Psychoneuroendocrinology [JOURNAL]
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200 papers
Considerations and practical recommendations for identifying perimenopause in longitudinal research.
Huibregtse ME, Taylor L, Prochaska T … +7 more , Arnold AR, Epperson CN, Chahine EB, Smith AK, Powers A, Michopoulos V, Stevens JS
Psychoneuroendocrinology · 2026 Apr · PMID 41576711 · Publisher ↗
Approximately half of the global population will live to experience the menopausal transition, which is associated with significant quality of life concerns and economic costs. Due to research and funding inequities, the...
Approximately half of the global population will live to experience the menopausal transition, which is associated with significant quality of life concerns and economic costs. Due to research and funding inequities, there exist significant gaps in knowledge about the menopausal transition and how to improve health outcomes. One tool that is needed to push women's health research forward is the ability to prospectively and accurately identify reproductive stage throughout the female lifespan. In the current paper we review the current criteria for reproductive staging and historical research methods of determining stage, including retrospective and prospective approaches. We discuss important considerations surrounding recall intervals, limitations of the 2011 Stages of Reproductive Aging Workshop + 10 (STRAW+10) criteria, and data privacy concerns. We provide recommendations for the design and execution of future studies, including digital data processing algorithms that can clearly implement operational definitions of STRAW+ 10 reproductive stages. Standardizing STRAW+ 10 terminology and validating methods to collect, process, and analyze prospectively tracked vaginal bleeding data will facilitate more precise and reliable reproductive staging that are critically needed to increase our understanding of how perimenopause increases risk for adverse health outcomes and develop novel interventions to increase quality of life during reproductive aging.
Stress protection by your group - increasing group size reduces physiological stress contagion.
Dorn T, Auer A, Walther LM … +3 more , Sauter C, Bandle E, Wirtz PH
Psychoneuroendocrinology · 2026 Apr · PMID 41576710 · Publisher ↗
BACKGROUND & OBJECTIVES: Stress contagion refers to the spread of stress from one person to another. We previously established a standardized, controlled experimental paradigm to study stress contagion in humans. While s...
BACKGROUND & OBJECTIVES: Stress contagion refers to the spread of stress from one person to another. We previously established a standardized, controlled experimental paradigm to study stress contagion in humans. While stress contagion effects have been characterized on a physiological level, potential modulating factors are beginning to be understood. Using our paradigm, we tested for the first time whether the number of observers, i.e. observer group size, modulates physiological stress contagion in stress observers. METHODS: Our experimental condition comprised three groups of stress observers varying in group sizes of two ("Group 1", n = 30), three ("Group 2", n = 31), or more observers ("Group 3", n = 31), with each group observing one stressed participant. The data assessment comprised up to 5 healthy young male participants, with one participant randomly assigned to undergo an adapted version of the Trier Social Stress Test ("TSST participants", n = 57) and the remaining participants observing him disguised as panel member(s) ("stress observers", n = 92) in addition to one panel confederate. We repeatedly assessed salivary cortisol, salivary alpha-amylase, and heart rate. RESULTS: The TSST induced significant increases in all physiological parameters under study (p ´ s < =.025) without reactivity differences between TSST participants of the three experimental groups (p ´ s > =.23). When comparing the physiological reactivity to direct stress observation, the stress-observer-groups significantly differed in terms of cortisol (p = .029) with overall higher reactivity in smaller observer groups. Further analyses confirmed a linear effect in terms of higher reactivity with lower observer group size (p = .046). There were no group-by-time interactions in salivary alpha-amylase and heart rate reactivity. DISCUSSION: Our results suggest that when directly observing stress in other individuals, observer group size has a differential effect on physiological stress contagion systems. While we found evidence for modulating effects on hypothalamic-pituitary-adrenal axis reactivity in terms of higher cortisol stress contagion reactivity with lower observer group size, observer group size did not relate to the sympathetic-adrenal-medullary axis. Potential implications remain to be elucidated.
Multicenter comparison of LC-MS/MS, radioimmunoassay, and ELISA for assessment of salivary progesterone and estradiol.
Dlugash G, Rauh M, Carré JM … +4 more , Marcellus A, Plachecki S, Hampson E, Schultheiss OC
Psychoneuroendocrinology · 2026 Apr · PMID 41570522 · Publisher ↗
INTRODUCTION: For psychoneuroendocrinology, accurate measurement of progesterone (P4) and estradiol (E2) in saliva is crucial for understanding the menstrual cycle phase and its impact on physiology and behavior. Althoug...
INTRODUCTION: For psychoneuroendocrinology, accurate measurement of progesterone (P4) and estradiol (E2) in saliva is crucial for understanding the menstrual cycle phase and its impact on physiology and behavior. Although enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA) are the preferred methods and are more often found in research labs, liquid chromatography-mass spectrometry (LC-MS/MS) may provide a more valid salivary steroids assessment. In this study, we aimed to compare the performance of LC-MS/MS, ELISA, and RIA to measure salivary P4 and E2. METHOD: Samples were collected from 120 participants, 81 men and 39 women, in the morning and evening. Additionally, women provided samples during the early follicular (cycle days 3-5) and luteal cycle phases (cycle days 21-23) using the forward-count method. The study considered natural hormone fluctuations (e.g., the diurnal and menstrual cycles) and quality control samples as validity criteria for method evaluation. A total of 336 samples and quality control samples were analyzed using one RIA, two ELISA, and two LC-MS/MS methods across four labs. Correlational analyses were performed to assess inter-lab x inter-method reliability, intra-lab x inter-method reliability, and inter-lab x intra-method reliability. RESULTS: For P4, natural hormone fluctuations in menstrual cycles were detected by all methods. However, in contrast to both LC-MS/MS methods, all immunoassays (IAs) detected an unexpected diurnal decline of P4. For E2, they were found only by LC-MS/MS and RIA. In terms of means, for P4 and E2, ELISA and RIA produced higher values compared to LC-MS/MS. For P4, the inter- and intra-method convergence was r ≥ .92. As for E2, inter-method correlations were between r = -.12 and r = .23, while the ELISA intra-method comparison showed a correlation coefficient of r = .85. DISCUSSION: Our findings suggest that while LC-MS/MS, RIA, and ELISA were capable of meeting most of the specified criteria for P4, only LC-MS/MS and RIA were able to perform similarly sufficiently at low E2 levels. LC-MS/MS provided more accurate and reliable measurements for P4 and E2, especially at low concentrations, but encountered challenges, too. Although RIA showed comparable performance to LC-MS/MS, it still suffered partly from cross-reactivity. ELISA often overestimated hormone levels and exhibited greater divergence. These differences highlight the importance of carefully selecting methods and considering their limitations in research applications.
Chemotherapy-induced estradiol reduction is associated with less relief of pre-chemotherapy anxiety in breast cancer patients.
Del Águila Á, Strehle LD, Yiadom SA … +9 more , Sardesai SD, Williams NO, Gatti-Mays ME, Stover DG, Sudheendra PK, Wesolowski R, Gorka SM, Andridge RR, Pyter LM
Psychoneuroendocrinology · 2026 Apr · PMID 41570521 · Full text
Chemotherapy-induced apoptosis of mature ovarian follicles in breast cancer patients likely results in decreased circulating estradiol (E), although this is rarely measured. Outside of cancer, sudden E reductions (e.g.,...
Chemotherapy-induced apoptosis of mature ovarian follicles in breast cancer patients likely results in decreased circulating estradiol (E), although this is rarely measured. Outside of cancer, sudden E reductions (e.g., post-childbirth) are associated with increased anxiety and depressive symptoms. About half of breast cancer patients undergoing chemotherapy report anxiety and depressive symptoms, which is a major reason for discontinuing or changing chemotherapy treatment. This study examined the relationship between E reductions and anxiety/depressive symptoms, during chemotherapy. As a secondary outcome, intolerance of uncertainty was also assessed. Blood samples and patient-reported questionnaires were collected from 77 breast cancer patients. Plasma E concentrations were quantified using ELISA. Chemotherapy-induced reductions in circulating E were associated with less relief from pre-chemotherapy anxiety symptoms and intolerance of uncertainty during chemotherapy, regardless of age and menopausal status. Conversely, participants whose E concentrations did not decrease experienced relief from pre-chemotherapy anxiety symptoms and intolerance of uncertainty during chemotherapy. Similar trends were observed for depressive symptoms. These findings suggest that monitoring circulating E levels may provide valuable mechanistical insights into patients' psychological responses during chemotherapy and could inform more personalized approaches to supportive care.
Maternal prenatal depression and anxiety and steroid hormones in amniotic fluid.
Seikku T, Lahti-Pulkkinen M, Girchenko P … +9 more , Salo V, Heinonen K, Tukiainen T, Phelan E, Billen M, Simpson JP, Reynolds RM, Homer NZM, Räikkönen K
Psychoneuroendocrinology · 2026 Apr · PMID 41564711 · Publisher ↗
Maternal prenatal depression and anxiety (PDA) have been associated with increased risks of adverse birth and neurodevelopmental outcomes in children. While fetal exposure to too high or low levels of steroid hormones ha...
Maternal prenatal depression and anxiety (PDA) have been associated with increased risks of adverse birth and neurodevelopmental outcomes in children. While fetal exposure to too high or low levels of steroid hormones has been proposed as a potential biological mechanism underlying these effects, few studies have directly investigated this hypothesis using fetal tissue samples, and the existing studies have been limited to examining cortisol, cortisone or testosterone. We studied associations between PDA and steroid hormones in amniotic fluid by measuring a panel of 17 steroid hormones - including progestogens, mineralocorticoids, glucocorticoids, androgens and estrogens - and their substrate-to-product ratios in 173 women with singleton pregnancies undergoing amniocentesis during second trimester. The fetuses had no chromosomal abnormalities. We defined any PDA as meeting at least one of the following criteria: reported symptoms above clinical cut off (CES-D ≥ 20 or STAI state or trait anxiety ≥ 40) during pregnancy, lifetime diagnosis (ICD-10 codes F31-33, F41-43), and/or lifetime medication purchases (ATC-codes N06A, N05B). Elastic net regression identified two glucocorticoid metabolites, 20α-dihydrocortisol and 5β-tetrahydrocortisol, with lower amniotic fluid levels in fetuses of mothers with PDA compared to those without PDA (unadjusted mean difference -0.37 SD units, 95 % CI: [-0.68, -0.07]; and -0.40 SD units, 95 % CI: [-0.70, -0.10], respectively). The model with both steroids remained significant after adjusting for maternal age, body mass index, education, smoking during pregnancy, parity, gestational age at amniocentesis and fetal sex, and in sensitivity analyses excluding mothers with diabetes and hypertensive disorders (p-values < .05) and was not moderated by fetal sex (p-value > .40). PDA was not significantly associated with any substrate-to-product ratios of the steroids, used as proxies of steroid hormone metabolizing enzymes, after correction for multiple testing. This study provides support for the prenatal programming hypothesis of PDA influencing fetal environment through suboptimal levels of steroid hormones and highlights the need to expand to a comprehensive panel of steroid metabolism.
Mixed evidence for stress effects on cortisol-testosterone coupling in Syrian refugee and Jordanian non-refugee adolescents.
Glass DJ, Godwin J, Koehn J … +4 more , Dajani R, Hadfield K, Panter-Brick C, Martin M
Psychoneuroendocrinology · 2026 Apr · PMID 41564710 · Full text
INTRODUCTION: Pubertal development is governed by the HPA and HPG axes. Co-upregulation of the HPA/HPG during adolescence is hypothesized to produce positive cortisol-testosterone coupling to promote developmental demand...
INTRODUCTION: Pubertal development is governed by the HPA and HPG axes. Co-upregulation of the HPA/HPG during adolescence is hypothesized to produce positive cortisol-testosterone coupling to promote developmental demands of puberty, then attenuate post-puberty. However, effects of trauma and poverty-related stress on hormonal coupling are less substantiated. METHODS: We analyzed cross-sectional biological, sociodemographic, and displacement/poverty-related stress data from Syrian refugee and Jordanian non-refugee adolescents living in Northern Jordan (n = 768). We quantified free cortisol and free testosterone from dried bloodspots using mass spectrometry. We used Bayesian hierarchical models to assess the hypothesis that cortisol and testosterone are positively coupled during puberty but de-couple at later stages, and that patterns of hormonal coupling and de-coupling would vary by refugee status and indicators of early life stressors. RESULTS: We report some evidence for the hypothesis that cortisol and testosterone are coupled during pubertal ages 10-19. Positive hormonal coupling was most consistent among Syrian females with relatively higher lifetime trauma, distress/insecurity, household wealth, and mental health and resilience scores and Jordanian males, counterintuitively, with lower lifetime trauma, household wealth, mental health, and resilience scores. CONCLUSIONS: Our study contributes to understanding HPA and HPG patterning and integration across a wide range of adolescent ages among adolescents affected by conflict and poverty related stressors. Our findings offer limited support for the underlying hormonal coupling hypothesis, underscoring how growing bodies may be sensitive to environmental conditions at the extremes and that life history patterning varies with socioecological conditions.
Linking allostatic load, heart rate variability and brain functional networks and structures in healthy men.
Solano-Atehortua JM, Castrillón G, Suarez-Revelo JX … +8 more , Sánchez-López JD, Vargas-Tejada DA, Valentina HC, Calderón JC, Gallo-Villegas J, Ospina-Serrano YV, Caicedo-Jaramillo JD, Miranda-Angulo AL
Psychoneuroendocrinology · 2026 Apr · PMID 41564709 · Publisher ↗
INTRODUCTION: The allostatic load index (ALI) measures the cumulative physiological burden exerted on the body by chronic stress known as allostatic load (AL). The relationship between ALI and heart rate variability (HRV...
INTRODUCTION: The allostatic load index (ALI) measures the cumulative physiological burden exerted on the body by chronic stress known as allostatic load (AL). The relationship between ALI and heart rate variability (HRV), as well as the brain moderation effect on this relationship in healthy individuals, is underexplored. METHODS: In this cross-sectional study of 88 healthy men (21-40 years) from Medellín, Colombia, we calculated two ALIs composed of four and seven biomarkers (ALI-4 and ALI-7) using a quartile-based risk summation method. Functional and structural neuroimaging metrics were derived from magnetic resonance imaging. Multiple linear regression models were used to evaluate the associations between the ALIs and HRV metrics derived from a 24-hour Holter. Exploratory interaction models tested whether the functional connectivity strength (FCS) of default mode (DMN), salience (SN) and control subnetworks (CEN), their cortical thickness as well as the volume of subcortical structures, moderated the ALI-HRV association. RESULTS: ALI-7 was positively associated with the LF/HF ratio (β = 0.09, p = 0.004, 95 % CI = 0.03-0.15). Exploratory interactions suggested that ALI-7's association with the standard deviation of the NN intervals (SDNN) was moderated by the FCS in the posterior DMN and by cortical thickness in the anterior SN. However, none of these interactions remained significant after false discovery rate correction. CONCLUSION: In healthy men, higher ALI was associated with reduced HRV as indicated by higher LF/HF ratio. Larger studies, including women, are needed to confirm the predictive value of ALI-7 and to elucidate the brain moderation effect on the AL-HRV relationship.
C-reactive protein predicts aggression in adolescent depression: Non-suicidal self-injury moderation and immunomodulatory shift.
Han X, Yu X, Hu X … +6 more , Huang H, Zhang G, Chen X, Cha M, Hu L, Liu N
Psychoneuroendocrinology · 2026 Apr · PMID 41558120 · Publisher ↗
Major depressive disorder (MDD) in adolescents is frequently accompanied by aggression and non-suicidal self-injury (NSSI), yet reliable biomarkers for predicting these behavioral risks remain limited. This study employe...
Major depressive disorder (MDD) in adolescents is frequently accompanied by aggression and non-suicidal self-injury (NSSI), yet reliable biomarkers for predicting these behavioral risks remain limited. This study employed a combined cross-sectional and longitudinal design to investigate the role of peripheral inflammatory markers in aggression among 214 adolescent inpatients with MDD and 60 healthy controls. We found that C-reactive protein (CRP) emerged as notable independent predictor of aggressive behavior, showing a high area under the curve (AUC=0.91) in this sample, suggesting its potential discriminatory performance that warrants further validation. Notably, NSSI significantly moderated the CRP-aggression link, with a stronger association observed in patients without NSSI. Furthermore, sex-specific IL-6 elevations were identified in female NSSI⁺ patients. Longitudinal analyses revealed a dynamic "immunomodulatory shift," where systemic immune-inflammation index (SII) and lymphocyte-to-monocyte ratio (LMR) transitioned from positive to negative predictors of aggression over time. These preliminary findings highlight the potential of CRP as a clinically accessible indicator for aggression risk and underscore the temporal complexity of immune-behavior interactions in adolescent depression. These preliminary findings remain to be verified through independent cohorts in future studies.
Receiving caregiver support and its association with hair hormones in people living with Alzheimer's disease: The role of caregivers' perspective taking.
Huo M, Kim K, Brown CK … +2 more , Gilligan M, Wang W
Psychoneuroendocrinology · 2026 Apr · PMID 41547342 · Full text
Receiving support in later life is often experienced as stressful, but for people living with dementia (PLWD) support is an unavoidable necessity for daily functioning. The current study examined the association between...
Receiving support in later life is often experienced as stressful, but for people living with dementia (PLWD) support is an unavoidable necessity for daily functioning. The current study examined the association between receiving support in this unique context and PLWD's hair cortisol, dehydroepiandrosterone (DHEA), and DHEA-to-cortisol ratio, which serve as non-invasive, objective physiological measures that may reflect longer-term HPA-axis activity related to stress. Further, we explored whether caregivers' perspective taking-their ability to understand PLWD's thoughts and feelings-moderated associations between support receipt and hair hormones. Participants included 58 couples managing mild-to-moderate Alzheimer's disease (M = 77.60 for PLWD; M = 75.48 for caregivers). PLWD self-reported the frequency of emotional and practical support received from their spousal caregivers. Hair samples were collected from the posterior vertex to assess cortisol and DHEA concentrations and were assayed using enzyme immunoassay (EIA) method. Caregivers reported their own perspective taking and both spouses' demographic characteristics. Multiple regressions showed that receiving more frequent emotional support and less frequent practical support from spousal caregivers were associated with higher hair cortisol concentrations in PLWD. Yet, these associations were only evident if caregivers had greater perspective taking. In addition, caregiver perspective taking exacerbated the negative association between receiving emotional support and the DHEA-to-cortisol ratio. By using hair hormones, this study offers preliminary insights into PLWD's stress-related physiological processes in the context of intensive caregiving. Findings refine our understanding of the benefits and costs of caregivers' perspective taking and inform caregiver interventions.
Impact of chronic oxytocin on gaze and pupil dynamics during live dyadic interactions in children with autism.
Prinsen J, Daniels N, Moerkerke M … +2 more , Boets B, Alaerts K
Psychoneuroendocrinology · 2026 Apr · PMID 41547341 · Publisher ↗
Reciprocal gaze, the mutual exchange of eye contact, plays a key role in human communication and bonding, yet it is often experienced as challenging for individuals with autism. In recent years, administration of the neu...
Reciprocal gaze, the mutual exchange of eye contact, plays a key role in human communication and bonding, yet it is often experienced as challenging for individuals with autism. In recent years, administration of the neuropeptide oxytocin is increasingly considered a novel approach for supporting social experiences in children with autism, but insights regarding its effects on mutual gaze or pupil dynamics remain limited-particularly regarding how chronic, repeated dosing impacts these processes. This double-blind, randomized, placebo-controlled trial examined the effects of four weeks of chronic intranasal oxytocin administration on gaze behavior and pupil dynamics during live dyadic interactions in school-aged children with autism (aged 8-12 years, 15 oxytocin, 20 placebo). While the overall duration of fixations toward the face remained unchanged, oxytocin altered the distribution of gaze, resulting in a more balanced pattern of looking toward and away from the face of a live interaction partner, an effect observed only in the oxytocin group and not in the placebo group. In addition, the four-week oxytocin administration period induced a relative increase in pupil dilation, an index of sympathetic arousal and attentional engagement, with this heightened autonomic responsivity showing a moderate association with children's self-reported feelings of secure attachment. Together, these findings indicate that repeated oxytocin administration may modulate gaze parameters in live social interactions in children with autism. While cautiously encouraging, future work will be needed to further delineate whether these changes meaningfully reflect ameliorated experience and comfort in social settings.
Trauma exposure, PTSD, and methylation of the blood brain barrier claudin-5 gene.
Wolf EJ, Zhao X, Madison A … +6 more , Carbaugh J, Fortier CB, Milberg WP, Traumatic Stress Brain Research Group, Logue MW, Miller MW
Psychoneuroendocrinology · 2026 Apr · PMID 41547340 · Full text
Posttraumatic stress disorder (PTSD) is associated with early onset of neurological conditions, but the mechanism by which PTSD relates to diseases of the central nervous system is unclear. One possibility is that PTSD p...
Posttraumatic stress disorder (PTSD) is associated with early onset of neurological conditions, but the mechanism by which PTSD relates to diseases of the central nervous system is unclear. One possibility is that PTSD perpetuates breakdown of the blood brain barrier (BBB), allowing for bidirectional passage of molecules across the periphery and central nervous system that promote neuropathology. Preclinical studies have implicated claudin-5 (CLDN5), a protein integral to the integrity of the BBB tight junctions, in the pathogenesis of depression. Based on this, we evaluated if trauma exposure and PTSD related to CLDN5 epigenetics in blood among 1311 trauma-exposed individuals (primarily Veterans) and in the brain tissue from 100 decedents. Three (out of 19) CLDN5 DNA methylation (DNAm) probes, cg00804504, cg17411190, and cg21872764, were significantly associated with trauma exposure or PTSD severity after multiple testing correction in blood. The latter two probes also showed association with PTSD diagnosis in ventromedial prefrontal cortex. The most strongly associated DNAm probe, cg21872764, also evidenced associations with the neuropathology biomarker neurofilament light in plasma. CLDN5 expression was strongly associated with estimated proportion of brain endothelial cells. The cross-sectional associations observed in this study highlight the importance of studying the link between traumatic stress and early onset of neuropathology. Future research is needed to test the mechanistic hypothesis that trauma exposure and chronic PTSD alter CLDN5 DNAm, lead to increased BBB permeability and allow for bidirectional passage of neuroinflammatory molecules across the BBB.
Precommitment promotes healthier food choices under stress.
Forbes PAG, Raio CM, Kalenscher T
Psychoneuroendocrinology · 2026 Apr · PMID 41544323 · Publisher ↗
Stress can result in unhealthier food choices with detrimental consequences for our health. Precommitment is a behavioural strategy whereby individuals restrict their future choice set and can promote healthier food choi...
Stress can result in unhealthier food choices with detrimental consequences for our health. Precommitment is a behavioural strategy whereby individuals restrict their future choice set and can promote healthier food choices - we may forgo buying cake when grocery shopping so we are not tempted to eat it at home. Yet, it is not known whether precommitment can buffer the effects of stress on food choices by providing opportunities to avoid unhealthy food altogether, enabling healthier food choices under stress. To investigate this, we developed a novel 'precommit-to-eat' paradigm which involved two stages. This enabled us to first assess precommitment decisions (precommitment stage) and, subsequently, participants' propensity to select healthier items to eat in a food choice stage (choice stage). Participants (n = 29) who all reported generally trying to eat healthily completed this two-stage paradigm twice - once under acute stress and once in a non-stressful control condition. The propensity to choose unhealthier but tastier food to eat increased with subjective stress, but this effect was counteracted by stress-related increases in precommitment. Thus, our findings show the effectiveness of precommitment under stress. This has important implications for interventions aimed at promoting healthier food choices, especially in stressful environments, that could particularly benefit individuals with lower dietary restraint.
Sex-specific associations between loneliness and hair cortisol among older African American adults.
Knauft K, Rodriguez-Stanley J, Davis KM … +5 more , Rappaport LM, Luca F, Joseph NT, Engeland CG, Zilioli S
Psychoneuroendocrinology · 2026 Apr · PMID 41539174 · Full text
Loneliness has been linked to increased risk of cardiovascular disease, which disproportionately affects African American adults. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, as measured by long-term a...
Loneliness has been linked to increased risk of cardiovascular disease, which disproportionately affects African American adults. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, as measured by long-term accumulation of cortisol in hair, may be one pathway through which loneliness increases cardiovascular disease risk. However, the relationship between loneliness and hair cortisol levels among African American adults has not yet been explored. Further, both loneliness and cortisol activity differ across age and sex. To better understand the association between loneliness and HPA axis activity among middle-aged and older African American adults, the present study examined the degree to which age and sex interacted with loneliness to predict hair cortisol concentrations. Data were obtained from 340 African American adults (M = 66.06, SD = 5.46, range = 55-75; 87.1 % female), who provided hair samples and reported their loneliness level as a part of The Heart of Detroit Study. Results showed that sex significantly moderated the association between loneliness and hair cortisol. Loneliness was positively associated with hair cortisol concentrations in male, but not female, participants. These findings suggest that sex-specific associations may exist between loneliness and hair cortisol.
Personality moderates the predictive value of serum serotonin for antidepressant remission in depressive disorders.
Kim JM, Kang HJ, Kim JW … +4 more , Jhon M, Lee JY, Kim SW, Shin IS
Psychoneuroendocrinology · 2026 Apr · PMID 41539173 · Publisher ↗
Blood-based biomarkers such as peripheral serotonin (5-HT) hold promise for predicting antidepressant response in depression, but findings have been inconsistent. Personality traits linked to serotonergic function may mo...
Blood-based biomarkers such as peripheral serotonin (5-HT) hold promise for predicting antidepressant response in depression, but findings have been inconsistent. Personality traits linked to serotonergic function may moderate this relationship. This study examined whether personality type (PT) moderates the relationship between baseline serum serotonin (s5-HT) levels and antidepressant remission at 12 weeks. In a prospective, naturalistic study, 1086 outpatients with depressive disorders received stepwise pharmacotherapy. PT was classified as resilient or vulnerable using cluster analysis of the Big Five Inventory. Baseline s5-HT was measured and analyzed as both categorical (median split) and continuous variables. Remission was defined as a Hamilton Depression Rating Scale (HAMD) score ≤ 7 at week 12. Logistic regression tested the main and interaction effects of PT and s5-HT, adjusting for covariates. No direct association was found between PT and s5-HT levels. However, higher s5-HT significantly predicted remission only in the resilient group, showing a significant PT × s5-HT interaction. These findings identify personality as a moderator of the relationship between peripheral serotonin and antidepressant response. This biopsychosocial interaction may help explain prior inconsistencies and may provide preliminary insights relevant to individualized care, pending further validation.
Mild hyperthyroidism regulates the acute stress response in virgin female rats.
Neira FJ, Sánchez MB, Pennacchio GE … +6 more , Michel Lara MC, Troncoso ME, Soaje M, Jahn GA, Mackern-Oberti JP, Valdez SR
Psychoneuroendocrinology · 2026 Apr · PMID 41539172 · Publisher ↗
Hyperthyroidism (HyperT) is a thyroid disorder affecting an estimated 0.2-1.3 % of the global population. The clinical implications of this pathology are significant, particularly when considering its close association w...
Hyperthyroidism (HyperT) is a thyroid disorder affecting an estimated 0.2-1.3 % of the global population. The clinical implications of this pathology are significant, particularly when considering its close association with stress-related disorders that impact vulnerable populations, especially women at reproductive age. This study investigated the modulatory role of mild HyperT on the neuroendocrine stress response in virgin female Wistar rats. Two experimental groups were evaluated: a group with induced mild hyperthyroidism (HyperT) and a virgin control group (Control), each assessed under basal (non-stress) and acute stress conditions according to the corresponding experimental protocol. We evaluated the hormonal release (corticosterone and progesterone) induced by ether vapor inhalation and restraint stress in both experimental groups. Furthermore, we quantified the gene expression of receptors for glucocorticoids, progesterone, estrogen, and thyroid hormones, as well as the prolactin receptor and its downstream signaling pathway components in the medial basal hypothalamus (MBH) and hippocampus (HpC). Mild HyperT attenuates the ether stress-induced corticosterone release while responses induced by restraint stress were similar to controls. In the MBH, HyperT increased STAT5b and glucocorticoid receptor (GR) gene expression, and significantly decreased the progesterone receptor PRB/PRA ratio. In the HpC, HyperT increased the prolactin receptor (PRLR), STAT5b, and specific thyroid receptor isoforms (TRα2, TRβ2). Our findings demonstrate that mild hyperthyroidism differentially modulates the acute stress response depending on the stressor type, and may provide insight into the possible neurochemical mechanisms in key brain regions involved in the regulation of the stress response.
Premenstrual syndrome (PMS) symptom emergence across the cycle in relation to hormonal and psychological components in a community sample.
Casto KV, Stern J
Psychoneuroendocrinology · 2026 Mar · PMID 41538978 · Publisher ↗
For many individuals, the days leading up to menstruation are associated with aversive mood, behavioral, and physical symptoms, a condition known as premenstrual syndrome (PMS). Severe levels of these symptoms can lead t...
For many individuals, the days leading up to menstruation are associated with aversive mood, behavioral, and physical symptoms, a condition known as premenstrual syndrome (PMS). Severe levels of these symptoms can lead to clinical diagnosis of premenstrual dysphoria (PMDD). Although prior research has uncovered important psychological and hormonal predictors of PMS/PMDD symptoms in clinical populations, more research is needed to understand how these factors relate in a subclinical population. A test of the menstrual timing and hormonal links to symptom experience alongside factors related to stress would be advantageous for identifying mechanistic underpinnings of symptom severity, factors that might indicate early risk for clinical diagnosis, as well as subclinical factors affecting people's wellbeing. In a community sample of naturally cycling women (N = 257), we conducted within-subject analyses of PMS symptom reporting and levels of salivary progesterone and cortisol across the cycle and in relation to stress and trait neuroticism. On average, women in this study reported increased PMS symptoms in the days leading up to menstrual onset and decreased symptoms at mid cycle, a pattern that was linked to progesterone levels. Higher levels of experienced stress and trait neuroticism were also positively correlated with PMS symptoms. Yet, main effects for PMS symptom and stress timing across the cycle occurred above and beyond controlling for neuroticism. This research has implications for a broader understanding of the connection between the menstrual cycle and psycho-social experiences as well as risk for clinical psychopathology.
Hair cortisol concentration and adolescent mental health: Insight from the Queensland Twin Adolescent Brain Project.
Finlay S, Suvarna B, Adegboye O … +4 more , Rudd D, McDermott B, van Eijk L, Sarnyai Z
Psychoneuroendocrinology · 2026 Mar · PMID 41534425 · Publisher ↗
INTRODUCTION: Adolescence is a stress-sensitive period for neurodevelopment and mental health, with chronic stress implicated in the onset of psychological disorders. Hair cortisol concentration (HCC) serves as a non-inv...
INTRODUCTION: Adolescence is a stress-sensitive period for neurodevelopment and mental health, with chronic stress implicated in the onset of psychological disorders. Hair cortisol concentration (HCC) serves as a non-invasive biomarker of long-term hypothalamic-pituitary-adrenal (HPA) axis activity, yet its relevance to adolescent mental health remains inconsistently characterised. METHODS: This longitudinal study examined HCC in 302 community-dwelling adolescent twins from Brisbane, Australia, with data collected at two sessions approximately two years apart, following a standardised assessment protocol. Three cm long hair samples were analysed to quantify cumulative stress exposure over three months, and participants completed self-reported measures of depression, anxiety, daily stress, social support, and adverse childhood experiences (ACEs). Linear mixed-effects models and quantile regression were used to examine mean-level and distributional associations between HCC and psychological and environmental variables. RESULTS: Average HCC decreased significantly between sessions, with no main effect of sex, twin zygosity, or pubertal stage. In males, a higher average HCC at the second session was associated with elevated general anxiety, whereas in females, a higher average HCC was linked to higher exposure to severe lifetime stress. No associations were found between average HCC and ACEs. CONCLUSION: These findings suggest that average HCC, reflecting cumulative cortisol secretion over the three months before each assessment, provides a stable measure of long-term cortisol in adolescents, although its associations with psychosocial stressors were limited in this cohort. Rather than functioning as a broadly sensitive biomarker of chronic stress, HCC may capture specific stress-related processes in certain subgroups, and its utility may depend on the type, timing, and chronicity of stress exposure.
Intersectionality, social stress, and biological embedding: Toward intersectional psychoneuroendocrinology.
Cook SH, Mishra AA
Psychoneuroendocrinology · 2026 Mar · PMID 41506053 · Publisher ↗
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Within-person associations between daily ovarian steroid levels and mood-related symptoms in ovulatory and anovulatory early adolescents.
Stumper A, Klusmann H, Peters JR … +1 more , Andersen EH
Psychoneuroendocrinology · 2026 Mar · PMID 41500030 · Full text
BACKGROUND: Accumulating evidence suggests some adult females experience hormone sensitivity, or neurobehavioral sensitivity to normal fluctuations in ovarian steroid hormones, across the menstrual cycle. However, this w...
BACKGROUND: Accumulating evidence suggests some adult females experience hormone sensitivity, or neurobehavioral sensitivity to normal fluctuations in ovarian steroid hormones, across the menstrual cycle. However, this work has yet to be adequately extended to adolescent populations, despite the significant increase in risk for affective disorders among females after menarche. AIMS: The current study aimed to determine whether hormone sensitivity could be observed in a sample of early adolescent females by examining the within-person associations between daily levels of estrone and progesterone metabolites that are marked for urinary excretion (estrone-3glucuronide or E1G and pregnanediol glucuronide or PdG, respectively) and daily mood symptoms across one menstrual cycle. METHOD: The current study assessed mood ratings and collected dried urine strips for analysis of E1G and PdG across one full menstrual cycle (up to 48 days) in a sample of peripubertal female adolescents aged 11-14. Within-person multilevel models, run in the full sample and separately for ovulatory cycles (N = 31) and anovulatory cycles (N = 23), evaluated the associations between E1G and PdG and mood symptoms. RESULTS: In the full sample, E1G was negatively associated with mean total symptom score ((b = -.02, 95 % CI = -0.03 - -0.002), irritability (b = -.003, 95 % CI = -0.06 - -0.001), anhedonia (b = -.03, 95 % CI = -0.05 - -0.01), concentration difficulty (b = -.03, 95 % CI = -0.05 - -0.002), and conflicts (b = -.03, 95 % CI = -0.05 - -0.004). In the ovulatory group, E1G was negatively associated with mean total symptom score (b = -.02, 95 % CI = -0.04 - -0.004), hopelessness (b = -0.02, 95 % CI = -0.04 - -0.001), rejection sensitivity (b = -0.03, 95 % CI = -0.06 - -0.001), irritability (b = -0.05, 95 % CI = -0.09 - -0.01), concentration difficulties (b = -0.03, 95 % CI = -0.06 - -0.01), and overwhelm (b = -0.03, 95 % CI = -0.06 - -0.0001). In the anovulatory group, E1G was associated only with anhedonia (b = -0.05, 95 % CI = -0.10 - -0.01). CONCLUSIONS: These results demonstrate small associations between normal decreases in E1G and mood symptoms across the menstrual cycle in an adolescent sample, though these effects were largely limited to ovulatory cycles. Results highlight the importance of considering ovulation status in this population and differ from the adult literature in important ways that highlight the need for more work on how hormone sensitivity differs between adolescents and adults.
The influence of glucose administration on stress reactivity and long-term memory in adult men and women.
Meier M, Merz CJ, Rüttgens T … +2 more , Wolf OT, Pruessner JC
Psychoneuroendocrinology · 2026 Mar · PMID 41475334 · Publisher ↗
Stress and the associated cortisol release have profound effects on long-term memory (LTM). While glucose increases the cortisol stress response and exhibits memory enhancing effects in non-stressful situations, the inte...
Stress and the associated cortisol release have profound effects on long-term memory (LTM). While glucose increases the cortisol stress response and exhibits memory enhancing effects in non-stressful situations, the interaction of glucose and stress on LTM has rarely been studied. The aim of this study was to investigate whether the glucose-related amplification of the cortisol stress response would enhance LTM formation. Overall, N = 62 healthy, fasted adults (age M = 23.13, SD = 3.02; 54.84 % female) participated. They consumed a drink containing water or glucose and underwent a non-stressful control task or the Trier Social Stress Test with Objects, during which panel members interact with certain objects (central) while leaving others untouched (peripheral). At the estimated cortisol peak, they encoded a wordlist. On the next day, they retrieved the objects and the words. We repeatedly assessed subjective stress, salivary cortisol and blood glucose concentrations and recorded an electrocardiogram. Glucose increased blood glucose concentrations, and the stressor led to a significant increase in cortisol as compared with the control task. Changes in cortisol were more pronounced in the glucose as compared with the water groups. Heart rate was elevated in the glucose as compared with the water groups during the recovery. Central objects were better remembered than peripheral objects when encoded during stress. Additionally, emotional words were remembered better as compared with neutral words. These effects were not modulated by glucose. These findings suggest that emotional information is remembered better than neutral information independent of stress and glucose intake. Stress enhances LTM of stressor-relevant information and glucose intake increases the cortisol stress response. However, these factors do not appear to interact. Glucose availability may thus play a less decisive role when memorizing a stressful episode.
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