Ylide-Stabilized Phosphenium Cations: Impact of the Substitution Pattern on the Coordination Chemistry.

Although N-heterocyclic phosphenium (NHP) cations have received considerable research interest due to their application in organocatalysis, including asymmetric synthesis, phosphenium cations with other substitution patterns have hardly been explored. Herein, the preparation of a series of ylide-substituted cations of type [YPR]+ (with Y=Ph3 PC(Ph), R=Ph, Cy or Y) and their structural and coordination properties are reported. Although the diylide-substituted cation forms spontaneous from the chlorophosphine precursor, the monoylidylphosphenium ions required the addition of a halide-abstraction reagent. The molecular structures of the cations reflected the different degrees of electron donation from the ylide to the phosphorus center depending on the second substituent. Molecular orbital analysis confirmed the stronger donor properties of the ylide systems compared to NHPs with the mono-ylide substituted cations featuring a more pronounced electrophilicity. This was mirrored by the reaction of the cations towards gold chloride, in which only the diylide-substituted cation [Y2 P]+ formed the expected LAuCl]+ complex, while the monoylide-substituted compounds reacted to the chlorophosphine ligands by transfer of the chloride from gold to the phosphorus center. These results demonstrate the tunability of ylide-functionalized phosphorus cations, which should allow for further applications in coordination chemistry in the future.

Contemplative Mental Training Reduces Hair Glucocorticoid Levels in a Randomized Clinical Trial.

OBJECTIVE: This study aimed to investigate the effect of regular contemplative mental training on endocrine and psychological indices of long-term stress. METHODS: An open-label efficacy trial that comprised three distinct 3-month long modules targeting attention and interoception, socioaffective, or sociocognitive abilities through dyadic exercises and secularized meditation practices was conducted with healthy adults. Participants underwent the training for 3 or 9 months, or were assigned to a retest control cohort. Chronic stress indices were assayed at four time points: pretraining and after 3, 6, and 9 months. The main outcome measures were cortisol (HC) and cortisone (HE) concentration in hair and self-reported long-term stress. RESULTS: Of 362 initially randomized individuals, 30 dropped out before study initiation (n = 332; mean [SD] age = 40.7 [9.2] years; 197 women). Hair-based glucocorticoid assays were available from n = 227, and questionnaire data from n = 326. Results from three separate training cohorts (TC1-3) revealed consistent decreases in HC and HE levels over the first three (TC3) to 6 months (TC1 and TC2) of training, with no further reduction at the final 9-month mark (baseline to end of training differences, HC, TC1: t(355) = 2.59, p = .010, contrast estimate (est.) [SE] = 0.35 [0.14]; HC, TC2: t(363) = 4.06, p < .001, est. = 0.48 [0.12]; HC, TC3: t(368) = 3.18, p = .002, est. = 0.41 [0.13]; HE, TC1: t(435) = 3.23, p = .001, est. = 0.45 [0.14]; HE, TC2: t(442) = 2.60, p = .010, est. = 0.33 [0.13]; HE, TC3: t(446) = 4.18, p < .001, est. = 0.57 [0.14]). Training effects on HC increased with individual compliance (practice frequency), and effects on both HC and HE were independent of training content and unrelated to change in self-reported chronic stress. Self-reported stress, and cortisol-to-dehydroepiandrosterone ratios as an exploratory endpoint, were also reduced, albeit less consistently. CONCLUSIONS: Our results point to the reduction of long-term cortisol exposure as a mechanism through which meditation-based mental training may exert positive effects on practitioners' health.Trial Registration: ClinicalTrials.gov identifier: NCT01833104.

Hair cortisol levels in posttraumatic stress disorder and metabolic syndrome.

Individuals with post-traumatic stress disorder (PTSD) evidence increased rates of metabolic syndrome (MetS), and both PTSD and MetS are associated with alterations in hypothalamic-pituitary-adrenal (HPA) axis function. Few investigations have examined the possible role of HPA-axis dysfunction in the co-occurrence of PTSD and MetS. In a case-control study, we aimed to determine whether hair cortisol concentrations (HCC) were associated with (i) PTSD caseness and severity and (ii) PTSD and MetS co-occurrence. We used the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) to determine PTSD diagnoses and severity scores in 216 females of mixed ancestry aged between 20 and 79 years (M = 43.8, SD =13.3). Hair samples, representing a three-month retrospective window of cortisol levels, were obtained and analyzed utilizing liquid chromatography-tandem mass spectrometry. We constructed multivariate linear regression models to evaluate whether PTSD diagnosis, PTSD severity, and MetS comorbidity were associated with HCC, controlling for potential confounders. HCC were significantly higher (adj ß = 0.154, p = .033; Cohen's d = 0.44) in PTSD patients (n = 110) than trauma-exposed controls (n = 106) and CAPS severity scores (adj ß = 0.207, p = .005) were significantly associated with HCC. MetS was not associated with HCC and there were no significant interactions between PTSD and MetS on HCC. This study provides evidence of a chronically dysregulated neuroendocrine mediated stress response in PTSD, with a clear dose-response relationship. HCC do not, however, appear to have specificity for the comorbidity of PTSD and MetS in this sample.LAY SUMMARYWe found that levels of the stress hormone, cortisol, measured in hair samples were significantly higher in South African women with post-traumatic stress disorder (PTSD) than in women who had also experienced trauma but did not have PTSD. Hair cortisol levels were, however, not associated with metabolic syndrome, a cluster of risk factors for heart disease, in the women studied. We thus show that South African women with PTSD have elevated long-term stress hormone levels and that this effect is related to PTSD and not solely due to trauma exposure.

Altered reward learning and hippocampal connectivity following psychosocial stress.

Acute stress has a profound influence on learning, as has been demonstrated in verbal learning or fear conditioning. However, its effect on appetitive conditioning is still unclear. Fear conditioning research suggests the possibility of overgeneralization of conditioning to the CS- under acute stress due to its effect on prefrontal and hippocampal processing. In this study, participants (N = 56 males) were subjected to the Trier Social Stress Test or a placebo version. After that, all participants underwent an appetitive conditioning paradigm in the fMRI, in which one neutral cue (CS+) was repeatedly paired with reward, while another (CS-) was not. Importantly, the stress-group revealed overgeneralization of conditioning to the CS- on the behavioral level. On the neural level, stressed participants showed increased connectivity between the hippocampus and amygdala, vACC, and OFC, which maintain specificity of conditioning and also showed reduced differential activation. The results indicate overgeneralization of appetitive conditioning promoted by maladaptive balancing of pattern separation and pattern completion in the hippocampus under acute stress and are discussed with respect to clinical implications.

Neural correlates of subjective CS/UCS association in appetitive conditioning.

Explicit knowledge of conditioned stimulus (CS)/unconditioned stimulus (UCS) associations is proposed as important factor in classical conditioning. However, while previous studies have focused on its roles in fear conditioning, it has been neglected in the context of appetitive conditioning. The present functional magnetic resonance study aimed to investigate neural activation and functional connectivity linked to subjective CS/UCS association in appetitive conditioning. In total, 85 subjects participated in an appetitive acquisition procedure in which a neutral stimulus (CS+) was paired with a monetary reward, while another neutral stimulus (CS-) was never paired with the reward. Directly afterwards, subjective CS/UCS association was assessed by measuring the extent to which the CS+ was thought to be associated with the UCS compared to the CS-. Close relationships were established between subjective CS/UCS association and activations in the primary visual cortex (V1) during the early phase of conditioning and in the striatum during the late conditioning phase. In addition, we observed inverse relationships between subjective CS/UCS association and both V1/ventromedial prefrontal cortex (vmPFC) and striatal/vmPFC connectivity. The results suggest the involvement of decoupling vmPFC connectivity in reward learning in general and the roles of attentional processes in the formation of the subjective CS/UCS association during the early phase and reward prediction during the late phase of appetitive conditioning.

Childhood Trauma, Perceived Stress, and Hair Cortisol in Adults With and Without Cardiovascular Disease.

OBJECTIVE: Childhood trauma has been associated with greater psychological and physical morbidity, including a greater risk of developing cardiovascular disease (CVD). This may partially reflect trauma-induced disturbances in how stress is later perceived and regulated. This study evaluated the associations of childhood trauma with perceived stress and hair cortisol concentrations (HCC) in a large sample of adults with coronary artery disease (CAD) and in non-CVD patients experiencing other nonfatal illnesses. Whether sex, age, or CVD status influenced these associations was also examined. METHODS: A total of 1124 men and women (aged 65.2 [6.9] years) recruited from a hospital cohort completed the Childhood Trauma and Perceived Stress Questionnaires, whereas hair samples were obtained from 598 participants. Health status was confirmed via medical records. RESULTS: Moderate to severe childhood trauma was experienced by 359 participants. Childhood trauma was associated with greater perceived stress levels for the past 2 years (r = .308, p = .01; ß = 0.263, p < .001), but not 3-month cortisol secretion in hair. Perceived stress correlated negatively with age (r = -.241, p < .001). In secondary analyses, age moderated the relation between sexual abuse and perceived stress (ß = -0.067, p = .016). Although sexual abuse was associated with greater levels of perceived stress among all participants, this relation was strongest in younger individuals. CONCLUSIONS: Participants who experienced trauma in their youth reported greater levels of perceived stress, but not HCC, in late adulthood. Whether this suggests intact hypothalamic-pituitary-adrenal regulation in those exposed to childhood trauma or whether this reflects the characteristics of our sample requires further investigation.

Exploring the multidimensional complex systems structure of the stress response and its relation to health and sleep outcomes.

To gain a comprehensive understanding of the multidimensional complex systems structure of the stress response and related health outcomes, we utilized network analysis in a sample of 328 healthy participants in two steps. In a first step, we focused on associations between measures of basal hypothalamic-pituitary-adrenal axis functioning and subjective stress perceptions. In a second step, we linked these diverse stress-related measures to biomarkers and self-reports of health and sleep. Overall, measures clustered depending on their method of assessment, with high correlations between different saliva-based indices of diurnal cortisol regulation, between cortisol and cortisone levels in hair, between different biological health indicators (systemic inflammatory activity and body mass index), between state (experience sampling) and trait (questionnaire-based) self-reports of stress and wellbeing, and between different self-reports of sleep. Bridges between clusters suggested that if individuals perceive stress throughout their daily lives this is reflected in their total salivary cortisol output possibly contributing to long-term cortisol accumulation in hair. Likewise, earlier awakening time may contribute to cortisol accumulation in hair via an influence on awakening cortisol processes. Our results show that while meaningful connections between measures exist, stress is a highly complex construct composed of numerous aspects. We argue that network analysis is an integrative statistical approach to address the multidimensionality of the stress response and its effects on the brain and body. This may help uncover pathways to stress-related disease and serve to identify starting points for prevention and therapeutic intervention.

Reduced self-regulation mirrors the distorting effects of burnout symptomatology on task difficulty perception during an inhibition task.

Burnout, a pathological consequence of chronic work stress, shows an increasing incidence rate in industrialized countries. Previous findings indicate that burnout may be linked to a detachment of the negative association between subjectively appraised task demand and cognitive performance, which is typically seen in healthy individuals. The present study sought to confirm this relationship and to investigate whether this dissociation is mirrored in a biological marker of self-regulation, i.e., resting vagally mediated heart rate variability (HRV). A heterogeneous sample (N = 65) of working adults (M age = 43.3, SD = 10; 23.1 % male) with varying degrees of burnout symptomatology completed three cognitive tasks (2-back, number-letter, and go/nogo) to assess different domains of executive functioning (updating, set-shifting, and inhibition), and respective demand ratings. Additionally, vagally mediated HRV at rest, operationalized as the root-mean square differences of successive R-R intervals (RMSSD), was recorded. Burnout symptomatology moderated the association between subjective task difficulty and performance parameters of the go/nogo task, such that higher burnout scores were associated with reductions in the naturally occurring negative association between self-rated task demand and response inhibition. Intriguingly, this pattern was mirrored when replacing burnout with HRV. These findings suggest that burnout symptomatology, and individual differences in self-regulatory capacities (indexed by resting HRV), may alter one's capacity for accurate task evaluation, a mechanism which could potentially underlie the dissociation between self-rated cognitive function and actual performance among individuals experiencing burnout.

Biological stress indicators as risk markers for increased alcohol use following traumatic experiences.

Alcohol misuse is a common sequela of traumatic event experiences causing considerable morbidity and mortality. Although biological stress indicators have been identified as useful risk markers for the development of trauma-related disorders, no such biological indicators exist for the risk of increased alcohol use after trauma exposure. This is the first study to prospectively investigate the predictive value of long-term cortisol levels and acute stress reactivity for the risk of increased alcohol use following traumatic events. Male soldiers were examined before and 12 months following deployment using a standardized diagnostic interview. We analyzed the moderating role of baseline hair cortisol concentrations (HCCs, n = 153) as well as baseline salivary cortisol and alpha-amylase stress reactivity in response to a laboratory stressor (n = 145) in the association between new-onset traumatic events (according to the DSM-IV A1 criterion) and subsequent daily alcohol use. No main effects of pre-traumatic HCC or salivary stress markers on subsequent change in alcohol use were observed. However, we found that with decreasing HCC, the number of new-onset traumatic events was more strongly associated with subsequent alcohol use independent from changes in posttraumatic stress disorder symptoms. No such relation was seen for the acute stress reactivity data. Taken together, this study provides first evidence suggesting that individual differences in long-term cortisol regulation are involved in the association between traumatic experiences and subsequent alcohol use. HCC may thus serve as a potential target in the early identification of individuals vulnerable for increased alcohol use following traumatic events.

Commentary: The importance of exploring dose-dependent, subtype-specific, and age-related effects of maltreatment on the HPA axis and the mediating link to psychopathology. A response to Fisher (2017).

We greatly appreciate Dr. Fisher's commentary that provides an excellent backdrop and well-considered perspective on our findings. We agree that our results mesh well with previous work documenting hypocortisolism among youth who experienced early adversity, especially neglect. Moreover, as also perceptively noted by Dr. Fisher, our cross-sectional data provide support for the notion that hypocortisolism is not simply a transient phenomenon, but, rather, a persistent pattern characterizing maltreated youth. Specifically, the consistency of the between group effect (from age 9.69 onwards) on a multimonth index of cumulative cortisol and the dose-dependent gradient of cortisol secretion within the maltreated group, which was related to the number of subtypes and the length of exposure to maltreatment, lend weight to this view.

Reduced hair cortisol after maltreatment mediates externalizing symptoms in middle childhood and adolescence.

BACKGROUND: The enduring impact of childhood maltreatment on biological systems and ensuing psychopathology remains incompletely understood. Long-term effects of stress may be reflected in cumulative cortisol secretion over several months, which is now quantifiable via hair cortisol concentrations (HCC). We conducted a first comprehensive investigation utilizing the potential of hair cortisol analysis in a large sample of maltreated and nonmaltreated children and adolescents. METHOD: Participants included 537 children and adolescents (3-16 years; 272 females) with maltreatment (n = 245) or without maltreatment histories (n = 292). Maltreated subjects were recruited from child protection services (CPS; n = 95), youth psychiatric services (n = 56), and the community (n = 94). Maltreatment was coded using the Maltreatment Classification System drawing on caregiver interviews and complemented with CPS records. Caregivers and teachers reported on child mental health. HCC were assessed in the first 3 cm hair segment. RESULTS: Analyses uniformly supported that maltreatment coincides with a gradual and dose-dependent reduction in HCC from 9 to 10 years onwards relative to nonmaltreated controls. This pattern emerged consistently from both group comparisons between maltreated and nonmaltreated subjects (27.6% HCC reduction in maltreated 9-16-year-olds) and dimensional analyses within maltreated subjects, with lower HCC related to greater maltreatment chronicity and number of subtypes. Moreover, both group comparisons and dimensional analyses within maltreated youth revealed that relative HCC reduction mediates the effect of maltreatment on externalizing symptoms. CONCLUSIONS: From middle childhood onwards, maltreatment coincides with a relative reduction in cortisol secretion, which, in turn, may predispose to externalizing symptoms.

Maternal prenatal stress and child atopic dermatitis up to age 2 years: The Ulm SPATZ health study.

BACKGROUND: Evidence linking maternal psychosocial stress during pregnancy to subsequent child atopic dermatitis (AD) is growing, but the definition of AD is diverse and results are inconsistent. We aimed to analyze the relationship between stress and AD using alternative measurements of stress and AD. METHODS: In the Ulm SPATZ Health Study, chronic stress and symptoms of anxiety and depression were assessed by standardized self-reported questionnaires in 934 mothers of singletons following delivery in Ulm, Germany, from 04/2012-05/2013. Maternal hair cortisol concentrations (HCCs, n = 626) at childbirth and the cumulative incidences of parent-reported child AD symptoms, parent-, and pediatrician-reported AD diagnoses were assessed until age 2 years (n = 787). Overall, 205 dermatologic examinations were performed in 167 children showing AD symptoms. Crude and adjusted risk ratios (RR, aRR) with 95% confidence intervals were estimated. RESULTS: Maternal stress and anxiety were associated with child AD symptoms by trend (RR and aRR: 1.5 (1.0,2.3) for the highest vs. the lowest quarter of chronic stress; aRR: 1.4 (1.0,2.0) for possible anxiety symptoms vs. no symptoms). No relationship was found between stress or related constructs and AD diagnoses nor could we show consistent associations between maternal HCC and child AD. However, a higher RR of child AD was evident in families not yet affected by AD in siblings given maternal depressive symptoms, examined in the crude model. CONCLUSIONS: Stress measurements or related constructs are linked to AD symptoms, but association with AD diagnoses is limited. The reason for this divergence still needs further research.

The Association of Hair Cortisol with Self-Reported Chronic Psychosocial Stress and Symptoms of Anxiety and Depression in Women Shortly after Delivery.

BACKGROUND: Psychosocial stress during pregnancy including anxiety and depression is known to have adverse health effects on newborns. However, measuring these psychological constructs is complex with psychological, endocrinological, and physiological systems being affected. Hair cortisol concentrations (HCC), assumed to reflect long-term endocrine consequences of stress exposure, represent a promising instrument for epidemiological research. However, the association between HCC and questionnaire-based instruments is unclear. METHODS: In the Ulm SPATZ Health Study, mothers were recruited shortly after delivery in the University Medical Centre Ulm, Germany between April 2012 and May 2013. HCC of 768 participants were determined in scalp-near 3 cm maternal hair segments, assumed to reflect cortisol exposure over the last trimester of pregnancy. Chronic stress, anxiety, and depressive symptomatology were self-reported in questionnaire-based instruments. Spearman correlation coefficients between HCC and these instruments as well as means of HCC in highly and low stressed subgroups were calculated. RESULTS: HCC were not correlated with self-reported chronic stress, anxiety, or depressive symptomatology. Furthermore, the investigation of sub-populations did not reveal substantial differences of HCC across highly and low stressed women. CONCLUSIONS: HCC were not found to correlate with self-reports of chronic stress, anxiety, or depressive symptomatology. Among other things, these findings could reflect problems with questionnaire-based assessments obtained shortly after delivery such as recall bias and/or suggest that associations between cortisol secretion and psychosocial stress are difficult to detect due to, e.g. a strong physiological increase of cortisol in the last trimester.

Hair Cortisol Concentrations in Adolescent Girls with Anorexia Nervosa are Lower Compared to Healthy and Psychiatric Controls.

OBJECTIVE: In anorexia nervosa (AN) hypercortisolism has been described using urine, plasma and saliva samples as short-term markers for the hypothalamic-pituitary-adrenal (HPA)-axis. Here, for the first time, we analyse hair cortisol concentration (HCC) as a marker for long-term integrated cortisol secretion in female patients with AN compared to female healthy controls (HC) and female psychiatric controls (PC). METHODS: HCC was assessed in 22 female adolescent psychiatric inpatients with AN compared to 20 female HC and to 117 female PC of the same age range. For further analyses we examined the associations of age and body mass index (BMI) with HCC. RESULTS: Log HCC was lower in AN-patients compared to HC (p = 0.030). BMI-standard deviation scores (SDS) but not age correlated with log HCC (BMI-SDS: r = 0.19, bias corrected accelerated 95% confidence interval: [.04, .34], p = 0.015; age: r = 0.10, bias corrected accelerated 95% confidence interval: [-.07, .25], p = 0.213) when combining AN, HC and PC samples. DISCUSSION: We find lower HCC in AN, compared to HC and PC, respectively. Based on the relationship between HCC and BMI-SDS across AN, HC and PC, we argue that HCC might not capture endocrine alterations because of AN pathology-related processes but rather shows consistent relationships with BMI, which extent even to the very low range of BMI values, as present in AN patients. Alternatively, incorporation of cortisol into the hair follicle might have been compromised because of trophic hair follicle disturbances that had been reported in AN patients, previously. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

Toward standardization of hair cortisol measurement: results of the first international interlaboratory round robin.

BACKGROUND: The importance of hair cortisol as a long-term retrospective measure of systemic cortisol exposure is being increasingly recognized, and over recent years, the field of hair cortisol analysis has seen rapid expansion with laboratories around the globe, integrating hair cortisol analysis into their study designs. These laboratories use different methods of analysis, and presently, no attempt has been made to compare them. To move toward clinical utilization of this novel method, international benchmark reference values must be established. For that end, 4 leading laboratories in hair cortisol testing set up a protocol for comparison of the methods used by them. METHODS: Four immunoassay methods and 2 liquid chromatograph-mass spectrometry (LC-MS/MS) methods were compared by analyzing the same hair samples representing the low, intermediate, and high ranges of hair cortisol concentrations (HCC). RESULTS: HCC determined by the 4 immunoassay methods were highly and positively intercorrelated (r(2) between 0.92 and 0.97; all P < 0.0001) in all comparisons of individual laboratories. Additionally, each laboratory's immunoassay HCC had significant positive correlations (r(2) between 0.88 and 0.97; all P < 0.0001) with each of the 2 LC-MS/MS methods, which produced practically identical results. CONCLUSIONS: This study indicates that laboratories using immunoassays can use a correction factor that will convert results into standard LC-MS/MS equivalents.

Analyzing pathways from childhood maltreatment to internalizing symptoms and disorders in children and adolescents (AMIS): a study protocol.

BACKGROUND: Effective interventions for maltreated children are impeded by gaps in our knowledge of the etiopathogenic mechanisms leading from maltreatment to mental disorders. Although some studies have already identified individual risk factors, there is a lack of large-scale multilevel research on how psychosocial, neurobiological, and genetic factors act in concert to modulate risk of internalizing psychopathology in childhood following maltreatment. To help close this gap, we aim to delineate gender-specific pathways from maltreatment to psychological disorder/resilience. To this end, we examine the interplay of specific maltreatment characteristics and psychological, endocrine, metabolomic, and (epi-)genomic stress response patterns as well as cognitive-emotional/social processes as determinants of developmental outcome. Specifically, we will explore endocrine, metabolomic, and epigenetic mechanisms leading from maltreatment to a higher risk of depression and anxiety disorders. METHODS/DESIGN: Four large samples amounting to a total of N = 920 children aged 4-16 years will be assessed: Two cohorts with prior internalizing psychopathology and controls will be checked for maltreatment and two cohorts with substantiated maltreatment will be checked for internalizing (and externalizing) psychopathology. We will apply a multi-source (interview, questionnaires, official records), multi-informant strategy (parents, children, teachers) to assess maltreatment characteristics (e.g., subtypes, developmental timing, chronicity) and psychopathological symptoms, supplemented with multiple measurements of risk and protective factors and cutting-edge laboratory analyses of endocrine, steroid metabolomic and epigenetic factors. As previous assessments in the two largest samples are already available, longitudinal data will be generated within the three year study period. DISCUSSION: Our results will lay the empirical foundation for (a) detection of early biopsychosocial markers, (b) development of screening measures, and

Reduced memory skills and increased hair cortisol levels in recent Ecstasy/MDMA users: significant but independent neurocognitive and neurohormonal deficits.

OBJECTIVES: The goals of this study were to measure the neurocognitive performance of recent users of recreational Ecstasy and investigate whether it was associated with the stress hormone cortisol. METHODS: The 101 participants included 27 recent light users of Ecstasy (one to four times in the last 3 months), 23 recent heavier Ecstasy users (five or more times) and 51 non-users. Rivermead paragraph recall provided an objective measure for immediate and delayed recall. The prospective and retrospective memory questionnaire provided a subjective index of memory deficits. Cortisol levels were taken from near-scalp 3-month hair samples. RESULTS: Cortisol was significantly raised in recent heavy Ecstasy users compared with controls, whereas hair cortisol in light Ecstasy users was not raised. Both Ecstasy groups were significantly impaired on the Rivermead delayed word recall, and both groups reported significantly more retrospective and prospective memory problems. Stepwise regression confirmed that lifetime Ecstasy predicted the extent of these memory deficits. CONCLUSIONS: Recreational Ecstasy is associated with increased levels of the bio-energetic stress hormone cortisol and significant memory impairments. No significant relationship between cortisol and the cognitive deficits was observed. Ecstasy users did display evidence of a metacognitive deficit, with the strength of the correlations between objective and subjective memory performances being significantly lower in the Ecstasy users.

Trauma exposure is associated with increased context-dependent adjustments of cognitive control in patients with posttraumatic stress disorder and healthy controls.

Recent evidence has suggested that posttraumatic stress disorder (PTSD) is associated with alterations in prefrontal-cortex-dependent cognitive processes (e.g., working memory, cognitive control). However, it remains unclear whether these cognitive dysfunctions are related to PTSD symptomatology or trauma exposure. Furthermore, regarding cognitive control, research has only focused on the integrity of selected control functions, but not their dynamic regulation in response to changing environmental demands. Therefore, the present study investigated dynamic variations in interference control, in addition to overall interference susceptibility and working memory (WM) performance in matched groups of 24 PTSD patients and 26 traumatized and 30 nontraumatized healthy controls. The Simon task was used to measure overall interference susceptibility and the flexible adjustment of cognitive control, on the basis of the occurrence of response conflicts (conflict adaptation effect). WM performance was assessed with the forward and backward digit span tasks. Since we have previously shown that trauma exposure per se is associated with reduced hair cortisol concentrations (HCC), we further explored whether PTSD/trauma-related cognitive alterations are related to HCC in proximal 3-cm hair segments. The results revealed that PTSD patients and traumatized controls showed significantly more pronounced conflict adaptation effects than nontraumatized controls. Moreover, the conflict adaptation effect was positively related to the number of lifetime traumatic events and the frequency of traumatization. The groups did not differ in overall interference susceptibility or WM performance. Exploratory analyses revealed no association between HCC and the observed cognitive differences. These results suggest that context-driven control adjustments constitute a sensitive correlate of trauma exposure, irrespective of PTSD.

Consistent associations between measures of psychological stress and CMV antibody levels in a large occupational sample.

Cytomegalovirus (CMV) is a herpes virus that has been implicated in biological aging and impaired health. Evidence, largely accrued from small-scale studies involving select populations, suggests that stress may promote non-clinical reactivation of this virus. However, absent is evidence from larger studies, which allow better statistical adjustment for confounding and mediating factors, in more representative samples. The present study involved a large occupational cohort (N=887, mean age=44, 88% male). Questionnaires assessed psychological (i.e., depression, anxiety, vital exhaustion, SF-12 mental health), demographic, socioeconomic (SES), and lifestyle variables. Plasma samples were analyzed for both the presence and level of CMV-specific IgG antibodies (CMV-IgG), used as markers for infection status and viral reactivation, respectively. Also assessed were potential biological mediators of stress-induced reactivation, such as inflammation (C-reactive protein) and HPA function (awakening and diurnal cortisol). Predictors of CMV infection and CMV-IgG among the infected individuals were analyzed using logistic and linear regression analyses, respectively. Confirming prior reports, lower SES (education and job status) was positively associated with infection status. Among those infected (N=329), higher CMV-IgG were associated with increased anxiety (ß=.14, p<.05), depression (ß=.11, p=.06), vital exhaustion (ß=.14, p<.05), and decreased SF-12 mental health (ß=-.14, p<.05), adjusting for a range of potential confounders. Exploratory analyses showed that these associations were generally stronger in low SES individuals. We found no evidence that elevated inflammation or HPA-function mediated any of the associations. In the largest study to date, we established associations between CMV-IgG levels and multiple indicators of psychological stress. These results demonstrate the robustness of prior findings, and extend these to a general working population. We propose that stress-induced CMV replication warrants further research as a psychobiological mechanism linking stress, aging and health.