Salivary glucocorticoid receptor gene DNA methylation and cortisol output in relation to lifestyle, psychological distress, and cognition in university students.

Is Stress Reactivity an Intermediary Mechanism in the Association Between NR3C1 Methylation and Adolescent Loneliness?

This study examined whether saliva-derived DNA methylation in the glucocorticoid receptor (NR3C1) gene was linked to loneliness through dysregulation of the hypothalamic-pituitary-adrenal axis (HPA-axis) in 101 early adolescents (Mage = 11.61 years, SDage = 0.64, 55.45% girls). Using person-centered analyses to account for interindividual differences in adolescents' stress reactivity, we identified three subgroups of cortisol responders to a social evaluative stressor: A hyporesponsive subgroup (30.5%), a moderate-responsive subgroup (44.2%), and a hyperresponsive subgroup (25.3%). Exploratory analyses also identified subgroups for two markers of the autonomous nervous system (ANS), that is, heart rate (HR) and skin conductance (SC). Furthermore, the indirect effects from NR3C1 methylation to early adolescent loneliness via individual differences in stress responses were examined. Results indicated that higher NR3C1 methylation levels were associated with a lower probability of belonging to the most reactive stress response subgroups for cortisol and HR, and to the high mean-level subgroup for SC. Additionally, higher probabilities of belonging to the low mean-level SC subgroup were associated with higher levels of loneliness. However, there was no evidence that NR3C1 methylation was associated with early adolescent loneliness, either directly or indirectly via stress reactivity. These findings highlight significant individual differences in stress reactivity, emphasizing the need to explicitly consider such variability in future research. Moreover, the results suggest that NR3C1 methylation is linked to individual differences in stress responding, warranting further investigation.

association of BDNF Val66Met polymorphism with hPa and saM axis reactivity to psychological and physical stress

Glucocorticoid receptor gene (NR3C1) DNA methylation, early-life trauma, and resilience in obsessive-compulsive disorder

Introduction Hypothalamic-pituitary-adrenal (HPA) axis dysregulation has been implicated in obsessive-compulsive disorder (OCD), but epigenetic changes in HPA axis-related genes remain poorly understood. We investigated whether DNA methylation of the glucocorticoid receptor gene (NR3C1), particularly within exon 1F, is associated with OCD and examined its relationship with stress resilience and early-life trauma. Methods A total of 275 patients with OCD and 200 healthy controls (aged 19–40 years) were recruited. DNA methylation at three CpG sites within NR3C1 exon 1F was measured using pyrosequencing. Group differences were examined using multivariate analysis of covariance (MANCOVA), and structural equation modeling (SEM) was conducted to evaluate resilience-mediated pathways linking NR3C1 methylation, early-life trauma, and OCD status. Results Compared to healthy controls, DNA methylation at NR3C1 exon 1F was significantly reduced in women with OCD (p < 0.001), which remained significant in a drug-naïve or drug-free subset. No overall multivariate difference was observed in men. SEM revealed that stress resilience partially mediated the association between NR3C1 methylation and OCD status (indirect β = −0.117, p = 0.014). While early-life trauma was associated with lower methylation at a specific CpG site, the mediation effect of DNA methylation between trauma and OCD did not reach statistical significance. Conclusion These findings suggest that epigenetic alterations of NR3C1 may contribute to stress-related vulnerability in OCD, with resilience representing a key psychological pathway linking stress-related biological processes, including HPA-axis regulation, to clinical outcomes.

Investigation of psychosocial stress and DNA methylation in genes related to immune response, metabolism, and calcium signaling among African American and White middle-aged adults

Chronic psychological stress is an environmental factor associated with chronic disease risk and health disparities. Since environmental stressors alter gene expression and physiologic responses through epigenetic mechanisms, perceived discrimination (PD) or the subjective experience of receiving negative treatment related to personal characteristics may influence DNA methylation (DNAm) of CpGs within genes linked to chronic disease. Using the Illumina 850K EPIC chip and psychosocial stress associated discrimination scales including the Lifetime, Racial, and Everyday Discrimination scales, we identified novel CpGs and differentially methylated positions (DMPs) associated with PD in the context of age, sex, and poverty status among African American and White adults and ones that overlap previous findings of differentially methylated sites (or genes) with discrimination, inflammation and chronic disease. Ingenuity Pathway Analysis (IPA) identified several pathways associated with the DNAm patterns and PD with age, sex, and/or poverty status. With age, the white adipose tissue browning pathway was activated among African American participants. This was related to the differential methylation found in the CACNA1H, PRDM16, and BDNF genes. Among White participants, the opioid signaling pathway was activated and significantly enriched for the genes FGR, POMC, and RPS6KA2. Additionally, CpG sites associated with PD among White participants with poverty status revealed that the netrin signaling, opioid signaling, and calcium signaling pathways were activated and significantly enriched for differentially methylated genes including NFATC1 and NFATC2. The identified novel DNAm genes associated with PD transduce effects through biological pathways related to inflammation and immune response, white adipose tissue browning, and calcium signaling.

Anxiety and depression symptoms in relation to body mass index, fruit and vegetable intake, and physical activity among nutrition students in Peru: a cross-sectional study

Background Anxiety and depression are common among university students and may negatively affect their wellbeing and academic performance. However, evidence regarding their co-occurrence and their relationship with BMI and lifestyle-related factors in Peruvian students remains limited. This study aimed to analyze the association between anxiety, depression, BMI, and lifestyle-related factors among nutrition students at a private university in northern Peru. Methods A cross-sectional study was conducted with 405 university students. Anxiety and depressive symptoms were assessed using the Generalized Anxiety Disorder-2 (GAD-2) and the Patient Health Questionnaire-2 (PHQ-2). A cut-off score of ≥3 was used to identify clinically relevant symptoms. Data were collected on body mass index (BMI), sleep duration, physical activity (PA), and fruit and vegetable (F/V) consumption. Associations were evaluated using Poisson regression models with robust variance to estimate prevalence ratios (PR) and 95% confidence intervals (95% CI). Results The prevalence of anxiety and depression symptoms was 57.3 and 26.4%, respectively. Anxiety symptoms was significantly associated with depression (aPR = 4.53; 95% CI: 2.63–7.80). Compared with normal weight, overweight and obesity were associated with a higher prevalence of anxiety (overweight: aPR = 1.22; 95% CI: 1.01–1.48; obesity: aPR = 1.43; 95% CI: 1.10–1.87) and depression (overweight: aPR = 1.27; 95% CI: 1.00–1.62; obesity: aPR = 1.61; 95% CI: 1.12–2.32). Engaging in PA ≥ 5 times per week was associated with a lower prevalence of depression (aPR = 0.35; 95% CI: 0.14–0.85), whereas consuming <5 servings/day of F/V was associated with a higher prevalence of depression (aPR = 1.52; 95% CI: 1.14–2.02). Conclusion Anxiety and depression symptoms were highly prevalent and strongly interrelated. Excess body weight, low PA, and low F/V consumption were associated with poorer mental health indicators, highlighting the importance of integrated health-promotion strategies among university students.

Stress-related salivary biomarkers - cortisol, dehydroepiandrosterone, alpha amylase, and suicidal ideation among young women living in Kampala's informal settlements.

BACKGROUND Young women living in informal urban settlements experience intersecting structural disadvantages that may contribute to stress-related physiological changes and suicidal ideation. Evidence on salivary stress biomarkers in this population remains limited. OBJECTIVE To examine associations between salivary cortisol, dehydroepiandrosterone (DHEA), α-amylase, the cortisol-to-DHEA ratio, and suicidal ideation among young women in Kampala's informal settlements. METHODS This cross-sectional analysis included 300 women aged 18-24 years recruited from three informal settlements in Kampala, Uganda. Suicidal ideation was assessed using four items from the Columbia-Suicide Severity Rating Scale. Morning and afternoon salivary biomarkers were measured using COBAS E411 and C-111 analyzers. Independent-samples t-tests compared biomarker levels by suicidal ideation status, and modified Poisson regression examined adjusted associations. The final model was used to estimate the prevalence ratio (PR) and its 95% confidence interval (CI). RESULTS Overall, 46.0% reported suicidal ideation and 57.7% met the threshold for probable depression. Approximately 39% had DHEA values below published reference ranges at both collection times. Participants reporting suicidal ideation had lower square root-transformed morning DHEA levels than those without ideation (3.96 vs. 4.65; p = 0.048) and higher square root-transformed morning cortisol-to-DHEA ratios (1.19 vs. 1.00; p = 0.027). In the adjusted model, each one-unit increase in the square root-transformed morning cortisol-to-DHEA ratio was associated with a 12% higher prevalence of suicidal ideation (PR = 1.12; 95% CI: 1.04-1.21). CONCLUSION Suicidal ideation was common, and square root-transformed morning cortisol-to-DHEA ratios were independently associated with suicidal ideation. These findings highlight the importance of understanding suicidality through integrated biological, psychological, and social perspectives and reinforce the need for accessible, gender-responsive suicide prevention and mental health services in low-resource urban settings.