Pub Date : 2025-11-12DOI: 10.1016/j.psyneuen.2025.107689
A-K. Lennartsson , I.H. Jonsdottir
Background
Psychosocial stress has been suggested to contribute to low-grade inflammation, which in turn can, if persisting, increase the risk of developing a wide range of chronic disorders. The aim of this study was to investigate the level of CRP in response to acute psychosocial stress in healthy men and women, whether the responses related to general stress activation. Since it is known that CRP level in general is associated with BMI, we also aimed to investigate whether CRP response during acute stress is related to BMI and overweight.
Method
Thirty men and 19 women, aged 30—50 years (mean age 39 years, SD 5.6 years), were included in the study. The participants underwent the Trier Social Stress Test (TSST), and CRP was measured in serum together with measurements of general stress activation.
Results
CRP levels slightly and temporarily increased in response to acute psychosocial stress. CRP response was positively related to the response of ACTH and cortisol. The CRP response was also positively associated with BMI and the overweight individuals exhibited a larger stress-induced CRP increase.
Conclusion
The results support the idea that stress may contribute to low-grade inflammation, which in turn can constitute one important pathogenic link between stress and adverse health, especially in overweight individuals.
{"title":"High sensitivity C-reactive protein in response to acute stress in healthy men and women","authors":"A-K. Lennartsson , I.H. Jonsdottir","doi":"10.1016/j.psyneuen.2025.107689","DOIUrl":"10.1016/j.psyneuen.2025.107689","url":null,"abstract":"<div><h3>Background</h3><div>Psychosocial stress has been suggested to contribute to low-grade inflammation, which in turn can, if persisting, increase the risk of developing a wide range of chronic disorders. The aim of this study was to investigate the level of CRP in response to acute psychosocial stress in healthy men and women, whether the responses related to general stress activation. Since it is known that CRP level in general is associated with BMI, we also aimed to investigate whether CRP response during acute stress is related to BMI and overweight.</div></div><div><h3>Method</h3><div>Thirty men and 19 women, aged 30—50 years (mean age 39 years, SD 5.6 years), were included in the study. The participants underwent the Trier Social Stress Test (TSST), and CRP was measured in serum together with measurements of general stress activation.</div></div><div><h3>Results</h3><div>CRP levels slightly and temporarily increased in response to acute psychosocial stress. CRP response was positively related to the response of ACTH and cortisol. The CRP response was also positively associated with BMI and the overweight individuals exhibited a larger stress-induced CRP increase.</div></div><div><h3>Conclusion</h3><div>The results support the idea that stress may contribute to low-grade inflammation, which in turn can constitute one important pathogenic link between stress and adverse health, especially in overweight individuals.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"184 ","pages":"Article 107689"},"PeriodicalIF":3.6,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145499994","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 : 2025-11-12DOI: 10.1016/j.psyneuen.2025.107690
Margo D. Nathan , Primavera A. Spagnolo , Leilah K. Grant , Shadab A. Rahman , Irene Gonsalvez , Jessica Harder , Hannah Kim , Aleta Wiley , Hadine Joffe
Background
The menopausal transition (MT) represents a period of increased risk for depressive symptoms. Emergence of these symptoms may reflect dysregulations in affect caused by fundamental MT characteristics, particularly sleep disturbance, estradiol decline, and vasomotor symptoms (VMS). Using an experimental paradigm mimicking menopause, we examined the effects of MT-related characteristics on affect.
Methods
38 premenopausal women without affective disorders completed a 6-day experimental paradigm comprising 2 nights of unfragmented sleep followed by 3 nights of provoked sleep fragmentation, during the high-estradiol mid-to-late-follicular menstrual phase. A subset (n = 27) repeated the paradigm after leuprolide-suppressed estradiol (low-estradiol). Positive affect (PA) and negative affect (NA) ratings were obtained daily using the Positive and Negative Affect Schedule.
Results
Sleep fragmentation adversely influenced PA and NA acutely after one night of fragmentation (p < 0.007). This effect persisted following 3 nights of sleep fragmentation for NA (p = 0.02), but not PA (p = 0.46). Conversely, estradiol suppression increased PA (p = 0.0.03) but not NA (p = 0.51). In the low-estradiol condition, women who developed VMS trended toward having a more pronounced and sustained reduction in PA over three nights of sleep fragmentation compared to those who did not (p = 0.09).
Conclusions
Our findings show that MT-related characteristics significantly disrupt both positive and negative affect, potentially underlying emergence of depressive symptoms during this reproductive stage. We observed differential effects on positive and negative affect, with sleep fragmentation having a greater effect on NA and estradiol and VMS having a greater effect on PA, suggesting benefit for tailoring interventions that target specific types of affect regulation.
{"title":"Impact of sleep fragmentation and estradiol suppression on positive and negative affect: Results of an experimental model of menopause","authors":"Margo D. Nathan , Primavera A. Spagnolo , Leilah K. Grant , Shadab A. Rahman , Irene Gonsalvez , Jessica Harder , Hannah Kim , Aleta Wiley , Hadine Joffe","doi":"10.1016/j.psyneuen.2025.107690","DOIUrl":"10.1016/j.psyneuen.2025.107690","url":null,"abstract":"<div><h3>Background</h3><div>The menopausal transition (MT) represents a period of increased risk for depressive symptoms. Emergence of these symptoms may reflect dysregulations in affect caused by fundamental MT characteristics, particularly sleep disturbance, estradiol decline, and vasomotor symptoms (VMS). Using an experimental paradigm mimicking menopause, we examined the effects of MT-related characteristics on affect.</div></div><div><h3>Methods</h3><div>38 premenopausal women without affective disorders completed a 6-day experimental paradigm comprising 2 nights of unfragmented sleep followed by 3 nights of provoked sleep fragmentation, during the high-estradiol mid-to-late-follicular menstrual phase. A subset (n = 27) repeated the paradigm after leuprolide-suppressed estradiol (low-estradiol). Positive affect (PA) and negative affect (NA) ratings were obtained daily using the Positive and Negative Affect Schedule.</div></div><div><h3>Results</h3><div>Sleep fragmentation adversely influenced PA and NA acutely after one night of fragmentation (p < 0.007). This effect persisted following 3 nights of sleep fragmentation for NA (p = 0.02), but not PA (p = 0.46). Conversely, estradiol suppression increased PA (p = 0.0.03) but not NA (p = 0.51). In the low-estradiol condition, women who developed VMS trended toward having a more pronounced and sustained reduction in PA over three nights of sleep fragmentation compared to those who did not (p = 0.09).</div></div><div><h3>Conclusions</h3><div>Our findings show that MT-related characteristics significantly disrupt both positive and negative affect, potentially underlying emergence of depressive symptoms during this reproductive stage. We observed differential effects on positive and negative affect, with sleep fragmentation having a greater effect on NA and estradiol and VMS having a greater effect on PA, suggesting benefit for tailoring interventions that target specific types of affect regulation.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"184 ","pages":"Article 107690"},"PeriodicalIF":3.6,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145565205","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 : 2025-11-12DOI: 10.1016/j.psyneuen.2025.107691
Bin Li , Ruixi Ming , Hongzhou Guo
Heat stress (HS), a prevalent occupational and environmental hazard, has increasingly been recognized as a major contributor to multiple physiological disorders. The hypothalamus, a key regulator of thermoregulation and endocrine signaling, is especially susceptible to metabolic and inflammatory disturbances induced by HS. This study investigates the interplay among lipid metabolism, blood–brain barrier (BBB) integrity, and neuroinflammation in the hypothalamus under HS conditions, with a specific focus on apolipoprotein A1 (APOA1) as a potential protective factor. To achieve this, we integrated proteomic and lipidomic analyses with experimental validation in porcine and murine models. Proteomic analysis identified 266 differentially expressed proteins (DEPs) in the hypothalamus following HS, with significant enrichment in lipid metabolism pathways—especially glycerophospholipid (GP) metabolism—in which APOA1 displayed a marked increase. Lipidomic profiling further revealed HS-induced disruptions in phosphatidylcholine (PC), phosphatidylethanolamine (PE), and cardiolipin (CL) metabolism. Additionally, blood–brain barrier integrity was compromised, as evidenced by increased perivascular IgG extravasation, reduced pericyte coverage, and decreased expression of tight junction proteins ZO-1 and Occludin. HS also triggered pronounced neuroinflammation, characterized by elevated levels of iNOS, GFAP, and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6). Notably, administration of D-4F, an APOA1 mimetic peptide, alleviated blood–brain barrier damage, reduced neuroinflammation, and preserved synaptic integrity, thereby suggesting a neuroprotective role for APOA1 in HS-induced hypothalamic dysfunction. These findings underscore the critical role of lipid metabolism in maintaining hypothalamic homeostasis under HS conditions and position APOA1 as a key regulator with potential therapeutic implications for mitigating HS-related neuroinflammatory and metabolic disturbances.
{"title":"Protective effects of liver-derived apolipoprotein A1 against heat stress-induced hypothalamic lipid metabolism and blood-brain barrier integrity","authors":"Bin Li , Ruixi Ming , Hongzhou Guo","doi":"10.1016/j.psyneuen.2025.107691","DOIUrl":"10.1016/j.psyneuen.2025.107691","url":null,"abstract":"<div><div>Heat stress (HS), a prevalent occupational and environmental hazard, has increasingly been recognized as a major contributor to multiple physiological disorders. The hypothalamus, a key regulator of thermoregulation and endocrine signaling, is especially susceptible to metabolic and inflammatory disturbances induced by HS. This study investigates the interplay among lipid metabolism, blood–brain barrier (BBB) integrity, and neuroinflammation in the hypothalamus under HS conditions, with a specific focus on apolipoprotein A1 (APOA1) as a potential protective factor. To achieve this, we integrated proteomic and lipidomic analyses with experimental validation in porcine and murine models. Proteomic analysis identified 266 differentially expressed proteins (DEPs) in the hypothalamus following HS, with significant enrichment in lipid metabolism pathways—especially glycerophospholipid (GP) metabolism—in which APOA1 displayed a marked increase. Lipidomic profiling further revealed HS-induced disruptions in phosphatidylcholine (PC), phosphatidylethanolamine (PE), and cardiolipin (CL) metabolism. Additionally, blood–brain barrier integrity was compromised, as evidenced by increased perivascular IgG extravasation, reduced pericyte coverage, and decreased expression of tight junction proteins ZO-1 and Occludin. HS also triggered pronounced neuroinflammation, characterized by elevated levels of iNOS, GFAP, and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6). Notably, administration of D-4F, an APOA1 mimetic peptide, alleviated blood–brain barrier damage, reduced neuroinflammation, and preserved synaptic integrity, thereby suggesting a neuroprotective role for APOA1 in HS-induced hypothalamic dysfunction. These findings underscore the critical role of lipid metabolism in maintaining hypothalamic homeostasis under HS conditions and position APOA1 as a key regulator with potential therapeutic implications for mitigating HS-related neuroinflammatory and metabolic disturbances.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"184 ","pages":"Article 107691"},"PeriodicalIF":3.6,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145557419","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 : 2025-11-12DOI: 10.1016/j.psyneuen.2025.107688
Meingold H. Chan , Mandy Meijer , Sarah M. Merrill , Maggie P.Y. Fu , David Lin , Julia L. MacIsaac , Jenna L. Riis , Douglas A. Granger , Elizabeth A. Thomas , Michael S. Kobor
Saliva is widely used in biomedical population research, including epigenetic analyses to investigate gene-environment interplay and identify biomarkers. Its minimally invasive collection procedure makes it ideal for studies in pediatric populations. Saliva is a heterogenous tissue composed of immune and buccal epithelial cells (BEC). Amongst the many epigenetic marks, DNA methylation (DNAm) is the most studied in human populations. DNAm profiles are often highly cell type (CT)-specific. CT composition can drive salivary DNAm associations with environments or health as well as epigenetic age acceleration (EAA), which is the discrepancy between chronological and biological age derived from DNAm. To address this, reference-based CT deconvolution and statistical adjustment with estimated CT in DNAm analyses have become a common practice. However, it remains unclear how different CT reference panels—constructed from adult versus pediatric samples—affect DNAm results. Additionally, whether DNAm and EAA associations in saliva primarily originate from immune cells or BECs, or if they persist across saliva samples despite varying CT proportions, still requires more investigations. The current study used salivary DNAm samples obtained from 529 children (mean age=7.26 years, SD=0.26 years) in a community-based cohort, the Family Life Project. Our results demonstrated that the child reference panel outperformed the adult one based on goodness of fit measure and highlighted the impact of estimated CT discrepancies across reference panels on DNAm associations. Upon stratifying the salivary DNAm samples into three subsamples—primarily BECs, primarily immune cells, and an approximately equal mix of both, we found significantly different EAAs across stratified samples when CT proportions were not accounted for. In both the contexts of DNAm and EAA associations, we detected stronger effects of cotinine concentrations, a tobacco smoke-exposure biomarker, in the subsample with primarily immune cells. We discussed the implications of our findings for the interpretation and replication of epigenetic research involving pediatric saliva samples.
{"title":"Not all saliva samples are equal: The role of cellular heterogeneity in DNA methylation and epigenetic age analyses with biological and psychosocial factors","authors":"Meingold H. Chan , Mandy Meijer , Sarah M. Merrill , Maggie P.Y. Fu , David Lin , Julia L. MacIsaac , Jenna L. Riis , Douglas A. Granger , Elizabeth A. Thomas , Michael S. Kobor","doi":"10.1016/j.psyneuen.2025.107688","DOIUrl":"10.1016/j.psyneuen.2025.107688","url":null,"abstract":"<div><div>Saliva is widely used in biomedical population research, including epigenetic analyses to investigate gene-environment interplay and identify biomarkers. Its minimally invasive collection procedure makes it ideal for studies in pediatric populations. Saliva is a heterogenous tissue composed of immune and buccal epithelial cells (BEC). Amongst the many epigenetic marks, DNA methylation (DNAm) is the most studied in human populations. DNAm profiles are often highly cell type (CT)-specific. CT composition can drive salivary DNAm associations with environments or health as well as epigenetic age acceleration (EAA), which is the discrepancy between chronological and biological age derived from DNAm. To address this, reference-based CT deconvolution and statistical adjustment with estimated CT in DNAm analyses have become a common practice. However, it remains unclear how different CT reference panels—constructed from adult versus pediatric samples—affect DNAm results. Additionally, whether DNAm and EAA associations in saliva primarily originate from immune cells or BECs, or if they persist across saliva samples despite varying CT proportions, still requires more investigations. The current study used salivary DNAm samples obtained from 529 children (mean age=7.26 years, SD=0.26 years) in a community-based cohort, the Family Life Project. Our results demonstrated that the child reference panel outperformed the adult one based on goodness of fit measure and highlighted the impact of estimated CT discrepancies across reference panels on DNAm associations. Upon stratifying the salivary DNAm samples into three subsamples—primarily BECs, primarily immune cells, and an approximately equal mix of both, we found significantly different EAAs across stratified samples when CT proportions were not accounted for. In both the contexts of DNAm and EAA associations, we detected stronger effects of cotinine concentrations, a tobacco smoke-exposure biomarker, in the subsample with primarily immune cells. We discussed the implications of our findings for the interpretation and replication of epigenetic research involving pediatric saliva samples.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"184 ","pages":"Article 107688"},"PeriodicalIF":3.6,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145565213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-11DOI: 10.1016/j.psyneuen.2025.107685
I. Martín-Estal , D. León Rojas , J.L. Díaz-Gómez, A.J. del Rio-Pascual, J. Rodríguez-de-Ita, F. Castorena-Torres
Adverse Childhood Experiences (ACEs) are highly prevalent and associated to severe health outcomes in the Mexican adult population. However, their biological correlates during early childhood remain poorly understood. We conducted a cross-sectional study in Mexican children, aged 3–5 years, to examine the association between neuroendocrine biomarker hair levels related to hypothalamic-pituitary-adrenal (HPA) axis (cortisol, cortisone, and DHEA) and the number and type of ACEs in this population. Additionally, we analyzed the effect of sociodemographic characteristics of the population (age, sex and urbanity stratum). The study included 237 children and 226 caregivers from the national ACESMEXICO cohort. Caregivers provided self-reported sociodemographic and child-related information, and hair samples from 178 children were analyzed for neuroendocrine biomarkers. The Pediatric ACEs and Related Life-Events Screener (PEARLS) was used to gather ACEs data. Linear regression models adjusted by age, sex and urbanity stratum, tested associations between cumulative ACEs categories and individual ACEs, and log-tansformed steroid levels. Children with two ACEs had higher cortisone levels compared with those with none, whereas the ≥ 3 ACEs group showed a marginal increase. These findings suggest a threshold response. Children with parents who abused drugs showed higher cortisol hair levels even when controlling for total ACEs. Elevated DHEA levels were associated with economic difficulties, rural living, younger age, and male sex, independent of the number of ACEs. These findings provide novel evidence that associates ACEs with neuroendocrine alterations in Mexican preschool children, highlighting rural–urban disparities. Exposure to adversities such as parental substance use significantly altered stress-related hormone levels, particularly among girls, emphasizing the need for gender- and context-sensitive approaches to childhood adversity interventions.
{"title":"Adverse childhood experiences and neuroendocrine biomarker changes in Mexican preschool children","authors":"I. Martín-Estal , D. León Rojas , J.L. Díaz-Gómez, A.J. del Rio-Pascual, J. Rodríguez-de-Ita, F. Castorena-Torres","doi":"10.1016/j.psyneuen.2025.107685","DOIUrl":"10.1016/j.psyneuen.2025.107685","url":null,"abstract":"<div><div>Adverse Childhood Experiences (ACEs) are highly prevalent and associated to severe health outcomes in the Mexican adult population. However, their biological correlates during early childhood remain poorly understood. We conducted a cross-sectional study in Mexican children, aged 3–5 years, to examine the association between neuroendocrine biomarker hair levels related to hypothalamic-pituitary-adrenal (HPA) axis (cortisol, cortisone, and DHEA) and the number and type of ACEs in this population. Additionally, we analyzed the effect of sociodemographic characteristics of the population (age, sex and urbanity stratum). The study included 237 children and 226 caregivers from the national ACESMEXICO cohort. Caregivers provided self-reported sociodemographic and child-related information, and hair samples from 178 children were analyzed for neuroendocrine biomarkers. The Pediatric ACEs and Related Life-Events Screener (PEARLS) was used to gather ACEs data. Linear regression models adjusted by age, sex and urbanity stratum, tested associations between cumulative ACEs categories and individual ACEs, and log-tansformed steroid levels. Children with two ACEs had higher cortisone levels compared with those with none, whereas the ≥ 3 ACEs group showed a marginal increase. These findings suggest a threshold response. Children with parents who abused drugs showed higher cortisol hair levels even when controlling for total ACEs. Elevated DHEA levels were associated with economic difficulties, rural living, younger age, and male sex, independent of the number of ACEs. These findings provide novel evidence that associates ACEs with neuroendocrine alterations in Mexican preschool children, highlighting rural–urban disparities. Exposure to adversities such as parental substance use significantly altered stress-related hormone levels, particularly among girls, emphasizing the need for gender- and context-sensitive approaches to childhood adversity interventions.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"184 ","pages":"Article 107685"},"PeriodicalIF":3.6,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145557439","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 : 2025-11-07DOI: 10.1016/j.psyneuen.2025.107681
Jonathan Seckl
{"title":"Glucocorticoid metabolism: A scientific lifetime in and beyond psychoneuroendocrinology","authors":"Jonathan Seckl","doi":"10.1016/j.psyneuen.2025.107681","DOIUrl":"10.1016/j.psyneuen.2025.107681","url":null,"abstract":"","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"183 ","pages":"Article 107681"},"PeriodicalIF":3.6,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145506532","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 : 2025-11-06DOI: 10.1016/j.psyneuen.2025.107676
Antoinette M. Landor , Katharine H. Zeiders , Alaysia M. Brown , Kayla M. Osman , Evelyn D. Sarsar , Jasmine Godwin
Empirical research has identified ethnic-racial discrimination as a fundamental driver of health disparities and a key contributor to poorer physical health outcomes among African American and Latino populations. Colorism–bias that generally privileges lighter skin over darker skin–has also been linked to adverse health outcomes; however, little to no research has explored how the intersection of colorism and racism “gets under the skin” to influence physical health, particularly among young adults. Grounded in an intersectional framework, the present study recognizes that multiple systems of oppression—namely racism and colorism—do not operate independently but intersect to uniquely impact individuals based on their racialized and phenotypic identities. Using a sample of African American and Latino young adults, the current study examined whether skin tone may be indirectly associated with poorer physical health due to its association with ethnic-racial discrimination and diurnal cortisol patterns. Findings indicated that darker skin young adults experienced more ethnic-racial discrimination, which in turn, was associated with flatter diurnal cortisol slopes. Flatter diurnal slopes were also marginally related to poorer self-reported health over time. Taken together, these results underscore the importance of applying an intersectional lens to understanding health disparities, highlighting how the interwoven impacts of colorism and racism function as sociocultural stressors that become biologically embedded, ultimately influencing the physical health of racially and ethnically marginalized young adults.
{"title":"How colorism gets “under the skin”: The role of ethnic-racial discrimination and diurnal cortisol in the physical health of African American and Latino young adults","authors":"Antoinette M. Landor , Katharine H. Zeiders , Alaysia M. Brown , Kayla M. Osman , Evelyn D. Sarsar , Jasmine Godwin","doi":"10.1016/j.psyneuen.2025.107676","DOIUrl":"10.1016/j.psyneuen.2025.107676","url":null,"abstract":"<div><div>Empirical research has identified ethnic-racial discrimination as a fundamental driver of health disparities and a key contributor to poorer physical health outcomes among African American and Latino populations. Colorism–bias that generally privileges lighter skin over darker skin–has also been linked to adverse health outcomes; however, little to no research has explored how the intersection of colorism and racism “gets under the skin” to influence physical health, particularly among young adults<strong>.</strong> Grounded in an intersectional framework<strong>,</strong> the present study recognizes that multiple systems of oppression—namely racism and colorism—do not operate independently but intersect to uniquely impact individuals based on their racialized and phenotypic identities. Using a sample of African American and Latino young adults, the current study examined whether skin tone may be indirectly associated with poorer physical health due to its association with ethnic-racial discrimination and diurnal cortisol patterns. Findings indicated that darker skin young adults experienced more ethnic-racial discrimination, which in turn, was associated with flatter diurnal cortisol slopes. Flatter diurnal slopes were also marginally related to poorer self-reported health over time. Taken together, these results underscore the importance of applying an intersectional lens to understanding health disparities<strong>,</strong> highlighting how the interwoven impacts of colorism and racism function as sociocultural stressors that become biologically embedded, ultimately influencing the physical health of racially and ethnically marginalized young adults.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"184 ","pages":"Article 107676"},"PeriodicalIF":3.6,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145621508","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 : 2025-11-06DOI: 10.1016/j.psyneuen.2025.107677
Darha M. Ponder , Suzanne Vrshek-Schallhorn , Chelsea B. Crayton , Alexandra M. Cupito , Gabriela Livas , Michaeline Jensen , Anne Fletcher
Theory and evidence link first-generation college students and minoritized race/ethnicity with heightened life stress exposure and potentially alterations in biological stress reactivity as adversity gets “under the skin,” but more evidence and statistical tools are needed to understand how multiple minoritized identities influence health. In 171 emerging adults, we tested hypotheses that these intersecting identities increase life stress exposure, measured with the UCLA Life Stress Interview; we also probe properties of four statistical approaches to modeling intersectional identities’ influence. In a subset of n = 150, growth curve modeling tested the hypothesis that more minoritized identities intensify discrimination’s effect on blunted cortisol reactivity to an explicit negative evaluative variant (n = 77) versus a control variant (n = 73) of the Trier Social Stress Test. Results link both minoritized identities with elevated exposure to non-interpersonal chronic stress (t = 3.85, p < .001), and minoritized race/ethnicity with elevated interpersonal chronic stress (t = 2.743, p = .007). Of the statistical approaches examined, an identity cumulative risk score demonstrated high sensitivity, consistent with developmental research. Finally, cumulative minoritized identities moderated the relationship between self-reported discrimination and cortisol reactivity to negative evaluative lab-based stress (t = 2.12, p = 0.035), driven by a significant discrimination and cortisol blunting association in those with both minoritized identities. Taken together, we provide evidence to support modeling intersectional identities as a cumulative risk score with post-hoc tests, and evidence that first-generation student status and minoritized race/ethnicity cumulatively heighten stress exposure and intensify the effect of discrimination on a maladaptive marker of stress-responding.
{"title":"First-generation college student status and minoritized race and ethnicity: Intersectional predictors of life stress exposure and lab-based cortisol reactivity","authors":"Darha M. Ponder , Suzanne Vrshek-Schallhorn , Chelsea B. Crayton , Alexandra M. Cupito , Gabriela Livas , Michaeline Jensen , Anne Fletcher","doi":"10.1016/j.psyneuen.2025.107677","DOIUrl":"10.1016/j.psyneuen.2025.107677","url":null,"abstract":"<div><div>Theory and evidence link first-generation college students and minoritized race/ethnicity with heightened life stress exposure and potentially alterations in biological stress reactivity as adversity gets “under the skin,” but more evidence and statistical tools are needed to understand how multiple minoritized identities influence health. In 171 emerging adults, we tested hypotheses that these intersecting identities increase life stress exposure, measured with the UCLA Life Stress Interview; we also probe properties of four statistical approaches to modeling intersectional identities’ influence. In a subset of <em>n</em> = 150, growth curve modeling tested the hypothesis that more minoritized identities intensify discrimination’s effect on blunted cortisol reactivity to an explicit negative evaluative variant (<em>n</em> = 77) versus a control variant (<em>n</em> = 73) of the Trier Social Stress Test. Results link both minoritized identities with elevated exposure to non-interpersonal chronic stress (<em>t</em> = 3.85, <em>p</em> < .001), and minoritized race/ethnicity with elevated interpersonal chronic stress (<em>t</em> = 2.743, <em>p</em> = .007). Of the statistical approaches examined, an identity cumulative risk score demonstrated high sensitivity, consistent with developmental research. Finally, cumulative minoritized identities moderated the relationship between self-reported discrimination and cortisol reactivity to negative evaluative lab-based stress (<em>t</em> = 2.12, <em>p</em> = 0.035), driven by a significant discrimination and cortisol blunting association in those with both minoritized identities. Taken together, we provide evidence to support modeling intersectional identities as a cumulative risk score with post-hoc tests, and evidence that first-generation student status and minoritized race/ethnicity cumulatively heighten stress exposure and intensify the effect of discrimination on a maladaptive marker of stress-responding.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"184 ","pages":"Article 107677"},"PeriodicalIF":3.6,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145527973","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 : 2025-11-06DOI: 10.1016/j.psyneuen.2025.107683
Dan Yao , Jing Li , Yong Lu , A’lin Sun , Xinglong Pang , Qiqi Yi , Zhongliang Zhu , Dongli Song , Yushan Lu , Hui Li
Prenatal stress (PS) is a well-established risk factor for depression-like behaviors in adolescent offspring. The prolactin receptor long-form (PRLR-LF), which has been implicated in depression pathogenesis, activates the downstream Janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) signaling cascade. Immunoprecipitation assays demonstrated that nuclear STAT5 physically interacts with the glucocorticoid receptor (GR), forming a transcriptional repressor complex that attenuates GR-dependent gene expression. Given the critical role of hippocampal GR in stress responses and depression, we hypothesized that the PRLR-LF-JAK2/STAT5-GR pathway in the hippocampus mediates depression-like behavior in prenatally stressed offspring. We established a prenatal restraint stress model and assessed depression-like behavior using sucrose preference and forced swim tests. To establish causality, we genetically modulated PRLR-LF expression through hippocampal microinjection of AAV-mediated overexpression or knockdown constructs in 21-day-old offspring. The results show that PS significantly upregulated hippocampal PRLR-LF expression and JAK2/STAT5 phosphorylation while downregulating GR expression and nuclear translocation--effects observed exclusively in female offspring. PRLR-LF knockdown in PS-exposed females attenuated depression-like behavior, normalizing JAK2/STAT5 activation and GR dysfunction. Conversely, PRLR-LF overexpression in control females induced depression-like behavior and replicated GR suppression in the hippocampus. These results demonstrate that the hippocampal PRLR-LF-JAK2/STAT5-GR pathway drives sex-specific vulnerability to PS-induced depression in adolescent offspring, offering a mechanistic target for therapeutic intervention.
产前压力（PS）是青少年后代抑郁样行为的一个公认的危险因素。长型催乳素受体（PRLR-LF）激活下游Janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 （STAT5）信号级联，与抑郁症的发病机制有关。免疫沉淀实验表明，核STAT5与糖皮质激素受体（GR）物理相互作用，形成转录抑制复合物，减弱GR依赖的基因表达。鉴于海马GR在应激反应和抑郁中的关键作用，我们假设海马PRLR-LF-JAK2/STAT5-GR通路介导了产前应激后代的抑郁样行为。我们建立了一个产前约束应激模型，并使用蔗糖偏好和强迫游泳测试来评估抑郁样行为。为了确定因果关系，我们通过在21日龄后代的海马中微量注射aav介导的过表达或敲低构建物，从基因上调节PRLR-LF的表达。结果表明，PS显著上调海马PRLR-LF表达和JAK2/STAT5磷酸化，下调GR表达和核易位，这些作用仅在雌性后代中观察到。暴露于ps的女性PRLR-LF敲低可减轻抑郁样行为，使JAK2/STAT5激活和GR功能障碍正常化。相反，对照组雌性PRLR-LF过表达诱导了抑郁样行为，并在海马中复制了GR抑制。这些结果表明，海马PRLR-LF-JAK2/STAT5-GR通路驱动青春期后代对ps诱导的抑郁的性别特异性易感性，为治疗干预提供了机制靶点。
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Pub Date : 2025-11-05DOI: 10.1016/j.psyneuen.2025.107675
Monika Wójtowicz‑Marzec , Agnieszka Maria Berendt , Danuta Zarzycka , Jacek Bogucki , Janusz Kocki
Background
Prenatal psychosocial stress is linked to adverse maternal-infant outcomes, plausibly via stress-responsive endocrine pathways and epigenetic regulation. We examined associations between prenatal stress and maternal DNA methylation (DNAm) at key psychoneuroendocrine loci.
Methods
We conducted a PROSPERO-registered (CRD420251058768), PRISMA-aligned systematic review with quantitative evidence synthesis (QES). Searches (2014–2025) identified observational studies and one randomized trial sampling blood and saliva/buccal. Effects were standardized as Hedges’ g and pooled with random-effects only for like-for-like subsets (k ≥ 2). Dependence was handled with multilevel models and robust variance estimation; risk of bias and certainty used ROBINS-I/RoB 2 and GRADE.
Results
Findings for NR3C1 exon 1 F were heterogeneous across tissue, timing, and stress domain; outcomes were non-commensurable, so no single pooled estimate was computed. For FKBP5, intron 7 (k = 2) showed lower DNAm with greater trauma/PTSD burden (SMD = −0.36, 95 % CI −0.67 to −0.05; I² ≈ 0 %). Single-study contrasts suggested higher DNAm at intron 2 and lower DNAm at intron 5 with depressive symptoms. For OXTR (DNAm/mRNA), only single-study results were comparable; signals varied by phenotype/genotype. Absolute DNAm differences were typically < 1–3 %. Overall certainty was low to very low.
Conclusions
Prenatal stress is associated with detectable yet context-dependent epigenetic variation in peripheral tissues. No single CpG or region is ready for clinical use. Progress requires region- and tissue-matched replication, harmonized stress phenotyping with cell-type adjustment, and meta-analysis-friendly, open reporting.
{"title":"Stress-induced gene regulation in pregnant women: A systematic review and quantitative evidence synthesis","authors":"Monika Wójtowicz‑Marzec , Agnieszka Maria Berendt , Danuta Zarzycka , Jacek Bogucki , Janusz Kocki","doi":"10.1016/j.psyneuen.2025.107675","DOIUrl":"10.1016/j.psyneuen.2025.107675","url":null,"abstract":"<div><h3>Background</h3><div>Prenatal psychosocial stress is linked to adverse maternal-infant outcomes, plausibly via stress-responsive endocrine pathways and epigenetic regulation. We examined associations between prenatal stress and maternal DNA methylation (DNAm) at key psychoneuroendocrine loci.</div></div><div><h3>Methods</h3><div>We conducted a PROSPERO-registered (CRD420251058768), PRISMA-aligned systematic review with quantitative evidence synthesis (QES). Searches (2014–2025) identified observational studies and one randomized trial sampling blood and saliva/buccal. Effects were standardized as Hedges’ g and pooled with random-effects only for like-for-like subsets (k ≥ 2). Dependence was handled with multilevel models and robust variance estimation; risk of bias and certainty used ROBINS-I/RoB 2 and GRADE.</div></div><div><h3>Results</h3><div>Findings for NR3C1 exon 1 F were heterogeneous across tissue, timing, and stress domain; outcomes were non-commensurable, so no single pooled estimate was computed. For FKBP5, intron 7 (k = 2) showed lower DNAm with greater trauma/PTSD burden (SMD = −0.36, 95 % CI −0.67 to −0.05; I² ≈ 0 %). Single-study contrasts suggested higher DNAm at intron 2 and lower DNAm at intron 5 with depressive symptoms. For OXTR (DNAm/mRNA), only single-study results were comparable; signals varied by phenotype/genotype. Absolute DNAm differences were typically < 1–3 %. Overall certainty was low to very low.</div></div><div><h3>Conclusions</h3><div>Prenatal stress is associated with detectable yet context-dependent epigenetic variation in peripheral tissues. No single CpG or region is ready for clinical use. Progress requires region- and tissue-matched replication, harmonized stress phenotyping with cell-type adjustment, and meta-analysis-friendly, open reporting.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"183 ","pages":"Article 107675"},"PeriodicalIF":3.6,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145513697","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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