Psychoneuroendocrinology [JOURNAL]
Sun
200 papers
Effects of acute stress on social conformity: Testing competing hypotheses.
Bahr JH, Mojzisch A, Häusser JA … +2 more , Duderstadt V, Germar M
Psychoneuroendocrinology · 2026 Jun · PMID 42000609 · Publisher ↗
While prior research has focused on stress effects in individual decision-making, far less is known about its impact in social contexts, where judgments are shaped by others' opinions. Theoretical and empirical work offe...
While prior research has focused on stress effects in individual decision-making, far less is known about its impact in social contexts, where judgments are shaped by others' opinions. Theoretical and empirical work offers competing predictions as to whether acute stress increases or decreases social conformity. Across two preregistered experiments (total N = 217), we tested these competing hypotheses using the Trier Social Stress Test - Online Version (TSST-OL; Study 1) and the Maastricht Acute Stress Test (MAST; Study 2) to induce stress. Participants were randomly assigned to either a stress or a control condition and completed a perceptual decision-making task measuring conformity. Results provided evidence for reduced conformity under stress, particularly in Study 1 and in pooled analyses. This pattern is consistent with the stress-breeds-social-independence hypothesis. Exploratory mediation analyses further suggest that this effect is linked to lower perceived competence of others. In contrast, other psychological (e.g., state self-esteem, sense of agency, mood) and physiological variables (i.e., salivary cortisol) were affected by stress but were unrelated to conformity. Furthermore, we examined potential moderators of the stress-induced decrease in conformity, including gender and the social embeddedness of the situation, but did not observe evidence for moderation by these variables. Taken together, the overall pattern of results, including the pooled analyses, provides evidence that acute stress reduces social conformity.
Androgens and estrogens rapidly facilitate short-term memory in the dorsal hippocampus of male mice.
LaDouceur KE, Aspesi D, Nielsen KM … +3 more , Cantini D, Sheppard PAS, Choleris E
Psychoneuroendocrinology · 2026 Jun · PMID 41997012 · Publisher ↗
Sex steroid hormones influence cognition through both classical delayed genomic and rapid mechanisms. While rapid estrogenic modulation of memory in the dorsal hippocampus (dHPC) is well established in females, the exten...
Sex steroid hormones influence cognition through both classical delayed genomic and rapid mechanisms. While rapid estrogenic modulation of memory in the dorsal hippocampus (dHPC) is well established in females, the extent to which the sex hormones rapidly regulate short-term memory (STM) in males remains unresolved. Here, we investigated the rapid effects of the testosterone metabolites 17β-estradiol (E2) and dihydrotestosterone (DHT) on hippocampal-mediated STM in castrated CD1 male mice. Bilateral infusions into the dHPC were administered prior to testing object placement, object recognition, and social recognition STM, all completed within 40 min of treatment to capture rapid effects. Both E2 and DHT rapidly facilitated performance across paradigms, demonstrating that androgenic and estrogenic signaling within the male dHPC rapidly facilitates social and non-social STM processes. These findings extend the limited literature on sex steroid regulation of male cognition and underscore the importance of considering both estrogenic and androgenic pathways in models of hippocampal memory processing, with potential implications for understanding sex-specific vulnerabilities to cognitive decline and neuropsychiatric disorders.
Presence of a friend is associated with progesterone response after social exclusion.
Duarte K, Byrd-Craven J
Psychoneuroendocrinology · 2026 Jun · PMID 41997011 · Publisher ↗
Social exclusion is a common form of indirect aggression and carries significant social and health costs. Close friendships may protect against exclusion and shape physiological responses. While oxytocin and cortisol hav...
Social exclusion is a common form of indirect aggression and carries significant social and health costs. Close friendships may protect against exclusion and shape physiological responses. While oxytocin and cortisol have received substantial attention in this context, progesterone is also implicated in affiliative motivation and may be sensitive to social threat. The present study examined progesterone responses to social exclusion and subsequent reunion with a close friend. Female participants (N = 31) provided salivary progesterone samples at baseline, following exclusion (Yale Interpersonal Stressor; YIPS), and after reunion with a friend. During reunion, participants either received active support from their friend (venting), passive support (friend present but no discussion), or no support (alone). Results indicated a significant increase in progesterone from baseline to post-exclusion, which remained elevated at reunion. Trajectories also varied significantly: passive support sustained progesterone across phases, active support produced only a transient boost, and no support was associated with flat responses.
Differential stability and covariation of diurnal and stress-reactive HPA axis functions in adolescents with and without maltreatment risk.
Korom M, Carrera P, Garnett ML … +6 more , Sellers T, Patel K, Tottenham N, Laurenceau JP, Donzella B, Dozier M
Psychoneuroendocrinology · 2026 Jun · PMID 41990568 · Full text
The hypothalamic-pituitary-adrenal (HPA) axis is a key component of the neuroendocrine system that produces cortisol to regulate both sleep-wake cycles and stress physiology. Prior research shows that early maltreatment...
The hypothalamic-pituitary-adrenal (HPA) axis is a key component of the neuroendocrine system that produces cortisol to regulate both sleep-wake cycles and stress physiology. Prior research shows that early maltreatment disrupts both the diurnal and stress-reactive functions of the HPA axis. However, previous studies-primarily conducted in healthy populations-have reported inconsistent associations between these two functions, and it remains unclear whether their association is moderated by maltreatment history and/or pubertal development. The clinical or at-risk status of the sample may be particularly relevant, as persistently disrupted diurnal cortisol regulation may more reliably predict disrupted stress reactivity than a well-regulated diurnal system that can flexibly adapt to daily demands. The present study addressed this gap by examining the association between diurnal and stress-regulatory functions of the HPA axis in 13-year-old adolescents with and without a history of maltreatment risk (referred to as high- and low-risk, respectively). Our analyses revealed that diurnal cortisol levels were significantly more stable in the high-risk group than in the low-risk group and that maltreatment risk moderated the association between diurnal morning-to-evening cortisol slope and stress reactivity (but not recovery or intercept). Specifically, a flatter-and therefore less optimal or more dysregulated-diurnal slope was coupled with blunted stress reactivity during the Trier Social Stress Task for youth in the high-risk group but not in the low-risk group. Exploratory analyses further showed that, in the high-risk group only, pubertal development moderated this effect, such that more mature adolescents exhibited the strongest decoupling of the diurnal slope and stress reactivity. Together, these findings highlight maltreatment history and pubertal development as key factors for understanding how diurnal cortisol parameters and stress reactivity become dynamically linked-and potentially reorganized-across adolescence.
Links between hormonal and pubertal development, and adolescent females' risk for affective symptoms.
Evans AI, Kogan SM, Koss KJ … +3 more , House EM, Geier CF, Oshri A
Psychoneuroendocrinology · 2026 Jun · PMID 41985217 · Full text
Depression and anxiety symptoms surge during adolescence, particularly in females, yet the biological mechanisms underlying this vulnerability remain poorly understood. Although estrogen has traditionally been emphasized...
Depression and anxiety symptoms surge during adolescence, particularly in females, yet the biological mechanisms underlying this vulnerability remain poorly understood. Although estrogen has traditionally been emphasized, androgens such as dehydroepiandrosterone (DHEA) and testosterone may represent distinct pathways to affective symptom risk. The present study examined whether increases in testosterone predict internalizing symptoms in adolescent females by examining hormonal and physical aspects of pubertal development and testing whether testosterone effects persist beyond estradiol and observable maturation. Using data from 5476 females (ages 9-13) in the Adolescent Brain Cognitive Development Study, we analyzed annual salivary DHEA, testosterone, and estradiol alongside caregiver-reported pubertal development and youth-reported internalizing symptoms. Latent change score models captured developmental dynamics: univariate models characterized growth trajectories, bivariate coupling models tested directional hormonal influences, and the final model evaluated whether testosterone and pubertal development changes predicted internalizing symptoms, controlling for estradiol, age, and assay covariates. Testosterone increased gradually across early adolescence, whereas DHEA showed accelerating, nonlinear growth. Increases in testosterone predicted higher internalizing symptoms between ages 10 and 12 (b = 0.041, 95% CI [0.007, 0.076]; b = 0.075, 95% CI [0.009, 0.142]). Observable pubertal development was negatively associated with internalizing symptoms at one assessment. Estradiol predicted subsequent pubertal development and showed concurrent associations with internalizing symptoms at two assessments but did not explain the testosterone-internalizing link. Increases in testosterone predicted internalizing symptoms after accounting for observable maturation and estradiol, identifying a specific vulnerability window between ages 10-12 with implications for early identification and timing of preventive interventions.
Oxytocin and early life stress in late preterm newborns: an exploratory study.
Consales A, Arioli M, Addabbo M … +11 more , Bulf H, Silvestri V, Turati C, Battezzati A, Ravasenghi S, Colombo L, Petrelli A, Tiraferri V, Fumagalli M, Macchi Cassia V, Giannì ML
Psychoneuroendocrinology · 2026 Jun · PMID 41985216 · Publisher ↗
Oxytocin, a neuropeptide traditionally associated with labor and lactation, has been increasingly recognized for its broader roles, including maintaining physiological stability amidst environmental challenges. Previous...
Oxytocin, a neuropeptide traditionally associated with labor and lactation, has been increasingly recognized for its broader roles, including maintaining physiological stability amidst environmental challenges. Previous studies on preterm infants have reported inconsistent results regarding oxytocin responses to maternal contact. The present study investigated peripheral oxytocin levels in late preterm newborns (34 - 36 weeks gestation), an epidemiologically relevant and neurodevelopmentally vulnerable subgroup of preterm infants. Fifty newborns (males 56%, median gestational age = 36.1 weeks) were enrolled between April 2022 and September 2023. Timing and type of first maternal contact (within the first hour post-birth or later; skin-to-skin or not), maternal mental health, attachment, and tactile interactions during the first two days of life were assessed using self-report questionnaires. Neonatal oxytocin levels were measured from blood samples collected after 48 h of life. Higher oxytocin levels were observed in twins (p = 0.05, d = 0.67), newborns delivered by caesarean section (p = 0.002, d = 1.14), and those who experienced delayed first maternal contact (p = 0.005, d = 1.18) or lacked skin-to-skin contact (p = 0.001, d = 1.35). Oxytocin levels were also positively correlated with maternal age (rho = 0.38, p = 0.02). In multivariate analyses, lack of skin-to-skin contact predicted higher oxytocin levels after 48 h of life (p = .019, η²ₚ =.27). Although interpretation is limited by the absence of data on maternal oxytocin administration - which, despite ongoing debate on its placental transfer, may account for the observed differences - our results reinforce previous speculations on the context-dependent nature of oxytocin regulation in preterm infants. Elevated oxytocin levels under stressful conditions may reflect an adaptive neuroendocrine response potentially buffering the developing brain against excessive glucocorticoid exposure.
Trauma exposure, perceived stress and morning cortisol levels among Palestinian boys in the Gaza Strip and West Bank.
Arvisais O, Raymond C, Mahhou MA … +4 more , Bluteau J, Joma A, Mc Mullin S, Abu-Jamei Y
Psychoneuroendocrinology · 2026 Jun · PMID 41967319 · Publisher ↗
Millions of children worldwide grow up under conditions of war and armed conflict, yet the risks associated with data collection in such highly adverse contexts mean that very few cortisol datasets are available from the...
Millions of children worldwide grow up under conditions of war and armed conflict, yet the risks associated with data collection in such highly adverse contexts mean that very few cortisol datasets are available from these regions. This descriptive study aimed to document salivary morning cortisol levels (MCL), trauma exposure and perceived effects, as well as perceived stress in Palestinian boys (N = 115), ages 9-11, living in the Gaza Strip (n = 62) and the West Bank (n = 53). Salivary cortisol was sampled at awakening and 30 min post-awakening over three consecutive days, and mean values were used to compute MCL as an index of basal hypothalamic-pituitary-adrenal (HPA) activity. Results show that in both groups, self-reported perceived stress levels were descriptively higher relative to a published U.S. reference sample. Children in both regions reported substantial exposure to traumatic events and associated perceived effects. When descriptively compared with published normative cortisol awakening response values, salivary MCL showed divergent patterns across regions, with markedly higher values in the Gaza Strip and considerable variability in the West Bank. Exploratory correlational analyses suggested region-specific associations: in the West Bank, greater perceived effect of trauma was associated with higher MCL, whereas in the Gaza Strip, no association was found with perceived stress or trauma. These findings provide rare descriptive data on salivary cortisol among children growing up under chronic war exposure and underscore the importance of building comparative datasets to better understand how adverse environments shape stress physiology.
Human chorionic gonadotropin alpha and beta levels are associated with maternal demographic characteristics and psychosocial measures of stress and discrimination.
Adibi JJ, Liang HW, Xun X … +5 more , Carpio K, Layden A, O'Connor TG, Barrett ES, Koistinen H
Psychoneuroendocrinology · 2026 Jun · PMID 41966751 · Publisher ↗
INTRODUCTION: Human chorionic gonadotropin (hCG) is a heterodimeric hormone regulated in part by the maternal neuroendocrine-placenta axis. Serum levels of the beta subunit (hCGβ) are higher in Black vs. White pregnancie...
INTRODUCTION: Human chorionic gonadotropin (hCG) is a heterodimeric hormone regulated in part by the maternal neuroendocrine-placenta axis. Serum levels of the beta subunit (hCGβ) are higher in Black vs. White pregnancies. The underlying causes of the difference remain unclear. The objective of the study was to measure associations of maternal demographic and anthropometric characteristics, and self-reported measures of stress and discrimination with hCG and its subunits in a racially diverse sample. METHODS: Serum samples were provided by longitudinal birth cohorts in Rochester, NY and in Pittsburgh, PA. Research participants were enrolled in early pregnancy from 2015 to 2019. Serum hCG levels in the first and second trimesters, measured by immunofluorometric assays (IFMA) as intact hCG, its hyperglycosylated form (h-hCG) and free alpha and beta subunits (hCGα and hCGβ), were normalized for gestational day of blood draw as the multiple of the median (MoM). Minimally adjusted generalized linear models were fit to explore associations of exposures, including maternal demographic characteristics, pregnancy characteristics, perceived stress, depression, stressful life events, experiences of discrimination and everyday discrimination, with serum levels of hCGs. RESULTS: Research subjects (n = 451) identified as Black (24%) and White (59%). hCGα was lower (-0.35 log MoM; 95% CI -0.45, -0.24) in Black vs. White participants and intact hCG and hCGβ were higher (0.19 log MoM; 95% CI 0.02, 0.36). Body mass index, weight, gravidity and smoking were negatively associated with hCGα. Maternal age, education, income, and partnered (vs. single) status were positively associated with hCGα. Number of stressful life events and experiences of discrimination were negatively associated with hCGα. Everyday discrimination was positively associated with hCGβ. CONCLUSION: An hCG-subunit specific pattern of association was described with maternal social and psychosocial experience in early pregnancy. More work is needed to understand these differences and their applicability to interventions to reduce stress and its long-term impacts on maternal and child health.
Visceral hypersensitivity following adult chronic social defeat stress is associated with microglial remodeling in the anterior cingulate cortex.
Matsuo A, Kanaya M
Psychoneuroendocrinology · 2026 Jun · PMID 41966750 · Publisher ↗
Stress contributes significantly to visceral pain hypersensitivity in irritable bowel syndrome (IBS). Although stress during critical developmental periods, such as chronic social defeat stress (CSDS) in adolescence or e...
Stress contributes significantly to visceral pain hypersensitivity in irritable bowel syndrome (IBS). Although stress during critical developmental periods, such as chronic social defeat stress (CSDS) in adolescence or early-life adversities, like maternal separation, has been extensively researched and is known to increase visceral pain sensitivity, little is known about the effects of CSDS on visceral pain processing in full adulthood. This gap is important because IBS onset and exacerbation of symptoms frequently occur in adults experiencing chronic psychosocial stress. Using a CSDS protocol in adult mice, we examined changes in visceral pain thresholds, anxiety-like behavior, and neuroimmune plasticity, particularly focusing on microglia linked to pain and emotions. CSDS-exposed mice exhibited significantly reduced visceral pain thresholds and heightened visceral sensitivity, accompanied by adrenal gland hypertrophy, thymic atrophy, and elevated anxiety-like behavior. Morphological analysis revealed pronounced microglial process shrinkage and decreased branching within the anterior cingulate cortex (ACC) after CSDS, without considerable changes in traditional inflammation-associated mRNA levels. No microglial remodeling was detected in other regions. Microglial depletion with PLX3397 partially reduced visceral hypersensitivity, producing an intermediate phenotype, but did not improve anxiety-like behavior. Our findings suggest that microglia play a modulatory, but not exclusive role in stress-induced visceral pain. Regional differences indicate the ACC acts as a hub for chronic pain plasticity, governed by complex microglial and circuit-level mechanisms.
Biology, conflict, and mental health: New Insights on a Critical and Growing Global Issue.
Jankovic-Rankovic J, Gettler LT
Psychoneuroendocrinology · 2026 Jun · PMID 41962376 · Publisher ↗
Abstract loading — click title to view on PubMed.
Distinctions in theory of mind (ToM) and serum chemokine profiles between adolescent patients with depressive disorder with suicidal attempt and non-suicidal counterparts: A case-control study.
Zheng H, Liu S, Liu L … +7 more , Liu W, Wen X, Yang Y, Li M, Shen X, Cao X, Zhong H
Psychoneuroendocrinology · 2026 Jun · PMID 41931930 · Publisher ↗
BACKGROUND: Substantial evidence suggests an association between suicide-related behaviors in patients with depressive disorders and impaired social cognitive functioning and immune dysfunction.This study aims to identif...
BACKGROUND: Substantial evidence suggests an association between suicide-related behaviors in patients with depressive disorders and impaired social cognitive functioning and immune dysfunction.This study aims to identify the characteristics of adolescents with depressive disorders who have attempted suicide from social cognitive and immune perspectives and to explore potential risk factors for suicidal attempts. METHODS: This study included 166 adolescents with depressive disorders, who were divided into a suicide attempt group (SA, 86 cases) and a non-suicide attempt group (NSA, 80 cases) based on the presence or absence of suicide attempt behavior, along with 23 healthy controls (HC). Social cognition was assessed using the Theory of Mind Story Picture Task, and serum chemokines were detected using the Meso Scale Discovery (MSD) electrochemiluminescence (ECL) detection technique. RESULTS: Regarding ToM, the SA group showed higher scores in comprehension of deception than the NSA group (p = 0.017); the NSA group had lower scores in sense of reality, personal detection of deception, and total ToM than the HC group (all p < 0.05). For chemokines, the SA group had lower Eotaxin-2 levels than the HC group (p = 0.003), and the NSA group exhibited significantly lower levels of Eotaxin, Eotaxin-2, Eotaxin-3, and MCP-1 than the SA group (all p < 0.05). The regression model (R²=0.268) indicated that comprehension of deception (β=0.85, OR=2.34, p = 0.045), MINI score (β=0.09, OR=1.10, p < 0.001), and serum Eotaxin level (β=0.02, OR=1.02, p < 0.001) were independent risk factors for suicidal attempts. Specifically, enhanced comprehension of deception (a core ToM component) and elevated Eotaxin levels were positively associated with suicidal behavior in adolescent depressive patients. CONCLUSION: Assessing social cognition, particularly the comprehension of deception through Theory of Mind evaluations, contributes to a better understanding and identification of suicidal behaviors. Moreover, elevated serum Eotaxin levels serve as a significant risk factor for suicidal behavior in adolescents with depressive disorders.
The effect of GLP-1 receptor agonists on anxiety: A systematic review.
Yi YT, Zheng YJ, Bargiota SI … +9 more , Dri CE, Teopiz KM, Wong S, Han Le G, Kwan ATH, Cao B, Ho R, Balanag EMP, McIntyre RS
Psychoneuroendocrinology · 2026 Jun · PMID 41931929 · Publisher ↗
Anxiety-like behaviors are highly prevalent and frequently co-occur with metabolic conditions such as type 2 diabetes and obesity, suggesting the potential for shared biological mechanisms. Although glucagon-like peptide...
Anxiety-like behaviors are highly prevalent and frequently co-occur with metabolic conditions such as type 2 diabetes and obesity, suggesting the potential for shared biological mechanisms. Although glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for glycemic control and weight management, emerging evidence indicates that they may also influence neuroinflammation, neuroplasticity, and affective regulation. However, findings across preclinical and clinical studies remain fragmented, and no systematic synthesis has directly evaluated their effects on anxiety-like behaviors. This review addresses this gap by examining whether GLP-1 RA administration reduces anxiety-like behaviors or clinically coded anxiety outcomes. Following PRISMA guidelines, preclinical and clinical studies were systematically identified, screened using PICOS-defined criteria, and evaluated with validated quality assessment tools. Across animal studies, GLP-1 RAs consistently reduced anxiety-like behaviors and improved neurobiological markers related to stress resilience, while clinical cohorts demonstrated mixed but suggestive evidence of reduced anxiety incidence and lower suicidal ideation risk. These findings highlight the potential for GLP-1 RAs to modulate both metabolic and psychiatric pathways, underscoring the need for randomized controlled trials to clarify causal effects and inform their role in metabolic psychiatry.
Positive coping enhances children's emotional wellness via neuroendocrine modulation of cortisol awakening response and hippocampal circuitry.
Tian T, Chen B, Cao H … +9 more , Zhao Y, Gao H, Chen M, He Y, Xu J, Hao L, Jiang M, Xiong B, Qin S
Psychoneuroendocrinology · 2026 Jun · PMID 41903472 · Publisher ↗
Positive coping is a key developmental asset that supports active self-regulation in daily emotional challenges and may influence neurodevelopment through cortisol-related stress physiology relevant to hippocampal integr...
Positive coping is a key developmental asset that supports active self-regulation in daily emotional challenges and may influence neurodevelopment through cortisol-related stress physiology relevant to hippocampal integrity and behavioral adaptation in childhood. However, the neurobiological mechanism underlying how positive coping may impact hippocampal development during childhood remains unclear. In Study 1, we recruited 129 typically-developing children aged 6-12 years and assessed their positive coping style, cortisol awakening response (CAR) by cortisol-cortisol, and brain activity under an emotional processing task. In Study 2, 59 of them longitudinally underwent the same emotional task fMRI one year later. Behaviorally, positive coping was associated with better emotional regulation and lower anxiety at Time-1, and less decision hesitation in emotional decision-making at both Time-1 and Time-2. At the endocrine and neurocognitive level, positive coping was associated with greater CAR at Time-1, which was further linked with higher hippocampal activation and hippocampus-ventrolateral prefrontal (vlPFC) connectivity one year later. Besides, the hippocampal maturation may support the maturity of hippocampal-vlPFC connectivity one year later. The study highlights a cognitive-neuroendocrine framework in which positive coping may impact the hippocampal-neocortical pathway via CAR to enhance emotional wellness.
Variation in DNA methylation of the oxytocin gene is associated with prosocial, reward-related, decision-making.
Kroll CF, Leibold NK, Vingerhoets C … +5 more , Kenis G, van den Hove DLA, Riedl A, Schruers KRJ, Hernaus D
Psychoneuroendocrinology · 2026 Jun · PMID 41894898 · Publisher ↗
Human and animal studies suggest a critical role for central oxytocin (OXT) in social behavior. While experimentally manipulating central OXT levels via intranasal administration is a well-suited noninvasive option in hu...
Human and animal studies suggest a critical role for central oxytocin (OXT) in social behavior. While experimentally manipulating central OXT levels via intranasal administration is a well-suited noninvasive option in human research, existing findings are mixed, suggesting that the effects of exogenous OXT on social behavior are highly variable and dependent on other (e.g., biological) factors. Endogenous OXT synthesis is regulated by a wide range of molecular mechanisms including DNA methylation (DNAm). However, the link between DNAm of the OXT gene (OXT) and human social behavior has received little attention. We studied the relationship between OXT DNAm, intranasal OXT administration, and facets of human prosocial behavior and found preliminary evidence that OXT DNAm at three cytosine-phosphate-guanine (CpG) sites (i.e., GRCh37/hg19 =chr20: 3052,319; chr20: 3052,334; chr20:3052,345) is negatively associated with trust game investments. Associations with prosocial traits or interactions between OXT DNAm and OXT administration on trusting behavior and generosity were not significant. Our results suggest that variation in OXT DNAm is associated with trusting behavior but no (main or moderating) effect of exogenous OXT administration was observed. Importantly, because functional indices of OXT gene expression or endogenous OXT levels were not incorporated into the present analyses, the findings cannot speak to whether DNAm variation translates into measurable differences in oxytocinergic system activity in the brain. Further, our findings highlight the need for future research examining whether, and how, OXT DNAm is related to reward-related processes and their neurobiological underpinnings, including potential interactions between oxytocinergic and other neuromodulatory systems implicated in reward processing (e.g., dopaminergic or serotonergic systems). Future studies should investigate the relationship between OXT DNAm and trust game investments, determine functional consequences on the molecular level, and directly assess whether, and how, OXT DNAm is related to neurobiological processes involved in prosocial, reward-related, behavior.
Dynamic interaction between stress hormones and neutrophils promotes neutrophil extracellular trap formation with behavioral consequences.
Thangamani K, Prece H, Carter J … +5 more , Surendran J, Douglas O, Brengel E, Ferris C, Okeke E
Psychoneuroendocrinology · 2026 Jun · PMID 41894897 · Publisher ↗
Recent studies have highlighted the crosstalk between neuroendocrine responses and the immune system, but the mechanisms underlying this cooperation remain poorly understood. The stress response is associated with periph...
Recent studies have highlighted the crosstalk between neuroendocrine responses and the immune system, but the mechanisms underlying this cooperation remain poorly understood. The stress response is associated with peripheral inflammation suggesting that stress hormones including glucocorticoids and catecholamines modulate the function of innate immune cells like neutrophils. Likewise, inflammatory mediators produced by immune cells are known to contribute to psychiatric diseases like major depressive disorder (MDD). Here we investigated the dynamic relationship between stress hormones and neutrophils and their contribution to mood disorders. We found that chronic restraint stress led to a progressive elevation of plasma corticosterone (∼31.6% at day 14 and ∼46.1% at day 21) and increased neutrophil extracellular traps (NETs), evidenced by ∼60% higher extracellular DNA. Interestingly, the stress hormones, cortisol and epinephrine induced NET formation in human neutrophils ex vivo, with cortisol producing a strong dose-dependent increase (∼5-6-fold). Notably, NET-forming neutrophils upregulated adrenergic and glucocorticoid receptors and produced both cortisol and epinephrine, indicating a feed-forward autocrine/paracrine mechanism. Strikingly, administration of NET components to mice induced depressive-like behavior, resulting in ∼24% reduction in locomotor activity and exploratory behavior. Furthermore, glucocorticoid receptor activation in human volunteers increased gene expression of NET-associated proteins, and patients with MDD showed upregulation of these same genes. Our data highlight the bi-directional relationship between neuroendocrine processes and neutrophils that contribute to stress-induced increase in inflammation and the role of neutrophil inflammatory responses in propagation of behavioral changes following stress.
Metabolic insights into the 3xTg-AD Alzheimer model mice: Unraveling the hypothalamic-pituitary-thyroid axis and beyond.
Szabó A, Farkas S, Kádár A … +10 more , Török B, Fazekas CL, Sipos E, Bánrévi K, Correia P, Chaves T, Kovács T, Penksza V, Fekete C, Zelena D
Psychoneuroendocrinology · 2026 Jun · PMID 41856004 · Publisher ↗
The 3xTg-AD mouse model is widely used to study the pathomechanisms of Alzheimer's disease (AD) and to test potential therapies. During food-motivated cognitive tasks, however, increased food-directed behavior was observ...
The 3xTg-AD mouse model is widely used to study the pathomechanisms of Alzheimer's disease (AD) and to test potential therapies. During food-motivated cognitive tasks, however, increased food-directed behavior was observed in these animals, raising the possibility that metabolic factors may influence task performance. This prompted us to investigate the metabolic background of AD, with a focus on the hypothalamic-pituitary-thyroid (HPT) axis. Testing of food-motivated behavior (single pellet reaching, radial arm maze, staircase, and operant conditioning tests) started at 6 months of age in male mice and confirmed increased motivation for food in 3xTg-AD animals. The molecular background was examined at 8 months of age. Separate cohorts of 4- and 8-month-old male mice underwent metabolic measurements. Transgenic mice showed increased food and water intake, reduced fat mass, elevated lean mass, and a stable respiratory exchange ratio (RER), in contrast to the age-related decline in RER observed in controls. Free T4 levels were higher in 3xTg-AD than control animals, and molecular profiling revealed elevated thyrotropin-releasing hormone (TRH) and thyroid hormone-activating deiodinases DIO1 and DIO2 mRNA, alongside reduced expression of the thyroid hormone receptor beta 2 (THRB2) in the paraventricular nucleus (PVN) and pituitary. Expression levels of key appetite-regulating neuropeptides, including pro-opiomelanocortin (POMC), neuropeptide Y (NPY), cocaine- and amphetamine-regulated transcript (CART), and agouti-related peptide (AgRP) were significantly lower in 3xTg-AD mice. These findings indicate early alterations in energy homeostasis and HPT axis-related signaling in 3xTg-AD mice that may be associated with increased food-seeking behavior. Our data provide evidence for metabolic and neuroendocrine changes that accompany the behavioral phenotype of this model.
Beyond dose: Antipsychotic risk categories and sex-specific vulnerability to hyperprolactinemia in real-world longitudinal care.
Öztürk Yalçın Z, Bayraktar İ, Kaşıkcı M … +4 more , Yalçın N, Özçelik Eroğlu E, Yağcıoğlu AEA, Gürel ŞC
Psychoneuroendocrinology · 2026 Jun · PMID 41856003 · Publisher ↗
BACKGROUND: Antipsychotic-induced hyperprolactinemia is a common and clinically relevant adverse effect that may impair treatment adherence and long-term health outcomes. Although chlorpromazine-equivalent doses (CPZE) a...
BACKGROUND: Antipsychotic-induced hyperprolactinemia is a common and clinically relevant adverse effect that may impair treatment adherence and long-term health outcomes. Although chlorpromazine-equivalent doses (CPZE) are frequently used to standardize antipsychotic exposure, the relative contribution of drug-specific prolactin liability and patient sex in real-world longitudinal settings remains insufficiently characterized. METHODS: We conducted a retrospective longitudinal cohort study including adult patients treated with antipsychotics in inpatient and outpatient psychiatric settings over a ten-year period. Repeated serum prolactin measurements were analyzed using generalized estimating equations to account for within-subject correlations. Antipsychotics were classified into low-, moderate-, and high-risk categories based on established prescribing guidelines. Associations between prolactin levels and sex, antipsychotic risk category, CPZE, therapy type, antidepressant co-treatment, and aripiprazole use were examined. RESULTS: A total of 251 patients (539 prolactin measurements) were included. Female sex and treatment with high-risk antipsychotics were the strongest independent predictors of prolactin elevation. High-risk agents were associated with an average increase of approximately 40 ng/mL in prolactin levels, whereas low-risk agents were associated with significantly lower concentrations. Abnormal prolactin levels (>20 ng/mL in men; >25 ng/mL in women) were observed in 68.4% of men and 78.7% of women. Analyses using binary outcomes (normal vs abnormal prolactin) yielded conclusions consistent with the continuous models, with high-risk antipsychotic exposure significantly increasing the odds of hyperprolactinemia, particularly among women. After adjustment for drug-specific risk, CPZE was not independently associated with prolactin levels. Sex-stratified analyses showed greater susceptibility to hyperprolactinemia among women. Aripiprazole use was not independently associated with lower prolactin levels. CONCLUSION: In this real-world longitudinal cohort, prolactin dysregulation during antipsychotic treatment was driven primarily by drug-specific prolactin risk and biological sex rather than cumulative dose. These findings support a risk-based and sex-informed approach to antipsychotic prescribing and prolactin monitoring, particularly in women treated with high-risk agents.
Personality traits modulate temporal dynamics and cross-system coordination of acute stress responses in virtual reality.
Xu H, Huang J, Gou M … +7 more , Qi S, An H, Tan K, Hu Y, Chen Y, Xu J, Tan S
Psychoneuroendocrinology · 2026 Jun · PMID 41844482 · Publisher ↗
Acute stress is a primary risk factor for mental disorders. While prior virtual reality (VR) studies have utilized objective physiological measures to address biological heterogeneity, the specific temporal evolution and...
Acute stress is a primary risk factor for mental disorders. While prior virtual reality (VR) studies have utilized objective physiological measures to address biological heterogeneity, the specific temporal evolution and cross-system coordination of these responses remain less explored. To address this gap, we developed a multi-scenario virtual reality (VR) stress paradigm, and analyzed personality modulation of stress response dynamics in 44 healthy adults via high-density monitoring (continuous heart rate/heart rate variability/galvanic skin response; 9-timepoint cortisol sampling). The VR paradigm effectively elicited multi-system stress responses that are similar to those observed in the Trier Social Stress Test. Personality traits significantly modulated temporal trajectories (15/28 time × trait interactions p < 0.10) but poorly predicted peak intensity (3/36 regressions significant), suggesting personality primarily influences "how responses evolve" rather than "how strong." Psychoticism and trait anxiety predicted autonomic desynchronization, particularly sympathetic-parasympathetic decoupling during recovery (β = 0.339 h, p = 0.031). These findings advance a paradigm shift from "reactivity" to "regulatory capacity" in stress research, providing a scalable digital tool for individualized stress susceptibility assessment.
Daily discrimination and inflammation patterns among Black and Hispanic adolescents.
Crichlow QJ, Orihuela C, Granger DA … +2 more , Evans R, Mrug S
Psychoneuroendocrinology · 2026 Jun · PMID 41833127 · Publisher ↗
Discrimination has been identified as a potential contributor to health disparities, partly through its role in promoting inflammation, a key biological mechanism in the development of chronic disease. While most researc...
Discrimination has been identified as a potential contributor to health disparities, partly through its role in promoting inflammation, a key biological mechanism in the development of chronic disease. While most research has focused on adults, adolescents also experience racial discrimination, which has been linked to inflammation and later health risks. The present study examined the same-day and next-day relationships between daily racial discrimination and inflammation (i.e., salivary C-Reactive Protein (CRP) and cytokines) in Black and Hispanic adolescents. The sample included 92 adolescents (mean age = 13.07 years; 53.3% female). Participants reported daily discrimination across four days and provided morning and afternoon saliva samples for the measurement of CRP and cytokines (interleukin-6, interleukin-1 beta, and interleukin-8). Multilevel modeling was used to assess whether daily discrimination predicted same-day and next-day levels of inflammation. Results showed that daily discrimination predicted same-day decreases in CRP but was not a predictor of same-day cytokine levels. Additionally, daily discrimination did not predict next-day levels of CRP and was only marginally associated with next-day cytokines. The results suggest that discrimination contributes to daily fluctuations in inflammation levels. Future research should explore the role of protective factors and the long-term consequences of discrimination on adolescent health, which could inform interventions aimed at reducing racial health disparities.
Deconstructing the cortisol awakening response (CAR): Post-peak decline predicts health vulnerability in healthy females.
Smyth N, Thorn L, Flynn M … +2 more , Clow A, Evans P
Psychoneuroendocrinology · 2026 Jun · PMID 41831284 · Publisher ↗
BACKGROUND: The cortisol awakening response (CAR) has two regulatory pathways underlying its components typically not discriminated in CAR studies. The timing of the peak, post-peak secretion and overall levels were asse...
BACKGROUND: The cortisol awakening response (CAR) has two regulatory pathways underlying its components typically not discriminated in CAR studies. The timing of the peak, post-peak secretion and overall levels were assessed in relation to health in this directional hypothesis-driven study. METHOD: Healthy females (N = 61, aged 18-38 years) collected saliva at awakening and three further 15-min intervals over seven consecutive days in their domestic setting. Awakening and saliva sampling times were electronically monitored (EM). Participants provided self-reported sampling times as well as demographics and health status. Analyses were conducted for 56 participants providing full cortisol and health data. Participants were categorised as 'healthy' (N = 34; 61%) or 'less healthy' (N = 22; 39%) based on their self-ratings. RESULTS: Multilevel modelling using 'real time' sampling (EM-estimated) revealed significant cortisol growth curve shape differences between health groups. In comparison to the less healthy group, the healthy group showed lower secretion rates in the final sampling (3rd to 4th) interval with more negative rates (declines) and lower mean cortisol (over 7 study days and 4 samples). The less healthy had more final sample (later) peak cortisol concentrations. Receiver Operating Characteristic (ROC) analyses of CAR composite measures (decline, peak time, and mean levels) were conducted to optimise health status discrimination. Lower third to fourth sample secretion rate was the strongest discriminator, correctly detecting the health status of 71% of all participants. Lower cortisol concentration explained 68% and higher percentage of days with final (fourth) sample peaks explained 61%. Maximum detection was achieved by a combined decision criterion which correctly identified exactly three-quarters (75%) of cases. Findings were robust to known cortisol covariates. CONCLUSION: This novel CAR analysis offers insight into potential health vulnerability in younger healthy populations, perhaps an early indicator of hypothalamic-pituitary-adrenal (HPA) axis dysfunction.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe