Pub Date : 2026-01-14DOI: 10.1016/j.psyneuen.2026.107756
Xiaoyuan Han , Xin Yu , Xinyuan Hu , Hailiang Huang , Guofeng Zhang , Xiangyu Chen , Ming Cha , Lingming Hu , Ningning Liu
Major depressive disorder (MDD) in adolescents is frequently accompanied by aggression and non-suicidal self-injury (NSSI), yet reliable biomarkers for predicting these behavioral risks remain limited. This study employed a combined cross-sectional and longitudinal design to investigate the role of peripheral inflammatory markers in aggression among 214 adolescent inpatients with MDD and 60 healthy controls. We found that C-reactive protein (CRP) emerged as notable independent predictor of aggressive behavior, showing a high area under the curve (AUC=0.91) in this sample, suggesting its potential discriminatory performance that warrants further validation. Notably, NSSI significantly moderated the CRP-aggression link, with a stronger association observed in patients without NSSI. Furthermore, sex-specific IL-6 elevations were identified in female NSSI⁺ patients. Longitudinal analyses revealed a dynamic "immunomodulatory shift," where systemic immune-inflammation index (SII) and lymphocyte-to-monocyte ratio (LMR) transitioned from positive to negative predictors of aggression over time. These preliminary findings highlight the potential of CRP as a clinically accessible indicator for aggression risk and underscore the temporal complexity of immune–behavior interactions in adolescent depression. These preliminary findings remain to be verified through independent cohorts in future studies.
{"title":"C-reactive protein predicts aggression in adolescent depression: Non-suicidal self-injury moderation and immunomodulatory shift","authors":"Xiaoyuan Han , Xin Yu , Xinyuan Hu , Hailiang Huang , Guofeng Zhang , Xiangyu Chen , Ming Cha , Lingming Hu , Ningning Liu","doi":"10.1016/j.psyneuen.2026.107756","DOIUrl":"10.1016/j.psyneuen.2026.107756","url":null,"abstract":"<div><div>Major depressive disorder (MDD) in adolescents is frequently accompanied by aggression and non-suicidal self-injury (NSSI), yet reliable biomarkers for predicting these behavioral risks remain limited. This study employed a combined cross-sectional and longitudinal design to investigate the role of peripheral inflammatory markers in aggression among 214 adolescent inpatients with MDD and 60 healthy controls. We found that C-reactive protein (CRP) emerged as notable independent predictor of aggressive behavior, showing a high area under the curve (AUC=0.91) in this sample, suggesting its potential discriminatory performance that warrants further validation. Notably, NSSI significantly moderated the CRP-aggression link, with a stronger association observed in patients without NSSI. Furthermore, sex-specific IL-6 elevations were identified in female NSSI⁺ patients. Longitudinal analyses revealed a dynamic \"immunomodulatory shift,\" where systemic immune-inflammation index (SII) and lymphocyte-to-monocyte ratio (LMR) transitioned from positive to negative predictors of aggression over time. These preliminary findings highlight the potential of CRP as a clinically accessible indicator for aggression risk and underscore the temporal complexity of immune–behavior interactions in adolescent depression. These preliminary findings remain to be verified through independent cohorts in future studies.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"186 ","pages":"Article 107756"},"PeriodicalIF":3.6,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146011824","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 : 2026-01-14DOI: 10.1016/j.psyneuen.2026.107759
Juan M. Solano-Atehortua , Gabriel Castrillón , Jazmin X. Suarez-Revelo , Juan D. Sánchez-López , Daniel A. Vargas-Tejada , Hawkins-Caicedo Valentina , Juan C. Calderón , Jaime Gallo-Villegas , Yedselt V. Ospina-Serrano , Juan D. Caicedo-Jaramillo , Ana L. Miranda-Angulo
Introduction
The allostatic load index (ALI) measures the cumulative physiological burden exerted on the body by chronic stress known as allostatic load (AL). The relationship between ALI and heart rate variability (HRV), as well as the brain moderation effect on this relationship in healthy individuals, is underexplored.
Methods
In this cross-sectional study of 88 healthy men (21–40 years) from Medellín, Colombia, we calculated two ALIs composed of four and seven biomarkers (ALI-4 and ALI-7) using a quartile-based risk summation method. Functional and structural neuroimaging metrics were derived from magnetic resonance imaging. Multiple linear regression models were used to evaluate the associations between the ALIs and HRV metrics derived from a 24-hour Holter. Exploratory interaction models tested whether the functional connectivity strength (FCS) of default mode (DMN), salience (SN) and control subnetworks (CEN), their cortical thickness as well as the volume of subcortical structures, moderated the ALI–HRV association.
Results
ALI-7 was positively associated with the LF/HF ratio (β = 0.09, p = 0.004, 95 % CI = 0.03–0.15). Exploratory interactions suggested that ALI-7’s association with the standard deviation of the NN intervals (SDNN) was moderated by the FCS in the posterior DMN and by cortical thickness in the anterior SN. However, none of these interactions remained significant after false discovery rate correction.
Conclusion
In healthy men, higher ALI was associated with reduced HRV as indicated by higher LF/HF ratio. Larger studies, including women, are needed to confirm the predictive value of ALI-7 and to elucidate the brain moderation effect on the AL-HRV relationship.
适应负荷指数（ALI）衡量慢性应激（即适应负荷（AL））对身体施加的累积生理负担。ALI与心率变异性（HRV）之间的关系，以及在健康个体中大脑调节对这种关系的影响，尚未得到充分探讨。方法：在这项来自哥伦比亚Medellín的88名健康男性（21-40岁）的横断面研究中，我们使用基于四分位数的风险累加法计算了由4种和7种生物标志物（ALI-4和ALI-7）组成的两个ali。功能和结构神经成像指标来源于磁共振成像。使用多元线性回归模型来评估ali与24小时动态心电图得出的HRV指标之间的关系。探索性交互模型测试了默认模式（DMN）、显著性（SN）和控制子网络（CEN）的功能连接强度（FCS）、它们的皮质厚度以及皮质下结构的体积是否调节了ALI-HRV的关联。结果：ALI-7与LF/HF比值呈正相关（β = 0.09, p = 0.004,95% % CI = 0.03-0.15）。探索性相互作用表明，ALI-7与神经网络间隔标准差（SDNN）的关联被后DMN的FCS和前SN的皮质厚度所调节。然而，在错误发现率修正后，这些相互作用都不显着。结论：在健康男性中，较高的ALI与较高的LF/HF比值所表明的HRV降低相关。需要包括女性在内的更大规模的研究来证实ALI-7的预测价值，并阐明大脑调节对AL-HRV关系的影响。
{"title":"Linking allostatic load, heart rate variability and brain functional networks and structures in healthy men","authors":"Juan M. Solano-Atehortua , Gabriel Castrillón , Jazmin X. Suarez-Revelo , Juan D. Sánchez-López , Daniel A. Vargas-Tejada , Hawkins-Caicedo Valentina , Juan C. Calderón , Jaime Gallo-Villegas , Yedselt V. Ospina-Serrano , Juan D. Caicedo-Jaramillo , Ana L. Miranda-Angulo","doi":"10.1016/j.psyneuen.2026.107759","DOIUrl":"10.1016/j.psyneuen.2026.107759","url":null,"abstract":"<div><h3>Introduction</h3><div>The allostatic load index (ALI) measures the cumulative physiological burden exerted on the body by chronic stress known as allostatic load (AL). The relationship between ALI and heart rate variability (HRV), as well as the brain moderation effect on this relationship in healthy individuals, is underexplored.</div></div><div><h3>Methods</h3><div>In this cross-sectional study of 88 healthy men (21–40 years) from Medellín, Colombia, we calculated two ALIs composed of four and seven biomarkers (ALI-4 and ALI-7) using a quartile-based risk summation method. Functional and structural neuroimaging metrics were derived from magnetic resonance imaging. Multiple linear regression models were used to evaluate the associations between the ALIs and HRV metrics derived from a 24-hour Holter. Exploratory interaction models tested whether the functional connectivity strength (FCS) of default mode (DMN), salience (SN) and control subnetworks (CEN), their cortical thickness as well as the volume of subcortical structures, moderated the ALI–HRV association.</div></div><div><h3>Results</h3><div>ALI-7 was positively associated with the LF/HF ratio (β = 0.09, <em>p</em> = 0.004, 95 % CI = 0.03–0.15). Exploratory interactions suggested that ALI-7’s association with the standard deviation of the NN intervals (SDNN) was moderated by the FCS in the posterior DMN and by cortical thickness in the anterior SN. However, none of these interactions remained significant after false discovery rate correction.</div></div><div><h3>Conclusion</h3><div>In healthy men, higher ALI was associated with reduced HRV as indicated by higher LF/HF ratio. Larger studies, including women, are needed to confirm the predictive value of ALI-7 and to elucidate the brain moderation effect on the AL-HRV relationship.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"186 ","pages":"Article 107759"},"PeriodicalIF":3.6,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146019517","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 : 2026-01-13DOI: 10.1016/j.psyneuen.2026.107754
Paul A.G. Forbes , Candace M. Raio , Tobias Kalenscher
Stress can result in unhealthier food choices with detrimental consequences for our health. Precommitment is a behavioural strategy whereby individuals restrict their future choice set and can promote healthier food choices – we may forgo buying cake when grocery shopping so we are not tempted to eat it at home. Yet, it is not known whether precommitment can buffer the effects of stress on food choices by providing opportunities to avoid unhealthy food altogether, enabling healthier food choices under stress. To investigate this, we developed a novel ‘precommit-to-eat’ paradigm which involved two stages. This enabled us to first assess precommitment decisions (precommitment stage) and, subsequently, participants’ propensity to select healthier items to eat in a food choice stage (choice stage). Participants (n = 29) who all reported generally trying to eat healthily completed this two-stage paradigm twice – once under acute stress and once in a non-stressful control condition. The propensity to choose unhealthier but tastier food to eat increased with subjective stress, but this effect was counteracted by stress-related increases in precommitment. Thus, our findings show the effectiveness of precommitment under stress. This has important implications for interventions aimed at promoting healthier food choices, especially in stressful environments, that could particularly benefit individuals with lower dietary restraint.
{"title":"Precommitment promotes healthier food choices under stress","authors":"Paul A.G. Forbes , Candace M. Raio , Tobias Kalenscher","doi":"10.1016/j.psyneuen.2026.107754","DOIUrl":"10.1016/j.psyneuen.2026.107754","url":null,"abstract":"<div><div>Stress can result in unhealthier food choices with detrimental consequences for our health. Precommitment is a behavioural strategy whereby individuals restrict their future choice set and can promote healthier food choices – we may forgo buying cake when grocery shopping so we are not tempted to eat it at home. Yet, it is not known whether precommitment can buffer the effects of stress on food choices by providing opportunities to avoid unhealthy food altogether, enabling healthier food choices under stress. To investigate this, we developed a novel ‘precommit-to-eat’ paradigm which involved two stages. This enabled us to first assess precommitment decisions (precommitment stage) and, subsequently, participants’ propensity to select healthier items to eat in a food choice stage (choice stage). Participants (n = 29) who all reported generally trying to eat healthily completed this two-stage paradigm twice – once under acute stress and once in a non-stressful control condition. The propensity to choose unhealthier but tastier food to eat increased with subjective stress, but this effect was counteracted by stress-related increases in precommitment. Thus, our findings show the effectiveness of precommitment under stress. This has important implications for interventions aimed at promoting healthier food choices, especially in stressful environments, that could particularly benefit individuals with lower dietary restraint.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"186 ","pages":"Article 107754"},"PeriodicalIF":3.6,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981459","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 : 2026-01-13DOI: 10.1016/j.psyneuen.2026.107755
Katherine Knauft , Jacqueline Rodriguez-Stanley , Kristin M. Davis , Lance M. Rappaport , Francesca Luca , Nataria T. Joseph , Christopher G. Engeland , Samuele Zilioli
Loneliness has been linked to increased risk of cardiovascular disease, which disproportionately affects African American adults. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, as measured by long-term accumulation of cortisol in hair, may be one pathway through which loneliness increases cardiovascular disease risk. However, the relationship between loneliness and hair cortisol levels among African American adults has not yet been explored. Further, both loneliness and cortisol activity differ across age and sex. To better understand the association between loneliness and HPA axis activity among middle-aged and older African American adults, the present study examined the degree to which age and sex interacted with loneliness to predict hair cortisol concentrations. Data were obtained from 340 African American adults (Mage = 66.06, SD = 5.46, range = 55–75; 87.1 % female), who provided hair samples and reported their loneliness level as a part of The Heart of Detroit Study. Results showed that sex significantly moderated the association between loneliness and hair cortisol. Loneliness was positively associated with hair cortisol concentrations in male, but not female, participants. These findings suggest that sex-specific associations may exist between loneliness and hair cortisol.
{"title":"Sex-specific associations between loneliness and hair cortisol among older African American adults","authors":"Katherine Knauft , Jacqueline Rodriguez-Stanley , Kristin M. Davis , Lance M. Rappaport , Francesca Luca , Nataria T. Joseph , Christopher G. Engeland , Samuele Zilioli","doi":"10.1016/j.psyneuen.2026.107755","DOIUrl":"10.1016/j.psyneuen.2026.107755","url":null,"abstract":"<div><div>Loneliness has been linked to increased risk of cardiovascular disease, which disproportionately affects African American adults. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, as measured by long-term accumulation of cortisol in hair, may be one pathway through which loneliness increases cardiovascular disease risk. However, the relationship between loneliness and hair cortisol levels among African American adults has not yet been explored. Further, both loneliness and cortisol activity differ across age and sex. To better understand the association between loneliness and HPA axis activity among middle-aged and older African American adults, the present study examined the degree to which age and sex interacted with loneliness to predict hair cortisol concentrations. Data were obtained from 340 African American adults (<em>M</em><sub>age</sub> = 66.06, <em>SD</em> = 5.46, range = 55–75; 87.1 % female), who provided hair samples and reported their loneliness level as a part of The Heart of Detroit Study. Results showed that sex significantly moderated the association between loneliness and hair cortisol. Loneliness was positively associated with hair cortisol concentrations in male, but not female, participants. These findings suggest that sex-specific associations may exist between loneliness and hair cortisol.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"186 ","pages":"Article 107755"},"PeriodicalIF":3.6,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145963371","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 : 2026-01-13DOI: 10.1016/j.psyneuen.2026.107744
Gelena Dlugash , Manfred Rauh , Justin M. Carré , Ashley Marcellus , Susan Plachecki , Elizabeth Hampson , Oliver C. Schultheiss
Introduction
For psychoneuroendocrinology, accurate measurement of progesterone (P4) and estradiol (E2) in saliva is crucial for understanding the menstrual cycle phase and its impact on physiology and behavior. Although enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA) are the preferred methods and are more often found in research labs, liquid chromatography-mass spectrometry (LC-MS/MS) may provide a more valid salivary steroids assessment. In this study, we aimed to compare the performance of LC-MS/MS, ELISA, and RIA to measure salivary P4 and E2.
Method
Samples were collected from 120 participants, 81 men and 39 women, in the morning and evening. Additionally, women provided samples during the early follicular (cycle days 3–5) and luteal cycle phases (cycle days 21–23) using the forward-count method. The study considered natural hormone fluctuations (e.g., the diurnal and menstrual cycles) and quality control samples as validity criteria for method evaluation. A total of 336 samples and quality control samples were analyzed using one RIA, two ELISA, and two LC-MS/MS methods across four labs. Correlational analyses were performed to assess inter-lab x inter-method reliability, intra-lab x inter-method reliability, and inter-lab x intra-method reliability.
Results
For P4, natural hormone fluctuations in menstrual cycles were detected by all methods. However, in contrast to both LC-MS/MS methods, all immunoassays (IAs) detected an unexpected diurnal decline of P4. For E2, they were found only by LC-MS/MS and RIA. In terms of means, for P4 and E2, ELISA and RIA produced higher values compared to LC-MS/MS. For P4, the inter- and intra-method convergence was r ≥ .92. As for E2, inter-method correlations were between r = -.12 and r = .23, while the ELISA intra-method comparison showed a correlation coefficient of r = .85.
Discussion
Our findings suggest that while LC-MS/MS, RIA, and ELISA were capable of meeting most of the specified criteria for P4, only LC-MS/MS and RIA were able to perform similarly sufficiently at low E2 levels. LC-MS/MS provided more accurate and reliable measurements for P4 and E2, especially at low concentrations, but encountered challenges, too. Although RIA showed comparable performance to LC-MS/MS, it still suffered partly from cross-reactivity. ELISA often overestimated hormone levels and exhibited greater divergence. These differences highlight the importance of carefully selecting methods and considering their limitations in research applications.
{"title":"Multicenter comparison of LC-MS/MS, radioimmunoassay, and ELISA for assessment of salivary progesterone and estradiol","authors":"Gelena Dlugash , Manfred Rauh , Justin M. Carré , Ashley Marcellus , Susan Plachecki , Elizabeth Hampson , Oliver C. Schultheiss","doi":"10.1016/j.psyneuen.2026.107744","DOIUrl":"10.1016/j.psyneuen.2026.107744","url":null,"abstract":"<div><h3>Introduction</h3><div>For psychoneuroendocrinology, accurate measurement of progesterone (P4) and estradiol (E2) in saliva is crucial for understanding the menstrual cycle phase and its impact on physiology and behavior. Although enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA) are the preferred methods and are more often found in research labs, liquid chromatography-mass spectrometry (LC-MS/MS) may provide a more valid salivary steroids assessment. In this study, we aimed to compare the performance of LC-MS/MS, ELISA, and RIA to measure salivary P4 and E2.</div></div><div><h3>Method</h3><div>Samples were collected from 120 participants, 81 men and 39 women, in the morning and evening. Additionally, women provided samples during the early follicular (cycle days 3–5) and luteal cycle phases (cycle days 21–23) using the forward-count method. The study considered natural hormone fluctuations (e.g., the diurnal and menstrual cycles) and quality control samples as validity criteria for method evaluation. A total of 336 samples and quality control samples were analyzed using one RIA, two ELISA, and two LC-MS/MS methods across four labs. Correlational analyses were performed to assess inter-lab x inter-method reliability, intra-lab x inter-method reliability, and inter-lab x intra-method reliability.</div></div><div><h3>Results</h3><div>For P4, natural hormone fluctuations in menstrual cycles were detected by all methods. However, in contrast to both LC-MS/MS methods, all immunoassays (IAs) detected an unexpected diurnal decline of P4. For E2, they were found only by LC-MS/MS and RIA. In terms of means, for P4 and E2, ELISA and RIA produced higher values compared to LC-MS/MS. For P4, the inter- and intra-method convergence was <em>r</em> ≥ .92. As for E2, inter-method correlations were between <em>r</em> = -.12 and <em>r</em> = .23, while the ELISA intra-method comparison showed a correlation coefficient of <em>r</em> = .85.</div></div><div><h3>Discussion</h3><div>Our findings suggest that while LC-MS/MS, RIA, and ELISA were capable of meeting most of the specified criteria for P4, only LC-MS/MS and RIA were able to perform similarly sufficiently at low E2 levels. LC-MS/MS provided more accurate and reliable measurements for P4 and E2, especially at low concentrations, but encountered challenges, too. Although RIA showed comparable performance to LC-MS/MS, it still suffered partly from cross-reactivity. ELISA often overestimated hormone levels and exhibited greater divergence. These differences highlight the importance of carefully selecting methods and considering their limitations in research applications.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"186 ","pages":"Article 107744"},"PeriodicalIF":3.6,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030569","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 : 2026-01-12DOI: 10.1016/j.psyneuen.2026.107753
Erika J. Wolf , Xiang Zhao , Annelise Madison , Jack Carbaugh , Catherine B. Fortier , William P. Milberg , Traumatic Stress Brain Research Group, Mark W. Logue , Mark W. Miller
Posttraumatic stress disorder (PTSD) is associated with early onset of neurological conditions, but the mechanism by which PTSD relates to diseases of the central nervous system is unclear. One possibility is that PTSD perpetuates breakdown of the blood brain barrier (BBB), allowing for bidirectional passage of molecules across the periphery and central nervous system that promote neuropathology. Preclinical studies have implicated claudin-5 (CLDN5), a protein integral to the integrity of the BBB tight junctions, in the pathogenesis of depression. Based on this, we evaluated if trauma exposure and PTSD related to CLDN5 epigenetics in blood among 1311 trauma-exposed individuals (primarily Veterans) and in the brain tissue from 100 decedents. Three (out of 19) CLDN5 DNA methylation (DNAm) probes, cg00804504, cg17411190, and cg21872764, were significantly associated with trauma exposure or PTSD severity after multiple testing correction in blood. The latter two probes also showed association with PTSD diagnosis in ventromedial prefrontal cortex. The most strongly associated DNAm probe, cg21872764, also evidenced associations with the neuropathology biomarker neurofilament light in plasma. CLDN5 expression was strongly associated with estimated proportion of brain endothelial cells. The cross-sectional associations observed in this study highlight the importance of studying the link between traumatic stress and early onset of neuropathology. Future research is needed to test the mechanistic hypothesis that trauma exposure and chronic PTSD alter CLDN5 DNAm, lead to increased BBB permeability and allow for bidirectional passage of neuroinflammatory molecules across the BBB.
{"title":"Trauma exposure, PTSD, and methylation of the blood brain barrier claudin-5 gene","authors":"Erika J. Wolf , Xiang Zhao , Annelise Madison , Jack Carbaugh , Catherine B. Fortier , William P. Milberg , Traumatic Stress Brain Research Group, Mark W. Logue , Mark W. Miller","doi":"10.1016/j.psyneuen.2026.107753","DOIUrl":"10.1016/j.psyneuen.2026.107753","url":null,"abstract":"<div><div>Posttraumatic stress disorder (PTSD) is associated with early onset of neurological conditions, but the mechanism by which PTSD relates to diseases of the central nervous system is unclear. One possibility is that PTSD perpetuates breakdown of the blood brain barrier (BBB), allowing for bidirectional passage of molecules across the periphery and central nervous system that promote neuropathology. Preclinical studies have implicated claudin-5 (CLDN5), a protein integral to the integrity of the BBB tight junctions, in the pathogenesis of depression. Based on this, we evaluated if trauma exposure and PTSD related to <em>CLDN5</em> epigenetics in blood among 1311 trauma-exposed individuals (primarily Veterans) and in the brain tissue from 100 decedents. Three (out of 19) <em>CLDN5</em> DNA methylation (DNAm) probes, cg00804504, cg17411190, and cg21872764, were significantly associated with trauma exposure or PTSD severity after multiple testing correction in blood. The latter two probes also showed association with PTSD diagnosis in ventromedial prefrontal cortex. The most strongly associated DNAm probe, cg21872764, also evidenced associations with the neuropathology biomarker neurofilament light in plasma. <em>CLDN5</em> expression was strongly associated with estimated proportion of brain endothelial cells. The cross-sectional associations observed in this study highlight the importance of studying the link between traumatic stress and early onset of neuropathology. Future research is needed to test the mechanistic hypothesis that trauma exposure and chronic PTSD alter <em>CLDN5</em> DNAm, lead to increased BBB permeability and allow for bidirectional passage of neuroinflammatory molecules across the BBB.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"186 ","pages":"Article 107753"},"PeriodicalIF":3.6,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981458","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 : 2026-01-12DOI: 10.1016/j.psyneuen.2026.107752
Jae-Min Kim , Hee-Ju Kang , Ju-Wan Kim, Min Jhon, Ju-Yeon Lee, Sung-Wan Kim, Il-Seon Shin
Blood-based biomarkers such as peripheral serotonin (5-HT) hold promise for predicting antidepressant response in depression, but findings have been inconsistent. Personality traits linked to serotonergic function may moderate this relationship. This study examined whether personality type (PT) moderates the relationship between baseline serum serotonin (s5-HT) levels and antidepressant remission at 12 weeks. In a prospective, naturalistic study, 1086 outpatients with depressive disorders received stepwise pharmacotherapy. PT was classified as resilient or vulnerable using cluster analysis of the Big Five Inventory. Baseline s5-HT was measured and analyzed as both categorical (median split) and continuous variables. Remission was defined as a Hamilton Depression Rating Scale (HAMD) score ≤ 7 at week 12. Logistic regression tested the main and interaction effects of PT and s5-HT, adjusting for covariates. No direct association was found between PT and s5-HT levels. However, higher s5-HT significantly predicted remission only in the resilient group, showing a significant PT × s5-HT interaction. These findings identify personality as a moderator of the relationship between peripheral serotonin and antidepressant response. This biopsychosocial interaction may help explain prior inconsistencies and may provide preliminary insights relevant to individualized care, pending further validation.
{"title":"Personality moderates the predictive value of serum serotonin for antidepressant remission in depressive disorders","authors":"Jae-Min Kim , Hee-Ju Kang , Ju-Wan Kim, Min Jhon, Ju-Yeon Lee, Sung-Wan Kim, Il-Seon Shin","doi":"10.1016/j.psyneuen.2026.107752","DOIUrl":"10.1016/j.psyneuen.2026.107752","url":null,"abstract":"<div><div>Blood-based biomarkers such as peripheral serotonin (5-HT) hold promise for predicting antidepressant response in depression, but findings have been inconsistent. Personality traits linked to serotonergic function may moderate this relationship. This study examined whether personality type (PT) moderates the relationship between baseline serum serotonin (s5-HT) levels and antidepressant remission at 12 weeks. In a prospective, naturalistic study, 1086 outpatients with depressive disorders received stepwise pharmacotherapy. PT was classified as resilient or vulnerable using cluster analysis of the Big Five Inventory. Baseline s5-HT was measured and analyzed as both categorical (median split) and continuous variables. Remission was defined as a Hamilton Depression Rating Scale (HAMD) score ≤ 7 at week 12. Logistic regression tested the main and interaction effects of PT and s5-HT, adjusting for covariates. No direct association was found between PT and s5-HT levels. However, higher s5-HT significantly predicted remission only in the resilient group, showing a significant PT × s5-HT interaction. These findings identify personality as a moderator of the relationship between peripheral serotonin and antidepressant response. This biopsychosocial interaction may help explain prior inconsistencies and may provide preliminary insights relevant to individualized care, pending further validation.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"186 ","pages":"Article 107752"},"PeriodicalIF":3.6,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145963370","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 : 2026-01-11DOI: 10.1016/j.psyneuen.2026.107747
Theresa Dorn , Alisa Auer , Lisa-Marie Walther , Christine Sauter , Elisabeth Bandle , Petra H. Wirtz
Background & objectives
Stress contagion refers to the spread of stress from one person to another. We previously established a standardized, controlled experimental paradigm to study stress contagion in humans. While stress contagion effects have been characterized on a physiological level, potential modulating factors are beginning to be understood. Using our paradigm, we tested for the first time whether the number of observers, i.e. observer group size, modulates physiological stress contagion in stress observers.
Methods
Our experimental condition comprised three groups of stress observers varying in group sizes of two (“Group 1”, n = 30), three (“Group 2”, n = 31), or more observers (“Group 3”, n = 31), with each group observing one stressed participant. The data assessment comprised up to 5 healthy young male participants, with one participant randomly assigned to undergo an adapted version of the Trier Social Stress Test (“TSST participants”, n = 57) and the remaining participants observing him disguised as panel member(s) (“stress observers”, n = 92) in addition to one panel confederate. We repeatedly assessed salivary cortisol, salivary alpha-amylase, and heart rate.
Results
The TSST induced significant increases in all physiological parameters under study (p ´ s < =.025) without reactivity differences between TSST participants of the three experimental groups (p ´ s > =.23). When comparing the physiological reactivity to direct stress observation, the stress-observer-groups significantly differed in terms of cortisol (p = .029) with overall higher reactivity in smaller observer groups. Further analyses confirmed a linear effect in terms of higher reactivity with lower observer group size (p = .046). There were no group-by-time interactions in salivary alpha-amylase and heart rate reactivity.
Discussion
Our results suggest that when directly observing stress in other individuals, observer group size has a differential effect on physiological stress contagion systems. While we found evidence for modulating effects on hypothalamic-pituitary-adrenal axis reactivity in terms of higher cortisol stress contagion reactivity with lower observer group size, observer group size did not relate to the sympathetic–adrenal–medullary axis. Potential implications remain to be elucidated.
{"title":"Stress protection by your group – increasing group size reduces physiological stress contagion","authors":"Theresa Dorn , Alisa Auer , Lisa-Marie Walther , Christine Sauter , Elisabeth Bandle , Petra H. Wirtz","doi":"10.1016/j.psyneuen.2026.107747","DOIUrl":"10.1016/j.psyneuen.2026.107747","url":null,"abstract":"<div><h3>Background & objectives</h3><div>Stress contagion refers to the spread of stress from one person to another. We previously established a standardized, controlled experimental paradigm to study stress contagion in humans. While stress contagion effects have been characterized on a physiological level, potential modulating factors are beginning to be understood. Using our paradigm, we tested for the first time whether the number of observers, i.e. observer group size, modulates physiological stress contagion in stress observers.</div></div><div><h3>Methods</h3><div>Our experimental condition comprised three groups of stress observers varying in group sizes of two (“Group 1”, n = 30), three (“Group 2”, n = 31), or more observers (“Group 3”, n = 31), with each group observing one stressed participant. The data assessment comprised up to 5 healthy young male participants, with one participant randomly assigned to undergo an adapted version of the Trier Social Stress Test (“TSST participants”, n = 57) and the remaining participants observing him disguised as panel member(s) (“stress observers”, n = 92) in addition to one panel confederate. We repeatedly assessed salivary cortisol, salivary alpha-amylase, and heart rate.</div></div><div><h3>Results</h3><div>The TSST induced significant increases in all physiological parameters under study (<em>p</em> ´ s < =.025) without reactivity differences between TSST participants of the three experimental groups (<em>p</em> ´ s > =.23). When comparing the physiological reactivity to direct stress observation, the stress-observer-groups significantly differed in terms of cortisol (<em>p</em> = .029) with overall higher reactivity in smaller observer groups. Further analyses confirmed a linear effect in terms of higher reactivity with lower observer group size (<em>p</em> = .046). There were no group-by-time interactions in salivary alpha-amylase and heart rate reactivity.</div></div><div><h3>Discussion</h3><div>Our results suggest that when directly observing stress in other individuals, observer group size has a differential effect on physiological stress contagion systems. While we found evidence for modulating effects on hypothalamic-pituitary-adrenal axis reactivity in terms of higher cortisol stress contagion reactivity with lower observer group size, observer group size did not relate to the sympathetic–adrenal–medullary axis. Potential implications remain to be elucidated.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"186 ","pages":"Article 107747"},"PeriodicalIF":3.6,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146039020","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 : 2026-01-10DOI: 10.1016/j.psyneuen.2026.107743
Flavia Judith Neira , María Belén Sánchez , Gisela Erika Pennacchio , María Cecilia Michel Lara , Mariana Elizabeth Troncoso , Marta Soaje , Graciela Alma Jahn , Juan Pablo Mackern-Oberti , Susana Ruth Valdez
Hyperthyroidism (HyperT) is a thyroid disorder affecting an estimated 0.2–1.3 % of the global population. The clinical implications of this pathology are significant, particularly when considering its close association with stress-related disorders that impact vulnerable populations, especially women at reproductive age. This study investigated the modulatory role of mild HyperT on the neuroendocrine stress response in virgin female Wistar rats. Two experimental groups were evaluated: a group with induced mild hyperthyroidism (HyperT) and a virgin control group (Control), each assessed under basal (non-stress) and acute stress conditions according to the corresponding experimental protocol. We evaluated the hormonal release (corticosterone and progesterone) induced by ether vapor inhalation and restraint stress in both experimental groups. Furthermore, we quantified the gene expression of receptors for glucocorticoids, progesterone, estrogen, and thyroid hormones, as well as the prolactin receptor and its downstream signaling pathway components in the medial basal hypothalamus (MBH) and hippocampus (HpC). Mild HyperT attenuates the ether stress-induced corticosterone release while responses induced by restraint stress were similar to controls. In the MBH, HyperT increased STAT5b and glucocorticoid receptor (GR) gene expression, and significantly decreased the progesterone receptor PRB/PRA ratio. In the HpC, HyperT increased the prolactin receptor (PRLRL), STAT5b, and specific thyroid receptor isoforms (TRα2, TRβ2). Our findings demonstrate that mild hyperthyroidism differentially modulates the acute stress response depending on the stressor type, and may provide insight into the possible neurochemical mechanisms in key brain regions involved in the regulation of the stress response.
{"title":"Mild hyperthyroidism regulates the acute stress response in virgin female rats","authors":"Flavia Judith Neira , María Belén Sánchez , Gisela Erika Pennacchio , María Cecilia Michel Lara , Mariana Elizabeth Troncoso , Marta Soaje , Graciela Alma Jahn , Juan Pablo Mackern-Oberti , Susana Ruth Valdez","doi":"10.1016/j.psyneuen.2026.107743","DOIUrl":"10.1016/j.psyneuen.2026.107743","url":null,"abstract":"<div><div>Hyperthyroidism (HyperT) is a thyroid disorder affecting an estimated 0.2–1.3 % of the global population. The clinical implications of this pathology are significant, particularly when considering its close association with stress-related disorders that impact vulnerable populations, especially women at reproductive age. This study investigated the modulatory role of mild HyperT on the neuroendocrine stress response in virgin female Wistar rats. Two experimental groups were evaluated: a group with induced mild hyperthyroidism (HyperT) and a virgin control group (Control), each assessed under basal (non-stress) and acute stress conditions according to the corresponding experimental protocol. We evaluated the hormonal release (corticosterone and progesterone) induced by ether vapor inhalation and restraint stress in both experimental groups. Furthermore, we quantified the gene expression of receptors for glucocorticoids, progesterone, estrogen, and thyroid hormones, as well as the prolactin receptor and its downstream signaling pathway components in the medial basal hypothalamus (MBH) and hippocampus (HpC). Mild HyperT attenuates the ether stress-induced corticosterone release while responses induced by restraint stress were similar to controls. In the MBH, HyperT increased STAT5b and glucocorticoid receptor (GR) gene expression, and significantly decreased the progesterone receptor PRB/PRA ratio. In the HpC, HyperT increased the prolactin receptor (PRLR<sub>L</sub>), STAT5b, and specific thyroid receptor isoforms (TRα2, TRβ2). Our findings demonstrate that mild hyperthyroidism differentially modulates the acute stress response depending on the stressor type, and may provide insight into the possible neurochemical mechanisms in key brain regions involved in the regulation of the stress response.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"186 ","pages":"Article 107743"},"PeriodicalIF":3.6,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145963372","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}
Reciprocal gaze, the mutual exchange of eye contact, plays a key role in human communication and bonding, yet it is often experienced as challenging for individuals with autism. In recent years, administration of the neuropeptide oxytocin is increasingly considered a novel approach for supporting social experiences in children with autism, but insights regarding its effects on mutual gaze or pupil dynamics remain limited—particularly regarding how chronic, repeated dosing impacts these processes. This double-blind, randomized, placebo-controlled trial examined the effects of four weeks of chronic intranasal oxytocin administration on gaze behavior and pupil dynamics during live dyadic interactions in school-aged children with autism (aged 8–12 years, 15 oxytocin, 20 placebo). While the overall duration of fixations toward the face remained unchanged, oxytocin altered the distribution of gaze, resulting in a more balanced pattern of looking toward and away from the face of a live interaction partner, an effect observed only in the oxytocin group and not in the placebo group. In addition, the four-week oxytocin administration period induced a relative increase in pupil dilation, an index of sympathetic arousal and attentional engagement, with this heightened autonomic responsivity showing a moderate association with children’s self-reported feelings of secure attachment. Together, these findings indicate that repeated oxytocin administration may modulate gaze parameters in live social interactions in children with autism. While cautiously encouraging, future work will be needed to further delineate whether these changes meaningfully reflect ameliorated experience and comfort in social settings.
{"title":"Impact of chronic oxytocin on gaze and pupil dynamics during live dyadic interactions in children with autism","authors":"Jellina Prinsen , Nicky Daniels , Matthijs Moerkerke , Bart Boets , Kaat Alaerts","doi":"10.1016/j.psyneuen.2026.107745","DOIUrl":"10.1016/j.psyneuen.2026.107745","url":null,"abstract":"<div><div>Reciprocal gaze, the mutual exchange of eye contact, plays a key role in human communication and bonding, yet it is often experienced as challenging for individuals with autism. In recent years, administration of the neuropeptide oxytocin is increasingly considered a novel approach for supporting social experiences in children with autism, but insights regarding its effects on mutual gaze or pupil dynamics remain limited—particularly regarding how chronic, repeated dosing impacts these processes. This double-blind, randomized, placebo-controlled trial examined the effects of four weeks of chronic intranasal oxytocin administration on gaze behavior and pupil dynamics during live dyadic interactions in school-aged children with autism (aged 8–12 years, 15 oxytocin, 20 placebo). While the overall duration of fixations toward the face remained unchanged, oxytocin altered the <em>distribution</em> of gaze, resulting in a more balanced pattern of looking toward and away from the face of a live interaction partner, an effect observed only in the oxytocin group and not in the placebo group. In addition, the four-week oxytocin administration period induced a relative increase in pupil dilation, an index of sympathetic arousal and attentional engagement, with this heightened autonomic responsivity showing a moderate association with children’s self-reported feelings of secure attachment. Together, these findings indicate that repeated oxytocin administration may modulate gaze parameters in live social interactions in children with autism. While cautiously encouraging, future work will be needed to further delineate whether these changes meaningfully reflect ameliorated experience and comfort in social settings.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"186 ","pages":"Article 107745"},"PeriodicalIF":3.6,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981460","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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