Psychoneuroendocrinology [JOURNAL]
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200 papers
Neuroendocrine profiles in relation to female callous-unemotional traits and distress facilitation.
Auricht V, Goulter N, Kimonis ER
Psychoneuroendocrinology · 2026 Feb · PMID 41337875 · Publisher ↗
Emerging evidence supports that primary and secondary callous-unemotional (CU) variants show distinct physiological correlates, though prior research has exclusively distinguished CU variants based on psychosocial measur...
Emerging evidence supports that primary and secondary callous-unemotional (CU) variants show distinct physiological correlates, though prior research has exclusively distinguished CU variants based on psychosocial measures, rather than physiological indices, and focused on male samples. This study aimed to determine whether identified neuroendocrine (i.e., cortisol, dehydroepiandrosterone [DHEA], and testosterone) profiles mapped onto theoretically relevant psychosocial constructs consistent with CU variants, and whether profiles differed in emotional processing. Salivary samples from undergraduate women (M = 19.02 years; SD = 1.50) oversampled for high psychopathic/CU traits (N = 101) were assayed for basal cortisol, DHEA, and testosterone. Participants completed self-report measures of CU traits, maltreatment history, anxiety, and depression, and a dot-probe task assessing facilitation to emotional distress. Latent profile analysis revealed a 'hypoactive' profile with low cortisol, DHEA, and testosterone, and a 'hyperactive' profile with high cortisol, DHEA, and testosterone. Profiles partially aligned with psychosocial measures used to validate theoretical conceptualizations of CU variants, and the hyperactive profile showed greater facilitation to emotional distress relative to the hypoactive profile. Findings add to a limited literature on female CU traits in relation to neuroendocrine functioning and emotional processing. Our findings also provide preliminary evidence of possible congruency between physiological and psychosocial measures underlying the identification of CU variants.
Exogenous estradiol modulates entorhinal cortex contributions to episodic encoding of conditioned threat in women.
Oliver KI, Dahlgren K, Roeckner AR … +16 more , Hinojosa CA, Santos JLC, Taylor LS, Zeleke H, Murphy A, Johnson C, DelRosario D, Ely TD, Hinrichs R, Merrill NA, Young MR, Braden A, Powers A, Rooij SJHV, Michopoulos V, Stevens JS
Psychoneuroendocrinology · 2026 Feb · PMID 41319387 · Full text
Estradiol (E2) positively influences memory facilitation effects in older women and rodent models by targeting key memory-related brain regions. However, the impacts of E2 on emotional memory processes in younger women a...
Estradiol (E2) positively influences memory facilitation effects in older women and rodent models by targeting key memory-related brain regions. However, the impacts of E2 on emotional memory processes in younger women are less clear. As women are twice as likely as men to develop trauma related disorders such as posttraumatic stress disorder (PTSD), it is important to understand how hormones like E2 might impact threat memory mechanisms. Using a randomized, double-blinded, cross-over design, we administered transdermal E2 or placebo to 45 naturally-cycling, Black women (18-35 years) with a range of trauma-related symptoms during the early luteal (low endogenous E2) phase of their cycles. The following day, participants underwent a categorical threat conditioning paradigm during fMRI recording and completed a post-scan recognition test of images seen during the scanning session. The next month, participants repeated experimental procedures under the opposite patch condition. Blood samples taken day of scan showed a mean 80 pg/mL increase in serum E2 levels under E2 supplementation. While all participants showed an enhancement of threat on memory, such that threat-associated (CS+) images were later recognized better than neutral (CS-) pictures, neither E2 patch nor PTSD symptom severity predicted recognition performance. However, under placebo, greater bilateral entorhinal cortex (ERC) response during threat vs safety learning (CS+>CS-) was associated with greater post-scan recognition for CS+ compared to the CS- category, indicating greater ERC facilitation of episodic encoding and threat bias in the low E2 condition. We also found that the combination of high E2 and progesterone (P4) was associated with reduced ERC CS+ >CS- activity, potentially explaining why E2 supplementation did not facilitate CS+ >CS- recognition and suggesting an antagonistic role for P4 with E2 in memory facilitation. E2 produced an increase in ERC functional connectivity to the superior temporal gyrus during CS- encoding, which may suggest a shift in ERC engagement away from episodic encoding. These findings indicate that the post-ovulation drop in E2 and potential interactions with P4 facilitate the episodic encoding of safety and threat cues in women, given that exogenous E2 blocked these effects. This study provides novel causal evidence on the role of cyclical fluctuation in E2 in determining episodic components of memory for learned threat and safety.
Functional polygenic risk score of glucocorticoid-dependent regulatory element activity and its relation to clinical and stress-related phenotypes.
Linsen F, Habets PC, Milaneschi Y … +7 more , Penner-Goeke S, Mishuris B, Czamara D, Penninx BWJH, Binder EB, Meijer OC, Vinkers CH
Psychoneuroendocrinology · 2026 Feb · PMID 41319386 · Publisher ↗
BACKGROUND: Chronic stress and adverse life events are major contributors to depression and anxiety disorders. Genetic variants that influence glucocorticoid (GC) hormone responses may moderate the impact of stress on ps...
BACKGROUND: Chronic stress and adverse life events are major contributors to depression and anxiety disorders. Genetic variants that influence glucocorticoid (GC) hormone responses may moderate the impact of stress on psychiatric outcomes. Here, we use a functional polygenic risk score (fPRS) based on GC-responsive gene regulatory elements (GREs) following dexamethasone (DEX) exposure (DEX-fPRS) and examined its association with clinical and biological stress-related phenotypes. METHODS: We analyzed data from 2286 participants in the Dutch NESDA cohort, with baseline, 2-year, and 6-year follow-up visits, including 1115 with baseline depression/anxiety diagnoses. Univariable and multivariable regression models, adjusted for age, sex, batch, and ancestry principal components, were used to test associations between DEX-fPRS and lifetime diagnosis, cumulative symptom severity, and clinical features among cases (e.g. symptom severity, recurrence). Subgroup comparisons (e.g. single vs. recurrent episodes) and biological outcomes (salivary cortisol, immune markers) were also assessed. A vehicle-treated fPRS control (VEH-fPRS) was additionally tested, capturing genetic variants associated with baseline, non-GR-stimulated enhancer activity. Gene-environment interactions were tested and replication in the MARS cohort (N = 1160). RESULTS: In the full sample, DEX-fPRS showed no significant associations with lifetime diagnosis, symptom severity, or biological measures after Bonferroni correction (all p>0.05), although a nominally significant negative association was observed for morning cortisol (AUCg) in the univariable model (B=-0.05, p=0.03, p=0.19). Among cases, evening cortisol showed nominally significant negative associations in both models (univariable: B=-0.05, p=0.02, p=0.09; multivariable: B=-0.04, p=0.02, p=0.14). A significant positive association was found for recurrent vs. single episodes in both models (univariable: β=1.24, p=0.01, p=0.03; multivariable B=1.21, p=0.01, p=0.04). VEH-fPRS showed similar nominal associations for recurrent episodes (univariable: B=1.13, p=0.03, p=0.11; multivariable B=1.21, p=0.02, p=0.08) and a negative association for single episodes versus controls in the multivariable model (B=-1.52, p=0.02, p=0.07). No gene-environment interactions were detected, and none of the NESDA findings were replicated in the MARS cohort. CONCLUSION: While the DEX-fPRS was not associated with lifetime diagnosis or symptom severity, the results suggest a potential role in HPA axis sensitivity and episode recurrence. Notably, the VEH-fPRS, initially a control, may itself capture baseline transcriptional regulation. However, the lack of replication highlights the need for cautious interpretation and further validation.
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.
Landor AM, Zeiders KH, Brown AM … +3 more , Osman KM, Sarsar ED, Godwin J
Psychoneuroendocrinology · 2026 Feb · PMID 41313832 · Publisher ↗
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. Coloris...
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.
Plasma biomarkers in drug-naïve schizophrenia with severe cognitive impairment via targeted metabolomics.
Dong Y, Wang S, Qiu Y … +4 more , Su Q, Sun X, Li M, Li J
Psychoneuroendocrinology · 2026 Feb · PMID 41308587 · Publisher ↗
BACKGROUND: Cognitive impairment is the core symptom of schizophrenia (SZ). Early recognition of cognitive dysfunction is of great significance. Here, we used a metabolome-targeted approach to explore potential biomarker...
BACKGROUND: Cognitive impairment is the core symptom of schizophrenia (SZ). Early recognition of cognitive dysfunction is of great significance. Here, we used a metabolome-targeted approach to explore potential biomarkers associated with severe cognitive impairment in drug-naïve SZ patients. METHODS: Plasma metabolites from 108 SZ patients and 55 healthy controls (HC) were analyzed using liquid chromatography-mass spectrometry (LC-MS). Participants were split into discovery (n = 88) and validation (n = 75) sets. The cognitive function was assessed using MATRICS Consensus Cognitive Batter (MCCB), with cognitive deficit score ≥ 3 defined as "severe cognitive impairment" (SCI) and others as "non-severe cognitive impairment"(non-SCI). RESULTS: We found 21 candidate differential metabolites only present in SCI patients, and they were mainly involved in sphingolipid metabolism and glycerophospholipid metabolism. Furthermore, SM C20:2 and PC ae C36:2 were associated with social cognition and neurocognitive subdimensions of MCCB in SCI patients, while no similar results were found in non-SCI patients. The combination of SM C20:2 and PC ae C36:2 could modestly discriminated SCI subjects from non-SCI patients with an area under the curve (AUC) of 0.685 in discovery set and 0.720 in validation set. Moreover, these 2 candidate differential metabolites enabled distinguishing SZ patients from HC with an AUC of 0.717 in discovery set and 0.786 in validation set. CONCLUSIONS: Our study initially identified 21 candidate differential metabolites and 2 potentially important metabolic pathways related to SCI in drug-naïve SZ patients. SM C20:2 and PC ae C36:2 may serve as biomarkers for cognitive severity assessment in SZ patients.
Aging anxiety and epigenetic aging in a national sample of adult women in the United States.
Rodrigues M, Bather JR, Cuevas AG
Psychoneuroendocrinology · 2026 Feb · PMID 41297282 · Publisher ↗
BACKGROUND: Aging anxiety is a multidimensional psychosocial stressor with potential implications for women's long-term health, yet its biological embedding remains poorly understood. This study examined whether domain-s...
BACKGROUND: Aging anxiety is a multidimensional psychosocial stressor with potential implications for women's long-term health, yet its biological embedding remains poorly understood. This study examined whether domain-specific aging anxieties are associated with accelerated epigenetic aging, using second-generation methylation-based biomarkers. METHODS: Data were drawn from 726 women participating in the Midlife in the United States (MIDUS) study. Aging anxiety was assessed across three domains: declining attractiveness, declining health, and reproductive aging. Epigenetic aging was measured using two complementary second-generation clocks: GrimAge2, which estimates cumulative biological damage and predicts mortality risk, and DunedinPACE, which captures the current pace of biological aging. Multivariable linear regression models tested associations between aging anxiety and epigenetic age acceleration, adjusting sequentially for sociodemographic factors, chronic health conditions, and health behaviors. RESULTS: Greater declining health anxiety was significantly associated with higher DunedinPACE z-scores (0.07 SD increase, 95 % CI: 0.01, 0.13). This association attenuated to non-significance after adjusting for health behaviors (0.02 SD increase, 95 % CI: -0.04, 0.08), which could be potential mediators on the exposure-outcome association pathway. Higher cumulative aging anxiety was significantly associated with a 0.07 SD increase (95 % CI: 0.01, 0.14) in DunedinPACE, but this association attenuated to non-significance after adjusting for chronic health conditions (0.06 SD increase, 95 % CI: -0.01, 0.13) and health behaviors (0.03 SD increase, 95 % CI: -0.03, 0.08). CONCLUSION: Findings indicate that specific domains of aging anxiety, particularly fears about declining health, may manifest biologically and contribute to accelerated aging processes. These results support a biopsychosocial model in which subjective experiences of aging contribute to physiological decline. Future longitudinal studies are needed to clarify whether aging-related anxiety influences epigenetic aging trajectories among women.
Corrigendum to "U.S. men's testosterone (T), partnering, and residence with children: Evidence from a nationally-representative cohort (NHANES) and relevance to clinically low T" [Psychoneuroendocrinology 182 (2025) 107658].
Gettler LT, Dennis SH
Psychoneuroendocrinology · 2026 Feb · PMID 41297281 · Publisher ↗
Abstract loading — click title to view on PubMed.
Parent-child salivary cortisol synchrony in early childhood: A systematic review.
Jain M, Sokol E, Freehling E … +4 more , Kamath S, Lajiness-O'Neill R, Staples AD, Lawler JM
Psychoneuroendocrinology · 2026 Feb · PMID 41289650 · Publisher ↗
IMPORTANCE: Although parent-child cortisol synchrony is essential for the development of children's socio-emotional development, the research findings on what affects this synchrony are unclear. This lack of clarity make...
IMPORTANCE: Although parent-child cortisol synchrony is essential for the development of children's socio-emotional development, the research findings on what affects this synchrony are unclear. This lack of clarity makes it difficult to pinpoint the best areas to target when creating interventions to help improve synchrony between parents and their children. OBJECTIVE: We aimed to characterize the literature on parent-child cortisol synchrony and how various family-related risks and protective factors were associated with parent-child cortisol synchrony. EVIDENCE REVIEW: We searched 4 databases (CINAHL, PsycINFO, PubMed, and Web of Science) on August 25th, 2025. Backward and forward citation searching was also conducted. Eligible articles a) were peer-reviewed articles/theses/dissertations published in the English language, b) assessed children between 6 months and 8 years for diurnal cortisol, and between 0 months and 8 years for cortisol reactivity, c) included majority of children free of neurological, genetic, or major psychiatric disorders and born full-term, d) included parents with a mean age above 18 years, where the majority were free of neurological or genetic disorders, e) collected at least 2 salivary cortisol samples from both parent and child, in either home or lab, f) for cortisol reactivity, collected at least one saliva sample each before and after a challenging task, g) collected 2 saliva samples on the same day for diurnal cortisol, and h) reported any statistical association between parent and child cortisol. We used the Quality Assessment with Diverse Studies Tool for quality analysis. FINDINGS: We identified 33 unique studies, including a total of 5206 participants. All studies were observational, with 7 longitudinal studies. The scarce literature suggested positive child-to-parent synchrony in families without risk factors, but synchrony was absent or reduced in families with risk factors. Protective factors (e.g., parental sensitivity) led to more adaptive synchrony in parent-child dyads. CONCLUSIONS AND RELEVANCE: While the existing research suggested that parent-child cortisol synchrony is affected by both family risk and protective factors, too few studies existed to draw strong conclusions. More research is essential to develop better interventions for improving parent-child synchrony.
The mediating role of loneliness between psychosocial and physiological well-being in older adults.
Ho RTH, Lo TLT, Fong TCT … +6 more , Jiang D, Kwok JYY, Yeung DY, Choi NG, Warner LM, Chou KL
Psychoneuroendocrinology · 2026 Feb · PMID 41275755 · Publisher ↗
BACKGROUND: Loneliness is a risk factor for mental but also physical health concerns in older adults. This study aimed to examine the temporal associations among social relationships, mindfulness, and physiological funct...
BACKGROUND: Loneliness is a risk factor for mental but also physical health concerns in older adults. This study aimed to examine the temporal associations among social relationships, mindfulness, and physiological functioning and the potential mediating role of loneliness. METHODS: The present study recruited 141 older adults experiencing loneliness (M = 64.1 years, 76 % female) during the COVID-19 pandemic in Hong Kong. Participants completed a questionnaire that assessed loneliness, social network, perceived social support, and mindfulness, and provided six saliva samples for cortisol and C-reactive protein (CRP) over two days at baseline (T0) and 6-month follow-up (T1). Path analysis was conducted to examine the associations of changes in psychosocial and physiological variables via change in loneliness. RESULTS: The participants showed small to moderate increases in perceived social support and mindfulness and small to moderate decreases in loneliness and pre-lunch cortisol. Greater improvements in social relationships were significantly associated with changes toward steeper diurnal cortisol slopes, indicating a healthier cortisol pattern. Greater improvements in mindfulness and social relationships were indirectly associated with greater reductions in CRP via a decrease in loneliness. CONCLUSIONS: The present findings provided empirical support for temporal associations between social relationships, mindfulness, and physiological markers, with loneliness acting as a mediator, in older adults. The results suggest that interventions targeting loneliness, while promoting social engagement and mindfulness, could improve both psychosocial and physiological well-being in this population.
Demonstrating the potential of untargeted hair proteomics for personalized biomarkers in stress-associated disorders.
Sicorello M, Sprenger JC, Störkel LM … +5 more , Sarg B, Kremser L, Schmahl C, Niedtfeld I, Karabatsiakis A
Psychoneuroendocrinology · 2026 Feb · PMID 41275754 · Publisher ↗
Biomarker research in psychopathology increasingly employs high-dimensional Omics approaches. Yet, proteomics based on human hair remain largely unexplored, despite its potential to efficiently capture stable biological...
Biomarker research in psychopathology increasingly employs high-dimensional Omics approaches. Yet, proteomics based on human hair remain largely unexplored, despite its potential to efficiently capture stable biological signals accumulated over weeks to months. This study leveraged machine learning to investigate the potential of the hair proteome-all detectable peptides and proteins-as a biomarker source for stress-associated psychopathology. We analyzed protein profiles from hair segments of women with non-suicidal self-injury disorder and healthy controls (N = 68). Of 1114 identified proteins, 611 were sufficiently abundant for analyses. Partial Least Squares Discriminant Analysis achieved stable 84.4 % cross-validated accuracy for classification of clinical groups (p < .001), outperforming models based on data-derived clusters (60 %), stress-related proteins (73 %), and simulated hair cortisol from meta-analytic effect sizes (53-59 %). Predicted class probabilities strongly correlated with clinical symptoms and well-being (r > .60). Key predictive proteins were linked to pain perception, oxidative stress, and cholesterol homeostasis. Approximately 15 % of proteins differed significantly between groups, with the strongest candidates related to ribosomal function-an emerging target in depression. These findings establish hair proteomics as a promising, non-invasive biomarker source for psychiatric research with potential clinical applications in risk assessment and personalized interventions.
Increased social reward behavior in adolescent male and female rats exposed prenatally to alcohol is associated with altered dopamine receptor expression.
Sheehan AC, Leonetti AM, Murray SH … +5 more , Dhaliwal R, Stamp MA, Holman PJ, McCormick CM, Raineki C
Psychoneuroendocrinology · 2026 Feb · PMID 41275753 · Full text
Prenatal alcohol exposure (PAE) has detrimental consequences on cognitive, physiological, and social development. Adolescence, characterized by increased exploration, risk-taking, and social interaction, is a critical de...
Prenatal alcohol exposure (PAE) has detrimental consequences on cognitive, physiological, and social development. Adolescence, characterized by increased exploration, risk-taking, and social interaction, is a critical developmental stage that may amplify social deficits caused by PAE. This study examined how PAE affects social motivation in males and females across adolescent development using a social reward task to measure preferences for social and non-social stimuli at postnatal day (P)30, P40, P50, and P70. Our results demonstrated that PAE rats exhibited higher social motivation than controls during training and progressive ratio sessions. Extinction testing showed PAE males persisted in responding to the previously social side, resisting the typical shift to a non-social preference observed in controls. Dopamine receptor analysis revealed sex- and age-specific effects. Both PAE males and females showed increased D2 receptor expression in the nucleus accumbens (NAcc) at P30 and P50. In contrast, D3 receptor expression was decreased in the NAcc of P30 PAE males. In the medial amygdala, PAE females exhibited reduced D3 expression at P40 and P70, while PAE males showed similar reductions at P30 and P50. These findings suggest that PAE disrupts development of social motivation and dopamine receptor expression, with distinct effects based on sex and developmental stage. The observed increases in D2 expression, coupled with decreases in the inhibitory D3 receptor, may contribute to the heightened social motivation in PAE rats by shifting the balance of dopamine signaling toward increased reward sensitivity and reduced behavioral inhibition.
Heterogeneous cortisol patterns during the peripartum: Insights from a longitudinal trajectory analysis.
Dukic J, Johann A, Henninger M … +1 more , Ehlert U
Psychoneuroendocrinology · 2026 Feb · PMID 41270314 · Publisher ↗
BACKGROUND: The maternal hypothalamic-pituitary-adrenal (HPA) axis undergoes substantial physiological changes during pregnancy and postpartum, reflected in altered cortisol secretion patterns. However, research has show...
BACKGROUND: The maternal hypothalamic-pituitary-adrenal (HPA) axis undergoes substantial physiological changes during pregnancy and postpartum, reflected in altered cortisol secretion patterns. However, research has shown considerable heterogeneity in cortisol patterns across the peripartum period and in part contradictory findings. Individual courses of cortisol secretion and their determinants remain poorly understood. METHODS: In a longitudinal cohort of 127 healthy pregnant women, we assessed salivary cortisol at five time points from late pregnancy (gestational weeks 34-36 and 40) to eight weeks postpartum. Group-based trajectory modeling was applied to three cortisol measures to identify distinct cortisol secretion patterns. Associations with sociodemographic and psychological covariates were explored. RESULTS: Across all cortisol indices, two distinct trajectory groups emerged. The majority of women (79-86 %) exhibited stable, relatively lower cortisol levels during late pregnancy and postpartum, while a smaller subgroup (14-21 %) exhibited a consistently elevated and more variable cortisol trajectory. Trajectory groups showed high classification stability (98-99 %), but no sociodemographic or psychological variables significantly predicted group membership. CONCLUSIONS: Our findings reveal two distinct maternal cortisol trajectory subgroups across the peripartum period, reflecting heterogeneity in HPA axis regulation. The lack of significant associations with the measured covariates raises the possibility that unmeasured mechanisms, such as genetic or epigenetic influences, may contribute to these patterns. These distinct cortisol trajectories may reflect differing modes of neuroendocrine regulation, offering a potential explanation for inconsistencies in prior peripartum cortisol research.
Psychological and immunological benefits of eye movement desensitization and reprocessing in hashimoto thyroiditis: Preliminary findings from a randomized controlled trial.
Macarenco MM, Opariuc-Dan C, Georgescu T … +1 more , Căciuloiu L
Psychoneuroendocrinology · 2026 Feb · PMID 41265021 · Publisher ↗
OBJECTIVE: This study examined the effectiveness of Eye Movement Desensitization and Reprocessing (EMDR) in improving psychological functioning and modulating immune markers in adults with Hashimoto's thyroiditis (HT), a...
OBJECTIVE: This study examined the effectiveness of Eye Movement Desensitization and Reprocessing (EMDR) in improving psychological functioning and modulating immune markers in adults with Hashimoto's thyroiditis (HT), a chronic autoimmune disorder increasingly linked to early trauma. METHOD: In a randomized controlled trial, 91 adults with HT were assigned to EMDR plus treatment-as-usual (TAU), placebo plus TAU, or TAU alone. The EMDR protocol focused on processing ten distressing memories predating illness onset. Outcomes included anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) levels, and measures of depression, anxiety, stress, dissociation, alexithymia, trait anger, emotion regulation, and quality of life, assessed at baseline, posttreatment, and 3-month follow-up. RESULTS: EMDR led to significant improvements in dissociation, alexithymia, depression, anxiety, stress, trait anger, and emotion regulation, along with enhanced quality of life. These effects were maintained at follow-up and generally exceeded those of placebo or TAU. A significant reduction in anti-TPO levels was also observed in the EMDR group, although between-group effects at follow-up did not remain significant after correction for multiple comparisons. No significant differences were found in anti-TG levels. CONCLUSION: EMDR may offer a clinically relevant adjunctive intervention for individuals with HT, reducing psychological distress and potentially influencing immune activity. Findings on immunomodulation are preliminary and warrant further investigation in larger trials.
Not all saliva samples are equal: The role of cellular heterogeneity in DNA methylation and epigenetic age analyses with biological and psychosocial factors.
Chan MH, Meijer M, Merrill SM … +7 more , Fu MPY, Lin D, MacIsaac JL, Riis JL, Granger DA, Thomas EA, Kobor MS
Psychoneuroendocrinology · 2026 Feb · PMID 41265020 · Full text
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 stu...
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.
Self-compassion and stress responses among early adolescents.
Zieff G, Jameson T, Nutini A … +6 more , Battaglini AM, Jopling E, Grocott B, Rnic K, Puterman E, LeMoult J
Psychoneuroendocrinology · 2026 Feb · PMID 41265019 · Publisher ↗
INTRODUCTION: Self-compassion is an adaptive means of relating to oneself that encompasses elements of self-kindness, common humanity, and mindfulness. Self-compassion has positive associations with health and may dampen...
INTRODUCTION: Self-compassion is an adaptive means of relating to oneself that encompasses elements of self-kindness, common humanity, and mindfulness. Self-compassion has positive associations with health and may dampen biological and psychological stress responses, which would be particularly helpful for those with a history of early life adversity. The purpose of this study was to determine i) the association of trait self-compassion with cortisol and affective responses to an acute psychosocial stressor among early adolescents, and ii) whether this association differed by exposure to early life adversity (e.g., abuse, neglect). METHODS: Eighty-three early adolescents (M = 12.86 years; 47 % girls, 1 % non-binary) self-reported their trait self-compassion, completed a structured interview-based assessment to assess threat- and deprivation-related exposures to early life adversity, and underwent a psychosocial laboratory stressor (Trier Social Stress Test for Children; TSST-C). Salivary cortisol and self-reported positive and negative affect were measured at six timepoints before, during, and for 30 min following the stressor. We tested associations of self-compassion with trajectories (reactivity, recovery) and total levels (area under the curve with respect to ground; AUCg) of cortisol and positive and negative affect across the TSST-C, as well as moderating effects of early life adversity. Hierarchical linear models were used to test trajectories, and linear regression was used to test AUCg, with unstandardized (B) and standardized beta coefficients (β) reported, respectively. RESULTS: Self-compassion was not associated with total cortisol levels or trajectories of cortisol, positive affect, or negative affect (all p > 0.057). However, greater self-compassion was associated with higher sample 1 positive affect, B = 1.815, t(71) = 2.84, p = .006, and greater total positive affect levels, β = 0.411, t(62) = 3.90, p < .001. Similarly, self-compassion was associated with lower sample 1 negative affect, B = -1.261, t(72) = -2.35, p = 0.022, and less total negative affect levels, β = -0.269, t(75) = -2.45, p = 0.017. Additionally, sensitivity analyses indicated that at higher levels of early-life threat exposure, greater self-compassion was associated with higher sample 1 positive affect. CONCLUSION: Among adolescents - including those exposed to threat-related forms of early life adversity- self-compassion may impart more general, diffuse beneficial effects on affect rather than buffering affective or cortisol responses to an acute stressor.
Impact of sleep fragmentation and estradiol suppression on positive and negative affect: Results of an experimental model of menopause.
Nathan MD, Spagnolo PA, Grant LK … +6 more , Rahman SA, Gonsalvez I, Harder J, Kim H, Wiley A, Joffe H
Psychoneuroendocrinology · 2026 Feb · PMID 41265018 · Full text
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, particu...
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.
Gut feelings: Dysbiosis of gut microbiota and short-chain fatty acids associated with prenatal depression, pregnancy-related anxiety, and prenatal combined depression and anxiety.
Fan X, Wei Y, Zang T … +7 more , Tu Y, Liu L, Tian H, Li X, Cheng H, Bai J, Liu Y
Psychoneuroendocrinology · 2026 Feb · PMID 41259824 · Publisher ↗
OBJECTIVES: The role of the gut microbiota and short-chain fatty acids (SCFAs) in psychiatric disorders in pregnant women has not been fully elucidated. Therefore, this study aimed to investigate the association between...
OBJECTIVES: The role of the gut microbiota and short-chain fatty acids (SCFAs) in psychiatric disorders in pregnant women has not been fully elucidated. Therefore, this study aimed to investigate the association between the gut microbiota and its metabolite SCFAs and prenatal depression, pregnancy-related anxiety, and prenatal combined depression and anxiety. METHODS: In total 200 pregnant women in the third trimester were recruited for this study. The Edinburgh Postnatal Depression Scale and Pregnancy-Related Anxiety Questionnaire Revised-2 were used to evaluate pregnant women's anxiety and depression, and stool samples were collected for gut microbiome and SCFAs. RESULTS: This study found that reduced abundance of Allobaculum and Cetobacterium were associated with pregnancy-related anxiety in women. Furthermore, the enrichment of Anaerofustis, Gemella, and Staphylococcus and the reduction of Tyzzerella and unclassified_f_UCG-011 were associated with prenatal depression. This study was the first to indicate that women with comorbid prenatal anxiety and depression share similarities in gut microbiota and SCFAs with women with prenatal depression (Anaerofustis, Gemella, Staphylococcus, Tyzzerella, and isohexanoic acid). This study also found that certain gut microbial profiles were associated with prenatal comorbid anxiety and depression. While receiver operating characteristic analysis suggests a limited ability of the gut microbiota alone to predict prenatal psychological distress problems, the integration of phenotypic variables into the model significantly improved the model's predictive ability. CONCLUSION: Our findings suggested that dysbiosis of gut microbiota and SCFAs are associated with prenatal psychiatric disorders. Alterations of the gut microbiota may have the potential as biomarkers for distinguishing prenatal psychiatric disorders.
Protective effects of liver-derived apolipoprotein A1 against heat stress-induced hypothalamic lipid metabolism and blood-brain barrier integrity.
Li B, Ming R, Guo H
Psychoneuroendocrinology · 2026 Feb · PMID 41259823 · Publisher ↗
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...
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.
Adverse childhood experiences and neuroendocrine biomarker changes in Mexican preschool children.
Martín-Estal I, Rojas DL, Díaz-Gómez JL … +3 more , Del Rio-Pascual AJ, Rodríguez-de-Ita J, Castorena-Torres F
Psychoneuroendocrinology · 2026 Feb · PMID 41259822 · Publisher ↗
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...
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.
Adverse childhood experiences patterns and biological aging in a representative sample of older Americans.
Zhang X, Slopen N, Binns AA … +1 more , Cuevas AG
Psychoneuroendocrinology · 2026 Feb · PMID 41253003 · Publisher ↗
BACKGROUND: Adverse childhood experiences (ACEs) are common, co-occurring risk factors for poor long-term health. Emerging research links ACEs to accelerated biological aging, yet most studies rely on singular or cumulat...
BACKGROUND: Adverse childhood experiences (ACEs) are common, co-occurring risk factors for poor long-term health. Emerging research links ACEs to accelerated biological aging, yet most studies rely on singular or cumulative indicators and often overlook differences by race, sex, and adversity type, potentially yielding imprecise estimates. OBJECTIVES: To identify latent ACEs classes by race and sex using latent class analysis (LCA) and examine their associations with biological aging measured by DNA methylation-based epigenetic clocks. METHODS: We analyzed 3586 participants from the Health and Retirement Study, a nationally representative cohort of U.S. older adults. LCA identified ACEs classes based on nine indicators, including physical abuse, household substance use, and socioeconomic adversity. Biological aging was measured using GrimAge, PhenoAge, and DunedinPoAm clocks. Epigenetic age acceleration (EAA) was calculated as residuals of GrimAge/PhenoAge regressed on chronological age. RESULTS: Latent Low Adversity and Financial Adversity classes were identified among Black and White participants, and among Hispanic participants we identified Parental Low Education and Socioeconomic Adversity classes. Men exhibited higher GrimAge EAA than women across all groups. Among Black and White women, Financial Adversity was associated with elevated GrimAge EAA and a faster DunedinPoAm pace compared to the Low Adversity group. Among Hispanic women, Socioeconomic Adversity was linked to higher PhenoAge EAA and faster DunedinPoAm pace relative to those in the Parental Low Education group. CONCLUSION: Women in the adversity classes demonstrated more accelerated biological aging than those in low adversity classes. Findings underscore the value of intersectional, person-centered approaches to understanding adversity's role in biological aging and the need for targeted health interventions.
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