Higher levels of plasma Adrenocorticotropic hormone (ACTH) are associated with lower suicidal ideation in depressed patients compared to controls and suicide attempters, independently from depression severity.

Introduction: Suicidal ideation, an important risk factor for suicide attempts, has an unclear neurobiological basis and is potentially linked to the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and immune-inflammatory systems. While inflammatory markers have been associated with suicide attempts and, to a lower extent suicidal ideation, the data on the role of a stress-response system is less robust, with most studies carried out with cortisol showing inconsistent results. The present study extends on the previous studies implicating stress-response and immune-inflammatory systems in suicidal thoughts and behaviours, focusing on the associations of several stress-response (adrenocorticotropic hormone (ACTH), cortisol, and dehydroepiandrosterone (DHEA)) and immune-inflammatory (C-reactive protein (CRP),interle ukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-alpha)) with suicidal ideation severity in recent suicide attempters, patients with major depressive disorder, and non-psychiatric controls. Methods: This observational study included 156 adults from three Vilnius hospitals, recruited into one of the three groups in equal parts: recent suicide attempters, patients with major depressive disorder in current depressive episode, and non-psychiatric controls. Measures included the Hamilton Depression Rating Scale (HDRS-17) and the Beck Scale for Suicide Ideation/Suicide Severity Index (BSS/SSI), alongside sociodemographic data, alcohol, tobacco use, and morning blood samples, measuring plasma ACTH, cortisol, DHEA, CRP, and IL-6. Data were analysed with non-parametric tests, Kendall's tau correlation, and multivariate linear regression adjusted for confounders. Results: We found a negative correlation between the plasma ACTH levels and suicidal ideation severity (tau = -0.130, p = 0.033), which was driven by the patients with major depressive disorder (tau = -0.237, p = 0.031). Suicidal ideation severity was also negatively correlated with TNF-alpha (tau = -0.231; p < 0.001), positively correlated with IL-6 (tau = 0.154, p = 0.015), and CRP levels (tau = 0.153, p = 0.015), but no differences were observed in group-stratified analyses. The association between plasma ACTH levels and suicidal ideation severity in patients with major depressive disorder remained robust to adjustment for major confounders (adjusted for age, sex, education years, body mass index, smoking status, plasma CRP and PEth concentration (measuring chronic alcohol exposure), and antidepressant use) in the linear regression model (t = -2.71, p = 0.011), as well as additionally adjusting for depression severity (t = -2.99, p = 0.006). Discussion: The present study shows an association between plasma ACTH levels and suicidal ideation severity in patients with major depressive disorder, robust to adjustment for antidepressant use and depression severity. This finding highlights the potential role of ACTH, in elucidating the effects of stress and mental health disorders. Our findings underscore the importance of the HPA axis in the diagnosis and treatment of suicidal ideation in major depressive disorder and invite further research on interventions targeting this pathway.

Significantly elevated phosphatidylethanol levels in recent suicide attempters, but not in depressed controls and healthy volunteers.

INTRODUCTION: Suicide is a complex transdiagnostic phenomenon. It is strongly associated with, but not exclusive to major depressive disorder (MDD). Hazardous alcohol drinking has also been linked to an increased risk of suicidal behaviours, however, it is often underreported. The study aimed to evaluate whether an objective measure of chronic alcohol use, phosphatidylethanol (PEth) could be useful as a biomarker in clinical practice. METHOD: ology. The present case-control multi-centric study recruited 156 participants into three study groups: 52 patients treated for major depressive disorder (MDD), 51 individuals immediately following a suicide attempt (SA), and 53 volunteers. Sociodemographic data, medical history, and laboratory data, including PEth concentrations and C-reactive protein levels, were collected from study participants. RESULTS: PEth concentrations were the highest in suicide attempters (232,54 ± 394,01 ng/ml), followed by patients with MDD (58,39 ± 135,82 ng/ml), and the control group (24,45 ± 70,83 ng/ml) (Kruskall Wallis χ2 = 12.23, df = 2, p = .002). In a multinomial logistic regression model with adjustments, PEth concentration was able to predict belonging to suicide attempters' group, but not to depression group (p = .01). Suicide attempters were also more likely to underreport their recent alcohol consumption. LIMITATIONS: We did not analyze SA methods, psychiatric comorbidity and several other factors that might be associated with PEth levels, such as body mass index, race, and haemoglobin levels. Sample recruited in hospital settings may not be representative of the whole population. The results of this adult-only study cannot be generalized to adolescents. CONCLUSIONS: PEth levels in recent suicide attempters significantly exceeded those of patients with MDD and controls. Suicide attempters also were more likely to underreport their alcohol consumption when questioned about their consuption. PEth might be an interesting biomarker to evaluate individuals at risk of SA.

Dynamics of Physiological, Biochemical and Psychological Markers during Single Session of Virtual Reality-Based Respiratory Biofeedback Relaxation.

Psychological stress exposure is associated with long-lasting health effects including memory problems, depression, aches and pains, eating disorders, and alcohol or drug use. Thus, there is a need to develop effective stress management strategies that are easy to learn and practice. Respiratory biofeedback is an evidence-based stress management technique presenting breathing-related information to help subjects learn specific breathing skills for relaxation. It is suggested that the use of biofeedback techniques in conjunction with virtual reality makes biofeedback training an even more effective tool for stress management. The current study aimed to investigate dynamics of distinct stress indicators before, after, as well as during one brief virtual reality-based respiratory biofeedback session. Thirty-nine healthy volunteers participated in the study. Individuals provided their saliva samples and evaluated their mood status, fatigue, and strain level before and after the session. The subjects' heart and respiratory rate, heart rate variability, and galvanic skin response measures were recorded during the session. The results showed that after single 12 min relaxation session, there was a significant decrease in salivary cortisol concentration, heart and respiratory rate, as well as decrease in skin conductance values. Self-reported strain, fatigue level, and mood status also significantly improved. VR-based respiratory-biofeedback-assisted relaxation sessions might serve as an effective stress management strategy, as even single session had positive effects on subjects' autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis activity, as well as self-reported fatigue, strain level, and mood status.

Higher Levels of Stress-Related Hair Steroid Hormones Are Associated with the Increased SCORE2 Risk Prediction Algorithm in Apparently Healthy Women.

Cardiovascular diseases (CVDs) are the major cause of death worldwide. Although the importance of conventional CVD risk factors, including older age, male gender, hypertension, obesity, dyslipidemia and hyperglycemia, is well-studied, psychosocial stress, which is considered an independent CVD risk factor, requires further investigation. Thus, we aimed to investigate the association between long-term secretion of stress-related steroid hormones, including cortisol, cortisone and dehydroepiandrosterone, and the 10-year fatal and non-fatal CVD risk estimated by the SCORE2 risk prediction algorithm, as well as traditional CVD risk factors in a group of apparently healthy women. A total of 145 women (aged 50-64 years) participating in the national CVD prevention program were enrolled in the study. Sociodemographic, lifestyle, health-related characteristics, stress, anxiety and sleep quality indicators were evaluated using specific questionnaires. Anthropometric and arterial blood pressure measures were assessed by trained personnel, lipid and glucose metabolism biomarkers were measured using routine methods, and hair steroid hormone levels were determined by ultra-high-performance liquid chromatography-tandem mass spectrometry. The results showed that higher levels of hair cortisol and cortisone are associated with increased SCORE2 values. Moreover, significant associations between hair glucocorticoids and individual cardiovascular risk factors, including obesity, hypertension, dyslipidemia and hyperglycemia, were found. These findings indicate that stress-related hair steroid hormones might be valuable biomarkers for CVD prediction and prevention.

Effects of Virtual Reality-Based Relaxation Techniques on Psychological, Physiological, and Biochemical Stress Indicators.

Various relaxation techniques could benefit from merging with virtual reality (VR) technologies, as these technologies are easily applicable, involving, and user-friendly. To date, it is unclear which relaxation technique using biofeedback combined with VR technology is the most effective. The study aimed to compare the effectiveness of brief VR-based biofeedback-assisted relaxation techniques including electroencephalographic biofeedback, mindfulness-based biofeedback, galvanic skin response biofeedback, and respiratory biofeedback. Forty-three healthy volunteers (age 34.7 ± 7.2 years), comprising 28 (65%) women and 15 (35%) men, were enrolled in the study. All the participants were exposed to four distinct relaxation sessions according to a computer-generated random sequence. The efficacy of relaxation methods was evaluated by examining psychological, physiological, and biochemical stress indicators. All VR-based relaxation techniques reduced salivary steroid hormone (i.e., cortisol, cortisone, and total glucocorticoid) levels and increased galvanic skin response values. Similarly, all interventions led to a significantly reduced subjectively perceived psychological strain level. Three out of the four interventions (i.e., electroencephalographic, respiratory, and galvanic skin response-based biofeedback relaxation sessions) resulted in a decreased self-reported fatigue level. We suggest that newly developed VR-based relaxations techniques are potential tools for stress reduction and might be particularly suitable for individuals who are not capable of adhering to a strict and time-consuming stress management intervention schedule.

The Association between Endogenous Hair Steroid Hormones and Social Environmental Factors in a Group of Conscripts during Basic Military Training.

This study aimed to analyse the association between endogenous hair steroid hormones as reliable biological indicators of an individual's stress level and the social environmental factors experienced during military training that are manifested at the beginning of compulsory military service. Hair steroid hormone concentrations-cortisol, cortisone, dehydroepiandrosterone (DHEA), and testosterone-in a group of 185 conscripts were measured using the ultra-high performance liquid chromatography-tandem mass spectrometry method. Six subjective social environmental factors in the military-attitude towards the military and military service, adaptation to the military environment, team, task, and norm cohesion, as well as psychological (un)safety in the group-were evaluated using military-specific research questionnaires. Weak but significant negative correlations were identified between cortisol and adaptation (r = -0.176, p < 0.05), attitude (r = -0.147, p < 0.05) as well as between testosterone and task cohesion (r = -0.230, p < 0.01) levels. Additionally, a multiple forward stepwise regression analysis highlighted that cortisone variation might be partially explained by task cohesion; the DHEA-determined by psychological (un)safety in the group, attitude towards the military and military service, and norm cohesion; and the testosterone-determined by task cohesion and adaptation to the new military environment. The results of this study suggest that subjective measures of social factors can be used to predict hair steroid hormone levels as objective measures of the chronic stress perceived by conscripts during their basic military training.

Association of salivary steroid hormones and their ratios with time-domain heart rate variability indices in healthy individuals.

BACKGROUND: Stress system consists of the hypothalamicpituitary-adrenal (HPA) axis and the locus caeruleus/norepinephrine-autonomic nervous system (ANS). Traditionally, HPA axis activity is evaluated by measuring its end-product cortisol, while the activity of ANS is assessed using heart rate variability (HRV) indices. Alterations in cortisol levels and HRV measures during laboratory-based stress tasks were extensively studied in previous research. However, scarce data exist on the associations of HRV measures with the levels of other adrenal steroid hormones under baseline conditions. Thus, we aimed to evaluate the activity of the HPA axis by measuring salivary cortisol, cortisone, dehydroepiandrosterone (DHEA) levels, and their ratios and to examine its association with HRV measures in a sample of healthy young and middle-aged adults. METHODS: For each participant (n=40), three data collection sessions taking place at the same time of the day were scheduled within five working days. Participants completed a self-reported questionnaire on sociodemographic and lifestyle characteristics, filled out t h e Perceived Stress Scale and State-Trait Anxiety Inventory. Also, saliva samples were collected, and physiological measures, including resting HR and HRV, were recorded during three data collection sessions. RESULTS: Statistically significant associations between diminished parasympathetic vagal tone evaluated by time domain HRV measures and higher salivary cortisol, lower DHEA levels, as well as decreased DHEA to cortisol ratio, were found. Also, physiological stress indicators (i.e., HRV) showed greater intraindividual stability compared with biochemical biomarkers (i.e., salivary steroid hormones) within five days. CONCLUSIONS: Our findings suggest that both cortisol and DHEA mediate the link between two stress-sensitive homeostatic systems.

Towards a Personalized Approach in Pancreatic Cancer Diagnostics Through Plasma Amino Acid Analysis.

BACKGROUND/AIM: Body fluid biomarkers may provide means for early pancreatic cancer diagnosis, patient stratification, application of personalized approaches and, finally, improved outcomes. Amino acids are the most frequently distinguished metabolite class in the metabolomics of pancreatic cancer patients. They have been identified as pre-diagnostic and diagnostic markers and associated with pancreatic cancer risk factors. MATERIALS AND METHODS: Deep phenotyping and quantitative amino acid analysis were performed in patients scheduled for pancreatic surgery due to pancreatic tumors (n=75). RESULTS: Significant differences in plasma amino acid concentrations were observed between diagnostic categories (malignant vs. benign lesions and histological cancer types) and pancreatic ductal adenocarcinoma stages. Characteristic patterns of plasma amino acid concentration dynamics according to cancer stage were identified. CONCLUSION: Standardization of metabolomics methods and deep phenotyping may provide means for improved patient stratification and effective personalized approaches in pancreatic cancer prevention, early diagnosis and treatment.