The ReCoDe addiction research consortium: Losing and regaining control over drug intake-Findings and future perspectives.

Substance use disorders (SUDs) are seen as a continuum ranging from goal-directed and hedonic drug use to loss of control over drug intake with aversive consequences for mental and physical health and social functioning. The main goals of our interdisciplinary German collaborative research centre on Losing and Regaining Control over Drug Intake (ReCoDe) are (i) to study triggers (drug cues, stressors, drug priming) and modifying factors (age, gender, physical activity, cognitive functions, childhood adversity, social factors, such as loneliness and social contact/interaction) that longitudinally modulate the trajectories of losing and regaining control over drug consumption under real-life conditions. (ii) To study underlying behavioural, cognitive and neurobiological mechanisms of disease trajectories and drug-related behaviours and (iii) to provide non-invasive mechanism-based interventions. These goals are achieved by: (A) using innovative mHealth (mobile health) tools to longitudinally monitor the effects of triggers and modifying factors on drug consumption patterns in real life in a cohort of 900 patients with alcohol use disorder. This approach will be complemented by animal models of addiction with 24/7 automated behavioural monitoring across an entire disease trajectory; i.e. from a naïve state to a drug-taking state to an addiction or resilience-like state. (B) The identification and, if applicable, computational modelling of key molecular, neurobiological and psychological mechanisms (e.g., reduced cognitive flexibility) mediating the effects of such triggers and modifying factors on disease trajectories. (C) Developing and testing non-invasive interventions (e.g., Just-In-Time-Adaptive-Interventions (JITAIs), various non-invasive brain stimulations (NIBS), individualized physical activity) that specifically target the underlying mechanisms for regaining control over drug intake. Here, we will report on the most important results of the first funding period and outline our future research strategy.

Characterization of hair cortisol concentration pre-conception and during pregnancy.

BACKGROUND: The hypothalamic pituitary adrenal (HPA) axis is a system involved in stress and pregnancy regulation, and hair cortisol concentration (HCC) is a promising biomarker of its activity. Assessing factors that influence HCC in the prenatal period is critical to understand whether and how HPA axis (dys-)regulation influences maternal health and child development, particularly in high-risk populations from low- and middle-income countries (LMICs). AIMS: This study aimed at characterizing preconception and pregnancy HCC with respect to multiple sociodemographic, pregnancy-related, and hair-related factors. METHODS: In a sample of N = 2581 pregnant women in Perú, participants from two cohort studies provided a 6 cm scalp hair sample at three prenatal timepoints. Each hair sample was cut into two segments of 3 cm that represent cortisol secretion at four times: preconception, first-, second- and third trimester of pregnancy. Hair cortisol was extracted using liquid chromatography tandem mass spectrometry (LC-MS/MS). Spearman correlations, paired t-tests, and ANOVA were used to assess differences in log-transformed values of HCC (logHCC) across maternal sociodemographic, pregnancy-related, and hair-related factors. Multivariable linear regressions were used to examine independent associations of HCCs with selected correlates. RESULTS: Mean logHCC values showed an increase across the four prenatal periods. Preconception BMI was consistently associated with HCC in all three trimesters, while difficulty accessing basic foods, education, hair dyeing, and infant sex showed time-specific associations with HCCs. In sensitivity analyses, we detected no substantial segment effects in the associations of HCCs with maternal characteristics. CONCLUSION: This study is the largest to characterize HCC in pregnant women from a LMIC. Our findings provide a foundation for the use of HCC as a biomarker of prenatal HPA axis activity for future studies. This foundation may contribute to finding valid biomarkers of stress-response systems to promote maternal and child health.

Differences in Physicians' Ratings of Work Stressors and Resources Associated With Digital Transformation: Cross-Sectional Study.

BACKGROUND: The emergence of the COVID-19 pandemic rapidly accelerated the need and implementation of digital innovations, especially in medicine. OBJECTIVE: To gain a better understanding of the stress associated with digital transformation in physicians, this study aims to identify working conditions that are stress relevant for physicians and differ in dependence on digital transformation. In addition, we examined the potential role of individual characteristics (ie, age, gender, and actual implementation of a digital innovation within the last 3 years) in digitalization-associated differences in these working conditions. METHODS: Cross-sectional web-based questionnaire data of 268 physicians (mean age 40.9, SD 12.3 y; n=150, 56% women) in Germany were analyzed. Physicians rated their chronic stress level and 11 relevant working conditions (ie, work stressors such as time pressure and work resources such as influence on sequence) both before and after either a fictional or real implementation of a relevant digital transformation at their workplace. In addition, a subsample of individuals (60; n=33, 55% women) submitted self-collected hair samples for cortisol analysis. RESULTS: The stress relevance of the selected working conditions was confirmed by significant correlations with self-rated chronic stress and hair cortisol levels (hair F) within the sample, all of them in the expected direction (P values between .01 and <.001). Multilevel modeling revealed significant differences associated with digital transformation in the rating of 8 (73%) out of 11 working conditions. More precisely, digital transformation was associated with potentially stress-enhancing effects in 6 working conditions (ie, influence on procedures and complexity of tasks) and stress-reducing effects in 2 other working conditions (ie, perceived workload and time pressure). Younger individuals, women, and individuals whose workplaces have implemented digital innovations tended to perceive digitalization-related differences in working conditions as rather stress-reducing. CONCLUSIONS: Our study lays the foundation for future hypothesis-based longitudinal research by identifying those working conditions that are stress relevant for physicians and prone to differ as a function of digital transformation and individual characteristics.

The Association Between Pre-Pregnancy and First-Trimester Hair Cortisol and Preterm Birth: A Causal Inference Model.

Background Adverse life events and chronic psychological distress before and during pregnancy have frequently been associated with preterm birth (PTB) but the biological underpinnings remain unclear. We investigated the association between corticosteroid levels in pre-pregnancy and first-trimester hair and the risk of PTB. Methods We followed 1,808 pregnant women from a prospective pre-birth cohort study in Lima, Perú. Hair samples were taken at the end of the first pregnancy trimester. The two most proximal 3cm segments to the scalp (representing pre-pregnancy and first-trimester) were analyzed to obtain hair cortisol and cortisone concentrations (HCC and HCNC). PTB was defined as birth < 37 completed gestational weeks. We constructed four generalized propensity scores for pre-pregnancy and first-trimester HCC and HCNC to create corresponding inverse probability weights before fitting marginal structural models for estimating the effect of HCC and HCNC on PTB risk. Results Pre-pregnancy Log HCC was not independently associated with PTB risk (RR = 0.97; 95%CI: 0.79, 1.19). In contrast, one SD increase from the mean first-trimester Log HCC was independently associated with a 37% (95%CI: 1.11, 1.69) increased risk of PTB. Although imprecise, pre-pregnancy Log HCNC was negatively associated with PTB risk (RR = 0.84; 95%CI: 0.58, 1.20), whereas the association between first-trimester Log HCNC and PTB risk was positive (RR = 1.20; 95%CI: 0.87, 1.65). Conclusions Our findings show that chronic corticosteroid levels in early pregnancy are causally linked to PTB risk in pregnant Peruvian women. This finding contributes to understanding the biological underpinnings of PTB better to enhance PTB prevention.

The association between maternal prenatal hair cortisol concentration and preterm birth: A systematic review and meta-analysis.

BACKGROUND: The risk of preterm birth (PTB) increases when experiencing stress during pregnancy. Chronic stress has been associated with a dysregulation of the hypothalamic-pituitary-adrenal axis, for which hair cortisol concentration (HCC) is a promising biomarker. However, previous studies on the association between HCC and PTB yielded inconsistent results. This systematic review and meta-analysis synthesized previous studies on the association between maternal HCC before and during pregnancy and spontaneous PTB. METHODS: Data was extracted from N = 11 studies with k = 19 effect sizes retrieved from PubMed, Embase, Web of Science, CINAHL and citation searching by hand in June 2023 and updated in October 2023. Standardized mean differences were calculated, and a random-effects three-level meta-analysis was conducted. Effect heterogeneity was assessed using Q and I2. RESULTS: HCC during pregnancy was higher among PTB than term groups, but effects were not statistically significant (z = 0.11, 95% CI: - 0.28, 0.51, p = .54) and total heterogeneity was high (Q16 = 60.01, p < .001, I2Total = 92.30%). After leaving out two possible outlier studies in sensitivity analyses, HCC was lower among preterm compared to term delivering groups, although not statistically significant (z = - 0.06, 95% CI: - 0.20, 0.08, p = .39) but with a substantially reduced total heterogeneity (Q12 = 16.45, p = .17, I2Total = 42.15%). No moderators affected the estimates significantly, but an effect of trimester and gestational age at delivery is likely. CONCLUSION: There is currently no evidence of prenatal HCC differences between PTB and term groups as effects were small, imprecise, and not significant. Low statistical power and methodological weaknesses of the small-scale studies challenge possible biological inferences from the small effects, but further research on HCC during pregnancy is highly encouraged.

Preliminary results of anti-inflammatory cytokine concentrations predicting therapy outcome in panic disorder.

Background: Patients with panic disorder (PD) show alterations of the immune reactivity to acute stress, which could serve as a marker for effective treatment. Nevertheless, the effect of immune reactivity under acute stress before treatment on therapy outcome remains unclear. Methods: A total of N = 16 PD patients performed the Trier Social Test. Blood sample collection of anti-inflammatory cytokine IL-10 accompanied the TSST. The Mobility Inventory was handed out for the assessment of avoidance behavior before and after treatment. Area under the curve with respect to the ground (AUCG) and increase (AUCI) were calculated for assessed cytokine levels and were used as predictors for therapy outcome in regression analyses. Results: AUCG significantly predicts avoidance behavior in company after treatment (ß = -0.007, p = .033) but not avoidance behavior alone (ß = -0.003, p = .264). AUCI does not significantly predict therapy outcome. Conclusion: Higher concentrations of anti-inflammatory cytokine IL-10 under acute stress before treatment predicts less avoidance behavior in company after therapy. Immune markers seem to play a crucial role in the maintenance of mental disorders such as PD. Underlying mechanisms and IL-10 as a marker for individualized treatments should be investigated in future studies.

Longitudinal effects of maternal depressive and anxious symptomatology on child hair cortisol and cortisone from pregnancy to 5-years: The EDEN mother-child cohort.

Exposure to maternal depressive and anxious symptomatology in utero and after birth can affect child outcomes. One proposed mechanism is through changes in child stress hormone levels, however current studies present inconsistent findings, and further research is needed to better understand the impact of maternal mental health on child stress response. This study aims to add to the limited literature by analysing longitudinal data ranging from 24 weeks amenorrhea to 5 years postpartum among 281 mother-child pairs from the French EDEN mother-child birth cohort. Hair cortisol and cortisone data were collected from children at four time points: birth, 1, 3, and 5 years. Mothers reported depressive symptomatology via the Center for Epidemiologic Studies Depression Scale (CES-D) (at 24-weeks amenorrhea, 3-, and 5-year follow-up), and the Edinburgh Postnatal Depression Scale (EPDS) (at 4, 8 and 12 months postpartum). Prenatal anxiety symptomatology was measured via the State Anxiety Inventory (STAI) at 24 weeks amenorrhea. Group-based trajectory modelling indicated a 1-cluster classification of longitudinal child hair cortisol, cortisone and cortisol-to-cortisone ratio, as analyses did not reveal a classification by subgroups representing different child profiles. After inverse probability weighting, small effects showed prenatal depressive symptomatology was significantly associated to higher levels of child hair cortisone at one year. Prenatal anxiety symptomatology was significantly linked to higher levels of child cortisol measured at birth and cortisone at birth and at 1 year. Postpartum depressive symptomatology at 8 months was related to higher levels of cortisone among 3-year-olds. These effects were not moderated by child sex or maternal socio-economic status. Further research is needed to understand why there are associations at some time points and not others to determine any potential buffering factors.

Exploring the potential of stratum corneum biomarkers for assessing psychological distress in health care workers: An observational pilot study.

Backgrounds: The detection of biomarkers of a stress response in the stratum corneum (SC) could be used as objective assessment of early stress symptoms and monitoring of stress reduction interventions in health care workers (HCWs). Aim: The aim of this study is to explore SC biomarkers of immune and hormonal response and skin barrier for assessment of psychological distress (PD) in HCWs. Methods: Twenty-five female HCWs and 25 non-HCWs participated. SC samples were collected using adhesive tapes at baseline and 3-5 days later (T1). We analyzed 24 biomarkers (immunological, vascular, hormones, and natural moisturizing factors). Stress symptoms were assessed using three scales of Copenhagen Psychosocial Questionnaire. The study involved: identifying SC biomarkers, correlating stress symptoms and biomarkers at baseline and T1, examining stress symptoms between the groups with a Mann-Whitney test, comparing stress symptoms and biomarkers between groups using Ordinary Least Regression and investigating temporal variability of SC biomarkers at baseline and T1 using a Wilcoxon-signed rank. Results: Fourteen SC biomarkers were identified. We found correlations between general stress and "IL18" (r = 0.55) physical stress and "IL1b" (r = 0.36) and cognitive stress and "MIP3a" (r = 0.38) at baseline and general stress and cortisol (r = -0.49), physical stress and cortisol (r = -0.60) and cortisone (r = -0.67) at T1. We found no differences in stress symptoms and biomarkers between the groups, except for "MIP3a" at baseline. Differences in the biomarker levels between two time points were found for "TARC," "VEGFA," "ILRA," "IL1RA/IL1a," "NMF," and "DHEA." Conclusion: The SC can be suitable biological material to assess biomarkers related to immune response, hormonal response, and skin barrier function. The SC biomarkers, showed strong, moderate and weak correlations with stress symptoms. Notably, these associations include cytokines of innate immunity and well-known stress hormones, cortisol and cortisone.

Stress-Induced Sensitization of Insula Activation Predicts Alcohol Craving and Alcohol Use in Alcohol Use Disorder.

BACKGROUND: Stress and alcohol cues trigger alcohol consumption and relapse in alcohol use disorder. However, the neurobiological processes underlying their interaction are not well understood. Thus, we conducted a randomized, controlled neuroimaging study to investigate the effects of psychosocial stress on neural cue reactivity and addictive behaviors. METHODS: Neural alcohol cue reactivity was assessed in 91 individuals with alcohol use disorder using a validated functional magnetic resonance imaging (fMRI) task. Activation patterns were measured twice, at baseline and during a second fMRI session, prior to which participants were assigned to psychosocial stress (experimental condition) or a matched control condition or physical exercise (control conditions). Together with fMRI data, alcohol craving and cortisol levels were assessed, and alcohol use data were collected during a 12-month follow-up. Analyses tested the effects of psychosocial stress on neural cue reactivity and associations with cortisol levels, craving, and alcohol use. RESULTS: Compared with both control conditions, psychosocial stress elicited higher alcohol cue-induced activation in the left anterior insula (familywise error-corrected p < .05) and a stress- and cue-specific dynamic increase in insula activation over time (F22,968 = 2.143, p = .007), which was predicted by higher cortisol levels during the experimental intervention (r = 0.310, false discovery rate-corrected p = .016). Cue-induced insula activation was positively correlated with alcohol craving during fMRI (r = 0.262, false discovery rate-corrected p = .032) and alcohol use during follow-up (r = 0.218, false discovery rate-corrected p = .046). CONCLUSIONS: Results indicate a stress-induced sensitization of cue-induced activation in the left insula as a neurobiological correlate of the effects of psychosocial stress on alcohol craving and alcohol use in alcohol use disorder, which likely reflects changes in salience attribution and goal-directed behavior.

Correlates of preconception and pregnancy hair cortisol concentrations.

Assessing factors that influence chronic stress biomarkers like hair cortisol concentrations (HCCs) in pregnancy is critical to prevent adverse pregnancy outcomes. Thus, we aimed to identify correlates of HCC preconception and during pregnancy. 2,581 pregnant women participated in the study. HCC was available at four time periods: pre-pregnancy (0-3 months preconception, n = 1,023), and in the first (1-12 weeks, n = 1,734), second (13-24 weeks, n = 1,534), and third (25-36 weeks, n = 835) trimesters. HCC was assessed using liquid chromatography tandem mass spectrometry (LC-MS/MS). Sociodemographic, pregnancy- and hair-related characteristics, and measures of psychosocial stress, were interrogated as potential correlates of HCC. Spearman correlations, paired t-tests, and ANOVA were used to assess differences in log-transformed values of HCC (logHCC) across maternal characteristics. Multivariable linear regressions were used to identify the correlates of HCCs after adjusting for confounders. Mean logHCC values increased across the four prenatal periods (P < 0.001). In multivariable analyses, pre-pregnancy BMI was consistently associated with all HCCs, while gestational age, economic hardship, hair dyeing, and depression, showed time-specific associations with HCC. In conclusion, this study showed evidence of factors influencing HCC levels before and during pregnancy. The most consistent association was seen with pre-pregnancy BMI. Depression was also associated with HCC concentrations.

Feasibility, acceptability and preliminary efficacy of a mental health self-management app in clinicians working during the COVID-19 pandemic: A pilot randomised controlled trial.

COVID-19 affected the well-being of healthcare workers (HCWs) globally. Mental health app interventions (MHAIs) may offer appropriate and accessible means to support HCWs' mental health. We conducted a pilot randomised controlled crossover trial involving 34 clinicians randomised to either a MHAI or a waitlisted group. After one month, outcome assessments were repeated and the waitlisted group then crossed over to the MHAI; they again completed outcome assessments after a month. The primary outcomes were feasibility, assessed with the Systems Usability Scale (SUS), and acceptability, assessed with the Client Satisfaction Questionnaire (CSQ). Secondary outcomes included efficacy for various mental health parameters. The SUS and CSQ scores indicated above average feasibility and acceptability. There was a significant difference in anxiety from baseline to 1-month follow-up between the groups, with greater improvement in the MHAI group. The groups differed in resilience and patient-related burnout from baseline to 1-month follow-up, with a trend towards significance, with greater improvements in the MHAI group. Anxiety and acute stress disorder severity improved significantly from pre- to post-intervention. We demonstrated that MHAIs hold potential for improving well-being of HCWs, although these findings will need to be replicated in adequately powered trials.

Exhaustion and cardiovascular risk factors: the role of vagally-mediated heart rate variability.

PURPOSE: Exhaustion symptoms are known to be associated with cardiovascular disease (CVD) risk; however, the underlying mechanisms remain unclear. Autonomic imbalance, as indicated by reductions in vagally-mediated heart rate variability (vmHRV), appears to be a valid candidate for such a biological link, as it has been associated with both exhaustion symptoms and CVD risk and mortality. METHODS: The present study examined a potential mediation of vmHRV on the association between exhaustion symptoms and self-reported CVD risk factors as well as the age dependency of this mediation in a large, heterogeneous sample of the Dresden Burnout Study (N = 388; 72.9% females; Mage = 42.61, SD = 11.67). RESULTS: Results indicate that exhaustion symptoms were indirectly associated with CVD risk factors through vmHRV even after adjusting for well-known confounders (i.e., sex, body mass index, depressive symptoms). Moreover, this pattern was significant only among middle-aged (i.e., 54.27 years) and older individuals. CONCLUSIONS: Our findings add to growing evidence that autonomic imbalance may be a key biological link between exhaustion symptoms and CVD risk in middle-aged and older individuals. Implications for public health are discussed.

Determination of nicotine and cotinine in human hair using online solid phase extraction coupled with liquid chromatography-tandem mass spectrometry and their relation to hair cortisol and cortisone.

Tobacco smoking is one of the critical public health threats all over the world. Since nicotine and its metabolite cotinine have been routinely used as the biomarkers to estimate the exposure to tobacco smoking, hair nicotine and cotinine analyses can provide of a retrospective index of nicotine and cotinine integrated over extended periods of several months prior to hair sampling to estimate the long-term exposure to tobacco smoking. Since the relationship between tobacco smoking and hypothalamic-pituitary-adrenal (HPA) axis is implicated in both stress response and nicotine addiction, better understanding of the association between hair nicotine, cotinine levels and hair cortisol, cortisone levels is an important prerequisite toward more adequate use of this method in future research. We here presented an online solid phase extraction (SPE) coupled with liquid chromatography- tandem mass spectrometry (LC-MS/MS) method for quantification of long-term integrated nicotine and cotinine in human hair. This method was applied to the analysis of hair nicotine and cotinine in 40 participants of smokers and nonsmokers (mean ± SD age: 46.25 ± 11.92 years; 40 % male) and the investigation of their association with hair cortisol and cortisone. Methanol together with glass tube was used for hair nicotine and cotinine extraction during the incubation time of 18-h. The limits of quantification were 1 pg/mg for nicotine as well as 0.1 pg/mg for cotinine. The inter- and intra-day coefficients of variation were below 15 %. The method recovery ranged between 90 % and 104 %. Group-level analyses revealed that smokers exhibited higher hair nicotine and cotinine levels compared to nonsmokers. Hair nicotine and cotinine levels showed significant positive associations with hair cortisol and cortisone levels in smokers (nicotine and cortisol: Spearman's ρ = 0.619, p = 0.005; cotinine and cortisol: Spearman's ρ = 0.468, p = 0.043; nicotine and cortisone: Spearman's ρ = 0.773, p = 0.000; cotinine and cortisone: Spearman's ρ = 0.531, p = 0.016), but not in nonsmokers. The presented online SPE LC-MS/MS method provides a simply and highly specific analytical strategy for the detection of nicotine and cotinine concentrations in human hair for the retrospective assessment of cumulative long-term nicotine and cotinine exposure. Furthermore, hair nicotine, cotinine levels correlate with hair cortisol, cortisone levels in smokers other than nonsmokers.

Hair Cortisol Research in Posttraumatic Stress Disorder - 10 Years of Insights and Open Questions. A Systematic Review.

BACKGROUND: Cortisol is one of the most extensively studied biomarkers in the context of trauma/posttraumatic stress disorder (PTSD). For more than a decade, hair cortisol concentrations (HCC) have been measured in this context, leading to a two-staged dysregulation model. Specifically, an elevated secretion during/immediately after trauma exposure eventually reverts to hyposecretion with increasing time since trauma exposure has been postulated. OBJECTIVE: The aim of our systematic review was to re-evaluate the two-staged secretion model with regard to the accumulated diagnostic, prognostic, and intervention-related evidence of HCC in lifetime trauma exposure and PTSD. Further, we provide an overview of open questions, particularly with re- spect to reporting standards and quality criteria. METHOD: A systematic literature search yielded 5,046 records, of which 31 studies were included. RESULTS: For recent/ongoing (traumatic) stress, the predictions of cortisol hypersecretion could be largely confirmed. However, for the assumed hyposecretion temporally more distal to trauma expo- sure, the results are more ambiguous. As most studies did not report holistic overviews of trauma his- tory and confounding influences, this may largely be attributable to methodological limitations. Data on the prognostic and intervention-related benefits of HCC remain sparse. CONCLUSION: Over the last decade, important insights could be gained about long-term cortisol secretion patterns following lifetime trauma exposure and PTSD. This systematic review integrates these insights into an updated secretion model for trauma/PTSD. We conclude with recommendations for improving HCC research in the context of trauma/PTSD in order to answer the remaining open questions.

Hair Cortisol and Perceived Stress-Predictors for the Onset of Tics? A European Longitudinal Study on High-Risk Children.

Some retrospective studies suggest that psychosocial stressors trigger the onset of tics. This study examined prospective hypothalamic-pituitary-adrenal (HPA) axis activity and perceived stress prior to tic onset. In the present study, 259 children at high risk for developing tics were assessed for hair cortisol concentration (HCC) and parent-on-child-reported perceived stress four-monthly over a three-year period. We used (i) generalised additive modelling (GAM) to investigate the time effects on HCC (hair samples n = 765) and perceived stress (questionnaires n = 1019) prior to tic onset and (ii) binary logistic regression to predict tic onset in a smaller subsample with at least three consecutive assessments (six to nine months before, two to five months before, and at tic onset). GAM results indicated a non-linear increasing course of HCC in children who developed tics, and a steady HCC course in those without tics, as well as a linear-increasing course of perceived stress in both groups. Logistic regression showed that with a higher HCC in hair samples collected in a range of two to five months before tic onset (which refers to cortisol exposure in a range of four to eight months), the relative likelihood of tic onset rose. Our study suggests increased stress prior to tic onset, as evidenced by higher HCC several months before tic onset.

Increased red blood cell deformation in children and adolescents after SARS-CoV-2 infection.

Severe coronavirus disease 2019 (COVID-19) is associated with hyperinflammation, hypercoagulability and hypoxia. Red blood cells (RBCs) play a key role in microcirculation and hypoxemia and are therefore of special interest in COVID-19 pathophysiology. While this novel disease has claimed the lives of many older patients, it often goes unnoticed or with mild symptoms in children. This study aimed to investigate morphological and mechanical characteristics of RBCs after SARS-CoV-2 infection in children and adolescents by real-time deformability-cytometry (RT-DC), to investigate the relationship between alterations of RBCs and clinical course of COVID-19. Full blood of 121 students from secondary schools in Saxony, Germany, was analyzed. SARS-CoV-2-serostatus was acquired at the same time. Median RBC deformation was significantly increased in SARS-CoV-2-seropositive compared to seronegative children and adolescents, but no difference could be detected when the infection dated back more than 6 months. Median RBC area was the same in seropositive and seronegative adolescents. Our findings of increased median RBC deformation in SARS-CoV-2 seropositive children and adolescents until 6 months post COVID-19 could potentially serve as a progression parameter in the clinical course of the disease with an increased RBC deformation pointing towards a mild course of COVID-19.

Endocannabinoid and perceived stress: Association analysis of endocannabinoid levels in hair versus levels in plasma and urine.

The endocannabinoid system is considered to play a role in a wide range of functions, including stress. Hair analysis of endocannabinoids presents a promising methodological advancement for the retrospective assessment of long-term cumulative endocannabinoid secretion. Despite promising pilot study results suggesting the usefulness of hair endocannabinoid assessments, it remains unclear whether hair endocannabinoid levels mirror systemic endocannabinoid levels accurately. Two independent studies were conducted to investigate to what extent hair endocannabinoid and N-Acylethanolamine levels reflect the systemic levels retrospectively. Endocannabinoid and N-Acylethanolamine levels were measured in 3 cm and 1 cm hair segments respectively, and compared with the averaged levels in multiple plasma samples collected during three months (Study I), and in multiple 24-hour urine samples collected over a month (Study II). In addition, the Perceived Stress Scale was used to assess the perceived stress throughout the studies. Against our hypothesis, no association was found between the endocannabinoid or N-Acylethanolamine levels in hair and plasma or urine. However, hair palmitoylethanolamide (PEA), oleoylethanolamide (OEA), and stearoylethanolamide (SEA) levels were positively correlated with perceived stress in Study I. The current findings suggest that hair endocannabinoid or N-Acylethanolamine levels might not accurately reflect the levels of peripheral circulating endocannabinoid or N-Acylethanolamine. Nevertheless, hair N-Acylethanolamine levels might emerge as a useful strategy in the study of some psychological phenotypes, such as stress.

Association between trauma exposure and glucocorticosteroid concentration in hair during pregnancy.

BACKGROUND: Traumatic events, including child abuse and intimate partner violence, are highly prevalent among women of child-bearing age. These traumatic experiences may impact maternal and offspring physical and mental health. A proposed mechanism for these effects is maternal hypothalamic-pituitary-adrenal (HPA) axis dysregulation which can be measured using hair corticosteroid levels. AIMS: This study aims to examine the association of child abuse and intimate partner violence exposure with HPA axis functioning, as measured by hair corticosteroid levels in a cohort of pregnant women. METHODS: We included data from 1822 pregnant women (mean gestational age 17 weeks) attending a prenatal clinic in Lima, Peru. We extracted cortisol and cortisone concentrations from hair samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Each participant provided 6-cm hair samples: 3 cm hair segment closest to the scalp reflecting HCC in early pregnancy (first three months), and 3-6 cm from the scalp reflecting HCC in pre-pregnancy (three months prior to conception). Multivariable linear regression procedures were used to assess the association between maternal trauma exposure and hair corticosteroid levels. RESULTS: Overall, women who experienced child abuse on average had higher levels of cortisol (p < 0.01) and cortisone (p < 0.0001) after adjustment for age, race, adult access to basic foods and hair treatments. For the hair segment reflecting early pregnancy, presence of child abuse was associated with a 0.120 log unit increase in cortisol and a 0.260 log unit increase in cortisone (p < 0.001). For the hair segment reflecting pre-pregnancy, a history of child abuse was associated with a 0.100 log unit increase in cortisol and a 0.180 log unit increase in cortisone (p < 0.01). Results also suggested an impact of intimate partner violence on HPA regulation; however, associations were not statistically significant after controlling for child abuse. CONCLUSIONS: These results underscore the long-lasting impacts of exposure to adversity and trauma during early life. Our study findings will have implications for research investigating HPA axis function and long-term effects of violence on corticosteroid regulation.

Maternal hair cortisol concentrations and its association with increased insulin resistance in midpregnancy.

PURPOSE: Stress and elevated maternal glycemia have negative effects on pregnancy. We evaluated the association of hair cortisol concentrations (HCC), a marker of chronic stress, with insulin resistance and gestational diabetes (GDM). METHODS: In total, 527 women from Lima, Peru, provided a hair sample in the second trimester of their pregnancy to measure HCC using liquid chromatography-tandem mass spectrometry. Each 6 cm of hair captured HCC in early (T1=1-12 weeks) and midpregnancy (T2 = 13-24 weeks). GDM diagnosis was conducted in midpregnancy. Multivariable regression models adjusted for putative risk factorsincluding maternal sociodemographic factors, diabetes history, and hair characteristics, were used to estimate the association of HCC with GDM and various glycemic traits. RESULTS: GDM was diagnosed in 122 (23%) women. Mean HCC across pregnancy was T1 = 3.7 (±3.4) pg/mg and T2 = 4.8 (±3.4) pg/mg. HCC was associated with increased log-transformed units of fasting insulin (T1 = 0.15 [0.03, 0.27], T2 = 0.17 [0.04, 0.30]), homeostasis model assessment for insulin resistance (T1 = 0.14 [0.01, 0.26], T2 = 0.17 [0.03, 0.30]), and homeostasis model assessment for ß-cell function (T1 = 0.20 [0.05, 0.34], T2 = 0.20 [0.04, 0.36]), but not with GDM (T1 = 0.95 [0.63, 1.40], T2 = 1.11 [0.74, 1.67]). CONCLUSIONS: Elevated maternal HCC was associated with abnormal insulin homeostasis in pregnancy. Dysregulation of the hypothalamic-pituitary-adrenal axis, as reflected by high HCC, may also contribute to insulin resistance syndrome in pregnancy.