Pub Date : 2026-02-01Epub Date: 2025-11-13DOI: 10.1016/j.psyneuen.2025.107693
Maitri Jain , Emily Sokol , Elizabeth Freehling , Sneha Kamath , Renée Lajiness-O'Neill , Angela D. Staples , Jamie M. Lawler
Importance
Although parent-child cortisol synchrony is essential for the development of children’s socio-emotional development, the research findings on what affects this synchrony are unclear. This lack of clarity makes it difficult to pinpoint the best areas to target when creating interventions to help improve synchrony between parents and their children.
Objective
We aimed to characterize the literature on parent-child cortisol synchrony and how various family-related risks and protective factors were associated with parent-child cortisol synchrony.
Evidence review
We searched 4 databases (CINAHL, PsycINFO, PubMed, and Web of Science) on August 25th, 2025. Backward and forward citation searching was also conducted. Eligible articles a) were peer-reviewed articles/theses/dissertations published in the English language, b) assessed children between 6 months and 8 years for diurnal cortisol, and between 0 months and 8 years for cortisol reactivity, c) included majority of children free of neurological, genetic, or major psychiatric disorders and born full-term, d) included parents with a mean age above 18 years, where the majority were free of neurological or genetic disorders, e) collected at least 2 salivary cortisol samples from both parent and child, in either home or lab, f) for cortisol reactivity, collected at least one saliva sample each before and after a challenging task, g) collected 2 saliva samples on the same day for diurnal cortisol, and h) reported any statistical association between parent and child cortisol. We used the Quality Assessment with Diverse Studies Tool for quality analysis.
Findings
We identified 33 unique studies, including a total of 5206 participants. All studies were observational, with 7 longitudinal studies. The scarce literature suggested positive child-to-parent synchrony in families without risk factors, but synchrony was absent or reduced in families with risk factors. Protective factors (e.g., parental sensitivity) led to more adaptive synchrony in parent-child dyads.
Conclusions and relevance
While the existing research suggested that parent-child cortisol synchrony is affected by both family risk and protective factors, too few studies existed to draw strong conclusions. More research is essential to develop better interventions for improving parent-child synchrony.
重要性：虽然亲子皮质醇同步性对儿童社会情感发展至关重要，但影响亲子皮质醇同步性的因素研究结果尚不清楚。由于缺乏明确性，在制定干预措施以帮助改善父母与子女之间的同步时，很难确定最佳目标领域。目的：我们旨在描述亲子皮质醇同步的文献特征，以及各种家庭相关风险和保护因素如何与亲子皮质醇同步相关。我们于2025年8月25日检索了4个数据库（CINAHL、PsycINFO、PubMed和Web of Science）。并进行了前后引文检索。符合条件的文章a)以英语发表的同行评审的文章/论文/论文，b)评估6个月至8岁儿童的皮质醇日变化，以及0个月至8岁儿童的皮质醇反应性，c)包括大多数无神经、遗传或主要精神疾病且足月出生的儿童，d)包括平均年龄在18岁以上的父母，其中大多数无神经或遗传疾病。E)在家中或实验室从父母和孩子身上收集至少2个唾液皮质醇样本，f)皮质醇反应性，在具有挑战性的任务之前和之后分别收集至少一个唾液样本，g)在同一天收集2个唾液样本用于每日皮质醇，h)报告父母和孩子皮质醇之间的任何统计关联。我们使用多样化研究质量评估工具进行质量分析。研究结果：我们确定了33项独特的研究，包括5206名参与者。所有研究均为观察性研究，其中7项为纵向研究。很少的文献表明，在没有危险因素的家庭中，孩子与父母的同步性是积极的，但在有危险因素的家庭中，同步性是缺失的或降低的。保护因素（例如，父母敏感性）导致亲子二代更强的适应性同步。结论及相关性：虽然现有研究表明亲子皮质醇同步受家庭风险因素和保护因素的影响，但研究太少，无法得出强有力的结论。更多的研究是必要的，以制定更好的干预措施，以改善亲子同步。
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Pub Date : 2026-02-01Epub Date: 2025-11-27DOI: 10.1016/j.psyneuen.2025.107708
Nevena Chuntova , Inès Ait Abdelmalek , Karine Lavallée-Rodrigue , Emma-Rose Thériault , Ryan Hogan , Ziad Guenoun , Jasmine Boulette , Ahmed Jérome Romain , L. Zachary DuBois , Robert-Paul Juster
Sexual and gender diverse (SGD) people face significant health disparities linked to chronic stigma exposure. Yet, the biological mechanisms underlying these inequities remain unexplored. This project examines how lifetime intersectional discrimination influences allostatic load (AL) —the cumulative biological 'wear and tear' of chronic stress—and explores the role of health behaviors (smoking, alcohol use, drug use, sleep quality and physical activity) as potential mediators in this pathway. Our team recruited 357 adults separated into 7 subgroups stratified by gender identity and sexual orientation. Blood samples and biometrics were collected from each participant and analysed to create a composite AL index incorporating 16 biomarkers across multiple physiological systems. Psychosocial variables including intersectional discrimination experiences and health behaviors were derived from validated questionnaires. Results show that intersectional discrimination experiences were positively associated with AL after controlling for age, indicating that both major discriminatory events and cumulative daily experiences independently contribute to physiological dysregulation through enacted stigma and discrimination exposure. Additionally, both gender identity and sexual orientation relate to differential AL patterns, with masculine-spectrum people (cisgender and transgender men) and sexual minority men (bisexual and gay men) showing the highest AL levels. Contrary to our hypothesis, health behaviors did not mediate the relationship between discrimination and AL, suggesting that discrimination may exert direct biological effects through stress response systems without requiring negative behavioral pathways. These findings provide further support for recognition of the impacts of structural and social determinants of health among SGD communities and the need for policy changes that protect against structural inequities.
{"title":"Intersectional stigma, health behaviors, and allostatic load among sexual and gender diverse people","authors":"Nevena Chuntova , Inès Ait Abdelmalek , Karine Lavallée-Rodrigue , Emma-Rose Thériault , Ryan Hogan , Ziad Guenoun , Jasmine Boulette , Ahmed Jérome Romain , L. Zachary DuBois , Robert-Paul Juster","doi":"10.1016/j.psyneuen.2025.107708","DOIUrl":"10.1016/j.psyneuen.2025.107708","url":null,"abstract":"<div><div>Sexual and gender diverse (SGD) people face significant health disparities linked to chronic stigma exposure. Yet, the biological mechanisms underlying these inequities remain unexplored. This project examines how lifetime intersectional discrimination influences allostatic load (AL) —the cumulative biological 'wear and tear' of chronic stress—and explores the role of health behaviors (smoking, alcohol use, drug use, sleep quality and physical activity) as potential mediators in this pathway. Our team recruited 357 adults separated into 7 subgroups stratified by gender identity and sexual orientation. Blood samples and biometrics were collected from each participant and analysed to create a composite AL index incorporating 16 biomarkers across multiple physiological systems. Psychosocial variables including intersectional discrimination experiences and health behaviors were derived from validated questionnaires. Results show that intersectional discrimination experiences were positively associated with AL after controlling for age, indicating that both major discriminatory events and cumulative daily experiences independently contribute to physiological dysregulation through enacted stigma and discrimination exposure. Additionally, both gender identity and sexual orientation relate to differential AL patterns, with masculine-spectrum people (cisgender and transgender men) and sexual minority men (bisexual and gay men) showing the highest AL levels. Contrary to our hypothesis, health behaviors did not mediate the relationship between discrimination and AL, suggesting that discrimination may exert direct biological effects through stress response systems without requiring negative behavioral pathways. These findings provide further support for recognition of the impacts of structural and social determinants of health among SGD communities and the need for policy changes that protect against structural inequities.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"184 ","pages":"Article 107708"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145669623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-05DOI: 10.1016/j.psyneuen.2025.107682
Xiaoyan Zhang , Natalie Slopen , Ariel A. Binns , Adolfo G. Cuevas
Background
Adverse childhood experiences (ACEs) are common, co-occurring risk factors for poor long-term health. Emerging research links ACEs to accelerated biological aging, yet most studies rely on singular or cumulative indicators and often overlook differences by race, sex, and adversity type, potentially yielding imprecise estimates.
Objectives
To identify latent ACEs classes by race and sex using latent class analysis (LCA) and examine their associations with biological aging measured by DNA methylation-based epigenetic clocks.
Methods
We analyzed 3586 participants from the Health and Retirement Study, a nationally representative cohort of U.S. older adults. LCA identified ACEs classes based on nine indicators, including physical abuse, household substance use, and socioeconomic adversity. Biological aging was measured using GrimAge, PhenoAge, and DunedinPoAm clocks. Epigenetic age acceleration (EAA) was calculated as residuals of GrimAge/PhenoAge regressed on chronological age.
Results
Latent Low Adversity and Financial Adversity classes were identified among Black and White participants, and among Hispanic participants we identified Parental Low Education and Socioeconomic Adversity classes. Men exhibited higher GrimAge EAA than women across all groups. Among Black and White women, Financial Adversity was associated with elevated GrimAge EAA and a faster DunedinPoAm pace compared to the Low Adversity group. Among Hispanic women, Socioeconomic Adversity was linked to higher PhenoAge EAA and faster DunedinPoAm pace relative to those in the Parental Low Education group.
Conclusion
Women in the adversity classes demonstrated more accelerated biological aging than those in low adversity classes. Findings underscore the value of intersectional, person-centered approaches to understanding adversity’s role in biological aging and the need for targeted health interventions.
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Pub Date : 2026-02-01Epub Date: 2025-12-02DOI: 10.1016/j.psyneuen.2025.107712
Harrison Dickens , L. Riley Gournay-Berman , Morgan Hill , Mikayla D.M. Joslin , Jamie Walker , Anastasia Makhanova , Ellen Leen-Feldner , Ivan Vargas
Background
Acute stress reactivity has been implicated in a wide range of physical and psychological disorders. Most literature has focused on laboratory paradigms that elicit neuroendocrine responses via socially evaluative stress. While shown to be effective at eliciting stress responses, these socially evaluative paradigms may only tap into a narrow range of stressors. Carbon dioxide (CO2) inhalation challenges have been shown to reliably elicit panic-relevant symptoms in healthy populations but evidence on the ability to elicit a neuroendocrine response is limited.
Methods
The current secondary analysis sought to examine the magnitude of neuroendocrine, sympathetic, and emotional response to a 5-minute, 10 % CO2-enriched air inhalation task in healthy volunteers. Seventy-five healthy adults (Mage: 27.2, 53.3 % female) completed the laboratory procedure.
Results
Results from mixed effects growth curve models found a significant linear (b = 0.006, df = 367, p < 0.001) and quadratic effect (b = −0.0001, df = 293, p < 0.001) of the challenge on salivary cortisol. The majority of the sample (57.3 %) experienced at least a 50 % increase in salivary cortisol from baseline. Women displayed a more blunted cortisol response than men (b = −0.00007, df = 293, p < 0.001). Hormonal contraceptive users, relative to naturally cycling women, also had a more blunted reactivity slope. Both heart rate and perceived fear also increased significantly in response to the task.
Conclusions
Findings from the current study suggest that the CO2 protocol employed in the current study can elicit meaningful neuroendocrine, sympathetic, and emotional responses.
背景：急性应激反应与广泛的生理和心理障碍有关。大多数文献都集中在通过社会评价压力引发神经内分泌反应的实验室范例上。虽然这些社会评价范式在引发压力反应方面被证明是有效的，但它们可能只涉及到一小部分压力源。二氧化碳（CO2）吸入挑战已被证明在健康人群中可靠地引发恐慌相关症状，但关于引发神经内分泌反应的能力的证据有限。方法：目前的二级分析旨在检查健康志愿者对5分钟，10 %二氧化碳浓度的空气吸入任务的神经内分泌、交感神经和情绪反应的大小。75名健康成人（男性：27.2%，女性：53.3 %）完成了实验室检查。结果：混合效应生长曲线模型的结果发现了显著的线性关系（b = 0.006, df = 367, p ）。结论：本研究的结果表明，本研究中采用的CO2方案可以引起有意义的神经内分泌、交感神经和情绪反应。
{"title":"Hypothalamic-pituitary-adrenal (HPA) axis stress response to a laboratory-based 10 % CO2 challenge in healthy adults","authors":"Harrison Dickens , L. Riley Gournay-Berman , Morgan Hill , Mikayla D.M. Joslin , Jamie Walker , Anastasia Makhanova , Ellen Leen-Feldner , Ivan Vargas","doi":"10.1016/j.psyneuen.2025.107712","DOIUrl":"10.1016/j.psyneuen.2025.107712","url":null,"abstract":"<div><h3>Background</h3><div>Acute stress reactivity has been implicated in a wide range of physical and psychological disorders. Most literature has focused on laboratory paradigms that elicit neuroendocrine responses via socially evaluative stress. While shown to be effective at eliciting stress responses, these socially evaluative paradigms may only tap into a narrow range of stressors. Carbon dioxide (CO<sub>2</sub>) inhalation challenges have been shown to reliably elicit panic-relevant symptoms in healthy populations but evidence on the ability to elicit a neuroendocrine response is limited.</div></div><div><h3>Methods</h3><div>The current secondary analysis sought to examine the magnitude of neuroendocrine, sympathetic, and emotional response to a 5-minute, 10 % CO<sub>2</sub>-enriched air inhalation task in healthy volunteers. Seventy-five healthy adults (<em>M</em><sub><em>age</em></sub> <em>:</em> 27.2, 53.3 % female) completed the laboratory procedure.</div></div><div><h3>Results</h3><div>Results from mixed effects growth curve models found a significant linear (<em>b</em> = 0.006, <em>df</em> = 367, <em>p</em> < 0.001) and quadratic effect (<em>b</em> = −0.0001, <em>df</em> = 293, <em>p</em> < 0.001) of the challenge on salivary cortisol. The majority of the sample (57.3 %) experienced at least a 50 % increase in salivary cortisol from baseline. Women displayed a more blunted cortisol response than men (<em>b</em> = −0.00007, <em>df</em> = 293, <em>p</em> < 0.001). Hormonal contraceptive users, relative to naturally cycling women, also had a more blunted reactivity slope. Both heart rate and perceived fear also increased significantly in response to the task.</div></div><div><h3>Conclusions</h3><div>Findings from the current study suggest that the CO<sub>2</sub> protocol employed in the current study can elicit meaningful neuroendocrine, sympathetic, and emotional responses.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"184 ","pages":"Article 107712"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145725766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-04DOI: 10.1016/j.psyneuen.2025.107684
Maurizio Sicorello , Jeanne-Carla Sprenger , Lisa M Störkel , Bettina Sarg , Leopold Kremser , Christian Schmahl , Inga Niedtfeld , Alexander Karabatsiakis
Biomarker research in psychopathology increasingly employs high-dimensional Omics approaches. Yet, proteomics based on human hair remain largely unexplored, despite its potential to efficiently capture stable biological signals accumulated over weeks to months. This study leveraged machine learning to investigate the potential of the hair proteome—all detectable peptides and proteins—as a biomarker source for stress-associated psychopathology. We analyzed protein profiles from hair segments of women with non-suicidal self-injury disorder and healthy controls (N = 68). Of 1114 identified proteins, 611 were sufficiently abundant for analyses. Partial Least Squares Discriminant Analysis achieved stable 84.4 % cross-validated accuracy for classification of clinical groups (p < .001), outperforming models based on data-derived clusters (60 %), stress-related proteins (73 %), and simulated hair cortisol from meta-analytic effect sizes (53–59 %). Predicted class probabilities strongly correlated with clinical symptoms and well-being (r > .60). Key predictive proteins were linked to pain perception, oxidative stress, and cholesterol homeostasis. Approximately 15 % of proteins differed significantly between groups, with the strongest candidates related to ribosomal function—an emerging target in depression. These findings establish hair proteomics as a promising, non-invasive biomarker source for psychiatric research with potential clinical applications in risk assessment and personalized interventions.
{"title":"Demonstrating the potential of untargeted hair proteomics for personalized biomarkers in stress-associated disorders","authors":"Maurizio Sicorello , Jeanne-Carla Sprenger , Lisa M Störkel , Bettina Sarg , Leopold Kremser , Christian Schmahl , Inga Niedtfeld , Alexander Karabatsiakis","doi":"10.1016/j.psyneuen.2025.107684","DOIUrl":"10.1016/j.psyneuen.2025.107684","url":null,"abstract":"<div><div>Biomarker research in psychopathology increasingly employs high-dimensional <em>Omics</em> approaches. Yet, proteomics based on human hair remain largely unexplored, despite its potential to efficiently capture stable biological signals accumulated over weeks to months. This study leveraged machine learning to investigate the potential of the hair proteome—all detectable peptides and proteins—as a biomarker source for stress-associated psychopathology. We analyzed protein profiles from hair segments of women with non-suicidal self-injury disorder and healthy controls (<em>N</em> = 68). Of 1114 identified proteins, 611 were sufficiently abundant for analyses. Partial Least Squares Discriminant Analysis achieved stable 84.4 % cross-validated accuracy for classification of clinical groups (p < .001), outperforming models based on data-derived clusters (60 %), stress-related proteins (73 %), and simulated hair cortisol from meta-analytic effect sizes (53–59 %). Predicted class probabilities strongly correlated with clinical symptoms and well-being (r > .60). Key predictive proteins were linked to pain perception, oxidative stress, and cholesterol homeostasis. Approximately 15 % of proteins differed significantly between groups, with the strongest candidates related to ribosomal function—an emerging target in depression. These findings establish hair proteomics as a promising, non-invasive biomarker source for psychiatric research with potential clinical applications in risk assessment and personalized interventions.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"184 ","pages":"Article 107684"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145577724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-25DOI: 10.1016/j.psyneuen.2025.107707
Lee T. Gettler , Sarah Hoegler Dennis
{"title":"Corrigendum to “U.S. men’s testosterone (T), partnering, and residence with children: Evidence from a nationally-representative cohort (NHANES) and relevance to clinically low T” [Psychoneuroendocrinology 182 (2025) 107658]","authors":"Lee T. Gettler , Sarah Hoegler Dennis","doi":"10.1016/j.psyneuen.2025.107707","DOIUrl":"10.1016/j.psyneuen.2025.107707","url":null,"abstract":"","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"184 ","pages":"Article 107707"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145621507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-25DOI: 10.1016/j.psyneuen.2025.107703
F. Linsen , P.C. Habets , Y. Milaneschi , S. Penner-Goeke , B. Mishuris , D. Czamara , B.W.J.H. Penninx , E.B. Binder , O.C. Meijer , C.H. Vinkers
<div><h3>Background</h3><div>Chronic stress and adverse life events are major contributors to depression and anxiety disorders. Genetic variants that influence glucocorticoid (GC) hormone responses may moderate the impact of stress on psychiatric outcomes. Here, we use a functional polygenic risk score (fPRS) based on GC-responsive gene regulatory elements (GREs) following dexamethasone (DEX) exposure (DEX-fPRS) and examined its association with clinical and biological stress-related phenotypes.</div></div><div><h3>Methods</h3><div>We analyzed data from 2286 participants in the Dutch NESDA cohort, with baseline, 2-year, and 6-year follow-up visits, including 1115 with baseline depression/anxiety diagnoses. Univariable and multivariable regression models, adjusted for age, sex, batch, and ancestry principal components, were used to test associations between DEX-fPRS and lifetime diagnosis, cumulative symptom severity, and clinical features among cases (e.g. symptom severity, recurrence). Subgroup comparisons (e.g. single vs. recurrent episodes) and biological outcomes (salivary cortisol, immune markers) were also assessed. A vehicle-treated fPRS control (VEH-fPRS) was additionally tested, capturing genetic variants associated with baseline, non-GR-stimulated enhancer activity. Gene-environment interactions were tested and replication in the MARS cohort (N = 1160).</div></div><div><h3>Results</h3><div>In the full sample, DEX-fPRS showed no significant associations with lifetime diagnosis, symptom severity, or biological measures after Bonferroni correction (all <em>p</em><sub>bonf</sub>>0.05), although a nominally significant negative association was observed for morning cortisol (AUCg) in the univariable model (B=-0.05, <em>p</em><sub>nominal</sub>=0.03, <em>p</em><sub>bonf</sub>=0.19). Among cases, evening cortisol showed nominally significant negative associations in both models (univariable: B=-0.05, <em>p</em><sub>nominal</sub>=0.02, <em>p</em><sub>bonf</sub>=0.09; multivariable: B=-0.04, <em>p</em><sub>nominal</sub>=0.02, <em>p</em><sub>bonf</sub>=0.14). A significant positive association was found for recurrent vs. single episodes in both models (univariable: β=1.24, <em>p</em><sub>nominal</sub>=0.01, <em>p</em><sub>bonf</sub>=0.03; multivariable B=1.21, <em>p</em><sub>nominal</sub>=0.01, <em>p</em><sub>bonf</sub>=0.04). VEH-fPRS showed similar nominal associations for recurrent episodes (univariable: B=1.13, <em>p</em><sub>nominal</sub>=0.03, <em>p</em><sub>bonf</sub>=0.11; multivariable B=1.21, <em>p</em><sub>nominal</sub>=0.02, <em>p</em><sub>bonf</sub>=0.08) and a negative association for single episodes versus controls in the multivariable model (B=-1.52, <em>p</em><sub>nominal</sub>=0.02, <em>p</em><sub>bonf</sub>=0.07). No gene-environment interactions were detected, and none of the NESDA findings were replicated in the MARS cohort.</div></div><div><h3>Conclusion</h3><div>While the DEX-fPRS was not associated with lifetime diagnosi
{"title":"Functional polygenic risk score of glucocorticoid-dependent regulatory element activity and its relation to clinical and stress-related phenotypes","authors":"F. Linsen , P.C. Habets , Y. Milaneschi , S. Penner-Goeke , B. Mishuris , D. Czamara , B.W.J.H. Penninx , E.B. Binder , O.C. Meijer , C.H. Vinkers","doi":"10.1016/j.psyneuen.2025.107703","DOIUrl":"10.1016/j.psyneuen.2025.107703","url":null,"abstract":"<div><h3>Background</h3><div>Chronic stress and adverse life events are major contributors to depression and anxiety disorders. Genetic variants that influence glucocorticoid (GC) hormone responses may moderate the impact of stress on psychiatric outcomes. Here, we use a functional polygenic risk score (fPRS) based on GC-responsive gene regulatory elements (GREs) following dexamethasone (DEX) exposure (DEX-fPRS) and examined its association with clinical and biological stress-related phenotypes.</div></div><div><h3>Methods</h3><div>We analyzed data from 2286 participants in the Dutch NESDA cohort, with baseline, 2-year, and 6-year follow-up visits, including 1115 with baseline depression/anxiety diagnoses. Univariable and multivariable regression models, adjusted for age, sex, batch, and ancestry principal components, were used to test associations between DEX-fPRS and lifetime diagnosis, cumulative symptom severity, and clinical features among cases (e.g. symptom severity, recurrence). Subgroup comparisons (e.g. single vs. recurrent episodes) and biological outcomes (salivary cortisol, immune markers) were also assessed. A vehicle-treated fPRS control (VEH-fPRS) was additionally tested, capturing genetic variants associated with baseline, non-GR-stimulated enhancer activity. Gene-environment interactions were tested and replication in the MARS cohort (N = 1160).</div></div><div><h3>Results</h3><div>In the full sample, DEX-fPRS showed no significant associations with lifetime diagnosis, symptom severity, or biological measures after Bonferroni correction (all <em>p</em><sub>bonf</sub>>0.05), although a nominally significant negative association was observed for morning cortisol (AUCg) in the univariable model (B=-0.05, <em>p</em><sub>nominal</sub>=0.03, <em>p</em><sub>bonf</sub>=0.19). Among cases, evening cortisol showed nominally significant negative associations in both models (univariable: B=-0.05, <em>p</em><sub>nominal</sub>=0.02, <em>p</em><sub>bonf</sub>=0.09; multivariable: B=-0.04, <em>p</em><sub>nominal</sub>=0.02, <em>p</em><sub>bonf</sub>=0.14). A significant positive association was found for recurrent vs. single episodes in both models (univariable: β=1.24, <em>p</em><sub>nominal</sub>=0.01, <em>p</em><sub>bonf</sub>=0.03; multivariable B=1.21, <em>p</em><sub>nominal</sub>=0.01, <em>p</em><sub>bonf</sub>=0.04). VEH-fPRS showed similar nominal associations for recurrent episodes (univariable: B=1.13, <em>p</em><sub>nominal</sub>=0.03, <em>p</em><sub>bonf</sub>=0.11; multivariable B=1.21, <em>p</em><sub>nominal</sub>=0.02, <em>p</em><sub>bonf</sub>=0.08) and a negative association for single episodes versus controls in the multivariable model (B=-1.52, <em>p</em><sub>nominal</sub>=0.02, <em>p</em><sub>bonf</sub>=0.07). No gene-environment interactions were detected, and none of the NESDA findings were replicated in the MARS cohort.</div></div><div><h3>Conclusion</h3><div>While the DEX-fPRS was not associated with lifetime diagnosi","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"184 ","pages":"Article 107703"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145649214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-26DOI: 10.1016/j.psyneuen.2025.107709
Katelyn I. Oliver , Kristina Dahlgren , Alyssa R. Roeckner , Cecilia A. Hinojosa , Justin L.C. Santos , Linzie S. Taylor , Helena Zeleke , Amy Murphy , Colin Johnson II , Dasani DelRosario , Timothy D. Ely , Rebecca Hinrichs , Natalie A. Merrill , Marisa R. Young , Andrea Braden , Abigail Powers , Sanne J.H. van Rooij , Vasiliki Michopoulos , Jennifer S. Stevens
Estradiol (E2) positively influences memory facilitation effects in older women and rodent models by targeting key memory-related brain regions. However, the impacts of E2 on emotional memory processes in younger women are less clear. As women are twice as likely as men to develop trauma related disorders such as posttraumatic stress disorder (PTSD), it is important to understand how hormones like E2 might impact threat memory mechanisms. Using a randomized, double-blinded, cross-over design, we administered transdermal E2 or placebo to 45 naturally-cycling, Black women (18–35 years) with a range of trauma-related symptoms during the early luteal (low endogenous E2) phase of their cycles. The following day, participants underwent a categorical threat conditioning paradigm during fMRI recording and completed a post-scan recognition test of images seen during the scanning session. The next month, participants repeated experimental procedures under the opposite patch condition. Blood samples taken day of scan showed a mean 80 pg/mL increase in serum E2 levels under E2 supplementation. While all participants showed an enhancement of threat on memory, such that threat-associated (CS+) images were later recognized better than neutral (CS-) pictures, neither E2 patch nor PTSD symptom severity predicted recognition performance. However, under placebo, greater bilateral entorhinal cortex (ERC) response during threat vs safety learning (CS+>CS-) was associated with greater post-scan recognition for CS+ compared to the CS- category, indicating greater ERC facilitation of episodic encoding and threat bias in the low E2 condition. We also found that the combination of high E2 and progesterone (P4) was associated with reduced ERC CS+ >CS- activity, potentially explaining why E2 supplementation did not facilitate CS+ >CS- recognition and suggesting an antagonistic role for P4 with E2 in memory facilitation. E2 produced an increase in ERC functional connectivity to the superior temporal gyrus during CS- encoding, which may suggest a shift in ERC engagement away from episodic encoding. These findings indicate that the post-ovulation drop in E2 and potential interactions with P4 facilitate the episodic encoding of safety and threat cues in women, given that exogenous E2 blocked these effects. This study provides novel causal evidence on the role of cyclical fluctuation in E2 in determining episodic components of memory for learned threat and safety.
{"title":"Exogenous estradiol modulates entorhinal cortex contributions to episodic encoding of conditioned threat in women","authors":"Katelyn I. Oliver , Kristina Dahlgren , Alyssa R. Roeckner , Cecilia A. Hinojosa , Justin L.C. Santos , Linzie S. Taylor , Helena Zeleke , Amy Murphy , Colin Johnson II , Dasani DelRosario , Timothy D. Ely , Rebecca Hinrichs , Natalie A. Merrill , Marisa R. Young , Andrea Braden , Abigail Powers , Sanne J.H. van Rooij , Vasiliki Michopoulos , Jennifer S. Stevens","doi":"10.1016/j.psyneuen.2025.107709","DOIUrl":"10.1016/j.psyneuen.2025.107709","url":null,"abstract":"<div><div>Estradiol (E2) positively influences memory facilitation effects in older women and rodent models by targeting key memory-related brain regions. However, the impacts of E2 on emotional memory processes in younger women are less clear. As women are twice as likely as men to develop trauma related disorders such as posttraumatic stress disorder (PTSD), it is important to understand how hormones like E2 might impact threat memory mechanisms. Using a randomized, double-blinded, cross-over design, we administered transdermal E2 or placebo to 45 naturally-cycling, Black women (18–35 years) with a range of trauma-related symptoms during the early luteal (low endogenous E2) phase of their cycles. The following day, participants underwent a categorical threat conditioning paradigm during fMRI recording and completed a post-scan recognition test of images seen during the scanning session. The next month, participants repeated experimental procedures under the opposite patch condition. Blood samples taken day of scan showed a mean 80 pg/mL increase in serum E2 levels under E2 supplementation. While all participants showed an enhancement of threat on memory, such that threat-associated (CS+) images were later recognized better than neutral (CS-) pictures, neither E2 patch nor PTSD symptom severity predicted recognition performance. However, under placebo, greater bilateral entorhinal cortex (ERC) response during threat vs safety learning (CS+>CS-) was associated with greater post-scan recognition for CS+ compared to the CS- category, indicating greater ERC facilitation of episodic encoding and threat bias in the low E2 condition. We also found that the combination of high E2 and progesterone (P4) was associated with reduced ERC CS+ >CS- activity, potentially explaining why E2 supplementation did not facilitate CS+ >CS- recognition and suggesting an antagonistic role for P4 with E2 in memory facilitation. E2 produced an increase in ERC functional connectivity to the superior temporal gyrus during CS- encoding, which may suggest a shift in ERC engagement away from episodic encoding. These findings indicate that the post-ovulation drop in E2 and potential interactions with P4 facilitate the episodic encoding of safety and threat cues in women, given that exogenous E2 blocked these effects. This study provides novel causal evidence on the role of cyclical fluctuation in E2 in determining episodic components of memory for learned threat and safety.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"184 ","pages":"Article 107709"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145621438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-12DOI: 10.1016/j.psyneuen.2025.107688
Meingold H. Chan , Mandy Meijer , Sarah M. Merrill , Maggie P.Y. Fu , David Lin , Julia L. MacIsaac , Jenna L. Riis , Douglas A. Granger , Elizabeth A. Thomas , Michael S. Kobor
Saliva is widely used in biomedical population research, including epigenetic analyses to investigate gene-environment interplay and identify biomarkers. Its minimally invasive collection procedure makes it ideal for studies in pediatric populations. Saliva is a heterogenous tissue composed of immune and buccal epithelial cells (BEC). Amongst the many epigenetic marks, DNA methylation (DNAm) is the most studied in human populations. DNAm profiles are often highly cell type (CT)-specific. CT composition can drive salivary DNAm associations with environments or health as well as epigenetic age acceleration (EAA), which is the discrepancy between chronological and biological age derived from DNAm. To address this, reference-based CT deconvolution and statistical adjustment with estimated CT in DNAm analyses have become a common practice. However, it remains unclear how different CT reference panels—constructed from adult versus pediatric samples—affect DNAm results. Additionally, whether DNAm and EAA associations in saliva primarily originate from immune cells or BECs, or if they persist across saliva samples despite varying CT proportions, still requires more investigations. The current study used salivary DNAm samples obtained from 529 children (mean age=7.26 years, SD=0.26 years) in a community-based cohort, the Family Life Project. Our results demonstrated that the child reference panel outperformed the adult one based on goodness of fit measure and highlighted the impact of estimated CT discrepancies across reference panels on DNAm associations. Upon stratifying the salivary DNAm samples into three subsamples—primarily BECs, primarily immune cells, and an approximately equal mix of both, we found significantly different EAAs across stratified samples when CT proportions were not accounted for. In both the contexts of DNAm and EAA associations, we detected stronger effects of cotinine concentrations, a tobacco smoke-exposure biomarker, in the subsample with primarily immune cells. We discussed the implications of our findings for the interpretation and replication of epigenetic research involving pediatric saliva samples.
{"title":"Not all saliva samples are equal: The role of cellular heterogeneity in DNA methylation and epigenetic age analyses with biological and psychosocial factors","authors":"Meingold H. Chan , Mandy Meijer , Sarah M. Merrill , Maggie P.Y. Fu , David Lin , Julia L. MacIsaac , Jenna L. Riis , Douglas A. Granger , Elizabeth A. Thomas , Michael S. Kobor","doi":"10.1016/j.psyneuen.2025.107688","DOIUrl":"10.1016/j.psyneuen.2025.107688","url":null,"abstract":"<div><div>Saliva is widely used in biomedical population research, including epigenetic analyses to investigate gene-environment interplay and identify biomarkers. Its minimally invasive collection procedure makes it ideal for studies in pediatric populations. Saliva is a heterogenous tissue composed of immune and buccal epithelial cells (BEC). Amongst the many epigenetic marks, DNA methylation (DNAm) is the most studied in human populations. DNAm profiles are often highly cell type (CT)-specific. CT composition can drive salivary DNAm associations with environments or health as well as epigenetic age acceleration (EAA), which is the discrepancy between chronological and biological age derived from DNAm. To address this, reference-based CT deconvolution and statistical adjustment with estimated CT in DNAm analyses have become a common practice. However, it remains unclear how different CT reference panels—constructed from adult versus pediatric samples—affect DNAm results. Additionally, whether DNAm and EAA associations in saliva primarily originate from immune cells or BECs, or if they persist across saliva samples despite varying CT proportions, still requires more investigations. The current study used salivary DNAm samples obtained from 529 children (mean age=7.26 years, SD=0.26 years) in a community-based cohort, the Family Life Project. Our results demonstrated that the child reference panel outperformed the adult one based on goodness of fit measure and highlighted the impact of estimated CT discrepancies across reference panels on DNAm associations. Upon stratifying the salivary DNAm samples into three subsamples—primarily BECs, primarily immune cells, and an approximately equal mix of both, we found significantly different EAAs across stratified samples when CT proportions were not accounted for. In both the contexts of DNAm and EAA associations, we detected stronger effects of cotinine concentrations, a tobacco smoke-exposure biomarker, in the subsample with primarily immune cells. We discussed the implications of our findings for the interpretation and replication of epigenetic research involving pediatric saliva samples.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"184 ","pages":"Article 107688"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145565213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-13DOI: 10.1016/j.psyneuen.2025.107694
Gabriel Zieff , Taylyn Jameson , Alison Nutini , Ashley M. Battaglini , Ellen Jopling , Bronwen Grocott , Katerina Rnic , Eli Puterman , Joelle LeMoult
Introduction
Self-compassion is an adaptive means of relating to oneself that encompasses elements of self-kindness, common humanity, and mindfulness. Self-compassion has positive associations with health and may dampen biological and psychological stress responses, which would be particularly helpful for those with a history of early life adversity. The purpose of this study was to determine i) the association of trait self-compassion with cortisol and affective responses to an acute psychosocial stressor among early adolescents, and ii) whether this association differed by exposure to early life adversity (e.g., abuse, neglect).
Methods
Eighty-three early adolescents (M = 12.86 years; 47 % girls, 1 % non-binary) self-reported their trait self-compassion, completed a structured interview-based assessment to assess threat- and deprivation-related exposures to early life adversity, and underwent a psychosocial laboratory stressor (Trier Social Stress Test for Children; TSST-C). Salivary cortisol and self-reported positive and negative affect were measured at six timepoints before, during, and for 30 min following the stressor. We tested associations of self-compassion with trajectories (reactivity, recovery) and total levels (area under the curve with respect to ground; AUCg) of cortisol and positive and negative affect across the TSST-C, as well as moderating effects of early life adversity. Hierarchical linear models were used to test trajectories, and linear regression was used to test AUCg, with unstandardized (B) and standardized beta coefficients (β) reported, respectively.
Results
Self-compassion was not associated with total cortisol levels or trajectories of cortisol, positive affect, or negative affect (all p > 0.057). However, greater self-compassion was associated with higher sample 1 positive affect, B = 1.815, t(71) = 2.84, p = .006, and greater total positive affect levels, β = 0.411, t(62) = 3.90, p < .001. Similarly, self-compassion was associated with lower sample 1 negative affect, B = -1.261, t(72) = -2.35, p = 0.022, and less total negative affect levels, β = -0.269, t(75) = -2.45, p = 0.017. Additionally, sensitivity analyses indicated that at higher levels of early-life threat exposure, greater self-compassion was associated with higher sample 1 positive affect.
Conclusion
Among adolescents – including those exposed to threat-related forms of early life adversity– self-compassion may impart more general, diffuse beneficial effects on affect rather than buffering affective or cortisol responses to an acute stressor.
自我同情是一种与自己相关的适应性手段，包含了自我仁慈、共同人性和正念的元素。自我同情与健康有积极的联系，可能会抑制生理和心理上的压力反应，这对那些早年经历过逆境的人尤其有帮助。本研究的目的是确定i)特质自我同情与皮质醇和对早期青少年急性社会心理压力的情感反应的关联，以及ii)这种关联是否因早期生活逆境（如虐待，忽视）而不同。方法：83名早期青少年（M = 12.86岁；47 %女孩，1 %非二性别）自我报告了他们的自我同情特质，完成了基于结构化访谈的评估，以评估早期生活逆境中与威胁和剥夺相关的暴露，并进行了心理社会实验室压力源（Trier Social Stress Test for Children; TSST-C）。唾液皮质醇和自我报告的积极和消极影响在压力源之前，期间和30 min后的六个时间点进行测量。我们测试了自我同情与皮质醇的轨迹（反应性、恢复）、总水平（相对于地面的曲线下面积；AUCg）、积极和消极情绪在TSST-C中的关联，以及早期生活逆境的调节作用。采用层次线性模型检验轨迹，采用线性回归检验AUCg，分别报告了未标准化(B)和标准化β系数（β）。结果：自我同情与总皮质醇水平或皮质醇轨迹、积极影响、消极影响无关（p均为 > 0.057）。然而，更大的自我同情与更高的样本1积极情绪相关，B = 1.815,t（71） = 2.84,p = 。β = 0.411,t（62） = 3.90，p 结论：在青少年中，包括那些早期经历过威胁相关逆境的青少年，自我同情可能会对情感产生更普遍、更广泛的有益影响，而不是缓冲对急性压力源的情感或皮质醇反应。
{"title":"Self-compassion and stress responses among early adolescents","authors":"Gabriel Zieff , Taylyn Jameson , Alison Nutini , Ashley M. Battaglini , Ellen Jopling , Bronwen Grocott , Katerina Rnic , Eli Puterman , Joelle LeMoult","doi":"10.1016/j.psyneuen.2025.107694","DOIUrl":"10.1016/j.psyneuen.2025.107694","url":null,"abstract":"<div><h3>Introduction</h3><div>Self-compassion is an adaptive means of relating to oneself that encompasses elements of self-kindness, common humanity, and mindfulness. Self-compassion has positive associations with health and may dampen biological and psychological stress responses, which would be particularly helpful for those with a history of early life adversity. The purpose of this study was to determine i) the association of trait self-compassion with cortisol and affective responses to an acute psychosocial stressor among early adolescents, and ii) whether this association differed by exposure to early life adversity (e.g., abuse, neglect).</div></div><div><h3>Methods</h3><div>Eighty-three early adolescents (<em>M</em> = 12.86 years; 47 % girls, 1 % non-binary) self-reported their trait self-compassion, completed a structured interview-based assessment to assess threat- and deprivation-related exposures to early life adversity, and underwent a psychosocial laboratory stressor (Trier Social Stress Test for Children; TSST-C). Salivary cortisol and self-reported positive and negative affect were measured at six timepoints before, during, and for 30 min following the stressor. We tested associations of self-compassion with trajectories (reactivity, recovery) and total levels (area under the curve with respect to ground; AUCg) of cortisol and positive and negative affect across the TSST-C, as well as moderating effects of early life adversity. Hierarchical linear models were used to test trajectories, and linear regression was used to test AUCg, with unstandardized (<em>B</em>) and standardized beta coefficients (<em>β)</em> reported, respectively.</div></div><div><h3>Results</h3><div>Self-compassion was not associated with total cortisol levels or trajectories of cortisol, positive affect, or negative affect (all <em>p</em> > 0.057). However, greater self-compassion was associated with higher sample 1 positive affect, <em>B</em> = 1.815, <em>t</em>(71) = 2.84, <em>p</em> = .006, and greater total positive affect levels, <em>β</em> = 0.411, <em>t</em>(62) = 3.90, <em>p</em> < .001. Similarly, self-compassion was associated with lower sample 1 negative affect, <em>B</em> = -1.261, <em>t</em>(72) = -2.35, <em>p</em> = 0.022, and less total negative affect levels, <em>β</em> = -0.269, <em>t</em>(75) = -2<em>.</em>45, <em>p</em> = 0.017. Additionally, sensitivity analyses indicated that at higher levels of early-life threat exposure, greater self-compassion was associated with higher sample 1 positive affect.</div></div><div><h3>Conclusion</h3><div>Among adolescents – including those exposed to threat-related forms of early life adversity– self-compassion may impart more general, diffuse beneficial effects on affect rather than buffering affective or cortisol responses to an acute stressor.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"184 ","pages":"Article 107694"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145565210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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