Characteristics of Psychoemotional Manifestations of Laboratory Rodents Undergoing Surgery when Modeling Preoperative Stress.

We studied psychoemotional characteristics and the blood level of corticosterone in sexually mature male C57BL/6 mice (n=40): intact (control), after simulating preoperative stress and surgery, after surgery, and after anesthesia alone. It was found that the anxiety index calculated on the basis of testing in the elevated plus maze was significantly higher in both groups of operated animals. The mice of both operated groups and animals exposed to anesthesia alone showed increased anxiety. Symptoms indicating a high probability of transition of anxiety into a psychoemotional disorder have been recorded.

The effectiveness of psychological interventions on diabetes distress and glycemic level in adults with type 2 diabetes: a systematic review and meta-analysis.

AIMS: The treatment of diabetes distress plays an important role in diabetes care; however, no meta-analysis has been performed to synthesize the short- and long-term effects of psychological interventions tailored for diabetes distress in people with type 2 diabetes. We aim to evaluate the evidence on tailored psychological interventions for diabetes distress as the primary outcome, focusing on individuals with type 2 diabetes. METHODS: Two reviewers independently searched eight databases from their inception to September 2024. EndNote X9 was used to screen records. The Revised Cochrane risk-of-bias tool for randomized trials was used to assess the risk of bias. The GRADE system was used to assess the overall certainty of the evidence. A random effect model was used to determine the mean difference or standardized mean difference with 95% CIs. Subgroup analyses based on several intervention characteristics and sensitivity analyses were also conducted. RESULTS: Totally, 22,279 records were yielded, and we finally included 18 studies in our systematic review. The meta-analysis included data from 16 studies representing 1639 participants. Interventions types included mindfulness-based and cognitive behavioral therapy, among others. Duration of interventions ranged from 4 weeks to 6 months. We found that psychological interventions that measured diabetes distress significantly reduced diabetes distress in the short-term in people with type 2 diabetes (SMD= -0.56; 95% CI= -0.90, -0.22; p = 0.001). Subgroup analysis indicated that this effect could be enhanced when delivered in a group format, by psychologist, using a technology component, or including participants having elevated baseline diabetes distress. However, the short- and long-term effects on HbA1c were non-significant, with results showing (MD = 0.02; 95% CI = -0.23 to 0.26; p = 0.89) and (MD = -0.27; 95% CI = -0.64 to 0.10; p = 0.15), respectively. The long-term effect on diabetes distress was also non-significant (SMD = -0.45; 95% CI = -0.93 to 0.03; p = 0.07). CONCLUSIONS: Psychological interventions tailored for diabetes distress in people with type 2 diabetes are effective in reducing the level of diabetes distress immediately after the intervention. More trials are still needed to further enrich the evidence in this area.

The correlation between stress score. Quality and duration of sleep with lipid profile and glycemic status.

Introduction: Diabetes (DM) is a disease of global concern. Studies have suggested that sleep disturbance is affiliated with insulin resistance and poor lipid. Impaired glucose tolerance precedes the diabetic state and we are aware that the blood glucose levels are deranged in these patients, but not much research is done to comment on the pattern of lipid abnormalities, sleep quality and stress in these patients. Hence our study is aimed to identify abnormal patterns or similarities in the above parameters in pre diabetic and diabetic groups. Materials & Methods: This is a cross - sectional study carried out at the tertiary care hospitals.The data of 45 pre diabetic and diabetic (30 to 70 years) were collected from the files history from Medical Records Department (MRD) after taking permission. The following parameters like glucose and lipid parameters were taken for the study and standard questionnaire was given to correlate the sleep and stress levels. Data analysis were done using SPSS (Statistical Package for Social Sciences) version write the verson number). Results: In the pre diabetic participants, sleep duration varied with stress levels (p=0.03) and their HDL was positively correlated to HbA1c (p=0.02) In the diabetic participants, TC (total cholesterol) varied with both stress (p=0.02) and sleep quality (p=0.001), LDL,& TC: HDL ratio varied only with sleep quality (p=0.04 ratio quality (p=0.01). Triglyceride levels were significantly higher in the diabetic group (p=0.04), as it is a major component of the triad of diabetic dyslipidemia. No other correlations or variations were significant. Conclusion: Poor sleep, abnormal lipid profiles, and stress may serve as risk factors predicting the onset of prediabetes and poor glycemic control. Confirming a direct relationship between these parameters through cohort or experimental studies could facilitate early detection of diabetes and encourage the adoption of appropriate healthy lifestyle measures.

The impact of psychological stress on physiological indicators in healthcare workers: a cross-sectional study.

Background: Medical health workers play an essential role in the healthcare system and face unique workplace stressors. However, the impact of psychological stress on their physical health has received less attention compared to the general population. Methods: We retrospectively analyzed the Self-rating Depression Scale (SDS) questionnaires and blood testing results from 1963 medical health workers. Multivariate linear regression analysis using a backward stepwise selection strategy to identify physical examination indicators that were significantly affected by depression. Results: Depression severity, as measured by SDS index score, was positively correlated with the levels of hemoglobin (coefficient 0.0027, p = 0.0412), platelet count (coefficient 0.0005, p = 0.0198), and uric acid (coefficient 0.0004, p = 0.0492), while negatively correlated with red blood cell count (coefficient-0.0895, p = 0.0406). Similar results were observed in the subgroup analysis stratified by age and sex. Conclusion: Our study found a significant association between higher levels of depression and specific physiological indicators in healthcare professionals, including elevated hemoglobin, platelet counts, and uric acid levels, as well as decreased red blood cell counts. These changes in blood parameters may reflect underlying physiological stress and inflammation, potentially increasing overall health risks for healthcare workers. Addressing these physiological changes may be crucial for mitigating the health risks associated with depression. To validate our findings and develop targeted interventions, larger multi-center studies are needed to further explore the relationship between depression severity and blood parameters in healthcare professionals.

Nicotine addiction and the influence of life adversity and acute stress on PYY: Prediction of early smoking relapse.

Early life adversity (ELA) is associated with earlier initiation and maintenance of tobacco smoking and with a greater risk of subsequent relapse. There is growing evidence that appetite hormones, including peptide YY (PYY), which modulates craving and satiety responses, play a role in stress and addiction processes. This study employed a quasi-experimental design to examine the association between ELA and circulating PYY stress responses in smokers and nonsmokers (N = 152, ages 19-73 years) to examine the effects of nicotine addiction. Smokers initiated a quit attempt as part of the study and were classified as either abstinent smokers or relapsed smokers based on their nicotine use during the follow-up period. PYY levels were measured at five timepoints during three lab sessions and compared between nonsmokers and the two smoking groups (abstainers, relapsers): while smokers were using nicotine ad libitum, 24 h after smokers initiated a quit attempt, and 4 weeks after smokers initiated a quit attempt. Multivariate analyses showed the main effects of time on PYY, which decreased over time within each session. The main effects of ELA during the first (ad libitum smoking) and second (24-h post-cessation for smokers) sessions indicated that experiencing ELA was associated with lower PYY. No systematic effect of nicotine addiction or relapse was observed in this study. These findings suggest that adults with higher ELA may experience lower PYY. Additional research is needed to further explore the role of PYY in stress and addiction processes.

The influence of the psychosocial stress on oral health status in the conditions of being in Ukraine during the prolonged state of martial law.

OBJECTIVE: Aim: To study the presence of clinical and biochemical correlations between psycho-emotional stress, level of cortisol and periodontal oral health status of the patients in Ukraine during prolonged martial law. PATIENTS AND METHODS: Materials and Methods: The comprehensive clinical and laboratory study covered 49 persons, including 20 patients with Gingivitis (40.8%) and 29 with Periodontitis (59.2%). Biochemical blood test was performed to determine the level of "stress hormone" - cortisol. Patients filled out the questionnaire by the method of V. Zung (low mood-subdepression scale) to determine psycho-emotional state in the conditions of prolonged martial law in Ukraine. RESULTS: Results: The research results showed that in the conditions of martial law in Ukraine, "stabilization" and "improvement" of the process of patients with Gingivitis was established in 50%, with Periodontitis - only in 41.4% of patients. In 54% of patients, a significant deterioration of clinical indices was established, compared to the indicators before the war. In patients with Periodontitis, РВІ index was 1.33 (0.62-1.43) score, which was not statistically significantly different from the initial level (p>0.05). Biochemical blood tests revealed an increased level of the hormone cortisol in 18% of patients. According to the method by V. Zung scale of mental states, the majority of patients (87%) showed low mood and emotional instability within the medium level (range 2 and 3). Correlation was identified, according to the Spearman coefficient (R=0.39, р<0.05), between scale assessments by V.Zung and the blood level of cortisol. CONCLUSION: Conclusions: Psycho-emotional stress is one of the leading pathogenetic factors in the deterioration of oral health status and the development of periodontal diseases, especially in people in Ukraine during prolonged martial law. Indicators of method by V. Zung scale of mental states and the level of cortisol are optimal markers of the need to correct the psycho-emotional state. For patients with increased levels of stress and fear, it is necessary to create special treatment-prevention schemes, taking into account greater attention to motivation to maintain the health of the oral cavity, as well as more frequent hygiene procedures.

Dynamic interplay of cortisol and BDNF in males under acute and chronic psychosocial stress - A randomized controlled study.

The neurotrophic protein brain-derived neurotrophic factor (BDNF) plays a pivotal role in brain function and is affected by acute and chronic stress. We here investigate the patterns of BDNF and cortisol stress reactivity and recovery under the standardized stress protocol of the TSST and the effect of perceived chronic stress on the basal BDNF levels in healthy young men. Twenty-nine lean young men underwent the Trier Social Stress Test (TSST) and a resting condition. Serum BDNF and cortisol were measured before and repeatedly after both conditions. The perception of chronic stress was assessed by the Trier Inventory for Chronic Stress (TICS). After the TSST, there was a significant increase over time for BDNF and cortisol. Stronger increase in cortisol in response to stress was linked to an accelerated BDNF decline after stress. Basal resting levels of BDNF was significantly predicted by chronic stress perception. The increased BDNF level following psychosocial stress suggest a stress-induced neuroprotective mechanism. The presumed interplay between BDNF and the HPA-axis indicates an antagonistic relationship of cortisol on BDNF recovery post-stress. Chronically elevated high cortisol levels, as present in chronic stress, could thereby contribute to reduced neurogenesis, and an increased risk of neurodegenerative conditions in persons suffering from chronic stress.

Divergent transcriptomic profiles in depressed individuals with hyper- and hypophagia implicating inflammatory status.

BACKGROUND: Major Depressive Disorder (MDD) is a heterogenous and etiologically complex disease often presenting with divergent appetitive phenotypes including Hyperphagic MDD (characterized by an increased appetite) and Hypophagic MDD (characterized by a decrease in appetite) which are closely related to comorbidities, including cardiometabolic disorders. Hyperphagia is associated with atypical depression, decreased stress-hormone signaling, a pro-inflammatory status, hypersomnia, and poorer clinical outcomes. Yet, our understanding of associated biological correlates of Hyperphagic and Hypophagic MDD remain fragmented. METHODS: We performed an exploratory study on peripheral blood RNA profiling using bulk RNAseq in unmedicated individuals with Hyperphagic and Hypophagic MDD (n = 7 and n = 13, respectively). RESULTS: At baseline, we discovered an increased expression of TADA2B in hyperphagic MDD with the significant enrichment of 72 gene ontology pathways mainly related to inflammation. In addition, we used the Maastricht Acute Stress Task to uncover stress-related transcriptomic profiles in Hyper- and Hypophagic MDD and discovered the upregulation of CCDC196 and the downregulation of SPATA33 in hyperphagic MDD. Gene ontology enrichment analysis after stress exposure showed pathways related to ribosomal activity. LIMITATIONS: The present findings are tempered primarily by the limited sample size, which requires independent replication of this exploratory study. However, stringent methods controlling for false positive findings mitigate the risk associated with sample size limitations. DISCUSSION: Limitations notwithstanding, findings suggest that hyper- and hypophagic MDD is associated with divergent RNA expression profiles in peripheral blood that are amplified by exposure to a controlled stress test. Our findings in a well-controlled study provide evidence for peripheral markers of a relevant endophenotype of MDD.

Maternal negative affect in pregnancy predicts cytokine levels which in turn predict birth outcomes - A prospective longitudinal study in a low-risk population.

BACKGROUND: Stress and negative mood in pregnancy have been linked to less favorable birth outcomes, but the mechanisms underlying this effect remain largely unknown. We examined associations between emotions in pregnancy, pro- and anti-inflammatory cytokines (IFN-γ, IL-6, IL-8, IL-10, IL-12, IL-17, MCP-1, MIP-1ß, TNF-α) and birth outcomes (gestational age at birth and birth weight) in a low-risk sample. METHODS: At each trimester of pregnancy, participants (N = 74) completed the Positive and Negative Affect Schedule, Perceived Stress Scale, Edinburgh Postnatal Depression Scale, and State-Trait Anxiety Inventory. They provided blood samples in the third trimester. Multivariate regression with a reduction of dimensionality (orthogonal projection to latent structures) was used to assess associations between maternal emotions, cytokine levels, and birth outcomes. RESULTS: We found significant positive associations between negative mood (depressive symptoms in the second and third trimesters and negative affect in the third trimester) and anti-inflammatory cytokine IL-10 levels, and negative associations between maternal distress in the second and third trimesters and pro-/anti-inflammatory cytokine ratios (IFN-γ/IL-10, TNF-α/IL-10 and IL-6/IL-10). Higher levels of pro-inflammatory cytokines IFN-γ, IL-12, IL-17, and TNF-α were associated with younger gestational age at birth and lower birth weight. LIMITATIONS: We did not control for relevant factors such as social support, health-related behaviors, or cortisol levels. CONCLUSIONS: Negative mood in mid- and late pregnancy may shift cytokine balance toward the anti-inflammatory cytokine dominance. Our results provide further evidence for the negative association between pro-inflammatory cytokines in late pregnancy and gestational age at birth/birth weight, which we observed even in a low-risk population.

Associations between prenatal stress with offspring inflammation, depression and anxiety.

PURPOSE: Few longitudinal studies have investigated the mediating role of inflammation during childhood in associations between prenatal maternal stress and adolescent mental health. The objective of this study was to examine the associations between prenatal maternal stress, concentrations of immune markers at age 9, and symptoms of generalized anxiety disorder (GAD) and depression during adolescence. METHODS: This study included 3723 mother-child pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC). Prenatal maternal stress was examined using 55 items measured during pregnancy. Inflammation was assessed using serum concentrations of interleukin-6 (IL-6) and C-reactive protein (CRP) when children were 9 years old. GAD and depression were assessed when children were 16 and 18 years of age, respectively. Analyses comprised of structural equation models. RESULTS: Prenatal maternal stress was associated with higher concentrations of IL-6 in childhood, and with greater symptoms of depression and GAD in adolescence. However, we did not observe associations between prenatal maternal stress and CRP; also, CRP and IL-6 were not associated with depression and GAD. There was no evidence that CRP and IL-6 mediated the associations between prenatal maternal stress and either GAD or depression. CONCLUSIONS: Prenatal maternal stress is associated with IL-6 levels in childhood, and with GAD and depression during adolescence. Future studies should examine immune activity at multiple points during development in relation to mental health into adulthood to determine whether inflammation at different points during development could increase risk for mental health problems among children whose mothers experienced significant stressors during pregnancy.

Effects of chronic stress on rat heart function following regional ischemia: a sex-dependent investigation.

Chronic psychological stress is a recognized, yet understudied risk factor for heart disease, with potential sex-specific effects. We investigated whether chronic stress triggers sex-dependent cardiac dysfunction in isolated Wistar rat hearts subjected to ischemia-reperfusion injury. The experimental cohort underwent 1 h of daily restraint stress for 4 wk versus matched controls, followed by euthanasia (sodium pentobarbital) and heart excision for ex vivo perfusion. Blood analysis revealed sex-specific alterations in stress hormones and inflammatory markers. When compared with controls, chronic restraint stress (CRS) males displayed decreased plasma brain-derived neurotrophic factor (BDNF) levels (P < 0.05), whereas CRS females exhibited elevated plasma adrenocorticotropic hormone (ACTH) (P < 0.01) and reduced corticosterone (P < 0.001) alongside lower serum estradiol (P < 0.001) and estradiol/progesterone ratio (P < 0.01). Of note, CRS females showed increased serum cardiac troponin T (P < 0.05) and tumor necrosis factor-α (TNF-α) (P < 0.01) with suppressed interleukin (IL)-1α, IL-1ß, IL-6, and IL-10 levels (P < 0.05) when compared with controls. Ex vivo Langendorff perfusions revealed that CRS female hearts displayed impaired postischemic functional recovery for baseline stroke volume (SV, P < 0.01), work performance (P < 0.05), aortic output (AO, P < 0.05), coronary flow (CF, P < 0.01), and overall cardiac output (CO, P < 0.01) when compared with matched controls and CRS males (P < 0.05). Our findings reveal intriguing sex-specific responses at both the systemic and functional levels in stressed hearts. Here, the dysregulation of stress hormones, proinflammatory state, and potential underlying cardiomyopathy in females following the stress protocol renders them more prone to damage following myocardial ischemia. This study emphasizes the importance of incorporating sex as a biological variable in cardiac research focusing on stress-related cardiomyopathy.NEW & NOTEWORTHY Although chronic psychological stress is a risk factor for cardiovascular diseases, the underlying mechanisms remain poorly understood. This study revealed that chronic restraint stress resulted in systemic changes (dysregulated stress hormones, proinflammatory state) and potential cardiomyopathy in females versus controls and their male counterparts. The stressed female hearts also displayed reduced functional recovery following ex vivo ischemia-reperfusion. This highlights the importance of incorporating sex as a biological variable in cardiac research.

Greater perceived stress and lower cortisol concentration increase the odds of depressive symptoms among adolescents.

BACKGROUND: Adolescent depression is a major public health concern. Although stress has been linked to more severe depression, its association with mild depression among adolescents is not understood. This study assesses the relationship between perceived stress and cortisol (a physiologic measure of stress) and examines the relationships between these stress measures and depressive symptoms among adolescents 13-19 years of age. METHODS: Stress was measured with the Perceived Stress Scale-10 and through salivary sampling for cortisol four times throughout the day. The Patient Health Questionnaire-9 was used to measure depressive symptoms (range 0-27), where ≥5 indicated the threshold for experiencing at least mild depressive symptoms. Spearman coefficients and multiple logistic regression models were used to examine the relationships between our variables of interest. RESULTS: The mean age of the 73 participants in our study was 15.82 years. 49 % of the participants reported depressive symptoms (PHQ-9 score ≥ 5). Both higher perceived stress (odds ratio [OR] = 1.11, p = 0.022) and lower cortisol (area-under-the curve; AUCG) (OR = 0.99, p = 0.009) were associated with increased odds of having depressive symptoms. LIMITATIONS: Few participants had moderate to severe PHQ-9 depression, therefore our study reported findings on mild depression or greater. CONCLUSIONS: Perceived stress and cortisol appear to reflect distinct, independent components of the stress experience. However, both greater perceived stress and less circulating cortisol may indicate difficulties in regulating stress as potential factors underlying depressive symptoms. Future research should focus on the different types of adolescent stressors and the importance of routine screening of stress and depression, including mild depression.

Bulk serum extracellular vesicles from stressed mice show a distinct proteome and induce behavioral and molecular changes in naive mice.

Chronic stress can trigger several pathologies including mood disorders for which no clear diagnostic molecular markers have been established yet. Attractive biomarker sources are extracellular vesicles (EVs). Evs are released by cells in health and disease and contain genetic material, proteins and lipids characteristic of the cell state. Here we show that Evs recovered from the blood of animals exposed to a repeated interrupted stress protocol (RIS) have a different protein profile compared to those obtained from control animals. Proteomic analysis indicated that proteins differentially present in bulk serum Evs from stressed animals were implicated in metabolic and inflammatory pathways and several of them were previously related to psychiatric disorders. Interestingly, these serum Evs carry brain-enriched proteins including the stress-responsive neuronal protein M6a. Then, we used an in-utero electroporation strategy to selectively overexpress M6a-GFP in brain neurons and found that M6a-GFP could also be detected in bulk serum Evs suggesting a neuronal origin. Finally, to determine if these Evs could have functional consequences, we administered Evs from control and RIS animals intranasally to naïve mice. Animals receiving stress EVs showed changes in behavior and brain M6a levels similar to those observed in physically stressed animals. Such changes could therefore be attributed, or at least in part, to EV protein transfer. Altogether these findings show that EVs may participate in stress signaling and propose proteins carried by EVs as a valuable source of biomarkers for stress-induced diseases.

Level of Cytokines and C3 Complement in the Blood of Rats under Conditions of Chronic Unpredictable Stress of Different Durations.

The parameters of the cytokine profile and functional activity of the complement system in the blood of rats were studied during different time periods of chronic unpredictable mild stress using a model of sequentially alternating low-intensity stress effects for 1, 2, 3, and 4 weeks. In the dynamics of observation, a general tendency towards multidirectional fluctuations in the concentration of cytokines was revealed: an increase in IL-10, but a decrease in IL-4 in comparison with the control. Statistically significant changes in the level of IL-10 were noted after 2, 3, and 4 weeks, IL-4 - after 2 and 4 weeks of stress loads. The percentage of lysis of the C3 component in rats gradually increased by the 2nd week of chronic stress, but then decreased and practically did not differ from the control values (intact animals) by the end of the study. These results illustrate the specificity of changes in the indicators of the C component of the complement system and the cytokine profile of the blood reflecting activity of the cellular and humoral components of the immune response in rats exposed to repeated stress factors of different origins and duration.

[Occupational chronic psychological stress and transaminase, HSP70 gene family and its proteins association of the interaction with metabolic syndrome].

OBJECTIVE: To explore the association of Occupational chronic psychological stress with transaminase, heat shock protein70(HSP70)gene family and their protein interaction with metabolic syndrome(MS). METHODS: A case-control study was used. According to the inclusion and exclusion criteria, from March 2015 to March 2016, 583 unrelated MS patients were selected as the case group and 585 unrelated healthy people as the control group among hospitalized and physical examination subjects aged 20-60 in Wuzhong People's Hospital and General Hospital of Ningxia Medical University. Questionnaire survey, physical examination, clinical and biochemical indicators, serum HSP70 level and five-locus polymorphism detection of HSP70 gene were carried out. GMDR 0.7 software was used to analyze the relationship between psychological stress, transaminase, HSP70 gene and its protein interaction and MS. RESULTS: After adjusting for age and sex, the rs1008438, rs1061581, rs539689 and rs222795 locus of HSP70 gene in the Co-dominant model and Dominant model and the rs222795 loci in the Over-dominant model carry wild homozygous genotype and heterozygous genotype were all related to the reduction of MS risk(OR<1, P<0.05). GMDR result: the 2-factor interaction model composed of psychological stress and serum HSP70, the 2-3 factor interaction model composed of transaminase activity, and the 2-6 factor interaction model composed of five locus of HSP70 gene, the 2-9 factor interaction model consisting of psychological stress and transaminase activity, HSP70 gene and its protein were all significantly associated with MS(P<0.01, P<0.05), all each factor interaction models were the best, and the 9-factor optimal interaction model had the highest risk of MS(OR=46.51, 95%CI 27.65-78.26), and the risk of MS in high-risk type was 45.23 times higher than that in low-risk type(95%CI 31.29-65.38, P<0.01). CONCLUSION: HSP70 gene family carrying wild-type alleles is a protective factor for MS. The interaction among Occupational chronic psychological stress interacts with transaminases, HSP70 gene and its serum proteins may be associated with MS. With the increase of involvement interaction factors, the risk of MS increased significantly. The interaction of multiple factors can greatly increase its risk.

Perceived glucose levels matter more than CGM-based data in predicting diabetes distress in type 1 or type 2 diabetes: a precision mental health approach using n-of-1 analyses.

AIMS/HYPOTHESIS: Diabetes distress is one of the most frequent mental health issues identified in people with type 1 and type 2 diabetes. Little is known about the role of glucose control as a potential contributor to diabetes distress and whether the subjective perception of glucose control or the objective glycaemic parameters are more important for the experience. With the emergence of continuous glucose monitoring (CGM), this is a relevant question as glucose values are now visible in real-time. We employed a precision monitoring approach to analyse the independent associations of perceived and measured glucose control with diabetes distress on a daily basis. By using n-of-1 analyses, we aimed to identify individual contributors to diabetes distress per person and analyse the associations of these individual contributors with mental health at a 3 month follow-up. METHODS: In this prospective, observational study, perceived (hypoglycaemia/hyperglycaemia/glucose variability burden) and measured glucose control (time in hypoglycaemia and hyperglycaemia, CV) were assessed daily for 17 days using an ecological momentary assessment (EMA) approach with a special EMA app and CGM, respectively. Mixed-effect regression analysis was performed, with daily diabetes distress as the dependent variable and daily perceived and CGM-measured metrics of glucose control as random factors. Individual regression coefficients of daily distress with perceived and CGM-measured metrics were correlated with levels of psychosocial well-being at a 3 month follow-up. RESULTS: Data from 379 participants were analysed (50.9% type 1 diabetes; 49.6% female). Perceived glucose variability (t=14.360; p<0.0001) and perceived hyperglycaemia (t=13.637; p<0.0001) were the strongest predictors of daily diabetes distress, while CGM-based glucose variability was not significantly associated (t=1.070; p=0.285). There was great heterogeneity between individuals in the associations of perceived and measured glucose parameters with diabetes distress. Individuals with a stronger association between perceived glucose control and daily distress had more depressive symptoms (ß=0.32), diabetes distress (ß=0.39) and hypoglycaemia fear (ß=0.34) at follow-up (all p<0.001). Individuals with a stronger association between CGM-measured glucose control and daily distress had higher levels of psychosocial well-being at follow-up (depressive symptoms: ß=-0.31; diabetes distress: ß=-0.33; hypoglycaemia fear: ß=-0.27; all p<0.001) but also higher HbA1c (ß=0.12; p<0.05). CONCLUSIONS/INTERPRETATION: Overall, subjective perceptions of glucose seem to be more influential on diabetes distress than objective CGM parameters of glycaemic control. N-of-1 analyses showed that CGM-measured and perceived glucose control had differential associations with diabetes distress and psychosocial well-being 3 months later. The results highlight the need to understand the individual drivers of diabetes distress to develop personalised interventions within a precision mental health approach.

Elevated level of prenatal testosterone and vitamin D3 deficiency during pregnancy, in the presence of prenatal maternal stress, and their association with the development of attention deficit hyperactivity disorder (ADHD)-like symptoms in toddlers.

INTRODUCTION: To investigate the hypothesis that the presence of prenatal maternal stress, increased level of prenatal testosterone, and low level of vitamin D3 in pregnancy is associated with the development of ADHD-like symptoms in toddlers (< 2 years old). MATERIAL AND METHODS: The study group comprised 53 pregnant women and 53 infants of these pregnancies. The population cohort of 53 pregnant women were recruited at their 35th to 37th week of pregnancy and investigated prospectively. The participants were selected through targeted selection. Maternal experience of stressful life events was assessed by stress standardised questionnaires, prenatal testosterone was determined in the mothers' saliva by using the immune enzymatic (ELISA) method, and maternal plasma D vitamin was measured using the ECLIA method, during pregnancy. When the age of the offspring was 6 months and then less than 2 years, the mothers completed the child behaviour and temperament checklist. RESULTS: A small but statistically significant association was found between the common symptom complex of ADHD and the level of testosterone and vitamin D3, in the presence of prenatal maternal stress. Multiple regression analysis showed that maternal stressful events during pregnancy significantly predicted ADHD behaviours in offspring. CONCLUSIONS: The study supported the hypothesis that prenatal maternal stress, increased level of prenatal testosterone, and low level of vitamin D3 during pregnancy increases the risk of development of ADHD-like symptoms in toddlers (< 2 years old). Also, the obtained results support the hypothesis that the influence of prenatal factors causes ADHD-like symptoms in offspring through a programming effect.

Increased plasma levels of neuro-related proteins in patients with stress-related exhaustion: A longitudinal study.

Exhaustion disorder (ED) is a stress-related disorder characterized by physical and mental symptoms of exhaustion. Recent data suggest that pathophysiological processes in the central nervous system are involved in the biological mechanisms underlying ED. The aims of this study were to investigate if plasma levels of neuro-related proteins differ between patients with ED and healthy controls, and, if so, to investigate if these differences persist over time. Using the Olink Neuro Exploratory panel, we quantified the plasma levels of 92 neuro-related proteins in 163 ED patients at the time of diagnosis (baseline), 149 patients at long-term follow-up (7-12 years later, median follow-up time 9 years and 5 months), and 100 healthy controls. We found that the plasma levels of 40 proteins were significantly higher in the ED group at baseline compared with the control group. Out of these, the plasma levels of 36 proteins were significantly lower in the ED group at follow-up compared with the same group at baseline and the plasma levels of four proteins did not significantly differ between the groups. At follow-up, the plasma levels of two proteins were significantly lower in the ED group compared with the control group. These data support the hypothesis that pathophysiological processes in the central nervous system are involved in the biological mechanisms underlying ED.

The relationship of peripheral blood cell inflammatory biomarkers and psychological stress in unmedicated major depressive disorder.

BACKGROUND: Recent research has explored the linkage between major depressive disorder (MDD) and inflammation, especially via altered peripheral blood immune markers. However, the relationship between several novel leukocyte-derived ratios (LDR) and psychological stress in MDD remains uncertain. This study aimed to explore the relationship between LDR, clinical characteristics, recent life events, and childhood maltreatment in MDD patients. METHODS: A cross-sectional case-control study was conducted involving 59 healthy controls (HC) and 50 unmedicated MDD patients. Subjects underwent psychological assessments and peripheral blood measurements. LDR assessed in this study included neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), white blood cell-to-mean platelet volume ratio (WMR), systemic immune inflammation index (SII), multiplication of neutrophil and monocyte counts (MNM), and systemic inflammation response index (SIRI). RESULTS: MDD patients displayed significant alterations in WMR, PLR, and MNM compared to HC, as well as correlations between several LDR and various clinical features (duration of untreated psychosis and dNLR, the nine-item Patient Health Questionnaire and PLR, the 7-item Generalized Anxiety Disorder Questionnaire and SIRI (NLR and dNLR). There was a significant difference in the comparison of WMR in first-episode patients than in recurrent patients. Analyses further revealed an association between Life Event Scale total scores and NLR (dNLR). No correlation was found between Childhood Trauma Questionnaire total (or subscale) scores and LDR. Additionally, WMR and dNLR presented potential predictive value for distinguishing between MDD and HC. CONCLUSION: The study concludes that MDD and some clinical features are associated with alterations in some peripheral blood LDR. These findings emphasize the potential role of peripheral blood LDR in the pathogenesis and clinical heterogeneity of MDD.

Evaluation of harmful drinking among professional drivers by direct ethanol biomarkers and its relation with psychological distress.

OBJECTIVE: This study aimed to evaluate the alcohol consumption among professional truck and bus drivers using direct ethanol biomarkers, and to explore its relationship with anxiety, depression, and stress. METHODS: The assessment of potential harmful drinking was conducted through the measurement of direct biomarkers: phosphatidylethanol (PEth), ethyl glucuronide (EtG), and ethyl sulfate (EtS), using dried blood spots (DBS). Additionally, self-reported data from the Alcohol Use Disorders Identification Test (AUDIT-C) were used. Emotional states, including depression, anxiety, and stress, were evaluated using the Depression, Anxiety, and Stress Scale (DASS-21). RESULTS: A total of 97 drivers participated in the study, with the majority being male (96%) and identified as truck drivers (75.3%). Among them, 43.3% reported working more than 10 h daily. The majority of volunteers exhibited normal levels of stress (81.4%), anxiety (83%), and depression (86.6%). According to the AUDIT-C assessment, 30.9% were categorized as having a moderate risk, while 11.3% were deemed to be at high risk for harmful alcohol consumption behavior. Ethyl glucuronide (EtG) and ethyl sulfate (EtS) levels, indicating recent ethanol consumption, were detected in 14.4% of the drivers. In contrast, the long half-life metabolite PEth (16:0-18:1) was present in 88.7% of the volunteers. A moderate correlation (rs = 0.45, p < .01) was observed between PEth levels and AUDIT-C scores. The Receiver Operating Characteristic (ROC) curve, utilizing a PEth threshold of ≥ 59.0 ng ml-1, displayed 78% sensitivity and 73% specificity in effectively distinguishing high risk for alcohol intake. Notably, no significant associations were found between alcohol consumption and levels of stress, depression, and anxiety. CONCLUSIONS: The study findings indicate a noteworthy proportion of drivers engaging in regular alcohol consumption alongside a demanding workload. Notably, PEth measurements highlighted an underreporting within the AUDIT-C self-reports. These results lend robust support for the utilization of biomarkers in assessing alcohol consumption patterns among drivers.