Psychoneuroendocrinology [JOURNAL]
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200 papers
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.
Feinmesser D, Shohat S, Gerda R … +6 more , Nin Nun A, Shoshani A, Samra NN, Verbeke W, Vrticka P, Ein-Dor T
Psychoneuroendocrinology · 2026 May · PMID 41690127 · Publisher ↗
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 analyz...
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.
Economic disparities in parental hair cortisol are associated with externalizing behavior in children.
Strack J, Hansen M, Jacobs L … +7 more , Turner A, Bulson V, Bendinskas K, Wiltshire CA, Gavin WJ, Davies PL, Merz EC
Psychoneuroendocrinology · 2026 May · PMID 41690126 · Publisher ↗
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 o...
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.
Multimodal brain-gut-sleep phenotypes predict delirium, long-term cognitive decline, and survival after colorectal cancer surgery.
Pan S, Wang G
Psychoneuroendocrinology · 2026 May · PMID 41690125 · Publisher ↗
BACKGROUND: Neuroimmune, circadian, autonomic, and gut-brain processes jointly shape vulnerability to postoperative delirium and long-term cognitive decline, yet their integrated contribution remains unclear. METHODS: In...
BACKGROUND: Neuroimmune, circadian, autonomic, and gut-brain processes jointly shape vulnerability to postoperative delirium and long-term cognitive decline, yet their integrated contribution remains unclear. METHODS: In this prospective cohort (n = 300), preoperative assessments included circadian actigraphy, gut microbial diversity and short-chain fatty acids, inflammatory cytokines (IL-6, CRP), nocturnal heart rate variability, sleep-wake characteristics, and psychological symptoms. Unsupervised clustering identified multimodal phenotypes. Outcomes included postoperative delirium, 36-month cognitive, fatigue, and sleep trajectories, and 3-year survival. Analyses used mixed-effects models, Cox regression, and gradient boosting. RESULTS: Four biobehaviorally coherent phenotypes emerged. Delirium incidence increased from 4.7 % in Phenotype A to 21.6 % in Phenotype D. Cognitive decline over 36 months followed the same gradient, with Phenotypes C-D showing progressive deterioration. Fatigue and sleep recovery displayed parallel phenotype-dependent stratification. Three-year disease-free survival ranged from 86.7 % (A) to 69.3 % (D), and overall survival from 91.2 % to 78.8 %. Relative to the resilient reference phenotype (A), phenotypes characterized by convergent multidomain dysregulation were independently associated with worse survival (HR 2.11 for DFS; HR 1.96 for OS). Machine-learning models ranked circadian amplitude, microbial diversity, SCFA concentrations, IL-6, and nocturnal heart rate variability as dominant contributors. CONCLUSIONS: Multimodal brain-gut-sleep phenotypes strongly predict delirium, long-term cognition, and survival after colorectal cancer surgery. These findings support a systems-based model in which perioperative resilience reflects coordinated regulation of circadian, microbial, autonomic, inflammatory, and psychological pathways.
Family member bereavement, salivary telomere length, and all-cause mortality in older adults: Findings from the Health and Retirement Study.
Chang M, Wilson PA, Robles TF
Psychoneuroendocrinology · 2026 May · PMID 41690124 · Publisher ↗
The biological aging mechanisms by which loss exposure relates to mortality are not well-understood, particularly among communities of color. In this pre-registered, longitudinal study, we evaluated whether salivary telo...
The biological aging mechanisms by which loss exposure relates to mortality are not well-understood, particularly among communities of color. In this pre-registered, longitudinal study, we evaluated whether salivary telomeres mediate associations between loss burden-premature and cumulative exposure to family member deaths over the lifetime-and mortality. Leveraging a prospective sample of 4837 U.S. older adults from the Health and Retirement Study who recorded at least one kin death, we tested whether participants' loss burden related to their salivary telomeres 2 years later (linear regression models) and, in turn, predicted all-cause mortality 14 years later (Cox regression models). Models adjusted for covariates including family size, socioeconomic status, and baseline health including smoking. Telomeres did not mediate relationships between loss burden and mortality. Higher loss burden and shorter telomeres each predicted higher odds of mortality. Unexpectedly in race-stratified models, more childhood loss related to longer telomeres among Hispanic participants, and younger kin deaths related to longer telomeres among Black participants. Findings highlight the limitations of salivary telomeres in explaining racial health disparities and the need to identify biological aging mechanisms after loss among communities of color.
Cortisol and C-reactive protein interact to predict depressive symptoms.
Doan SN, Hoell DJ, Fuller-Rowell TE
Psychoneuroendocrinology · 2026 Apr · PMID 41687317 · Publisher ↗
A growing literature has sought to characterize the physiological correlates of depression, particularly with respect to inflammatory hypothalamic-pituitary-adrenal functioning and inflammation. These systems are intrica...
A growing literature has sought to characterize the physiological correlates of depression, particularly with respect to inflammatory hypothalamic-pituitary-adrenal functioning and inflammation. These systems are intricately interrelated, but in relation to depression, have primarily been investigated independently. This study examined interactions between C-reactive protein (CRP), a widely studied inflammatory biomarker, and salivary cortisol in relation to depressive symptoms in a non-clinical sample of 18- to 25-year-olds. We analyzed data from 184 participants (M = 19.43 years, SD = 1.11, 59.8 % female) who provided dried blood spot and saliva samples, assayed for CRP and cortisol concentrations, respectively. Salivary cortisol was collected across the Trier Social Stress Task. Depressive symptoms were assessed with the Beck Depression Inventory. Covariate-adjusted linear regression models were used to test for main and interaction effects between cortisol and CRP on depressive symptoms. Controls included sex, age, parent income, race/ethnicity, BMI, and study site. In our sample, neither cortisol (b = -.01, SE b =.01, p = .17) nor CRP (b = -1.25, SE =.92, p = .18) were related to depressive symptom severity. However, there was a significant interaction effect (b =.04, SE b =.01, p = .001), such that cortisol reactivity was inversely related to depression among participants with low, but not moderate or high levels of CRP. Cortisol reactivity to moderate stressors appears to be beneficial, but our results suggest these benefits are attenuated by high inflammation. This indicates that inflammatory activity is an important contextual factor shaping the relationship between cortisol and depression, highlighting the utility of multi-system approaches to studying the physiological correlates of depression.
Association between allostatic load and incident dementia, and race/ethnic disparities in the association in the U.S. health and retirement study.
Kabeto MU, Sharma M, Ford D … +1 more , Faul JD
Psychoneuroendocrinology · 2026 May · PMID 41687258 · Publisher ↗
OBJECTIVE: 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 associa...
OBJECTIVE: 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. METHOD: 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. RESULTS: 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], p < .001). The association was attenuated (HR = 1.59, 95 % CI [1.08, 1.10], p < .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. DISCUSSION: 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.
Hypothalamic-pituitary-adrenal axis attenuation following child sexual abuse distinguishes posttraumatic stress trajectories from late adolescence to midlife.
Swerbenski H, Li Z, Putnam FW … +2 more , Russotti J, Noll JG
Psychoneuroendocrinology · 2026 May · PMID 41687257 · Full text
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-pituit...
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.
Long-term offspring loss in lactating rats: Neurobiological and emotional consequences in a novel animal model.
Demarchi L, Sanson A, Boos AL … +1 more , Bosch OJ
Psychoneuroendocrinology · 2026 Apr · PMID 41655506 · Publisher ↗
The maternal bond is a vital social connection that supports the survival and well-being of both the caregiver and offspring. Disruption of this bond, particularly following offspring loss, can result in profound trauma...
The maternal bond is a vital social connection that supports the survival and well-being of both the caregiver and offspring. Disruption of this bond, particularly following offspring loss, can result in profound trauma with long-lasting consequences. While considerable research has focused on the impact of maternal separation on offspring development, the biological effects of offspring loss on the mother remain largely unexplored. In this study, we examined the long-term effects of offspring loss on neuroplasticity, the oxytocin (OXT) and corticotropin-releasing factor (CRF) systems, and stress-coping behaviors in Sprague-Dawley rat mothers. We examined two groups of lactating mothers: (I) a control group, in which dams remained with their pups until natural weaning, and (II) a separated group, in which all offspring were removed on lactation day 1 and the mothers experienced offspring loss until the time corresponding to weaning (19 days). Our results reveal that pup removal increased oxytocin receptor binding-most prominently in the ventromedial hypothalamus (VMH)-and reduced dendritic spine density in this brain region, without altering estrogen receptor α or calbindin cell expression. Separated mothers additionally showed elevated plasma corticosterone levels and increased passive stress-coping behaviors in the forced swim test. Remarkably, passive stress-coping behavior was rescued by central CRF receptor blockade but not by central OXT treatment, indicating that the CRF system plays a critical role in the distress response to offspring loss. These findings establish a novel rat model to investigate the neurobiological consequences of maternal stress following offspring loss.
Pubertal neuroendocrine network characteristics and sex differences: A hair-based hormone network study.
Hou X, Xie M, Yi S … +3 more , Wei G, Deng H, Lin D
Psychoneuroendocrinology · 2026 Apr · PMID 41653860 · Publisher ↗
BACKGROUND: 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 coordina...
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Bias in hair cortisol measures for psychological stress: Self vs. professional collection.
Gatny H, Axinn W, Ghimire D … +5 more , West BT, Hermosilla S, Pradhan S, Dixit S, Chaudary I
Psychoneuroendocrinology · 2026 Apr · PMID 41653859 · Full text
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...
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.
The effect of timing and tempo of adrenarche on depression and anxiety in adolescence: A prospective cohort analysis.
Luo D, Sawyer SM, Husin HM … +2 more , Dashti SG, Vijayakumar N
Psychoneuroendocrinology · 2026 Apr · PMID 41650549 · Publisher ↗
BACKGROUND: A considerable proportion of life-time depression and anxiety emerges during childhood and adolescence. Some research has shown that pubertal maturity is associated with depression and anxiety. While most res...
BACKGROUND: A considerable proportion of life-time depression and anxiety emerges during childhood and adolescence. Some research has shown that pubertal maturity is associated with depression and anxiety. While most research has focused on gonadarche, the earlier phase of adrenarche remains less explored and understood. We aimed to examine the effects of timing and tempo of adrenarche on incidence and chronicity of depression and anxiety during adolescence. METHODS: Data were from the Child to Adult Transition Study (CATS), a longitudinal population-based cohort from Melbourne, Australia. CATS recruited Grade 3 students in 2012, who were followed up annually across adolescence. Adrenarchal timing was modelled as the level of adrenal hormones (DHEA, DHEAS, and testosterone) relative to peers at age 9 and tempo as the adrenal hormone progression rate relative to peers between 9 and 12. Incidence and chronicity of common mental disorders were defined using self-reported depressive and anxiety symptoms collected annually from age 12-18. G-computation was used to adjust for confounding. Missing data were handled via multiple imputation using chained equations. RESULTS: The study comprised 667 females and 572 males. Depression incidence (76 % females, 44 % males) and chronicity (34 % females, 7 % males) and anxiety incidence (69 % females, 36 % males) and chronicity (29 % females, 7 % males) were more common in female adolescents than males. Regardless of using DHEA, DHEAS, or testosterone as the index for adrenarche, the risk ratios for the association between timing and tempo of adrenarche and the incidence and chronicity of depression or anxiety were close to null and 95 % confidence intervals were inconclusive. CONCLUSIONS: This study did not identify a meaningful effect of adrenarchal timing and tempo on depression and anxiety in adolescents, suggesting that individual differences in adrenarche may not influence risk for later significant mental health difficulties.
Mediating role of maternal cortisol in the association between maternal serum creatinine and fetal cortisol exposure.
Lin Z, Zhang Z, Yang G … +2 more , Wang N, Peng J
Psychoneuroendocrinology · 2026 Apr · PMID 41650548 · Publisher ↗
BACKGROUND: Cortisol is the principal glucocorticoid regulated by the hypothalamic-pituitary-adrenal (HPA) axis and plays a crucial role in maintaining pregnancy and promoting fetal growth and development. Renal function...
BACKGROUND: Cortisol is the principal glucocorticoid regulated by the hypothalamic-pituitary-adrenal (HPA) axis and plays a crucial role in maintaining pregnancy and promoting fetal growth and development. Renal function is a key determinant of cortisol exposure. Given that serum creatinine serves as a key biomarker of renal function, it is plausible that maternal creatinine levels contribute to the regulation of fetal cortisol exposure, although the underlying mechanisms remain to be fully elucidated. OBJECTIVE: This study was designed to (1) examine the association between maternal serum creatinine and umbilical cord blood cortisol levels, (2) assess the potential mediating role of maternal cortisol in this relationship, and (3) investigate corresponding changes in the protein expression of placental 11β-HSD1 and 11β-HSD2. METHODS: This study employed a paired maternal-fetal design. At delivery, maternal serum, umbilical cord blood, and placental tissue were collected simultaneously from 103 mother-newborn pairs. Cortisol and cortisone levels in maternal and cord blood were measured, and protein expression of 11β-HSD1 and 11β-HSD2 in placental tissue was analyzed. Correlation and mediation analyses were performed to assess the relationships among maternal serum creatinine, maternal cortisol, and cord blood cortisol. RESULTS: Each unit increase in maternal serum creatinine was associated with a significant decrease in cord blood cortisol levels. Maternal cortisol levels were positively correlated with cord blood cortisol. Mediation analysis showed that maternal cortisol mediated 31.75 % of the association between maternal creatinine and cord blood cortisol. In the high-creatinine conditions, placental expression of 11β-HSD1 was significantly decreased, while expression of 11β-HSD2 was increased. CONCLUSION: Maternal cortisol showed evidence of partial mediation in the association between maternal renal function and fetal cortisol exposure. This observational finding highlights a potential link between maternal renal function and fetal glucocorticoid exposure and provides a basis for future studies to investigate the role of placental glucocorticoid regulation and fetal HPA axis development.
Female-biased vulnerability to transgenerational impact of paternal early-life stress.
Ishikawa I, Ohta KI, Imai M … +8 more , Ishikawa M, Kumei H, Kashima M, Fugo U, Suzuki S, Otabi H, Miki T, Nakamura Y
Psychoneuroendocrinology · 2026 Apr · PMID 41650547 · Publisher ↗
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 subjecte...
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 mt-Nd3 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.
Corrigendum to "Diurnal cortisol and rumination: Examining gender differences" [Psychoneuroendocrinology 179 (2025) 107517].
Stuart NC, Zoccola PM, Dickerson SS
Psychoneuroendocrinology · 2026 Apr · PMID 41619688 · Publisher ↗
Abstract loading — click title to view on PubMed.
Phase-dependent cytokine signatures in alcohol use disorder: A systematic review of psychoneuroimmune links to withdrawal severity and return to drinking.
Sokolova S, Skryabin V, Pozdniakov S … +4 more , Ivanchenko V, Vinokurova N, Ardamatskaya L, Masyakin A
Psychoneuroendocrinology · 2026 Apr · PMID 41610562 · Publisher ↗
BACKGROUND: Neuroimmune dysregulation is increasingly implicated in alcohol use disorder (AUD), yet the clinical utility of cytokine biomarkers remains unclear. OBJECTIVE: To synthesise evidence linking pro- and anti-inf...
BACKGROUND: Neuroimmune dysregulation is increasingly implicated in alcohol use disorder (AUD), yet the clinical utility of cytokine biomarkers remains unclear. OBJECTIVE: To synthesise evidence linking pro- and anti-inflammatory cytokines to AUD severity, withdrawal symptoms, and return-to-drinking risk, with emphasis on temporal staging and translational implications. METHODS: A systematic review and meta-analysis were conducted in accordance with PRISMA 2020 and PROSPERO (CRD420251060888). Six databases and grey literature sources were searched from January 1, 2000 to October 31, 2025 (updated for revision). Eligible studies assessed IL-6, IL-1β, IL-10, TNF-α, or CRP in adults with AUD or alcohol withdrawal, and reported correlations with validated clinical severity scales (e.g., AUDIT, CIWA-Ar) or relapse outcomes. Risk of bias, evidence certainty (GRADE), and heterogeneity were systematically evaluated. RESULTS: Thirteen studies (N = 1458) were included across active drinking/non-treatment-seeking samples, early abstinence/withdrawal (≤14 days), and post-detoxification/treatment-follow-up contexts where acute withdrawal was absent or not the primary focus. In early abstinence, IL-6 tended to be higher in AUD/AWS than controls; however, the pooled estimate was large but imprecise and highly heterogeneous (random-effects Hedges' g =1.21, 95 % CI -0.08-2.50; 2 studies; I²≈91 %). Higher baseline CRP was associated with lower subsequent alcohol use and weaker cue-reactivity in individual cohorts, but findings were heterogeneous and not pooled. For return-to-drinking outcomes, a single study provided extractable IL-1β group data comparing participants who returned to drinking with those who maintained abstinence; the single-study standardized effect was non-significant (Hedges' g=0.40, 95 % CI -0.12-0.92). Lower IL-17RB expression was associated with reduced relapse-free survival in a single study and should be considered preliminary. Methodological variability and incomplete control for hepatic/metabolic confounding limited pooling for several cytokines. CONCLUSIONS: Evidence supports phase-dependent cytokine signals in AUD, with IL-6 most consistently elevated during early abstinence and CRP showing pragmatic translational potential but substantial methodological heterogeneity. Evidence for IL-1β and IL-17RB as relapse-related markers remains preliminary due to limited extractable and non-uniform outcome reporting. Standardised, sex-stratified longitudinal studies with rigorous control for hepatic/metabolic factors and CNS validation are warranted.
Hair cortisol concentrations among youth in Ukraine: Associations with war experiences and post-traumatic-stress symptoms.
Skinner AT, Pavlova I, Godwin J … +2 more , Reilly EB, Georgiades A
Psychoneuroendocrinology · 2026 Apr · PMID 41610561 · Publisher ↗
OBJECTIVE: To explore relations between cortisol response measured by hair cortisol concentrations (HCC), war exposure (e.g., air alarms and explosions), and psychological distress for youth living in Ukraine during the...
OBJECTIVE: To explore relations between cortisol response measured by hair cortisol concentrations (HCC), war exposure (e.g., air alarms and explosions), and psychological distress for youth living in Ukraine during the current invasion. METHODS: 221 youth (Mage = 18.9 years; 20 % male) living in 5 regions of Ukraine from November 2023-March 2024 provided hair samples to assess HCC and self-report data measuring post-traumatic stress symptoms (PTS symptoms). Youth's region of residence was matched to air alarm and explosion data. RESULTS: Consistent with prior research examining HPA axis activity during chronic stress, we found that exposure to more air alarms and explosions were each associated with lower HCC. Contrary to our hypotheses, we found no relation between HCC and PTS symptoms. CONCLUSIONS: Our results suggest that youth experiencing chronic war exposure may adapt by down-regulating their cortisol production, which could generate long-term health problems such as immune dysregulation or increased inflammatory activity.
Social buffering of the cortisol stress response during the Minnesota Imaging Stress Test in Children.
Donzella B, Miller Z, Tsakonas NC … +2 more , Thomas KM, Gunnar MR
Psychoneuroendocrinology · 2026 Apr · PMID 41610560 · Full text
INTRODUCTION: To understand neural underpinnings of individual differences in physiological stress responding, most notably of the hypothalamic-pituitaryadrenocortical system, but also of the autonomic system, it is esse...
INTRODUCTION: To understand neural underpinnings of individual differences in physiological stress responding, most notably of the hypothalamic-pituitaryadrenocortical system, but also of the autonomic system, it is essential to rely on an imaging task that reliably elevates cortisol and measures of the autonomic nervous system activity, such as salivary alpha amylase. When the question also involves neural activity related to social stress buffering, it requires a task that shows differential stress responses as a function of varying social buffering partners. The purpose of this study was to examine whether the Minnesota Imaging Stress Test in Children (MISTiC) with social buffering conditions fulfilled these requirements. METHOD: 180 children ages 11 through 15 years (92 female) had salivary cortisol and salivary alpha amylase (sAA) samples taken during the MISTiC, a socially evaluative stressor modeled after the Trier Social Stress Test. Participants were randomly assigned to one of three social buffering conditions: Alone-No Buffer, Parent-as-Buffer, and Researcher-as-Buffer. Buffers interacted briefly with participants audiovisually at multiple points. Saliva samples for cortisol determination were taken 3 times during the hour preceding the MISTiC with the last serving as the pretest (T0) sample. Saliva was then collected post MISTiC at 25, 35, 45, 55, and 65 min after T0. The T0, 25, and 35 samples were assayed for sAA. RESULTS: 61 % of participants showed a significant increase in cortisol in response to the stressor (i.e., 115 % or greater) with roughly the same showing an increase in sAA. Change from T0 was analyzed for cortisol yielding a significant trials by condition interaction (p < .05). Post-hoc tests showed a significant difference between the Parent-as-Buffer and both the Alone-No Buffer and the Researcher-as-Buffer conditions, thus indicating that parents were still effective buffers for the cortisol response in this age range. The only significant effect for sAA was a trials effect, p < .001 with the same being true for self-ratings of stress, p < .001. Puberty (pre/early vs mid/late) did not moderate the response of social buffering condition on cortisol or sAA. CONCLUSION: The MISTiC is effective in elevating cortisol, sAA and perceived stress. For cortisol, the method used for buffering yielded significant differences by buffer type, suggesting that this paradigm is appropriate for assessing the neural systems underlying the social buffering of stress. Contrary to our prior work, pubertal stage did not moderate the effectiveness of the parent in buffering the child's cortisol response.
The relationship between chronic stress, co-occurring conditions, sleep, and autistic features including severity using hair cortisol concentration.
Chan NY, John JR, Mathew NE … +5 more , Masi A, Ong LK, Eapen V, Lin PI, Walker AK
Psychoneuroendocrinology · 2026 Apr · PMID 41610559 · Publisher ↗
BACKGROUND AND OBJECTIVE: Autism is highly heterogeneous and reliance on behavioural assessments alone may not provide sufficient insight into the unique characteristics of autistic individuals. Biomarkers, like hair cor...
BACKGROUND AND OBJECTIVE: Autism is highly heterogeneous and reliance on behavioural assessments alone may not provide sufficient insight into the unique characteristics of autistic individuals. Biomarkers, like hair cortisol concentration (HCC), may help unravel mechanisms underlying clinical variation in autism and support diagnostic measures, especially in young children who may not be able to effectively communicate their distress. We examined the relationship between HCC and autistic traits along with commonly co-occurring conditions including sleep disturbances in autistic children compared to non-autistic children. METHODS: We conducted a cross-sectional analysis utilising data from the Australian Autism Biobank comprising clinical and biological samples from Australian children aged 2-17 years. Primary analysis included multivariable linear regression analyses to identify significant associations with HCC after controlling for key sociodemographic covariates, including child's intelligence quotient (IQ). RESULTS: The study included 307 autistic children, 158 non-autistic siblings, and 124 unrelated non-autistic children. The commonly reported co-occurring conditions were global developmental delay (8.5 %), intellectual disability (6.1 %), and otitis media (6.1 %). Higher severity of autistic traits and in particular social affect issues, co-occurring attention-deficit/hyperactivity disorder (ADHD), internalising, and maladaptive behaviours were significantly associated with lower normalised HCC. Higher sleep anxiety and IQ were associated with higher HCC. Regarding sociodemographic factors, older age and higher family income were associated with lower HCC. CONCLUSION: The findings indicate the clinical value of HCC as a viable biomarker to identify subgroups based on co-occurring medical and mental health conditions. Further research to elucidate the link to individual and family/environmental factors as potential sources of stress is needed to offer targeted supports.
The effects of the chemical relaxer lye on hair cortisol concentrations.
Burnett CL, Crandall K, Osbourn DM … +1 more , Buchanan TW
Psychoneuroendocrinology · 2026 Apr · PMID 41605047 · Publisher ↗
BACKGROUND: The analysis of hair cortisol is a common tool in stress research. External factors such as chemical hair treatments can impact the integrity of hair cortisol. The use of chemical relaxers is more common amon...
BACKGROUND: The analysis of hair cortisol is a common tool in stress research. External factors such as chemical hair treatments can impact the integrity of hair cortisol. The use of chemical relaxers is more common among racialized populations who experience high chronic stress and are underrepresented in stress research. METHODS: 15 participants who identify as Black or Latinx were recruited to give a hair sample. The commonly used hair relaxer, lye, was applied to hair samples using a novel in vitro methodology to examine its impact on cortisol concentration. RESULTS: Bayesian multilevel model estimated a small group effect (M = 0.53, 95 % CI [-8.57, 9.32]), with only 55 % of the posterior distribution favoring higher cortisol in untreated samples, indicating no meaningful difference. CONCLUSION: The lack of effect of lye hair relaxer on cortisol supports the inclusion of participants who use this treatment in research and reinforces the utility of hair-based stress research in populations disproportionately affected by chronic stress. Addressing representation in stress research is essential, and these findings are a critical step toward developing more inclusive and equitable methodological practices.
Altered placental expression of neurotransmitter and stress-related molecules in first-episode psychosis during pregnancy: Implications for cytoarchitecture and function.
García-Montero C, Fraile-Martinez Ó, Boaru DL … +17 more , Castro-Martinez P, Leon-Oliva D, García-González B, Pérez-González I, Bravo C, Leon-Luis JA, Diaz-Pedrero R, Lopez-Gonzalez L, Barrena-Blázquez S, Bujan J, García-Honduvilla N, Alvarez-Mon MÁ, Presa M, Lahera G, Alvarez-Mon M, Saez MA, Ortega MA
Psychoneuroendocrinology · 2026 Apr · PMID 41579700 · Publisher ↗
BACKGROUND: First-episode psychosis during pregnancy (FEP-PW) is a rare but serious condition that intersects maternal mental health and placental-fetal biology. While psychosis is characterized by disruptions in percept...
BACKGROUND: First-episode psychosis during pregnancy (FEP-PW) is a rare but serious condition that intersects maternal mental health and placental-fetal biology. While psychosis is characterized by disruptions in perception and cognition, its impact on placental neuroendocrine signaling and fetal development remains poorly understood. The placenta, as a key mediator of intrauterine environment, expresses receptors involved in neurotransmission and stress response, potentially linking maternal psychopathology to fetal neurodevelopmental risk. OBJECTIVE: This study investigates the expression of five critical neuroendocrine and stress-related molecules-dopamine receptor D2 (DRD2), serotonin receptor 1B (HTR1B), glucocorticoid receptor (NR3C1), 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2), and melatonin receptor 1B (MTNR1B)-in placental tissue from women with FEP-PW compared to healthy pregnant controls (HC-PW). METHODS: Using a prospective case-control design, placental samples from 22 FEP-PW and 20 HC-PW women were analyzed. Gene expression was quantified by real-time quantitative polymerase chain reaction (RT-qPCR), and protein localization and abundance assessed via immunohistochemistry (IHC). RESULTS: Significant alterations in placental gene and protein expression were observed in FEP-PW placentas: DRD2, NR3C1, and HSD11B2 were markedly upregulated (all p < 0.001 at gene and protein levels), whereas HTR1B and MTNR1B were significantly downregulated compared to controls (p < 0.05, p < 0.01 respectively at gene level and p < 0.01, p < 0.001 at protein level). These findings indicate dysregulated dopaminergic, serotonergic, glucocorticoid, and melatonin signaling pathways in the placenta associated with maternal psychosis. CONCLUSIONS: Our results provide novel evidence of distinct placental molecular adaptations in FEP-PW, reflecting heightened maternal stress and disrupted neurohormonal environments. These alterations may contribute to adverse placental function and influence fetal neurodevelopmental trajectories, underscoring the placenta's role as a critical mediator in the maternal-placental-fetal axis in psychiatric disorders. Further research is needed to clarify the functional consequences and explore these molecules as potential biomarkers or therapeutic targets in perinatal psychiatry.
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