocin increased after oxytocin administration and whether trauma attenuated this effect. We conducted a randomized, double-blind, placebo-controlled, within-subjects study in 100 male adolescents living in residential youth care facilities. Participants self-administered intranasally 24 IU of oxytocin and placebo (one week later) and provided a saliva sample before and 15 min after administration. Salivary oxytocin increased significantly after oxytocin administration, but this effect might be inflated by exogenous oxytocin reaching the throat. Trauma did not moderate this effect. Our findings suggest that trauma did not attenuate the effect of oxytocin administration on salivary oxytocin, but more robust methodologies are recommended to draw more solid conclusions.

Endocannabinoid concentrations in hair and mental health of unaccompanied refugee minors.

Altered activity of the endocannabinoid (EC) system has been linked to dysregulated stress-reactivity and the development of trauma-related psychopathology. The EC system, with its main components anandamide (AEA), 2-arachidonoyl-glycerol (2-AG) and other N-acyl-ethanolamides, is considered to be a buffer system that protects against the negative effects of traumatic experiences on mental health. Recently, the use of hair analyses, a method to gain information on long-term cumulative system activity, has been introduced to the study of ECs. Here, we seek to extend current knowledge on the potential use of hair EC concentrations as a marker of trauma-related psychological symptoms as well as psychological resources. Ninety-one male URM from Syria and Afghanistan (mean age = 17.4 years) living in group homes of the Child Protection Services in Leipzig, Germany, completed assessments on traumatic life events (TLE), PTSD symptoms, depression, anxiety and somatic symptoms as well as on self-efficacy and prosocial behavior. Scalp-near 3 cm hair segments were obtained and EC concentrations quantified using liquid chromatography tandem mass spectrometry. Analyses revealed relatively week and inconsistent associations of hair ECs and psychological symptoms, with only a positive correlation between 2-AG and depression. Concerning prosocial behavior and self-efficacy positive relationships were found with oleoylethanolamide (OEA), stearoylethanolamide (SEA), and palmitoylethanolamide (PEA). Our findings add data concerning the utility of hair EC analyses for PNE research but on a whole fail to reveal a clear association pattern between hair ECs and mental health in URM.

A history of childhood trauma and allostatic load in patients with psychotic disorders with respect to stress coping strategies.

Elevated allostatic load (AL) index, which is a cumulative measure of biological dysregulations associated with stress exposure, has been demonstrated in patients with psychosis. However, it remains unknown whether a history of childhood trauma (CT) might contribute to elevated AL index in psychosis. Therefore, we aimed to investigate the association between AL index, a history of CT and coping styles in patients with psychotic disorders. Participants were 65 patients with schizophrenia-spectrum disorders and 56 healthy controls (HCs). The AL index was computed based on percentile distributions of 15 biomarkers in HCs. The AL index was significantly higher in patients with psychosis. A history of parental antipathy was associated with elevated AL index in both groups of participants. A history of any categories of CT and sexual abuse were associated with higher AL index only in patients with psychosis. Social diversion (seeking social interactions in case of stressful experiences) mediated the association between sexual abuse and the AL index in the group of patients. There was a significant direct effect of sexual abuse on the AL index (this specific CT was associated with higher AL index). However, indirect effect of sexual trauma on AL through social diversion was opposite to direct effect. Childhood adversities, especially sexual abuse and parental antipathy, might contribute to elevated AL index in patients with psychosis. The effect of sexual abuse on the AL index might be specific to psychosis. Engagement in social interactions in case of stressful situations might alleviate biological dysregulations associated with CT.

Early traumatic experiences impair the functioning of both components of the endogenous stress response system in adult people with eating disorders.

Childhood trauma is a non-specific risk factor for eating disorders (EDs). It has been suggested that this risk is exerted through trauma-induced long-lasting changes in the body stress response system. Therefore, we explored the activity of the hypothalamus-pituitary-adrenal axis and of the sympathetic nervous system in adult ED patients with or without a history of childhood trauma exposure. Salivary cortisol and alpha-amylase, a marker of the sympathetic nervous system activity, were measured at awakening and after 15, 30 and 60 min in 35 women with EDs. The Childhood Trauma Questionnaire (CTQ) was employed to assess exposure to childhood trauma and, according to the CTQ cut-off scores, 21 ED women were classified as maltreated (Mal) participants and 14 women as no-maltreated (noMal) ED participants. Compared to noMal ED women, Mal ED participants showed significantly decreased cortisol awakening response (between group difference: p = 0.0003) and morning salivary alpha-amylase secretion (between group difference: p = 0.02). Present results confirm that the cortisol awakening response of adult ED patients with childhood trauma exposure is lower than that of adult ED patients without childhood trauma experiences and show for the first time that also the morning secretion of salivary alpha-amylase is decreased in adult ED patients who have been exposed to early traumatic experiences. These results point for the first time to a dampening in the basal activity of both components of the endogenous stress response system in childhood maltreated adult ED women.

Stress, trauma, racial/ethnic group membership, and HPA function: Utility of hair cortisol.

Discrimination, poverty, and other aspects of the minority experience produce stress associated with health disparities. The hypothalamic-pituitary-adrenal (HPA) axis, a neuroendocrine subsystem usually monitored through assay of the hormone cortisol, is thought to play a key role in this relationship. Cortisol assay using hair specimens is a technology that promises to address important methodological problems in large-scale studies of health, well-being, and racial/ethnic status. The purpose of this study is to evaluate the potential of a hair cortisol assay-based method for studying trait-like HPA response to low to moderate levels of stress, associated with racial/ethnic discrimination and related social processes, among well-functioning young adults. The hair cortisol measure was shown to be highly reliable; it detected differences in gender and ethnic/racial identity and was correlated with a history of physical abuse and measures of experienced microaggression. The results support the promise of hair-based cortisol assay as a key methodology in health disparities research. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Victims of war-Psychoendocrine evidence for the impact of traumatic stress on psychological well-being of adolescents growing up during the Israeli-Palestinian conflict.

Violent conflicts are severe traumatic stressors with detrimental effects on physical and mental health, with children and adolescents being particularly at risk. For the hypothalamic-pituitary-adrenal (HPA) axis, characteristic patterns of dysregulation in trauma-exposed individuals have been shown. This study set out to investigate self-reported mental well-being in Palestinian adolescents growing up during the Israeli-Palestinian conflict. Hair cortisol concentrations (HCC) as a psychoendocrine marker for long-term HPA axis aberrations along with the potential protective factor sense of coherence (SoC; i.e., the global mindset to interpret the world and emerging stressors as comprehensible, manageable, and meaningful) were examined. Between 2014 and 2016, posttraumatic stress disorder (PTSD), depression, anxiety, HCC, and SoC were examined in 233 adolescents aged 11 to 16 from the West Bank. More than half of the participants reported trauma exposure, with 40% fulfilling the criteria of a preliminary PTSD diagnosis and a high prevalence of anxiety and depression. HCC was significantly elevated in the PTSD subgroup compared to the subgroup not exposed to any traumatic events (p = 0.046), with trauma-exposed individuals in between. HCC was further associated with typical sequelae of traumatic stress. Notably, SoC was inversely related to self-reported psychopathology, as well as to HCC in the trauma group. The results illustrate the situation of adolescents exposed to chronic traumatic stress and extend the literature on aberrant HPA axis functioning under such conditions. They also point out a central role of SoC, which may imply new strategies to aid individuals exposed to ongoing conflicts.

Telomere Length and Depression Among Ex-Prisoners of War: The Role of Subjective Age.

OBJECTIVES: Exposure to captivity increases the risk for multiple disturbances that may intensify during old age. In later phases of life, former-prisoners-of-war (ex-POWs) may suffer from depression as well as from accelerated aging, manifested in older subjective age and leukocyte telomere shortening. The current study assesses the link between these varied facets of increased vulnerability during old age and explores (a) the associations between subjective age and telomere length; (b) the mediating role of changes in subjective age over time within the associations between depression and telomere length. METHODS: Eighty-eight ex-POWs were assessed prospectively 30 (T1), 35 (T2), and 45 (T3) years after the 1973 Israeli Yom-Kippur War. Depression was assessed at T1; subjective age was assessed at T2 and T3; and telomere length and control variables were assessed at T3. RESULTS: Older subjective age at T3 was associated with concurrent shorter telomeres, beyond the effect of chronological age. Change in subjective age between T2 and T3 mediated the relations between depression at T1 and shorter telomeres at T3 beyond the effects of control variables. DISCUSSION: Findings suggest that the detrimental ramifications of accelerated subjective age involve premature cellular senesces, and may explain the relation between depression and accelerated aging processes among trauma victims. Hence, clinical interventions may seek to address accelerated subjective age among trauma survivors who suffer from depression.

Individual variability in behavior and functional networks predicts vulnerability using an animal model of PTSD.

Only a minority of individuals experiencing trauma subsequently develop post-traumatic stress disorder (PTSD). However, whether differences in vulnerability to PTSD result from a predisposition or trauma exposure remains unclear. A major challenge in differentiating these possibilities is that clinical studies focus on individuals already exposed to trauma without pre-trauma conditions. Here, using the predator scent model of PTSD in rats and a longitudinal design, we measure pre-trauma brain-wide neural circuit functional connectivity, behavioral and corticosterone responses to trauma exposure, and post-trauma anxiety. Freezing during predator scent exposure correlates with functional connectivity in a set of neural circuits, indicating pre-existing circuit function can predispose animals to differential fearful responses to threats. Counterintuitively, rats with lower freezing show more avoidance of the predator scent, a prolonged corticosterone response, and higher anxiety long after exposure. This study provides a framework of pre-existing circuit function that determines threat responses, which might directly relate to PTSD-like behaviors.

Deconstructing the Gestalt: Mechanisms of Fear, Threat, and Trauma Memory Encoding.

Threat processing is central to understanding debilitating fear- and trauma-related disorders such as posttraumatic stress disorder (PTSD). Progress has been made in understanding the neural circuits underlying the "engram" of threat or fear memory formation that complements a decades-old appreciation of the neurobiology of fear and threat involving hub structures such as the amygdala. In this review, we examine key recent findings, as well as integrate the importance of hormonal and physiological approaches, to provide a broader perspective of how bodily systems engaged in threat responses may interact with amygdala-based circuits in the encoding and updating of threat-related memory. Understanding how trauma-related memories are encoded and updated throughout the brain and the body will ultimately lead to novel biologically-driven approaches for treatment and prevention.

The Trier Social Stress Test in first episode psychosis patients: Impact of perceived stress, protective factors and childhood trauma.

Psychosis has been associated with abnormalities in hypothalamic-pituitary-adrenal axis functioning, which may emerge through heightened stress sensitivity following early life adversity - ultimately resulting in illness onset and progression. The present study assessed cortisol levels during an established psychosocial stress task and their association with current stress perception, putative protective factors and adverse childhood experiences in patients with a first episode of psychosis (FEP). A total of 100 volunteers participated in the study, 57 of whom were patients with a FEP (mean age 23.9 ± 3.8) and 43 healthy community controls (mean age 23.2 ± 3.9). Salivary cortisol, heart rate and blood pressure were measured at eight time points before and after the Trier Social Stress Test. Subjective stress and protective factors were assessed with the Perceived Stress Scale, the Self-Esteem Rating Scale and the Brief COPE. Early life adversity was assessed with the Childhood Trauma Questionnaire. Patients compared to controls showed significantly lower cortisol levels (F = 7.38; p = .008) throughout the afternoon testing period, but no difference in the cortisol response to the TSST. Heart rate was elevated and protective factors were lower in patients compared to controls. Attenuated cortisol levels were associated with higher levels of perceived stress, poor protective factors and more physical neglect during childhood. Our results suggest that attenuated baseline cortisol levels and not a blunted response during an acute stress task might be an indicator of heightened stress vulnerability and poor resilience in psychosis. The possible influence of childhood adversity and antipsychotic medication is discussed.

Translating basic research knowledge on the biological embedding of early-life stress into novel approaches for the developmental programming of lifelong health.

This review integrates scientific knowledge obtained over the past few decades on the biological mechanisms that contribute to the profound association between exposure to early adversity, including childhood trauma and prenatal stress, and the lifelong elevated risk to develop a broad range of diseases. We further discuss insights into gene-environment interactions moderating the association between early adversity and disease manifestation and we discuss the role of epigenetic and other molecular processes in the biological embedding of early adversity. Based on these findings, we propose potential mechanisms that may contribute to the intergenerational transmission of risk related to early adversity from the mother to the fetus. Finally, we argue that basic research knowledge on the biological embedding of early adversity must now be translated into novel intervention strategies that are mechanism-driven and sensitive to developmental timing. Indeed, to date, there are no diagnostic biomarkers of risk or mechanism-informed interventions that we can offer to victims of early adversity in order to efficiently prevent or reverse adverse health outcomes. Such translational efforts can be expected to have significant impact on both clinical practice and the public health system, and will promote precision medicine in pediatrics and across the lifespan.

Identification of a miRNAs signature associated with exposure to stress early in life and enhanced vulnerability for schizophrenia: New insights for the key role of miR-125b-1-3p in neurodevelopmental processes.

Epidemiological and clinical studies have provided evidence for a role of both genetic and environmental factors, such as stressful experiences early in life, in the pathogenesis of Schizophrenia (SZ) and microRNAs (miRNAs) have been suggested to play a key role in the interplay between the environment and our genome. In this study, we conducted a miRNOme analysis in different samples (blood of adult subjects exposed to childhood trauma, brain (hippocampus) of rats exposed to prenatal stress and human hippocampal progenitor cells treated with cortisol) and we identified miR-125b-1-3p as a down-regulated miRNA in all the three datasets. Interestingly, a significant down-regulation was observed also in SZ patients exposed to childhood trauma. To investigate the biological systems targeted by miR-125b-1-3p and also involved in the effects of stress, we combined the list of biological pathways modulated by predicted and validated target genes of miR-125b-1-3p, with the biological systems significantly regulated by cortisol in the in vitro model. We found, as common pathways, the CXCR4 signaling, the G-alpha signaling, and the P2Y Purigenic Receptor Signaling Pathway, which are all involved in neurodevelopmental processes. Our data, obtained from the combining of miRNAs datasets across different tissues and species, identified miR-125b-1-3p as a key marker associated with the long-term effects of stress early in life and also with the enhanced vulnerability of developing SZ. The identification of such a miRNA biomarker could allow the early detection of vulnerable subjects for SZ and could provide the basis for the development of preventive therapeutic strategies.

Prefrontal glutamate levels predict altered amygdala-prefrontal connectivity in traumatized youths.

BACKGROUND: Neurobiological models of stress and stress-related mental illness, including post-traumatic stress disorder, converge on the amygdala and the prefrontal cortex (PFC). While a surge of research has reported altered structural and functional connectivity between amygdala and the medial PFC following severe stress, few have addressed the underlying neurochemistry. METHODS: We combined resting-state functional magnetic resonance imaging measures of amygdala connectivity with in vivo MR-spectroscopy (1H-MRS) measurements of glutamate in 26 survivors from the 2011 Norwegian terror attack and 34 control subjects. RESULTS: Traumatized youths showed altered amygdala-anterior midcingulate cortex (aMCC) and amygdala-ventromedial prefrontal cortex (vmPFC) connectivity. Moreover, the trauma survivors exhibited reduced levels of glutamate in the vmPFC which fits with the previous findings of reduced levels of Glx (glutamate + glutamine) in the aMCC (Ousdal et al., 2017) and together suggest long-term impact of a traumatic experience on glutamatergic pathways. Importantly, local glutamatergic metabolite levels predicted the individual amygdala-aMCC and amygdala-vmPFC functional connectivity, and also mediated the observed group difference in amygdala-aMCC connectivity. CONCLUSIONS: Our findings suggest that traumatic stress may influence amygdala-prefrontal neuronal connectivity through an effect on prefrontal glutamate and its compounds. Understanding the neurochemical underpinning of altered amygdala connectivity after trauma may ultimately lead to the discovery of new pharmacological agents which can prevent or treat stress-related mental illness.

Revenge is sour, but is forgiveness sweet? Psychological health and cortisol reactivity among women with experiences of abuse.

This study examined the relations among women's experiences of abuse, forgiveness, revenge, psychological health, and physiological stress reactivity. Both dispositional (Study 1; N = 103) and state (Study 2; N = 258) forgiveness and vengeance were associated with psychological symptoms. However, the relation between revenge and greater depression was magnified among psychologically abused women, whereas-unexpectedly-the positive link between forgiveness and psychological health was strengthened among physically abused women. Moreover, while revenge coincided with increased cortisol reactivity following any relationship conflict, this was only evident for forgiveness following physical abuse. The complex interactions among these variables are discussed within a stress and coping framework.

Hair cortisol and childhood trauma predict psychological therapy response in depression and anxiety disorders.

OBJECTIVE: Around 30-50% of patients with depression and anxiety disorders fail to respond to standard psychological therapy. Given that cortisol affects cognition, patients with altered hypothalamic-pituitary-adrenal (HPA) axis functioning may benefit less from such treatments. To investigate this, reliable pretreatment cortisol measures are needed. METHOD: N = 89 outpatients with depression and anxiety disorders were recruited before undergoing therapy within an Improving Access to Psychological Therapies (IAPT) service. Three-month hair cortisol was determined, and the Childhood Trauma Questionnaire was administered. Patients were classified as responders if they showed significant decreases in depression (>= 6 points on the Patient Health Questionnaire) or anxiety (>= 5 points on the Generalised Anxiety Disorder Scale). RESULTS: Non-responders in terms of depression (57%) had lower pretreatment hair cortisol concentrations (P = 0.041) and reported more physical abuse (P = 0.024), sexual abuse (P = 0.010) and total trauma (P = 0.039) when compared to responders. Non-responders in terms of anxiety (48%) had lower pretreatment hair cortisol (P = 0.027), as well as higher levels of emotional abuse (P = 0.034), physical abuse (P = 0.042) and total trauma (P = 0.048). CONCLUSION: If future research confirms hair cortisol to be a predictor of psychological therapy response, this may prove a useful clinical biomarker which identifies a subgroup requiring more intensive treatment.

Impact of stress response systems on forced choice recognition in an experimental trauma film paradigm.

INTRODUCTION: Traumatic events are often followed by memory impairments of key features of the trauma. Stress hormones are involved in emotional memory formation. However, little is known about their influence during trauma on subsequent recognition memory. MATERIAL AND METHODS: A pooled analysis of two double-blind, placebo-controlled studies (N = 175) was performed to assess the influence of the noradrenergic system and the hypothalamus-pituitaryadrenal (HPA) axis on intrusion formation. Participants received either 10 mg yohimbine (stimulating noradrenergic activity), 0.15 mg clonidine (inhibiting noradrenergic activity), or placebo (noradrenergic manipulation study) or 20 mg hydrocortisone or placebo (hydrocortisone manipulation study), each 60 min before watching a distressing film depicting severe sexual and physical violence. After seven days, the participants performed a 24-item forced choice recognition test. Memory was assessed for pre-, peri-, and post-trauma film scenes. RESULTS: A significant film scene by intervention interaction indicated a differential influence of drug intervention on the number of correct pre-, peri-, and post-trauma film scene memories one week after the distressing film. Post hoc tests revealed that clonidine led to significantly fewer correct peri-trauma film scene memories compared to placebo and, on a trend level, to yohimbine. DISCUSSION: Pharmacological inhibition of noradrenaline during a distressing film leads to impaired emotional recognition memory for the peri-trauma film scene.