Adolescence is a stress-sensitive period for neurodevelopment and mental health, with chronic stress implicated in the onset of psychological disorders. Hair cortisol concentration (HCC) serves as a non-invasive biomarker of long-term hypothalamic-pituitary-adrenal (HPA) axis activity, yet its relevance to adolescent mental health remains inconsistently characterised.
Methods
This longitudinal study examined HCC in 302 community-dwelling adolescent twins from Brisbane, Australia, with data collected at two sessions approximately two years apart, following a standardised assessment protocol. Three cm long hair samples were analysed to quantify cumulative stress exposure over three months, and participants completed self-reported measures of depression, anxiety, daily stress, social support, and adverse childhood experiences (ACEs). Linear mixed-effects models and quantile regression were used to examine mean-level and distributional associations between HCC and psychological and environmental variables.
Results
Average HCC decreased significantly between sessions, with no main effect of sex, twin zygosity, or pubertal stage. In males, a higher average HCC at the second session was associated with elevated general anxiety, whereas in females, a higher average HCC was linked to higher exposure to severe lifetime stress. No associations were found between average HCC and ACEs.
Conclusion
These findings suggest that average HCC, reflecting cumulative cortisol secretion over the three months before each assessment, provides a stable measure of long-term cortisol in adolescents, although its associations with psychosocial stressors were limited in this cohort. Rather than functioning as a broadly sensitive biomarker of chronic stress, HCC may capture specific stress-related processes in certain subgroups, and its utility may depend on the type, timing, and chronicity of stress exposure.
{"title":"Hair cortisol concentration and adolescent mental health: Insight from the Queensland Twin Adolescent Brain Project","authors":"Sabine Finlay , Beena Suvarna , Oyelola Adegboye , Donna Rudd , Brett McDermott , Liza van Eijk , Zoltan Sarnyai","doi":"10.1016/j.psyneuen.2025.107730","DOIUrl":"10.1016/j.psyneuen.2025.107730","url":null,"abstract":"<div><h3>Introduction</h3><div>Adolescence is a stress-sensitive period for neurodevelopment and mental health, with chronic stress implicated in the onset of psychological disorders. Hair cortisol concentration (HCC) serves as a non-invasive biomarker of long-term hypothalamic-pituitary-adrenal (HPA) axis activity, yet its relevance to adolescent mental health remains inconsistently characterised.</div></div><div><h3>Methods</h3><div>This longitudinal study examined HCC in 302 community-dwelling adolescent twins from Brisbane, Australia, with data collected at two sessions approximately two years apart, following a standardised assessment protocol. Three cm long hair samples were analysed to quantify cumulative stress exposure over three months, and participants completed self-reported measures of depression, anxiety, daily stress, social support, and adverse childhood experiences (ACEs). Linear mixed-effects models and quantile regression were used to examine mean-level and distributional associations between HCC and psychological and environmental variables.</div></div><div><h3>Results</h3><div>Average HCC decreased significantly between sessions, with no main effect of sex, twin zygosity, or pubertal stage. In males, a higher average HCC at the second session was associated with elevated general anxiety, whereas in females, a higher average HCC was linked to higher exposure to severe lifetime stress. No associations were found between average HCC and ACEs.</div></div><div><h3>Conclusion</h3><div>These findings suggest that average HCC, reflecting cumulative cortisol secretion over the three months before each assessment, provides a stable measure of long-term cortisol in adolescents, although its associations with psychosocial stressors were limited in this cohort. Rather than functioning as a broadly sensitive biomarker of chronic stress, HCC may capture specific stress-related processes in certain subgroups, and its utility may depend on the type, timing, and chronicity of stress exposure.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"185 ","pages":"Article 107730"},"PeriodicalIF":3.6,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977680","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 : 2026-01-07DOI: 10.1016/j.psyneuen.2026.107742
Kathleen V. Casto , Julia Stern
For many individuals, the days leading up to menstruation are associated with aversive mood, behavioral, and physical symptoms, a condition known as premenstrual syndrome (PMS). Severe levels of these symptoms can lead to clinical diagnosis of premenstrual dysphoria (PMDD). Although prior research has uncovered important psychological and hormonal predictors of PMS/PMDD symptoms in clinical populations, more research is needed to understand how these factors relate in a subclinical population. A test of the menstrual timing and hormonal links to symptom experience alongside factors related to stress would be advantageous for identifying mechanistic underpinnings of symptom severity, factors that might indicate early risk for clinical diagnosis, as well as subclinical factors affecting people’s wellbeing. In a community sample of naturally cycling women (N = 257), we conducted within-subject analyses of PMS symptom reporting and levels of salivary progesterone and cortisol across the cycle and in relation to stress and trait neuroticism. On average, women in this study reported increased PMS symptoms in the days leading up to menstrual onset and decreased symptoms at mid cycle, a pattern that was linked to progesterone levels. Higher levels of experienced stress and trait neuroticism were also positively correlated with PMS symptoms. Yet, main effects for PMS symptom and stress timing across the cycle occurred above and beyond controlling for neuroticism. This research has implications for a broader understanding of the connection between the menstrual cycle and psycho-social experiences as well as risk for clinical psychopathology.
{"title":"Premenstrual syndrome (PMS) symptom emergence across the cycle in relation to hormonal and psychological components in a community sample","authors":"Kathleen V. Casto , Julia Stern","doi":"10.1016/j.psyneuen.2026.107742","DOIUrl":"10.1016/j.psyneuen.2026.107742","url":null,"abstract":"<div><div>For many individuals, the days leading up to menstruation are associated with aversive mood, behavioral, and physical symptoms, a condition known as premenstrual syndrome (PMS). Severe levels of these symptoms can lead to clinical diagnosis of premenstrual dysphoria (PMDD). Although prior research has uncovered important psychological and hormonal predictors of PMS/PMDD symptoms in clinical populations, more research is needed to understand how these factors relate in a subclinical population. A test of the menstrual timing and hormonal links to symptom experience alongside factors related to stress would be advantageous for identifying mechanistic underpinnings of symptom severity, factors that might indicate early risk for clinical diagnosis, as well as subclinical factors affecting people’s wellbeing. In a community sample of naturally cycling women (<em>N</em> = 257), we conducted within-subject analyses of PMS symptom reporting and levels of salivary progesterone and cortisol across the cycle and in relation to stress and trait neuroticism. On average, women in this study reported increased PMS symptoms in the days leading up to menstrual onset and decreased symptoms at mid cycle, a pattern that was linked to progesterone levels. Higher levels of experienced stress and trait neuroticism were also positively correlated with PMS symptoms. Yet, main effects for PMS symptom and stress timing across the cycle occurred above and beyond controlling for neuroticism. This research has implications for a broader understanding of the connection between the menstrual cycle and psycho-social experiences as well as risk for clinical psychopathology.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"185 ","pages":"Article 107742"},"PeriodicalIF":3.6,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978456","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 : 2025-12-31DOI: 10.1016/j.psyneuen.2025.107740
Allison Stumper , Hannah Klusmann , Jessica R. Peters , Elizabeth H. Andersen
Background
Accumulating evidence suggests some adult females experience hormone sensitivity, or neurobehavioral sensitivity to normal fluctuations in ovarian steroid hormones, across the menstrual cycle. However, this work has yet to be adequately extended to adolescent populations, despite the significant increase in risk for affective disorders among females after menarche.
Aims
The current study aimed to determine whether hormone sensitivity could be observed in a sample of early adolescent females by examining the within-person associations between daily levels of estrone and progesterone metabolites that are marked for urinary excretion (estrone-3glucuronide or E1G and pregnanediol glucuronide or PdG, respectively) and daily mood symptoms across one menstrual cycle.
Method
The current study assessed mood ratings and collected dried urine strips for analysis of E1G and PdG across one full menstrual cycle (up to 48 days) in a sample of peripubertal female adolescents aged 11–14. Within-person multilevel models, run in the full sample and separately for ovulatory cycles (N = 31) and anovulatory cycles (N = 23), evaluated the associations between E1G and PdG and mood symptoms.
Results
In the full sample, E1G was negatively associated with mean total symptom score ((b = −.02, 95 % CI = −0.03 – −0.002), irritability (b = −.003, 95 % CI = −0.06 – −0.001), anhedonia (b = −.03, 95 % CI = −0.05 – −0.01), concentration difficulty (b = −.03, 95 % CI = −0.05 – −0.002), and conflicts (b = −.03, 95 % CI = −0.05 – −0.004). In the ovulatory group, E1G was negatively associated with mean total symptom score (b = −.02, 95 % CI = −0.04 – −0.004), hopelessness (b = −0.02, 95 % CI = −0.04 – −0.001), rejection sensitivity (b = −0.03, 95 % CI = −0.06 – −0.001), irritability (b = −0.05, 95 % CI = −0.09 – −0.01), concentration difficulties (b = −0.03, 95 % CI = −0.06 – −0.01), and overwhelm (b = −0.03, 95 % CI = −0.06 – −0.0001). In the anovulatory group, E1G was associated only with anhedonia (b = −0.05, 95 % CI = −0.10 – −0.01).
Conclusions
These results demonstrate small associations between normal decreases in E1G and mood symptoms across the menstrual cycle in an adolescent sample, though these effects were largely limited to ovulatory cycles. Results highlight the importance of considering ovulation status in this population and differ from the adult literature in important ways that highlight the need for more work on how hormone sensitivity differs between adolescents and adults.
背景：越来越多的证据表明，一些成年女性在整个月经周期中对卵巢类固醇激素的正常波动具有激素敏感性或神经行为敏感性。然而，这项工作尚未充分扩展到青少年人群，尽管月经初潮后女性情感障碍的风险显着增加。目的：目前的研究旨在通过检测一个月经周期内每日雌激素和孕酮代谢物（分别为雌激素-3葡萄糖醛酸酯或E1G和孕二醇葡萄糖醛酸酯或PdG）水平与每日情绪症状之间的关系，确定是否可以在早期青春期女性样本中观察到激素敏感性。方法：目前的研究评估了情绪等级，并收集了干尿条，用于分析一个完整月经周期（长达48天）的E1G和PdG，样本为11-14岁的青春期女性青少年。在人多层次模型中，在全样本中分别运行排卵周期（N = 31）和无排卵周期（N = 23），评估E1G和PdG与情绪症状之间的关系。结果：在全样本中，E1G与平均总症状评分（b = - 0.02, 95 % CI = -0.03 - -0.002）、易怒（b = - 0.003, 95 % CI = -0.06 - -0.001）、快感缺乏（b = -0.03, 95 % CI = -0.05 - -0.01）、注意力集中困难（b = -0.03, 95 % CI = -0.05 - -0.002）和冲突（b = -0.03, 95 % CI = -0.05 - -0.004）呈负相关。在排卵期组，E1G与平均总症状评分（b = -0.02, 95 % CI = -0.04 - -0.004）、绝望（b = -0.02, 95 % CI = -0.04 - -0.001）、排斥敏感性（b = -0.03, 95 % CI = -0.06 - -0.001）、烦躁（b = -0.05, 95 % CI = -0.09 - -0.01）、注意力集中困难（b = -0.03, 95 % CI = -0.06 - -0.01）和压力（b = -0.03, 95 % CI = -0.06 - -0.0001）呈负相关。在无排卵组中，E1G仅与快感缺乏相关（b = -0.05, 95 % CI = -0.10 - -0.01）。结论：这些结果表明青春期样本中E1G的正常下降与整个月经周期的情绪症状之间存在很小的关联，尽管这些影响在很大程度上仅限于排卵周期。结果强调了考虑该人群的排卵状态的重要性，并且与成人文献在重要方面有所不同，强调需要更多的工作来研究青少年和成人之间激素敏感性的差异。
{"title":"Within-person associations between daily ovarian steroid levels and mood-related symptoms in ovulatory and anovulatory early adolescents","authors":"Allison Stumper , Hannah Klusmann , Jessica R. Peters , Elizabeth H. Andersen","doi":"10.1016/j.psyneuen.2025.107740","DOIUrl":"10.1016/j.psyneuen.2025.107740","url":null,"abstract":"<div><h3>Background</h3><div>Accumulating evidence suggests some adult females experience hormone sensitivity, or neurobehavioral sensitivity to normal fluctuations in ovarian steroid hormones, across the menstrual cycle. However, this work has yet to be adequately extended to adolescent populations, despite the significant increase in risk for affective disorders among females after menarche.</div></div><div><h3>Aims</h3><div>The current study aimed to determine whether hormone sensitivity could be observed in a sample of early adolescent females by examining the within-person associations between daily levels of estrone and progesterone metabolites that are marked for urinary excretion (estrone-3glucuronide or E1G and pregnanediol glucuronide or PdG, respectively) and daily mood symptoms across one menstrual cycle.</div></div><div><h3>Method</h3><div>The current study assessed mood ratings and collected dried urine strips for analysis of E1G and PdG across one full menstrual cycle (up to 48 days) in a sample of peripubertal female adolescents aged 11–14. Within-person multilevel models, run in the full sample and separately for ovulatory cycles (N = 31) and anovulatory cycles (N = 23), evaluated the associations between E1G and PdG and mood symptoms.</div></div><div><h3>Results</h3><div>In the full sample, E1G was negatively associated with mean total symptom score ((b = −.02, 95 % CI = −0.03 – −0.002), irritability (b = −.003, 95 % CI = −0.06 – −0.001), anhedonia (b = −.03, 95 % CI = −0.05 – −0.01), concentration difficulty (b = −.03, 95 % CI = −0.05 – −0.002), and conflicts (b = −.03, 95 % CI = −0.05 – −0.004). In the ovulatory group, E1G was negatively associated with mean total symptom score (<em>b</em> = −.02, 95 % CI = −0.04 – −0.004), hopelessness (<em>b</em> = −0.02, 95 % CI = −0.04 – −0.001), rejection sensitivity (<em>b</em> = −0.03, 95 % CI = −0.06 – −0.001), irritability (<em>b</em> = −0.05, 95 % CI = −0.09 – −0.01), concentration difficulties (<em>b</em> = −0.03, 95 % CI = −0.06 – −0.01), and overwhelm (<em>b</em> = −0.03, 95 % CI = −0.06 – −0.0001). In the anovulatory group, E1G was associated only with anhedonia (<em>b</em> = −0.05, 95 % CI = −0.10 – −0.01).</div></div><div><h3>Conclusions</h3><div>These results demonstrate small associations between normal decreases in E1G and mood symptoms across the menstrual cycle in an adolescent sample, though these effects were largely limited to ovulatory cycles. Results highlight the importance of considering ovulation status in this population and differ from the adult literature in important ways that highlight the need for more work on how hormone sensitivity differs between adolescents and adults.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"185 ","pages":"Article 107740"},"PeriodicalIF":3.6,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145918309","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 : 2025-12-30DOI: 10.1016/j.psyneuen.2025.107739
Stephanie H. Cook , Aura A. Mishra
{"title":"Intersectionality, social stress, and biological embedding: Toward intersectional psychoneuroendocrinology","authors":"Stephanie H. Cook , Aura A. Mishra","doi":"10.1016/j.psyneuen.2025.107739","DOIUrl":"10.1016/j.psyneuen.2025.107739","url":null,"abstract":"","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"185 ","pages":"Article 107739"},"PeriodicalIF":3.6,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926866","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 : 2025-12-25DOI: 10.1016/j.psyneuen.2025.107741
Maria Meier , Christian J. Merz , Tobias Rüttgens , Oliver T. Wolf , Jens C. Pruessner
Stress and the associated cortisol release have profound effects on long-term memory (LTM). While glucose increases the cortisol stress response and exhibits memory enhancing effects in non-stressful situations, the interaction of glucose and stress on LTM has rarely been studied. The aim of this study was to investigate whether the glucose-related amplification of the cortisol stress response would enhance LTM formation. Overall, N = 62 healthy, fasted adults (age M = 23.13, SD = 3.02; 54.84 % female) participated. They consumed a drink containing water or glucose and underwent a non-stressful control task or the Trier Social Stress Test with Objects, during which panel members interact with certain objects (central) while leaving others untouched (peripheral). At the estimated cortisol peak, they encoded a wordlist. On the next day, they retrieved the objects and the words. We repeatedly assessed subjective stress, salivary cortisol and blood glucose concentrations and recorded an electrocardiogram. Glucose increased blood glucose concentrations, and the stressor led to a significant increase in cortisol as compared with the control task. Changes in cortisol were more pronounced in the glucose as compared with the water groups. Heart rate was elevated in the glucose as compared with the water groups during the recovery. Central objects were better remembered than peripheral objects when encoded during stress. Additionally, emotional words were remembered better as compared with neutral words. These effects were not modulated by glucose. These findings suggest that emotional information is remembered better than neutral information independent of stress and glucose intake. Stress enhances LTM of stressor-relevant information and glucose intake increases the cortisol stress response. However, these factors do not appear to interact. Glucose availability may thus play a less decisive role when memorizing a stressful episode.
{"title":"The influence of glucose administration on stress reactivity and long-term memory in adult men and women","authors":"Maria Meier , Christian J. Merz , Tobias Rüttgens , Oliver T. Wolf , Jens C. Pruessner","doi":"10.1016/j.psyneuen.2025.107741","DOIUrl":"10.1016/j.psyneuen.2025.107741","url":null,"abstract":"<div><div>Stress and the associated cortisol release have profound effects on long-term memory (LTM). While glucose increases the cortisol stress response and exhibits memory enhancing effects in non-stressful situations, the interaction of glucose and stress on LTM has rarely been studied. The aim of this study was to investigate whether the glucose-related amplification of the cortisol stress response would enhance LTM formation. Overall, <em>N</em> = 62 healthy, fasted adults (age <em>M</em> = 23.13, <em>SD</em> = 3.02; 54.84 % female) participated. They consumed a drink containing water or glucose and underwent a non-stressful control task or the Trier Social Stress Test with Objects, during which panel members interact with certain objects (central) while leaving others untouched (peripheral). At the estimated cortisol peak, they encoded a wordlist. On the next day, they retrieved the objects and the words. We repeatedly assessed subjective stress, salivary cortisol and blood glucose concentrations and recorded an electrocardiogram. Glucose increased blood glucose concentrations, and the stressor led to a significant increase in cortisol as compared with the control task. Changes in cortisol were more pronounced in the glucose as compared with the water groups. Heart rate was elevated in the glucose as compared with the water groups during the recovery. Central objects were better remembered than peripheral objects when encoded during stress. Additionally, emotional words were remembered better as compared with neutral words. These effects were not modulated by glucose. These findings suggest that emotional information is remembered better than neutral information independent of stress and glucose intake. Stress enhances LTM of stressor-relevant information and glucose intake increases the cortisol stress response. However, these factors do not appear to interact. Glucose availability may thus play a less decisive role when memorizing a stressful episode.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"185 ","pages":"Article 107741"},"PeriodicalIF":3.6,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878747","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 : 2025-12-17DOI: 10.1016/j.psyneuen.2025.107729
Kristin M. Davis , Molly A. Wright , Christopher G. Engeland , Kyle W. Murdock
Background
Inflammation contributes to cardiovascular and metabolic disease development. Reducing disease risk by targeting inflammation is therefore desirable in prevention research. However, circulating markers of inflammation are often difficult to detect in younger individuals. Ex vivo stimulated cytokine production offers a promising alternative measure of immune function. Yet, few studies among younger adults have used this measure to date or have assessed its reliability over time.
Methods
First-year university students (N = 110, age 18–19 years) completed two study visits, one each at the beginning and end of their first semester. Circulating cytokines and lipopolysaccharide-stimulated cytokine production were assayed at each visit; composites for each were created using IL-1β, IL-6, and IFN-γ. Analyses excluded participants with CRP ≥ 10 mg/L. Pearson’s correlations were used to examine unadjusted associations between circulating and stimulated cytokine composites, within and across visits. Multiple linear regression was then used to test concurrent associations between the circulating and stimulated cytokine composites, and the within-person stability of each measure across visits, adjusting for sex, body mass index, perceived stress, physical activity, diet quality, and sleep quality.
Results
Study visits occurred 13 weeks ± 8 days apart. The circulating and stimulated cytokine composites were significantly correlated at visit 1 (r= 0.374, p<0.01) and at visit 2 (r=0.246, p = 0.02). This association remained significant in regression analyses at both visit 1 (B [95 % CI] = 0.407 [0.196, 0.617], p < 0.01) and visit 2 (B [95 % CI] = 0.312 [0.041, 0.584], p=0.03). The circulating cytokine composite at visit 1 was not significantly associated with the circulating cytokine composite at visit 2 in either correlation (r=-0.009, p=0.94) or regression (B [95 % CI] = -0.007 [-0.192, 0.179], p = 0.94) analyses. Stimulated cytokine production at visit 1 was significantly associated with stimulated cytokine production at visit 2 in both correlation (r=0.515, p<0.01) and regression analyses (B [95 % CI] = 0.497 [0.293 0.701], p<0.01).
Conclusions
Contrasting with some past research, circulating cytokines were significantly associated with stimulated cytokine production in the present sample concurrently at both visits. Stimulated cytokine production was more stable within-person across visits (∼13 weeks apart) compared to circulating cytokines in these students. Measurement of stimulated cytokines may be informative for understanding between-person differences in inflammation-related disease risk in younger adults, in part because they appear more stable compared to circulating cytokines.
{"title":"Systemic inflammation and ex vivo inflammatory responses in first semester university students","authors":"Kristin M. Davis , Molly A. Wright , Christopher G. Engeland , Kyle W. Murdock","doi":"10.1016/j.psyneuen.2025.107729","DOIUrl":"10.1016/j.psyneuen.2025.107729","url":null,"abstract":"<div><h3>Background</h3><div>Inflammation contributes to cardiovascular and metabolic disease development. Reducing disease risk by targeting inflammation is therefore desirable in prevention research. However, circulating markers of inflammation are often difficult to detect in younger individuals. <em>Ex vivo</em> stimulated cytokine production offers a promising alternative measure of immune function. Yet, few studies among younger adults have used this measure to date or have assessed its reliability over time.</div></div><div><h3>Methods</h3><div>First-year university students (N = 110, age 18–19 years) completed two study visits, one each at the beginning and end of their first semester. Circulating cytokines and lipopolysaccharide-stimulated cytokine production were assayed at each visit; composites for each were created using IL-1β, IL-6, and IFN-γ. Analyses excluded participants with CRP ≥ 10 mg/L. Pearson’s correlations were used to examine unadjusted associations between circulating and stimulated cytokine composites, within and across visits. Multiple linear regression was then used to test concurrent associations between the circulating and stimulated cytokine composites, and the within-person stability of each measure across visits, adjusting for sex, body mass index, perceived stress, physical activity, diet quality, and sleep quality.</div></div><div><h3>Results</h3><div>Study visits occurred 13 weeks ± 8 days apart. The circulating and stimulated cytokine composites were significantly correlated at visit 1 (r= 0.374, p<0.01) and at visit 2 (r=0.246, p = 0.02). This association remained significant in regression analyses at both visit 1 (<em>B</em> [95 % CI] = 0.407 [0.196, 0.617], p < 0.01) and visit 2 (<em>B</em> [95 % CI] = 0.312 [0.041, 0.584], p=0.03). The circulating cytokine composite at visit 1 was not significantly associated with the circulating cytokine composite at visit 2 in either correlation (r=-0.009, p=0.94) o<em>r</em> regression (<em>B</em> [95 % CI] = -0.007 [-0.192, 0.179], p = 0.94) analyses. Stimulated cytokine production at visit 1 was significantly associated with stimulated cytokine production at visit 2 in both correlation (r=0.515, p<0.01) and regression analyses (<em>B</em> [95 % CI] = 0.497 [0.293 0.701], p<0.01).</div></div><div><h3>Conclusions</h3><div>Contrasting with some past research, circulating cytokines were significantly associated with stimulated cytokine production in the present sample concurrently at both visits. Stimulated cytokine production was more stable within-person across visits (∼13 weeks apart) compared to circulating cytokines in these students. Measurement of stimulated cytokines may be informative for understanding between-person differences in inflammation-related disease risk in younger adults, in part because they appear more stable compared to circulating cytokines.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"185 ","pages":"Article 107729"},"PeriodicalIF":3.6,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788593","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 : 2025-12-16DOI: 10.1016/j.psyneuen.2025.107726
Rafaela Mrdjen-Hodžić , Olga Malev , Natalija Novokmet , Jelena Šarac , Dubravka Havaš Auguštin , Saša Missoni , Sofia Ana Blažević
Background
Maternal psychosocial stress during pregnancy has been associated with long-term developmental and metabolic consequences in offspring. Cortisol, a primary stress hormone, plays a central role in this process, and its levels may be influenced by environmental factors, such as geographic isolation. The aim of this study was to investigate the association between place of residence (islands or mainland) and newborn-sex on maternal cortisol levels (as a physiological indicator of stress) and neonatal anthropometry in the first Croatian Islands’ Birth Cohort Study (CRIBS).
Methods
A total of N = 337 pregnant women from the CRIBS cohort were included: N = 188 residing on islands and N = 149 residing on the mainland. Maternal plasma cortisol levels were measured during the second trimester using High performance liquid chromatography (HPLC). Anthropometry and cortisol data were analyzed using appropriate parametric and non-parametric tests, two-way ANOVA or ANCOVA for group comparisons, and mixed-effects modeling for repeated measures.
Results
Pre- and post- pregnancy BMI values were elevated in women residing on the islands in comparison to women residing on the mainland. Cortisol levels, birth weight, birth length, and head circumference were influenced by newborn sex. Mothers carrying female offspring had higher cortisol levels and their offspring lower developmental outcomes, with greater differences observed among island residents for birth weight and length.
Conclusion
Fetal sex and environmental context (mainland vs. island) influence maternal HPA axis regulation and early developmental outcomes, suggesting that island residents may experience unique stressors related to their environment. Sex-specific associations in maternal cortisol and neonatal growth highlight the importance of considering fetal sex in studies of prenatal stress biology. Future work should clarify how geographic isolation influences prenatal stress biology and identify actionable risks to improve maternal and child health.
{"title":"Sex-specific associations between second-trimester maternal cortisol and neonatal outcomes in island and mainland populations","authors":"Rafaela Mrdjen-Hodžić , Olga Malev , Natalija Novokmet , Jelena Šarac , Dubravka Havaš Auguštin , Saša Missoni , Sofia Ana Blažević","doi":"10.1016/j.psyneuen.2025.107726","DOIUrl":"10.1016/j.psyneuen.2025.107726","url":null,"abstract":"<div><h3>Background</h3><div>Maternal psychosocial stress during pregnancy has been associated with long-term developmental and metabolic consequences in offspring. Cortisol, a primary stress hormone, plays a central role in this process, and its levels may be influenced by environmental factors, such as geographic isolation. The aim of this study was to investigate the association between place of residence (islands or mainland) and newborn-sex on maternal cortisol levels (as a physiological indicator of stress) and neonatal anthropometry in the first Croatian Islands’ Birth Cohort Study (CRIBS).</div></div><div><h3>Methods</h3><div>A total of N = 337 pregnant women from the CRIBS cohort were included: N = 188 residing on islands and N = 149 residing on the mainland. Maternal plasma cortisol levels were measured during the second trimester using High performance liquid chromatography (HPLC). Anthropometry and cortisol data were analyzed using appropriate parametric and non-parametric tests, two-way ANOVA or ANCOVA for group comparisons, and mixed-effects modeling for repeated measures.</div></div><div><h3>Results</h3><div>Pre- and post- pregnancy BMI values were elevated in women residing on the islands in comparison to women residing on the mainland. Cortisol levels, birth weight, birth length, and head circumference were influenced by newborn sex. Mothers carrying female offspring had higher cortisol levels and their offspring lower developmental outcomes, with greater differences observed among island residents for birth weight and length.</div></div><div><h3>Conclusion</h3><div>Fetal sex and environmental context (mainland vs. island) influence maternal HPA axis regulation and early developmental outcomes, suggesting that island residents may experience unique stressors related to their environment. Sex-specific associations in maternal cortisol and neonatal growth highlight the importance of considering fetal sex in studies of prenatal stress biology. Future work should clarify how geographic isolation influences prenatal stress biology and identify actionable risks to improve maternal and child health.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"185 ","pages":"Article 107726"},"PeriodicalIF":3.6,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788603","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 : 2025-12-14DOI: 10.1016/j.psyneuen.2025.107728
Anna E. Soerensen , Stijn Vos , Marijke A.K.A. Braeken , Marion I. van den Heuvel , Bea R.H. Van den Bergh , Tim S. Nawrot
Background
Maternal distress has been associated with many offspring behavioural developmental outcomes, potentially through epigenetic modification of the glucocorticoid receptor NR3C1 or the imprinting control region between insulin-like growth factor 2 and H19 (IGF2/H19).
Methods
148 mother-infant pairs from the Prenatal Early Life Stress (PELS) cohort participated in this study. Maternal self-reported psychosocial and work-related factors were determined during pregnancy. NR3C1 and IGF2/H19 methylation levels were measured by bisulfite-pyrosequencing in the buccal cells of the infant (3–5 months). Infant and preschooler (4 years) temperament were assessed by the Infant- and Children’s Behavior Questionnaire (IBQ-R-vsf and CBQ-R-vsf, respectively). Linear mixed effect models, linear regression models and mediation analyses were used to test associations.
Findings
Maternal work-related physical and emotional demands were predictive of infant NR3C1 and IGF2/H19 methylation on several cytosine-phosphate-guanine sites. NR3C1 and IGF2/H19 methylation were associated with infant surgency. NR3C1 was found to mediate the association between maternal work-related physical demands and surgency in infancy.
Conclusions
Occupational stressors during pregnancy were shown to associate with NR3C1 and IGF2/H19 methylation in the infant, which may be linked with temperament.
{"title":"NR3C1 and IGF2/H19 methylation patterns predict infant and preschooler temperament: Links to maternal stress in pregnancy","authors":"Anna E. Soerensen , Stijn Vos , Marijke A.K.A. Braeken , Marion I. van den Heuvel , Bea R.H. Van den Bergh , Tim S. Nawrot","doi":"10.1016/j.psyneuen.2025.107728","DOIUrl":"10.1016/j.psyneuen.2025.107728","url":null,"abstract":"<div><h3>Background</h3><div>Maternal distress has been associated with many offspring behavioural developmental outcomes, potentially through epigenetic modification of the glucocorticoid receptor <em>NR3C1</em> or the imprinting control region between insulin-like growth factor 2 and <em>H19</em> (<em>IGF2/H19</em>).</div></div><div><h3>Methods</h3><div>148 mother-infant pairs from the Prenatal Early Life Stress (PELS) cohort participated in this study. Maternal self-reported psychosocial and work-related factors were determined during pregnancy. <em>NR3C1</em> and <em>IGF2/H19</em> methylation levels were measured by bisulfite-pyrosequencing in the buccal cells of the infant (3–5 months). Infant and preschooler (4 years) temperament were assessed by the Infant- and Children’s Behavior Questionnaire (IBQ-R-vsf and CBQ-R-vsf, respectively). Linear mixed effect models, linear regression models and mediation analyses were used to test associations.</div></div><div><h3>Findings</h3><div>Maternal work-related physical and emotional demands were predictive of infant <em>NR3C1</em> and <em>IGF2/H19</em> methylation on several cytosine-phosphate-guanine sites. <em>NR3C1</em> and <em>IGF2/H19</em> methylation were associated with infant surgency. <em>NR3C1</em> was found to mediate the association between maternal work-related physical demands and surgency in infancy.</div></div><div><h3>Conclusions</h3><div>Occupational stressors during pregnancy were shown to associate with <em>NR3C1</em> and <em>IGF2/H19</em> methylation in the infant, which may be linked with temperament.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"185 ","pages":"Article 107728"},"PeriodicalIF":3.6,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788592","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 : 2025-12-14DOI: 10.1016/j.psyneuen.2025.107727
D. Cantini , P. Paletta , C. Sexton , C. Schmidt , M. Cha , D. Aspesi , S. McGuinness , K. LaDouceur , M. Kavaliers , E. Choleris
The estrogen, 17β-estradiol (E2), rapidly facilitates social recognition in various regions of the social brain network. The medial amygdala (MeA) is heavily involved in the processing of social cues and expresses the three main estrogen receptors (ER): ERα, ERβ, and G Protein-Coupled ER (GPER).
All ERs, as well as oxytocin and its receptor (OTR) in the MeA are crucial for social recognition in female mice, suggesting an interplay between ERs and OTR in the rapid facilitation of this social behavior. Here, we demonstrate an interplay between E2 and the three ERs (ERα, ERβ, GPER) with OTR in the MeA underlying the rapid facilitation of social recognition. Ovariectomized female mice were bilaterally infused with a sub-effective dose of OTR antagonist (i.e. the highest dose that does not prevent social recognition) into the MeA via indwelling cannulae, prior to an infusion of either E2 or one of the three ER agonists: ERα agonist PPT, ERβ agonist DPN, GPER agonist G1. A social recognition paradigm designed to measure rapid effects of treatment was employed. In all conditions, the sub-effective dose of OTR antagonist prevented the rapid facilitation of social recognition by E2 and each of the three ER agonists. The results show that E2 and the three main ERs require OTRs to rapidly facilitate social recognition in the MeA of female mice, thus demonstrating a rapid, likely non-genomic, interplay between the estrogen and oxytocin systems in social cognitive processing within a key region of the social brain.
{"title":"Estrogen and oxytocin receptors interplay in the medial amygdala to rapidly facilitate social recognition","authors":"D. Cantini , P. Paletta , C. Sexton , C. Schmidt , M. Cha , D. Aspesi , S. McGuinness , K. LaDouceur , M. Kavaliers , E. Choleris","doi":"10.1016/j.psyneuen.2025.107727","DOIUrl":"10.1016/j.psyneuen.2025.107727","url":null,"abstract":"<div><div>The estrogen, 17β-estradiol (E2), rapidly facilitates social recognition in various regions of the social brain network. The medial amygdala (MeA) is heavily involved in the processing of social cues and expresses the three main estrogen receptors (ER): ERα, ERβ, and G Protein-Coupled ER (GPER).</div><div>All ERs, as well as oxytocin and its receptor (OTR) in the MeA are crucial for social recognition in female mice, suggesting an interplay between ERs and OTR in the rapid facilitation of this social behavior. Here, we demonstrate an interplay between E2 and the three ERs (ERα, ERβ, GPER) with OTR in the MeA underlying the rapid facilitation of social recognition. Ovariectomized female mice were bilaterally infused with a sub-effective dose of OTR antagonist (i.e. the highest dose that does not prevent social recognition) into the MeA via indwelling cannulae, prior to an infusion of either E2 or one of the three ER agonists: ERα agonist PPT, ERβ agonist DPN, GPER agonist G1. A social recognition paradigm designed to measure rapid effects of treatment was employed. In all conditions, the sub-effective dose of OTR antagonist prevented the rapid facilitation of social recognition by E2 and each of the three ER agonists. The results show that E2 and the three main ERs require OTRs to rapidly facilitate social recognition in the MeA of female mice, thus demonstrating a rapid, likely non-genomic, interplay between the estrogen and oxytocin systems in social cognitive processing within a key region of the social brain.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"185 ","pages":"Article 107727"},"PeriodicalIF":3.6,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145782626","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 : 2025-12-11DOI: 10.1016/j.psyneuen.2025.107722
Kendra L. Wilson , Bethany L. Boettner , Christopher R. Browning , Jodi L. Ford , Baldwin M. Way
Exposure to areas high in violent crime is a potent stressor that influences health outcomes by chronically undermining safety and upregulating biological stress responses. We tested the hypothesis that the association between cortisol, as measured in head hair, and inflammation, as measured by C-Reactive Protein (CRP) in capillary blood, is dependent on the degree of violent crime within adolescents’ everyday activity spaces. Because structural inequities cause Black adolescents to spend more time in areas with higher rates of violent crime, we tested this hypothesis in Black and White youth separately. 137 adolescents (Mage = 15.55, 57 % female, 52 % Black, 48 % White) participated in the study. We obtained continuous GPS-tracked data for one week to assess the average violent crime rate across the areas where participants spent time; biosamples were collected at the end of the week. Among Black adolescents, there was an interaction such that higher GPS-tracked activity space violent crime levels were associated with a positive and significant association between CRP and cortisol, consistent with models suggesting that stress can dysregulate immune-endocrine functioning. Conversely, for Black adolescents with low rates of exposure, cortisol had a negative association with CRP, consistent with a normative effect of glucocorticoid inhibition of inflammation. For White adolescents, cortisol and violence levels were significantly lower than for Black adolescents, and in this context, there was a weak main effect of violence exposure on CRP but no significant interaction. Results suggest the association between cortisol and inflammation varies across violent crime levels within the areas adolescents spend time and emphasize the importance of studying how an adolescent’s environment shapes biological responses to chronic stressors.
{"title":"The association between levels of GPS-tracked activity space violent crime and the relationship between cortisol and a biomarker of inflammation amongst Black and White adolescents","authors":"Kendra L. Wilson , Bethany L. Boettner , Christopher R. Browning , Jodi L. Ford , Baldwin M. Way","doi":"10.1016/j.psyneuen.2025.107722","DOIUrl":"10.1016/j.psyneuen.2025.107722","url":null,"abstract":"<div><div>Exposure to areas high in violent crime is a potent stressor that influences health outcomes by chronically undermining safety and upregulating biological stress responses. We tested the hypothesis that the association between cortisol, as measured in head hair, and inflammation, as measured by C-Reactive Protein (CRP) in capillary blood, is dependent on the degree of violent crime within adolescents’ everyday activity spaces. Because structural inequities cause Black adolescents to spend more time in areas with higher rates of violent crime, we tested this hypothesis in Black and White youth separately. 137 adolescents (M<sub>age</sub> = 15.55, 57 % female, 52 % Black, 48 % White) participated in the study. We obtained continuous GPS-tracked data for one week to assess the average violent crime rate across the areas where participants spent time; biosamples were collected at the end of the week. Among Black adolescents, there was an interaction such that higher GPS-tracked activity space violent crime levels were associated with a positive and significant association between CRP and cortisol, consistent with models suggesting that stress can dysregulate immune-endocrine functioning. Conversely, for Black adolescents with low rates of exposure, cortisol had a negative association with CRP, consistent with a normative effect of glucocorticoid inhibition of inflammation. For White adolescents, cortisol and violence levels were significantly lower than for Black adolescents, and in this context, there was a weak main effect of violence exposure on CRP but no significant interaction. Results suggest the association between cortisol and inflammation varies across violent crime levels within the areas adolescents spend time and emphasize the importance of studying how an adolescent’s environment shapes biological responses to chronic stressors.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"185 ","pages":"Article 107722"},"PeriodicalIF":3.6,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827218","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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