Psychoneuroendocrinology [JOURNAL]
Sun
200 papers
The interplay between loneliness, cortisol, and NK cell function: The role of cortisol in NK cell dysfunction.
Saurabh A, Baumer Y, Mendelsohn LG … +26 more , Aquino Peterson EM, Sandler D, Lopez De Leon SJ, Dave A, Baez AS, Ortiz-Whittingham LR, Pita MA, Cintron MA, Tarfa HA, Reynolds ST, Hicks SR, Sharda S, Seo JE, Lopez-Ocasio M, Dagur PK, Kuhn SA, Redekar NR, Troendle JF, Wells AL, Marah M, Tolentino KJ, Corley MJ, Maunakea AK, Nieman LK, Andrews MR, Powell-Wiley TM
Psychoneuroendocrinology · 2026 Jul · PMID 42105644 · Full text
Chronic psychosocial stressors contribute to cardiovascular disease (CVD) and related risk factors, particularly in under-resourced communities. Psychosocial stressors activate the hypothalamic-pituitary-adrenal (HPA) ax...
Chronic psychosocial stressors contribute to cardiovascular disease (CVD) and related risk factors, particularly in under-resourced communities. Psychosocial stressors activate the hypothalamic-pituitary-adrenal (HPA) axis, leading to sustained cortisol action on immune cells. Natural killer (NK) cells are altered in distribution and function in cardio-metabolic diseases; however, pathways linking cortisol as a marker of chronic stress to NK cell dysfunction remain understudied. We recruited 186 African American women from the Step It Up Community-Engaged, Digital Health Physical Activity Intervention study and collected cortisol, NK cell measures, and psychosocial stress measures using validated questionnaires, including chronic stress and loneliness. Plasma cortisol levels were negatively associated with NK cell proportions, and self-reported levels of loneliness modified this relationship (p = 0.011); among participants with higher loneliness, higher plasma cortisol levels were associated with lower proliferative NK cell proportions (β=-0.30, p = 0.04). In a subset of study participants (n = 24), plasma cortisol levels were directly associated with a loss of NK cell degranulation (β=-0.38, p = 0.03). Using an RNA sequencing dataset, we found that higher plasma cortisol levels were associated with suppressed gene expression related to NK cell cytotoxicity. Finally, in vitro experiments on freshly isolated primary NK cells revealed that cortisol reduces NK cell degranulation (p = 0.006) via FABP-4-induced upregulation of PD-1 expression (p = 0.01). In summary, our study provides evidence that in individuals with higher loneliness, cortisol may alter NK cell distribution and function. Furthermore, cortisol-mediated NK cell dysfunction may be facilitated in a FABP-4/PD-1 dependent manner, leading to impaired innate immune function and, potentially, contributing to worsening CVD risk.
Physical disorders and neuroendocrine vulnerability in the development of posttraumatic stress disorder: A 2-year injury cohort study.
Kang HJ, Kim JW, Kim SY … +6 more , Lee JY, Jang H, Kim JC, Kim SW, Shin IS, Kim JM
Psychoneuroendocrinology · 2026 Jul · PMID 42105643 · Publisher ↗
This study examined whether the association between early post-trauma cortisol levels and posttraumatic stress disorder (PTSD) onset is moderated by the burden of preexisting physical disorders (PDs), with attention to e...
This study examined whether the association between early post-trauma cortisol levels and posttraumatic stress disorder (PTSD) onset is moderated by the burden of preexisting physical disorders (PDs), with attention to earlier- versus delayed-onset PTSD. Given evidence that earlier-onset and delayed-onset PTSD may involve distinct temporal and pathophysiological mechanisms, we hypothesized that cortisol and number of PDs would more strongly predict earlier-onset PTSD. Data were drawn from a prospective cohort of 895 adults hospitalized for traumatic injuries. Morning serum cortisol was measured within one month post-trauma. The number of PDs was assessed as a count of affected organ system categories, based on a 15-category system that integrated medical history, treatment records, and self/caregiver reports, without accounting for severity or functional impact. PTSD was evaluated at 3, 6, 12, and 24 months using the CAPS-5, and classified as earlier-onset (≤6 months) or delayed-onset (>6 months). Logistic regression models tested main and interaction effects of cortisol and number of PDs on PTSD onset, controlling for relevant covariates. Neither cortisol nor number of PDs independently predicted PTSD onset. However, lower cortisol predicted earlier-onset PTSD only among individuals with higher number of PDs (adjusted interaction p = 0.021). No association was found in those with lower number of PDs or for delayed-onset PTSD. Cortisol and number of PDs were modestly negatively correlated. number of PDs moderates the association between early post-trauma cortisol and earlier-onset PTSD. These findings highlight a context-dependent biological vulnerability and may help explain prior inconsistencies in cortisol-PTSD research. Integrating somatic health status into early PTSD risk models may improve prediction and prevention strategies.
Pregnancy cortisol and postpartum depression: The moderating role of optimism.
Giles L, Perrot T, Tulipan T … +3 more , Allen VM, Campbell-Yeo M, Khoury JE
Psychoneuroendocrinology · 2026 Jul · PMID 42102515 · Publisher ↗
UNLABELLED: Postpartum depression (PPD) is one of the most common challenges following childbirth. Left unaddressed, PPD can have enduring consequences for both the birthing individual and child. There is a growing empha...
UNLABELLED: Postpartum depression (PPD) is one of the most common challenges following childbirth. Left unaddressed, PPD can have enduring consequences for both the birthing individual and child. There is a growing emphasis on promoting resilience to mitigate PPD. In addition, cortisol, the body's primary stress hormone, plays a central role in pregnancy, and disruptions in its regulation have been implicated in perinatal mood disturbances. This study investigated whether optimism, a resilience resource, moderates the association between prenatal hair cortisol concentration (HCC) and PPD symptoms. METHODS: Participants included 128 individuals, followed from pregnancy to 6 months postpartum. Optimism and HCC were measured during pregnancy, and depression was measured during pregnancy, at 2 weeks postpartum, and 6 months postpartum. The main and interactive effects of HCC and optimism on PPD were assessed using multiple linear regression. RESULTS: Higher optimism during pregnancy was associated with lower PPD symptoms at both 2 weeks and 6 months postpartum. Higher HCC during pregnancy was associated with lower PPD symptoms only at 2 weeks postpartum. A significant optimism×HCC interaction emerged at 6 months postpartum, indicating that the association between HCC and depressive symptoms differed by optimism level. Among individuals with low optimism, lower HCC was associated with greater depressive symptoms, whereas among those with high optimism, HCC showed little relation to depressive symptoms. CONCLUSIONS: Findings underscore the value of integrating psychological and physiological perspectives on perinatal mental health and suggest that optimism may serve as a protective factor against the long-term impact of physiological stress on PPD.
Effects of noradrenergic blockade on emotional working memory and its neural underpinnings: A randomized, double-blind, placebo-controlled trial.
Hempel M, Rosada C, Klockgeter J … +5 more , Lipka R, Metz S, Heekeren H, Grimm S, Wingenfeld K
Psychoneuroendocrinology · 2026 Jul · PMID 42090838 · Publisher ↗
The neurotransmitter noradrenaline (NA) has been previously associated with brain-wide regulatory functions for various cognitive as well as affective processes. Clonidine, an adrenoceptor agonist, predominantly stimulat...
The neurotransmitter noradrenaline (NA) has been previously associated with brain-wide regulatory functions for various cognitive as well as affective processes. Clonidine, an adrenoceptor agonist, predominantly stimulates α2-receptors, reducing NA release. However, the specific effects of clonidine, as well as NA's general impact on neural mechanisms underlying cognitive and affective processing remain incompletely understood. 74 healthy men were included in a double-blind, randomized, parallel-group functional magnetic resonance imaging (fMRI) study with two treatment conditions: single-dose clonidine (0.15 mg) and placebo. The fMRI procedure comprised a 2-back working memory (WM) task with positive, negative and neutral words used as stimuli. No behavioral effects of clonidine on WM performance for emotional or neutral words were observed. Clonidine primarily attenuated neural activation in response to emotional compared to neutral stimuli in the ventromedial prefrontal cortex (vmPFC). In the placebo condition, emotional activation of the vmPFC was negatively correlated with emotional WM accuracy, implying involvement of this region in emotional resource allocation during cognitive processing. Interestingly, no effects of clonidine on valence-specific (positive vs. negative condition) or general WM-related neural activation were found. Our results thus indicate that clonidine modulates neural mechanisms specifically associated with the processing of emotional information and emotional reactivity, suggesting a distinct role for NA in affective functions.
Associations between sedentary behavior and allostatic load: The 1970 British Cohort Study.
Chauntry AJ, Diana JC, Li Q … +16 more , Seeman T, Courtney JB, Tyne WP, Whittaker AC, Turner AI, Teychenne M, Lassalle PP, Zieff G, Gibbs BB, Diaz KM, Puterman E, Lin FC, Kowalsky RJ, Stoner L, Hanson ED, Meyer ML
Psychoneuroendocrinology · 2026 Jul · PMID 42090837 · Full text
BACKGROUND: Chronic/repeated exposure to psychological stressors can induce high allostatic load (AL), or multisystem physiological dysregulation, which increases cardiometabolic disease (CMD) risk. While moderate-to-vig...
BACKGROUND: Chronic/repeated exposure to psychological stressors can induce high allostatic load (AL), or multisystem physiological dysregulation, which increases cardiometabolic disease (CMD) risk. While moderate-to-vigorous physical activity (MVPA) is inversely related to AL, associations with sedentary behavior (SB) remain unclear. This study tested associations between multiple activPAL-derived SB metrics-total SB, SB breaks, and SB bout duration-and AL among middle-aged adults. METHODS: Participants (n = 8581; 46.8 ± 0.7 years; 52% female) represented the 1970 British Cohort Study (2016-2018 sweep), where SB was assessed via activPAL3 accelerometry to derive total SB time (h/day), SB break rate (# sit-to-stand transitions/hr of SB time), and mean SB bout duration (min/bout). Seven AL biomarkers were assessed: inflammatory (C-reactive protein), cardiovascular (systolic blood pressure [BP], diastolic BP, heart rate), and metabolic (HDL, total cholesterol, triglycerides). High AL was defined as ≥ 2 biomarkers in the highest-risk quartile. Cross-sectional logistic regression models tested associations between SB metrics and AL, adjusting for MVPA and other covariates. RESULTS: There were 5% higher odds of high AL per additional hour/day of total SB (OR=1.05; 95% CI: 1.01-1.09). Each additional break/SB hour was associated with 3% lower odds of high AL (OR=0.97; 95% CI: 0.94-0.99). Mean SB bout duration was not significantly associated with AL in fully adjusted models. CONCLUSIONS: Higher total SB and fewer breaks per sedentary hour were associated with greater AL. If longitudinal and experimental studies confirm causality and clinical relevance, reducing total SB time and increasing SB interruptions could be feasible strategies to reduce AL and mitigate stress-induced CMD risk.
Alteration of colonic circadian rhythm by gut microbiota dysbiosis and SCFA reduction links chronic stress-induced depressive-like behavior.
Wang X, Liu R, Lin Y … +1 more , Zhou M
Psychoneuroendocrinology · 2026 Jul · PMID 42090836 · Publisher ↗
BACKGROUND: Chronic stress partially leads to depression through the gut-brain axis, yet the underlying multi-level mechanisms remain unclear. This study aims to delineate the pathway from chronic restraint stress (CRS)...
BACKGROUND: Chronic stress partially leads to depression through the gut-brain axis, yet the underlying multi-level mechanisms remain unclear. This study aims to delineate the pathway from chronic restraint stress (CRS) to depressive-like behaviors, focusing on interactions among gut microbiota, their metabolites, and host transcriptional responses in the colon and hippocampus. METHODS: A CRS mice model was established and validated by behavioral tests. We performed 16S rRNA sequencing of gut microbiota, RNA-sequencing of colon and hippocampal tissues, and integrated these with assessments of intestinal histology, systemic and neuroinflammation, synaptic integrity, and levels of circulating neurotransmitters and microbial metabolites. Data were synthesized using bioinformatics and correlation network analyses. RESULTS: CRS induced significant depressive-like behaviors, hippocampal neuroinflammation, and synaptic damage. Additionally, it resulted in intestinal barrier damage, dysbiosis of the gut microbiota (e.g., an increase in Akkermansia/Dubosiella and a decrease in Ileibacterium), and a general decrease in fecal short-chain fatty acids (SCFAs). Transcriptomic analysis revealed tissue-specific disorders, with the circadian clock pathways in the colon (e.g. Nr1d1 and Nr1d2) being notably altered, while changes in the hippocampus were primarily concentrated on synaptic signaling. Correlation network analysis revealed significant correlations among microbiota alterations, reduced SCFAs, circadian clock gene dysregulation in the colon, systemic inflammation, and hippocampal pathological phenotypes. CONCLUSION: This study supports an integrated association framework linking gut microbiota imbalance, reduced SCFAs, colonic circadian alteration, and depressive-like behavior, and highlights a novel 'gut microbiota-SCFAs-colonic clock' axis associated with stress-related phenotypes. Disruption of this axis is correlated with systemic inflammation and alterations in the hippocampal synaptic gene network, providing a new target for the intervention of stress-related mental disorders.
Telomere trajectories from early adolescence to adulthood following early institutionalization: Protective effects of foster care in the Bucharest Early Intervention Project.
Mens MMJ, Harriman NW, Jopling E … +8 more , Hare M, Drury SS, Roy TR, Hastings WJ, Nelson CA, Zeanah CH, Fox NA, Slopen N
Psychoneuroendocrinology · 2026 Jul · PMID 42068785 · Full text
BACKGROUND: Early institutional rearing is associated with adverse biological and health outcomes in later life, including accelerated cellular aging as measured by telomere length. However, the extent to which foster ca...
BACKGROUND: Early institutional rearing is associated with adverse biological and health outcomes in later life, including accelerated cellular aging as measured by telomere length. However, the extent to which foster care intervention can mitigate these risks, and whether telomere dynamics predict cardiometabolic health in young adulthood remains unclear. OBJECTIVE: The present study aimed to estimate the association between early institutional care, randomization to foster care (intent-to-treat), and longitudinal changes in telomere length from ages 12-22 years among participants of the Bucharest Early Intervention Project (BEIP), and to determine whether the rate of telomere shortening predicts cardiometabolic health in early adulthood. METHODS: The study included 156 BEIP participants who had been randomly assigned to either foster care or care-as-usual, with an additional comparison group of never-institutionalized peers. Buccal DNA was collected, and telomere length (T/S ratio) was measured at two to five timepoints between the ages 12 and 22. Cardiometabolic health at age 22 was assessed using metabolic z-scores and criteria for metabolic syndrome. RESULTS: Participants assigned to foster care exhibited a significantly slower decline in telomere length over the 10-year period compared to those in care-as-usual. Ever-institutionalized and never-institutionalized groups had similar overall patterns of telomere decline. Sex-specific analyses indicated that among the foster care group, males had shorter telomere length at age 12 than females, but rates of telomere shortening were similar between sexes over time. The rate of telomere attrition between ages 12 and 22 was not associated with cardiometabolic outcomes at age 22. CONCLUSION: Foster care intervention during early childhood may protect against telomere shortening among previously institutionalized children, highlighting its role in buffering the long-term impact of early adversity on cellular aging. However, variation in telomere shortening during adolescence and young adulthood did not predict cardiometabolic risk at age 22.
Association of ADHD symptoms with the interactions within and between the HPA axis and melatonin system characterized by hair-based biomarkers.
Yi S, Hou X, Xu G … +4 more , Zhai T, Zhong X, Gao W, Deng H
Psychoneuroendocrinology · 2026 Jul · PMID 42068784 · Publisher ↗
BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is characterized by abnormal functions of neuroendocrine systems with circadian rhythm, especially for the hypothalamic-pituitary-adrenal (HPA) axis and the mel...
BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is characterized by abnormal functions of neuroendocrine systems with circadian rhythm, especially for the hypothalamic-pituitary-adrenal (HPA) axis and the melatonin-N-acetylserotonin (MEL-NAS) system and the interactions within and between them. However, the specific neuroendocrine mechanisms underlying ADHD remain poorly understood. This might be partly due to the clinical heterogeneity of the disorder and the inherent fluctuations of traditional acute biomarkers from biofluids, which fail to reflect long-term physiological homeostasis. METHODS: This study utilized a cross-sectional design and recruited 106 Chinese children with ADHD (age: 6-12 years) diagnosed by physicians according to DSM-IV criteria. Cortisol (F), cortisone (E), melatonin (MEL), and N-acetylserotonin (NAS) in hair and their ratios were employed as the biomarkers of the two systems and the interactions within and between them. The ADHD symptoms were assessed with the SNAP-IV scale that includes inattention, hyperactivity/impulsivity, and oppositional symptoms and filled by children's parents. The 1-cm hair strands closest to the scalp were collected for the analysis of the four hormones with liquid chromatography-tandem mass spectrometry. RESULTS: Oppositional symptoms showed significantly positive association with the MEL/NAS ratio (p < 0.05). After demographic variables and oppositional symptoms were controlled, hyperactivity/impulsivity showed significantly positive association with the F/NAS and E/NAS ratios (ps < 0.05), but it was not observed for inattention. CONCLUSION: The clinical heterogeneity of ADHD core symptoms is underpinned by distinct neuroendocrine network imbalances. There was the function dominance of stress-related signaling over the NAS-mediated neuroprotection underlying the hyperactivity/impulsivity. Additionally, there was a disturbance in circadian metabolic homeostasis underlying the oppositional symptoms.
Unipolar depressed inpatients without comorbid personality disorder exhibit elevated IL-6 levels at admission and a decrease after discharge: A longitudinal study.
Carniel BP, Alexandrino GB, Burin LM … +1 more , da Rocha NS
Psychoneuroendocrinology · 2026 Jul · PMID 42068783 · Publisher ↗
BACKGROUND: One-third of patients with unipolar depression (UD) do not achieve remission after treatment. There is a growing interest in the role of inflammation in the pathogenesis of UD; however, no study has evaluated...
BACKGROUND: One-third of patients with unipolar depression (UD) do not achieve remission after treatment. There is a growing interest in the role of inflammation in the pathogenesis of UD; however, no study has evaluated differences in cytokine levels between patients with UD with and without comorbid personality disorders (PD). We compared cytokine levels (IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10, and IL-17) among inpatients with and without comorbid PD, and healthy controls (HC). METHODS: Longitudinal study with three groups: UD (n = 53), UD+PD (n = 31), and HC (n = 100). Cytokine levels were compared at admission and discharge using one-way ANOVA and Bonferroni post hoc tests. Multiple linear regressions adjusted for potential confounders were conducted. Cytokine levels within each clinical group at admission and discharge were compared using a paired t-test. RESULTS: At admission, IL-6 and IL-17 levels were higher in both UD and UD+PD groups compared to the HC (p < 0.001), while IL-10 levels were higher in the UD group compared to the HC (0.043). IL-6 levels were higher in the UD group than in the UD+PD group (p = 0.039). At discharge, levels of IL-6 (p = 0.002) and IL-17 (p < 0.001) were higher in both clinical groups compared to the HC, with no differences between the UD and UD+PD groups. IL-6 levels were reduced in the UD group at discharge. Depressive symptoms improved in both clinical groups. CONCLUSION: Both clinical groups showed elevated cytokines compared to HC. Patients with UD without comorbid PD had higher IL-6 levels than those with the comorbidity at admission. These findings may have clinical implications for the therapeutic management of these patients, especially in the development of biologically based treatments targeting inflammatory mechanisms.
Effects of stress on brain activation changes: Recent developments.
Henze GI, Pruessner JC
Psychoneuroendocrinology · 2026 Jun · PMID 42066396 · Publisher ↗
Stress engages coordinated psychological, neuroendocrine, autonomic, and neural processes that enable adaptation to environmental demands but may contribute to vulnerability when stress is prolonged, uncontrollable, or s...
Stress engages coordinated psychological, neuroendocrine, autonomic, and neural processes that enable adaptation to environmental demands but may contribute to vulnerability when stress is prolonged, uncontrollable, or socially evaluative. Functional neuroimaging has become central to psychoneuroendocrinology by enabling direct investigation of how acute stress shapes brain activation and connectivity and how these neural responses interact with hypothalamic-pituitary-adrenal axis regulation. This editorial introduces the Special Issue "Effects of stress on brain activation changes: Recent developments" and outlines key conceptual and methodological advances in the field. We highlight progress from endocrine-marker-based stress research toward brain-based models of stress, emphasizing evidence from scanner-based paradigms such as the Montreal Imaging Stress Task and ScanSTRESS, as well as emerging multimodal approaches including fNIRS, PET, EEG, and harmonized large-scale analyses. We discuss recent developments concerning exposure-time effects, network-level models of stress processing, and the importance of functional connectivity. We further emphasize the need to account for individual and contextual variability, including sex, gender, developmental stage, clinical vulnerability, and real-world stress relevance. This Special Issue invites contributions that use neuroimaging to advance mechanistic, translational, and reproducible models of stress-related brain function.
Effects of sex, pubertal stage, and pubertal hormones on frontal and limbic responses to fearful and happy faces during early adolescence.
Qian Y, Swartz JR, Barendse MEA … +5 more , Taylor SL, Fine JR, Ruttle PL, Shirtcliff EA, Guyer AE
Psychoneuroendocrinology · 2026 Jun · PMID 42061116 · Full text
Adolescence is a key stage of brain development marked by heightened emotional reactivity, with variability across individuals and sexes. Puberty onset also initiates a cascade of changes that influence how the brain res...
Adolescence is a key stage of brain development marked by heightened emotional reactivity, with variability across individuals and sexes. Puberty onset also initiates a cascade of changes that influence how the brain responds to social-emotional information. To more fully characterize the role of sex and puberty in the brain's response to social-emotional cues during early adolescence, we tested the main and interactive effects of sex, pubertal stage, and pubertal hormone levels on neural activation to negative and positive facial expressions. Combining baseline and 2-year follow-up data from the Adolescent Brain Cognitive Development study (N = 13,182 observations at two timepoints; 53% male; ages 9-13), we examined neural activation to fearful and happy faces (vs. neutral faces) in the amygdala, anterior cingulate cortex (ACC), ventrolateral prefrontal cortex, ventromedial prefrontal cortex, and dorsolateral prefrontal cortex engaged during an emotional n-back fMRI task. Pubertal development was assessed via parent-report of the child's pubertal stage and salivary hormone levels additionally indexed maturational changes from puberty beyond stage-based milestone achievements. A significant pubertal stage × estradiol interaction was found on ACC activation to happy faces among girls, indicating that estradiol level was positively associated with ACC activation in prepubertal girls but negatively in late-pubertal girls. No significant main effects of sex, puberty stage or hormone levels, or any other interactions withstood multiple comparison correction. These findings suggest estradiol's effects on neural processing of positive social-emotional cues change across puberty among girls and may signify hormone-related shifts from emotional reactivity to regulation in the brain.
The neuro-immune gap in systemic autoimmunity: Integrated dysregulation of the HPA axis and autonomic flexibility in SLE and Sjögren's syndrome.
Uçar C, İnanç E, Dişli F … +2 more , Yolbaş S, Yıldız S
Psychoneuroendocrinology · 2026 Jun · PMID 42035732 · Publisher ↗
BACKGROUND: While systemic inflammation is the hallmark of Systemic Lupus Erythematosus (SLE) and Sjögren's Syndrome (SS), the failure of endogenous "anti-inflammatory brakes" remains poorly understood. The Hypothalamic-...
BACKGROUND: While systemic inflammation is the hallmark of Systemic Lupus Erythematosus (SLE) and Sjögren's Syndrome (SS), the failure of endogenous "anti-inflammatory brakes" remains poorly understood. The Hypothalamic-Pituitary-Adrenal (HPA) axis and the Autonomic Nervous System (ANS) constitute the body's primary neuro-immune regulatory circuit. This study investigates whether concurrent dysregulation of these two systems contributes to the persistent inflammatory state in SLE and SS. METHODS: In this cross-sectional study, we evaluated 40 patients with Systemic Lupus Erythematosus (SLE), 40 with Sjögren's Syndrome (SS), and 32 age- and sex-matched healthy controls. Cardiac autonomic modulation was quantified via Heart Rate Variability (HRV) analysis using short-term (5-minute) ECG recordings. The dynamic activity of the hypothalamic-pituitary-adrenal (HPA) axis was mapped through the Cortisol Awakening Response (CAR), utilizing salivary samples collected at four precise time points (awakening, +30 min, +60 min, and bedtime) and analyzed via ELISA. To ensure protocol reliability, only samples from participants with verified spontaneous awakening were included. Systemic inflammation was assessed through hemogram parameters and serum C-reactive protein (CRP, mg/dL) levels. RESULTS: Our data reveal a distinctive neuroendocrine-immune signature in both disorders. Both SLE and SS patients exhibited a significantly blunted CAR at 60 min (p < 0.05), suggesting a failure in the "anticipatory" stress response. Autonomic profiling showed widespread impairment in SDNN and Total Power (p < 0.05) across both groups. Notably, we identified a phenotypic divergence: SLE patients demonstrated a specific impairment in parasympathetic "vagal tone" (RMSSD and HF), whereas SS patients were characterized by a unique leukocyte and neutrophil depletion (p < 0.05). This suggests that while HPA hyporesponsiveness is a shared trait, the autonomic-immune coupling may follow disease-specific pathways. CONCLUSIONS: This study provides compelling evidence of interrelated regulatory alterations in the neuro-immune axis of SLE and SS patients. The combination of diminished cortisol signaling and impaired vagal modulation creates a "permissive environment" for chronic inflammation. By demonstrating that the degree of HPA suppression correlates with autonomic rigidity, we propose a new theoretical framework: systemic autoimmunity is not merely an immune defect but a dysregulation of the neuroendocrine-autonomic homeostatic loop. Targeting this "stress-axis" could provide a novel bio-behavioral window for therapeutic intervention and disease monitoring.
Observed positive support and cortisol reactivity/recovery among heterosexual cisgender and sexually and gender diverse couples.
Jacmin-Park S, Bőthe B, Juster RP … +1 more , Bergeron S
Psychoneuroendocrinology · 2026 Jun · PMID 42035731 · Publisher ↗
Positive romantic relationships are linked to physical health via stress buffering. Although a growing number of studies have found that couple interactions before or after the Trier Social Stress Test (TSST) modulate co...
Positive romantic relationships are linked to physical health via stress buffering. Although a growing number of studies have found that couple interactions before or after the Trier Social Stress Test (TSST) modulate cortisol reactivity and recovery in the stress-exposed individual, gaps remain concerning dyadic, cross-partner associations and specific positive support behaviors that could explain this buffering effect. Additionally, while sex assigned at birth, sociocultural gender, and sexual orientation have been shown to modulate stress reactive cortisol, such studies have not included sexual/gender diverse (SGD) couples. Therefore, the goal of this study was to examine dyadic associations between positive support behaviors and cortisol secretion among diverse couples. One hundred eighteen couples (51 SGD couples) took part in a two-hour laboratory protocol. One partner underwent the TSST and the other acted as a support during filmed discussions assessed by external coders using the Social Support Global Interaction Coding System's positive support dimensions (SCIS; problem description, emotional expression, attentiveness and listening, validation and emotional support, behavioral involvement, and interactional synchrony). Both partners provided seven saliva samples and completed sociodemographic measures. Multivariate analysis of variance and an independent sample t-test showed SGD partners displayed more behavioral involvement, and SGD couples displayed more interactional synchrony than their heterosexual cisgender (HC) counterparts. Path analyses based on the Actor-Partner Interdependence Moderation Model (APIMoM) showed within- and cross-partner associations between positive support behaviors and cortisol output and recovery among all couples. SGD stressed partners benefited from their own emotional expression during stress recovery, whereas HC stressed partners' display of attentiveness and listening was associated with their own delayed stress recovery. Findings suggest SGD couples may display more positive support behaviors than HC couples when facing stress. This study extends past research suggesting partner support can modulate reactivity and recovery by identifying specific support behaviors that relate to cortisol secretion among diverse couples.
Stress responses and habituation across biological systems: The role of trait and state resilience.
Barthel MC, Muehlhan M, Alexander N … +1 more , Vogel S
Psychoneuroendocrinology · 2026 Jun · PMID 42030692 · Publisher ↗
BACKGROUND: Resilience is assumed to shape how individuals respond and adapt to stress, potentially through mechanisms such as habituation to repeated exposure. However, few studies have tested links between self-reporte...
BACKGROUND: Resilience is assumed to shape how individuals respond and adapt to stress, potentially through mechanisms such as habituation to repeated exposure. However, few studies have tested links between self-reported resilience and biological stress regulation in a multisystem framework. Here, we tested whether resilience predicts stress reactivity and habituation across endocrine, autonomic, and subjective domains, and cumulative HPA-axis output. METHODS: Healthy adults (N = 120) underwent the Trier Social Stress Test (TSST) twice, one week apart. Stress reactivity and habituation were assessed repeatedly via salivary cortisol, salivary alpha-amylase (sAA), cardiovascular measures, and self-reports. Hair cortisol and cortisone were measured once to index cumulative HPA-axis output. Resilience was assessed using the Connor-Davidson Resilience Scale 25, Resilience Scale 25, and the State and Trait Assessment of Resilience Scale. RESULTS: The TSST reliably induced stress across all markers. HPA-axis and cardiovascular markers showed reduced responses on Day 2, consistent with habituation, whereas sAA showed no habituation. Trait resilience scales consistently predicted nominally significant reductions in subjective stress reactivity on Day 1 but were not significantly associated with habituation or cumulative HPA-axis output. State resilience remained stable across sessions and was unrelated to stress markers. CONCLUSION: Despite interindividual variability in stress reactivity and habituation, we found no evidence that self-reported resilience is associated with biological stress measures. While higher resilience may buffer subjective stress responses to novel psychosocial challenges, no corresponding associations with biological stress adaptation were observed. This pattern challenges assumptions about the relationship between resilience and physiological stress adaptation, underscoring conceptual and methodological challenges when delineating the biological correlates of resilience.
Investigating the association of a selected inflammatory protein panel with suicide attempts in the PsyCourse Study: A pilot study.
Oraki Kohshour M, Budde M, Solomon P … +20 more , Adorjan K, Heilbronner M, Navarro-Flores A, Reich-Erkelenz D, Schulte EC, Senner F, Arolt V, Baune BT, Dannlowski U, Fallgatter AJ, Figge C, Juckel G, Reininghaus EZ, Schmauß M, Wiltfang J, Falkai P, Poschmann J, Papiol S, Heilbronner U, Schulze TG
Psychoneuroendocrinology · 2026 Jun · PMID 42030691 · Publisher ↗
Suicide is a significant global public health issue and expected to contribute increasingly to the global burden of disease over the coming decades. Suicide attempts are much more common than completed suicides and repre...
Suicide is a significant global public health issue and expected to contribute increasingly to the global burden of disease over the coming decades. Suicide attempts are much more common than completed suicides and represent a major risk factor for and predictor of suicide. Increasing evidence links suicidal behavior to neuroinflammation, i.e., inflammatory processes in the brain. Therefore, in a subsample (n = 155) of the PsyCourse Study we investigated whether the circulating levels of 12 inflammatory proteins from the Olink® Explore 384 Inflammation Panel are associated with suicide attempts. We found significantly higher interleukin (IL)-1β levels in suicide attempters than in non-suicide attempters. Our finding indicates that the IL-1 signaling pathway plays a critical role in suicidal behavior and suggests that targeting this inflammatory pathway may help prevent suicide. This finding needs to be replicated in a larger sample.
Oxytocin dynamics and synchrony in mother-child dyads: Long-term neuroendocrine effects of maternal institutionalization.
Burenkova OV, Shurdova EM, Manasevich V … +6 more , Norkina M, Pashkina PE, Podturkin AA, Vodneva A, Zhukova MA, Grigorenko EL
Psychoneuroendocrinology · 2026 Jun · PMID 42025392 · Publisher ↗
Early institutional care (IC; orphanage) is a severe form of early psychosocial deprivation with documented long-term effects on social and caregiving functioning. Despite longstanding interest in oxytocin (OT) as a key...
Early institutional care (IC; orphanage) is a severe form of early psychosocial deprivation with documented long-term effects on social and caregiving functioning. Despite longstanding interest in oxytocin (OT) as a key neuroendocrine modulator of affiliative behavior and stress, OT dynamics and synchrony during mother-child interaction among mothers with IC history remain poorly understood. To our knowledge, this is the first study to characterize maternal and child OT responses and dyadic OT covariation in this population. We measured salivary OT in mothers with IC history and mothers raised in biological family care (BFC), and in their children, at baseline and after a structured mother-child interaction. OT response was defined as post-interaction OT after accounting for baseline OT. The sample included 53 mothers (36 BFC; 17 IC) and 44 children (32 BFC; 12 IC). Baseline and post-interaction OT levels did not differ between maternal groups in either dyadic member. However, statistically significant pre-post decline was revealed in BFC mothers but not IC mothers. Maternal OT response differed by maternal IC history: baseline OT predicted OT response among IC mothers but not among BFC mothers, and between-group differences in OT response were detectable primarily at average-to-higher (z ≥ -0.19) baseline OT, with a flatter pattern of baseline-to-post decrease in IC mothers than in BFC mothers at higher baseline OT. After accounting for baseline OT, children of IC mothers had lower post-interaction OT than children of BFC mothers; maternal age and depressive symptoms also contributed to child OT response variability. Dyad-level analyses indexed OT synchrony as correlation-based covariation between maternal and child OT measures and provided suggestive evidence of synchrony in BFC dyads at baseline and for OT response, whereas comparable correlations were not detected in IC dyads; between-group contrasts in these correlation-based indices were not consistently significant. Together, these findings extend IC research into an intergenerational parenting context and identify baseline-dependent maternal OT response and child OT response as candidate targets for replication in larger, multimodal studies integrating behavioral measures and stress physiology.
The influence of endogenous and exogenous sex steroid hormones and social hierarchy on decision-making: A systematic review.
Khosravi S, Kogler L, Derntl B … +1 more , Heysieattalab S
Psychoneuroendocrinology · 2026 Jun · PMID 42025391 · Publisher ↗
PURPOSE: Decision-making is a complex process influenced by factors such as hormone concentration and social hierarchy. This study underlines the intricate interplay between these biological and social factors, emphasizi...
PURPOSE: Decision-making is a complex process influenced by factors such as hormone concentration and social hierarchy. This study underlines the intricate interplay between these biological and social factors, emphasizing the necessity of considering both to comprehend the variability in decision-making processes. METHOD: The present systematic review summarizes and compares included studies that investigate the effect of sex steroid hormones (testosterone, estradiol, and progesterone) on decision-making (risky, uncertain, and social decision-making), and social hierarchy, as well as the effect of hormones and social hierarchy on decision-making. RESULT: The substantial evidence suggests testosterone's influence on decision-making shows gender-related variations. Endogenous testosterone isn't associated with uncertain choices, but both endogenous and exogenous testosterone correlate with riskier decisions, particularly among males. However, a non-negligible proportion of behavioral experiments revealed an inverse or non-significant association. Regarding social decisions, individuals with higher testosterone levels tended to reject unfair offers. Also, testosterone influences competitive behavior and risk-taking, particularly in victory situations. However, social hierarchy and individual traits like dominance and self-construal can moderate these effects. CONCLUSION: Evidence exists that testosterone influences risk-taking behavior and social decision-making, with these influences moderated by social hierarchy and dominance traits, whereas estradiol and progesterone research findings are limited and inconsistent. These results underscore the need for rigorous, sex-balanced research designs and careful consideration of both biological and social context when investigating decision-making.
Endogenous opioid peptides in trichotillomania: An exploratory analysis of focused and automatic hair-pulling subtypes.
Kilic C, Pirdogan Aydin E, Alsaadoni H
Psychoneuroendocrinology · 2026 Jun · PMID 42019415 · Publisher ↗
OBJECTIVE: Trichotillomania (TTM) is a body-focused repetitive behavior disorder characterized by recurrent hair pulling and functional impairment. Emerging evidence suggests that reward- and stress-related neurobiologic...
OBJECTIVE: Trichotillomania (TTM) is a body-focused repetitive behavior disorder characterized by recurrent hair pulling and functional impairment. Emerging evidence suggests that reward- and stress-related neurobiological mechanisms may contribute to its pathophysiology. This study investigated peripheral endogenous opioid peptide levels in TTM and examined differences across hair-pulling subtypes. METHODS: This cross-sectional, case-control study included 45 adults with DSM-5-diagnosed TTM and 45 age- and sex-matched healthy controls. TTM subtypes (focused vs. automatic) were determined through primarily clinical interviews, supported by the Milwaukee Inventory for Subtypes of Trichotillomania-Adult Version (MIST-A; focused n = 27, automatic n = 18). Plasma β-endorphin and met-enkephalin levels were measured by ELISA. Clinical severity was assessed using standardized scales. RESULTS: β-endorphin and met-enkephalin levels were significantly lower in the TTM group compared to healthy controls even after adjusting for depressive and anxiety symptoms. (both p < 0.001). β-Endorphin levels differed across TTM subtypes, with the lowest levels observed in the focused subtype. Focused hair-pulling severity was negatively correlated with β-endorphin levels, whereas automatic hair-pulling severity showed a positive correlation. Exploratory ROC analyses suggested both peptides may have preliminary discriminative value. CONCLUSION: These findings provide the first evidence of reduced peripheral endogenous opioid levels in TTM and suggest subtype-specific differences in opioid system functioning. Alterations in endogenous opioids may be associated with reward- and stress-related mechanisms underlying hair-pulling behavior, particularly in the focused subtype. Further longitudinal and multimodal studies are warranted to clarify the role of opioid signaling in TTM.
Peer victimization, pro-inflammatory, and antiviral gene expression pathways in adolescents.
Giletta M, Michels N, Slavich GM … +1 more , Cole SW
Psychoneuroendocrinology · 2026 Jun · PMID 42019414 · Publisher ↗
BACKGROUND: We examined how peer victimization during adolescence relates to immune-related gene expression activity to identify potential molecular pathways through which victimization may increase long-term health risk...
BACKGROUND: We examined how peer victimization during adolescence relates to immune-related gene expression activity to identify potential molecular pathways through which victimization may increase long-term health risk. METHOD: In 158 Dutch adolescents (12.9-15.6 y; 43.7% girls), we assessed self-reported peer victimization during the first two years of secondary school and collected dried blood spots (DBS) at the end of this period. Peer victimization experiences were reported every 6 months, at 4 time points, and were combined in two indicators: a cumulative victimization index across the 4 assessments and a categorical index distinguishing 'repeated', 'episodic' and 'no' victimization. We examined transcription factor activity for the pro-inflammatory nuclear factor kappa-B (NF-κB) and activator protein-1 (AP-1) signaling, and for the antiviral Interferon Regulatory Factors (IRF), using bioinformatic analyses on genome-wide expression data derived from DBS. Social inhibition and rejection sensitivity were tested as potential moderators. Analyses adjusted for age, gender, ethnicity, smoking, alcohol consumption, body mass index, and recent illness. RESULTS: Contrary to hypotheses, cumulative peer victimization was associated with downregulation of AP-1 but was unrelated to NF-κB and IRF activity. Neither social inhibition nor rejection sensitivity moderated these associations. Additionally, adolescents experiencing episodic victimization showed upregulated NF-κB, downregulated IRF, as well as downregulated AP-1, in comparison to non-victimized peers. No significant differences were found for repeated victimization. In exploratory analyses, proximal peer victimization, assessed concurrently with gene expression, was associated with upregulated NF-κB and AP-1, and strong downregulation of IRF. CONCLUSIONS: These findings provide preliminary evidence that peer victimization, particularly when recent or episodic, is associated with differences in immune-related gene expression in adolescents. Biological embedding of social stress may thus occur early in life and may largely depend on the timing and pattern of exposure.
Sex-dependent salivary microRNA expression profiles and psychophysiological responses to acute stress in healthy adults.
Ravenda S, Gerra MC, Barbetti M … +6 more , Salaris A, Provenzano L, Porciello G, Sgoifo A, Dallabona C, Carnevali L
Psychoneuroendocrinology · 2026 Jun · PMID 42013779 · Publisher ↗
MicroRNAs (miRNAs) have attracted great interest as potential biomarkers in several research domains, including acute and chronic stress conditions. While most of these studies focused on circulating blood miRNA levels,...
MicroRNAs (miRNAs) have attracted great interest as potential biomarkers in several research domains, including acute and chronic stress conditions. While most of these studies focused on circulating blood miRNA levels, the investigation on the feasibility and utility of miRNAs as biomarkers of stress in other biological fluids, such as saliva, has just started. The objective of the present study was to explore changes in the expression levels of candidate salivary miRNAs following acute stress in a sample (n = 111) of healthy participants, and to examine their potential associations with psychophysiological parameters and biological sex. Participants were exposed to an immersive multimodal environment stress test, i.e. the IMVEST protocol, which induced clear psychophysiological stress responses as evidenced by increased subjective perception of stress, elevated cortisol levels, increased heart rate, and reduced heart rate variability. Among the miRNAs that were reliably detectable in all participants, miR-21, miR-25, miR-26b, miR-29a, and miR-200a showed significant changes in their expression levels after stress exposure. Also, significant sex differences in expression levels and/or stress responses were found for miR-21, miR-23a, miR-26b, and miR-29a. These results suggest that these specific miRNAs may represent promising candidate markers associated with stress-related biological responses. On the other hand, other candidate miRNAs (miR-126, miR-144, and miR-183) showed significant changes after stress exposure and/or between sexes, but were detectable only in some participants, thus questioning their utility as reliable salivary biomarkers.
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