Psychoneuroendocrinology最新文献

{"title":"Does hair cortisol concentration reflect measurable regulatory biology of the HPA axis in healthy humans?","authors":"James L. Abelson ,&nbsp;Shaunna L. Clark ,&nbsp;Brisa N. Sánchez ,&nbsp;Stefanie E. Mayer ,&nbsp;Tobias Stalder ,&nbsp;Gahl Liberzon ,&nbsp;Hedieh Briggs ,&nbsp;Nirmala Rajaram ,&nbsp;Israel Liberzon","doi":"10.1016/j.psyneuen.2026.107778","DOIUrl":"10.1016/j.psyneuen.2026.107778","url":null,"abstract":"<div><div>Salivary cortisol measures and hair cortisol concentration (HCC) have been extensively used in epidemiological work to document links between stress biology and health. Though their value as stress biomarkers is well-established, little prior work grounds these field-friendly cortisol measures in the hypothalamic-pituitary-adrenal (HPA) axis regulatory biology that likely provides the mechanistic pathways connecting stress and health. Understanding mechanisms may facilitate intervention and disease prevention. Our prior work linked salivary cortisol measures to adrenal sensitivity and to glucocorticoid-mediated feedback inhibition. Here we utilized a subset of this healthy convenience sample (n = 117) to link HCC to laboratory probes of HPA axis regulatory biology. Over the course of a month, subjects participated in 5 regulatory tests: ACTH stimulation, dexamethasone/CRH test, metyrapone, dexamethasone suppression (DST), and Trier Social Stress Test. They provided hair samples at the beginning and end of that month and six days of saliva samples during it. All-subsets regressions were used to link hair cortisol to regulation. The best model explained 23 % of the variance in HCC (current and past month) using feedback sensitivity (8.7 %), adrenal sensitivity 8 %), and stress reactivity (5.3 %). These associational analyses require formal hypothesis testing in independent samples for confirmation; but adrenal sensitivity and feedback inhibition likely warrant more study as mediators of and perhaps mechanistic contributors to stress-health links demonstrated epidemiologically with HCC. Identifying ways to directly assess them in stress field work may have value. Future studies should also measure hair washing frequency (additional 19 % of variance explained) and recognize that HCC is not a simple way to quantify stress exposure or stress sensitivity.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"187 ","pages":"Article 107778"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146220944","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}

{"title":"Sex-specific influences of prenatal inflammation on offspring psychological symptoms in late midlife","authors":"Emma C. Smith ,&nbsp;Madeline R. Pike ,&nbsp;Ann M. Kring ,&nbsp;Ashby B. Cogan ,&nbsp;Elizabeth C. Breen ,&nbsp;Barbara A. Cohn ,&nbsp;Piera M. Cirillo ,&nbsp;Nickilou Y. Krigbaum ,&nbsp;Thomas M. Olino ,&nbsp;Lauren B. Alloy ,&nbsp;Lauren M. Ellman","doi":"10.1016/j.psyneuen.2026.107791","DOIUrl":"10.1016/j.psyneuen.2026.107791","url":null,"abstract":"<div><h3>Introduction</h3><div>Prenatal maternal inflammation (PNMI) is associated with offspring psychopathology with evidence for sex-specific effects. The current study examined psychological symptoms in offspring during late midlife following exposure to PNMI and explored differential effects of timing of exposure and offspring sex.</div></div><div><h3>Methods</h3><div>Mother-offspring dyads (N = 139) were ascertained from the Child Health and Development Studies (CHDS) cohort. Data were available for Interleukin (IL)-6, IL-8, IL-1 receptor antagonist (IL-1RA), and soluble tumor necrosis factor receptor-II (sTNF-RII) from archived trimester 1 (T1) and trimester 2 (T2) maternal prenatal sera. Offspring in late midlife (57–62 years) reported depressive (CES-D) and anxiety (STAI-A, trait form) symptoms, frequency of psychotic-like experiences (PLE; CAPE-P15), and were interview assessed for substance use disorder (SUD; SCID-5).</div></div><div><h3>Results</h3><div>Higher levels of T1 PNMI were related to greater frequency of PLE (IL-6, p &lt; 0.01), less depressive symptoms (sTNF-RII), and greater odds of SUD (IL-1RA) (both p &lt; 0.05). Offspring sex moderated an association between higher T1 PNMI and greater anxiety symptoms (IL-6), such that associations were stronger for male offspring. (p &lt; 0.05). In contrast, offspring sex moderated an association between higher T2 PNMI and greater depressive (IL-6, IL-8) and anxiety symptoms (IL-6, IL-1RA), such that associations were stronger for female offspring (IL-6 p &lt; 0.001; others p &lt; 0.05).</div></div><div><h3>Conclusions</h3><div>These findings show timing- and sex-specific relationships between PNMI and offspring psychological symptom domains in late midlife and further clarify the impact of PNMI on psychopathology at later stages of life.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"187 ","pages":"Article 107791"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146776614","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}

{"title":"Association between allostatic load and incident dementia, and race/ethic disparities in the association in the U.S. health and retirement study","authors":"Mohammed U. Kabeto ,&nbsp;Manoj Sharma ,&nbsp;Dawn Ford ,&nbsp;Jessica D. Faul","doi":"10.1016/j.psyneuen.2026.107779","DOIUrl":"10.1016/j.psyneuen.2026.107779","url":null,"abstract":"<div><h3>Objective</h3><div>Allostatic load (AL), the cumulative physiological burden of chronic stress, is a significant health issue and has been linked with adverse health outcomes, including cognitive decline. We examined the association between AL and incident dementia in the United States.</div></div><div><h3>Method</h3><div>We used data from the United States Health and Retirement Study (HRS) cohort (2016–2020) and the 2016 Venous Blood Study (VBS) to examine the association between AL quartile and incident dementia among participants who were aged 56 and older at baseline. Dementia status was determined by cognitive performance of immediate and delayed word recall, serial 7’s, backward count, as well as self-report of dementia and Alzheimer’s disease. A composite score of biomarkers from neuroendocrine, immune, metabolic, and cardiovascular systems was used to create AL quartiles. The Cox regression model was used to examine the association between AL quartile and incident dementia.</div></div><div><h3>Results</h3><div>Of the 6806 non-Hispanic White, non-Hispanic Black, and Hispanic participants, 331 (4.9 %) developed dementia by the end of 5 years, with an incident rate of 12.8 per 1000 person-years. In the age and sex adjusted model, incident dementia was higher in the highest AL quartile than the lowest AL quartile (HR = 1.96, 95 % CI [1.37, 2.80], <em>p</em> &lt; .001). The association was attenuated (HR = 1.59, 95 % CI [1.08, 1.10], <em>p</em> &lt; .05) after adjusting for sociodemographic and health behaviors. Race/ethnicity did not modify the association between AL and incident dementia despite higher incident dementia among minorities.</div></div><div><h3>Discussion</h3><div>The findings highlight the relationship between AL and incident dementia. Further studies of the context of social determinants of health with longer follow-up are needed. Findings may inform the need for interventions to reduce stress stimuli and regular monitoring of biomarkers, thereby delaying the onset of dementia.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"187 ","pages":"Article 107779"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146154169","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}

{"title":"Economic disparities in parental hair cortisol are associated with externalizing behavior in children","authors":"Jordan Strack ,&nbsp;Melissa Hansen ,&nbsp;Lydia Jacobs ,&nbsp;Alicia Turner ,&nbsp;Victoria Bulson ,&nbsp;Kestutis Bendinskas ,&nbsp;Cynthia A. Wiltshire ,&nbsp;William J. Gavin ,&nbsp;Patricia L. Davies ,&nbsp;Emily C. Merz","doi":"10.1016/j.psyneuen.2026.107796","DOIUrl":"10.1016/j.psyneuen.2026.107796","url":null,"abstract":"<div><div>Socioeconomic disadvantage has been repeatedly found to increase risk for internalizing and externalizing problems in children. Socioeconomic disadvantage is theorized to exert these effects in part through its effects on parent and child stress physiology. Yet, these mechanistic pathways are not well understood. In this study, we examined the associations among socioeconomic factors, parental hair cortisol concentration (HCC) and emotional distress, and children’s HCC and internalizing and externalizing symptoms. Participants were 106 typically developing 5- to 13-year-olds (57 % male; 74 % White, non-Hispanic/Latine) from a range of socioeconomic backgrounds. Hair samples 3 centimeters in length were collected from parents and children and assayed for cortisol. Parent self-reports of anxiety and depression symptoms and perceived stress were used to compute a parental emotional distress composite via factor analysis. Parents also reported on their children’s internalizing and externalizing symptoms. Results indicated that lower family income-to-needs ratio was significantly associated with increased parental HCC and emotional distress. Controlling for parental emotional distress, higher parental HCC was significantly associated with greater externalizing behavior in children. Lower family income-to-needs ratio was indirectly associated with higher child HCC via higher parental HCC. These findings point to elevated parental HCC as potentially part of the mechanisms explaining socioeconomic disparities in children’s mental health. Results align with calls for interventions that ensure economic resources and address caregiver well-being to support families and children.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"187 ","pages":"Article 107796"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172901","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}

{"title":"The creative mind in the shadow of depressive symptoms: Epigenetic variation in HPA axis genes is associated with the link between depressive symptoms and creative personality","authors":"Daniel Feinmesser ,&nbsp;Stav Shohat ,&nbsp;Roi Gerda ,&nbsp;Adi Nin Nun ,&nbsp;Anat Shoshani ,&nbsp;Nadra Nasser Samra ,&nbsp;Willem Verbeke ,&nbsp;Pascal Vrticka ,&nbsp;Tsachi Ein-Dor","doi":"10.1016/j.psyneuen.2026.107783","DOIUrl":"10.1016/j.psyneuen.2026.107783","url":null,"abstract":"<div><div>This cross-sectional study investigated the relationship between depressive symptoms and creative personality through the lens of epigenetic modifications within Hypothalamic-Pituitary-Adrenal (HPA) axis genes. By analyzing DNA methylation patterns in key HPA axis genes—including corticotropin-releasing hormone (CRH), its receptor (CRHR1), CRH binding protein (CRHBP), melanocortin 2 receptor (MC2R), steroidogenic acute regulatory protein (STAR), FK506 binding protein 5 (FKBP5), and the glucocorticoid receptor (NR3C1), we examined how methylation variation was associated with the depressive symptoms-creativity link in 371 participants (190 women, 181 men). Our findings revealed that among individuals with methylation patterns putatively associated with reduced HPA axis activity, higher depressive symptoms were positively associated with creative personality, suggesting that in this biological context, introspective aspects of depressive symptoms may coincide with creative propensities. Conversely, among individuals with methylation patterns putatively associated with heightened HPA axis activity, higher depressive symptoms were negatively associated with creative personality. These results suggest that the association between depressive symptoms and creativity is not uniform but differs based on methylation variation in genes involved in stress response regulation. The findings highlight the potential role of HPA axis-related biological factors in understanding individual differences in the depression-creativity relationship, though the cross-sectional design precludes causal inference.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"187 ","pages":"Article 107783"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172903","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}

{"title":"Hypothalamic-pituitary-adrenal axis attenuation following child sexual abuse distinguishes posttraumatic stress trajectories from late adolescence to midlife","authors":"Hannah Swerbenski ,&nbsp;Zhi Li ,&nbsp;Frank W. Putnam ,&nbsp;Justin Russotti ,&nbsp;Jennie G. Noll","doi":"10.1016/j.psyneuen.2026.107782","DOIUrl":"10.1016/j.psyneuen.2026.107782","url":null,"abstract":"<div><div>Biological embedding describes the process of responsive developmental adaptation whereby stress “gets under the skin.” Applied to the endocrine system, early chronic stress exposure may contribute to hypothalamic–pituitary–adrenal (HPA) axis attenuation, characterized by initial elevations in cortisol followed by less steep normative increases across development due to cumulative allostatic load. Simultaneously, posttraumatic stress symptoms (PTSS), including hyperarousal and hypervigilance, may potentially reinforce HPA attenuation in a feedback loop. Prospective, longitudinal assessments of HPA attenuation are rarely undertaken, obfuscating physiological underpinnings of posttraumatic stress. Using data from 164 female participants (45.6 % with confirmed child sexual abuse exposure), we approximated HPA attenuation by estimating morning cortisol intercepts and slopes from early adolescence to early adulthood. Growth mixture modeling was then used to identify distinct longitudinal patterns of PTSS from late adolescence to midlife. Four trajectories were identified: persistently high symptoms across adulthood (High Stable), increasing symptoms emerging over time (Increasing), declining symptoms following initially elevated levels (Decreasing), and consistently low symptoms (Low Stable). Cortisol intercepts and slopes were both significantly associated with PTSS trajectory membership, such that greater HPA attenuation was linked with chronic symptoms. For example, each 1-standard deviation decrease in cortisol slope (reflecting greater HPA attenuation) was associated with nearly threefold higher odds of belonging to the High Stable PTSS trajectory relative to the Low Stable trajectory (OR = 2.97, 95 % CI [1.40, 6.31], p = .005). Findings suggest etiologically distinct pathways to chronic and delayed posttraumatic stress, underscoring the importance of biologically-informed, developmentally tailored intervention strategies.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"187 ","pages":"Article 107782"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172780","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}

{"title":"Pubertal neuroendocrine network characteristics and sex differences: A hair-based hormone network study","authors":"Xuliang Hou ,&nbsp;Mingjun Xie ,&nbsp;Sanjun Yi ,&nbsp;Gao Wei ,&nbsp;Huihua Deng ,&nbsp;Danhua Lin","doi":"10.1016/j.psyneuen.2026.107770","DOIUrl":"10.1016/j.psyneuen.2026.107770","url":null,"abstract":"<div><h3>Background</h3><div>Puberty is a critical developmental stage involving profound remodeling of neuroendocrine and neuromodulatory systems. While hormonal changes from a single system have been well studied, the systemic coordination across multiple systems and its sex-specific pattern remain unclear.</div></div><div><h3>Methods</h3><div>We recruited 449 healthy adolescents (226 males, 223 females) and constructed the network that encompasses nine hormones representative of the HPA and HPG axes, ECS, and melatonin system. The hormones were measured from hair with LC–MS/MS. Hormonal networks were estimated via Spearman correlations. Expected influence (EI), bridge expected influence (bridge EI), and global strength were calculated. Sex differences were examined in global strength, edge weight, EI and bridge EI using the Network Comparison Test.</div></div><div><h3>Results</h3><div>The pubertal network showed the strongest coupling between metabolically related hormone pairs (i.e., F – E, MEL – NAS and T – P) and antagonistic pairs with cross-system associations (i.e., DHEA – NAS and DHEA – AEA). Cortisol, testosterone and melatonin with the highest EI were identified as hubs where testosterone emerged as a puberty-specific central node, but 1-AG exerted negative influence as an inhibitor. The pubertal network exhibited high global strength. Males showed significantly stronger global strength than females, but weaker edgeweight at the F − DHEA, E − NAS and T − NAS edges. Significant sex differences also appeared in both EI and bridge EI at nodes NAS and 1-AG.</div></div><div><h3>Conclusions</h3><div>Puberty is marked by intensified neuroendocrine integration and sex-specific reorganization. Cortisol and melatonin consistently act as central hubs, testosterone and progesterone show sex-differentiated roles, and 1-AG emerges as a potential inhibitory hormone. These findings highlight systemic bases of pubertal sexual differentiation and demonstrate the value of network analysis for mapping complex hormonal interactions.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"186 ","pages":"Article 107770"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137652","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}

{"title":"Female-biased vulnerability to transgenerational impact of paternal early-life stress","authors":"Ichiro Ishikawa ,&nbsp;Ken-ichi Ohta ,&nbsp;Motoharu Imai ,&nbsp;Masakazu Ishikawa ,&nbsp;Haruki Kumei ,&nbsp;Makoto Kashima ,&nbsp;Ube Fugo ,&nbsp;Shingo Suzuki ,&nbsp;Hikari Otabi ,&nbsp;Takanori Miki ,&nbsp;Yu Nakamura","doi":"10.1016/j.psyneuen.2026.107773","DOIUrl":"10.1016/j.psyneuen.2026.107773","url":null,"abstract":"<div><div>Early life adversity can have profound consequences that extend across generations, yet the epigenetic impact of paternal early life stress (ELS) on offspring neurodevelopment remains poorly understood. Here, we subjected F1 male rats to a maternal separation (MS) paradigm as a model of ELS and investigated the sex-specific transgenerational effects in their F2 offspring during adolescence (around 5 weeks of age), using behavioral tests and a transcriptomic profile of the medial prefrontal cortex (mPFC). Our findings revealed a female-biased vulnerability to paternal ELS. Specifically, female offspring of stressed fathers exhibited a range of deficits, including lower body weight and heightened anxiety-like behavior. This female-biased vulnerability extended to social behavior in a group setting; while sociability was impaired in both sexes, the deficit was more severe in females, who showed a greater reduction in social proximity. To elucidate the underlying neural mechanisms, we performed RNA sequencing on the mPFC, a key region for social behavior. This revealed a subtle but robust, female-specific transcriptomic signature, highlighted by the downregulation of the mitochondrial gene <em>mt-Nd3</em> and pathways related to synaptic organization. In contrast, males showed no coherent transcriptomic alterations. Our findings demonstrate that paternal ELS induces a female-biased vulnerability to transgenerational deficits, potentially mediated by impaired mitochondrial function in the mPFC during a critical developmental window. This study underscores the critical role of paternal early-life history in shaping offspring neurodevelopmental trajectories in a sex-dependent manner.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"186 ","pages":"Article 107773"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146133000","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}

{"title":"Bias in hair cortisol measures for psychological stress: Self vs. professional collection","authors":"Heather Gatny ,&nbsp;William Axinn ,&nbsp;Dirgha Ghimire ,&nbsp;Brady T. West ,&nbsp;Sabrina Hermosilla ,&nbsp;Saman Pradhan ,&nbsp;Sameer Dixit ,&nbsp;Indra Chaudary","doi":"10.1016/j.psyneuen.2026.107775","DOIUrl":"10.1016/j.psyneuen.2026.107775","url":null,"abstract":"<div><div>Population-representative samples of hair-based cortisol have the potential to revolutionize studies of psychological stress. However, to integrate hair-based cortisol measurement into large-scale studies, it is crucial to understand the limitations and potential biases associated with self-collection. This study examines the associations between individual, household, and community characteristics, sample collection method, and hair cortisol concentration (HCC). We conducted a random-assignment experiment within a cohort design, comparing self-collection to professional-collection of hair samples among young adults. We attempted contact and hair collection among n = 1181 individuals and obtained hair samples from n = 617 individuals ages 18–22 participating in the Chitwan Valley Family Study in Nepal. The primary outcomes were the ability to provide an analyzable hair sample (defined by sufficient weight, length, and identification of the root-end) and HCC in the top quintile. There was no difference in the probability of providing a hair sample between the self-collection and professional-collection groups. However, self-collection decreased the odds of providing an analyzable sample (OR, 0.47; 95 % CI, 0.23–0.94). Women had higher odds of providing analyzable samples (OR, 9.86; 95 % CI, 3.94–24.72), while being married reduced sample suitability (OR, 0.36; 95 % CI, 0.14–0.92). Women also had decreased odds of high HCC (OR, 0.50; 95 % CI, 0.30–0.83). Our findings show that self-collection of hair samples is feasible for large-scale studies. However, gender influences successful self-collection and is also associated with HCC. Adjusting for gender related bias is both essential and feasible to fully realize the potential of large-scale hair cortisol measurement.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"186 ","pages":"Article 107775"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137695","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}

{"title":"Trauma exposure, PTSD, and methylation of the blood brain barrier claudin-5 gene","authors":"Erika J. Wolf ,&nbsp;Xiang Zhao ,&nbsp;Annelise Madison ,&nbsp;Jack Carbaugh ,&nbsp;Catherine B. Fortier ,&nbsp;William P. Milberg ,&nbsp;Traumatic Stress Brain Research Group,&nbsp;Mark W. Logue ,&nbsp;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":"2026-04-01","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}