Psychoneuroendocrinology [JOURNAL]
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200 papers
First-generation college student status and minoritized race and ethnicity: Intersectional predictors of life stress exposure and lab-based cortisol reactivity.
Ponder DM, Vrshek-Schallhorn S, Crayton CB … +4 more , Cupito AM, Livas G, Jensen M, Fletcher A
Psychoneuroendocrinology · 2026 Feb · PMID 41242092 · Publisher ↗
Theory and evidence link first-generation college students and minoritized race/ethnicity with heightened life stress exposure and potentially alterations in biological stress reactivity as adversity gets "under the skin...
Theory and evidence link first-generation college students and minoritized race/ethnicity with heightened life stress exposure and potentially alterations in biological stress reactivity as adversity gets "under the skin," but more evidence and statistical tools are needed to understand how multiple minoritized identities influence health. In 171 emerging adults, we tested hypotheses that these intersecting identities increase life stress exposure, measured with the UCLA Life Stress Interview; we also probe properties of four statistical approaches to modeling intersectional identities' influence. In a subset of n = 150, growth curve modeling tested the hypothesis that more minoritized identities intensify discrimination's effect on blunted cortisol reactivity to an explicit negative evaluative variant (n = 77) versus a control variant (n = 73) of the Trier Social Stress Test. Results link both minoritized identities with elevated exposure to non-interpersonal chronic stress (t = 3.85, p < .001), and minoritized race/ethnicity with elevated interpersonal chronic stress (t = 2.743, p = .007). Of the statistical approaches examined, an identity cumulative risk score demonstrated high sensitivity, consistent with developmental research. Finally, cumulative minoritized identities moderated the relationship between self-reported discrimination and cortisol reactivity to negative evaluative lab-based stress (t = 2.12, p = 0.035), driven by a significant discrimination and cortisol blunting association in those with both minoritized identities. Taken together, we provide evidence to support modeling intersectional identities as a cumulative risk score with post-hoc tests, and evidence that first-generation student status and minoritized race/ethnicity cumulatively heighten stress exposure and intensify the effect of discrimination on a maladaptive marker of stress-responding.
Corrigendum to "Posttraumatic stress disorder and epigenetic signatures of inflammation in middle-aged women" [Psychoneuroendocrinology 182 (2025) 107654].
Liu J, Ratanatharathorn A, Yaskolka Meir A … +10 more , Murchland AR, Zhu Y, Roberts AL, Lawn RB, Sumner JA, Haneuse S, Liang L, Kubzansky LD, Koenen KC, Chibnik LB
Psychoneuroendocrinology · 2026 Feb · PMID 41240613 · Full text
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High sensitivity C-reactive protein in response to acute stress in healthy men and women.
Lennartsson AK, Jonsdottir IH
Psychoneuroendocrinology · 2026 Feb · PMID 41240612 · Publisher ↗
BACKGROUND: Psychosocial stress has been suggested to contribute to low-grade inflammation, which in turn can, if persisting, increase the risk of developing a wide range of chronic disorders. The aim of this study was t...
BACKGROUND: Psychosocial stress has been suggested to contribute to low-grade inflammation, which in turn can, if persisting, increase the risk of developing a wide range of chronic disorders. The aim of this study was to investigate the level of CRP in response to acute psychosocial stress in healthy men and women, whether the responses related to general stress activation. Since it is known that CRP level in general is associated with BMI, we also aimed to investigate whether CRP response during acute stress is related to BMI and overweight. METHOD: Thirty men and 19 women, aged 30-50 years (mean age 39 years, SD 5.6 years), were included in the study. The participants underwent the Trier Social Stress Test (TSST), and CRP was measured in serum together with measurements of general stress activation. RESULTS: CRP levels slightly and temporarily increased in response to acute psychosocial stress. CRP response was positively related to the response of ACTH and cortisol. The CRP response was also positively associated with BMI and the overweight individuals exhibited a larger stress-induced CRP increase. CONCLUSION: The results support the idea that stress may contribute to low-grade inflammation, which in turn can constitute one important pathogenic link between stress and adverse health, especially in overweight individuals.
Stress-induced gene regulation in pregnant women: A systematic review and quantitative evidence synthesis.
Wójtowicz-Marzec M, Berendt AM, Zarzycka D … +2 more , Bogucki J, Kocki J
Psychoneuroendocrinology · 2026 Jan · PMID 41232233 · Publisher ↗
BACKGROUND: Prenatal psychosocial stress is linked to adverse maternal-infant outcomes, plausibly via stress-responsive endocrine pathways and epigenetic regulation. We examined associations between prenatal stress and m...
BACKGROUND: Prenatal psychosocial stress is linked to adverse maternal-infant outcomes, plausibly via stress-responsive endocrine pathways and epigenetic regulation. We examined associations between prenatal stress and maternal DNA methylation (DNAm) at key psychoneuroendocrine loci. METHODS: We conducted a PROSPERO-registered (CRD420251058768), PRISMA-aligned systematic review with quantitative evidence synthesis (QES). Searches (2014-2025) identified observational studies and one randomized trial sampling blood and saliva/buccal. Effects were standardized as Hedges' g and pooled with random-effects only for like-for-like subsets (k ≥ 2). Dependence was handled with multilevel models and robust variance estimation; risk of bias and certainty used ROBINS-I/RoB 2 and GRADE. RESULTS: Findings for NR3C1 exon 1 F were heterogeneous across tissue, timing, and stress domain; outcomes were non-commensurable, so no single pooled estimate was computed. For FKBP5, intron 7 (k = 2) showed lower DNAm with greater trauma/PTSD burden (SMD = -0.36, 95 % CI -0.67 to -0.05; I² ≈ 0 %). Single-study contrasts suggested higher DNAm at intron 2 and lower DNAm at intron 5 with depressive symptoms. For OXTR (DNAm/mRNA), only single-study results were comparable; signals varied by phenotype/genotype. Absolute DNAm differences were typically < 1-3 %. Overall certainty was low to very low. CONCLUSIONS: Prenatal stress is associated with detectable yet context-dependent epigenetic variation in peripheral tissues. No single CpG or region is ready for clinical use. Progress requires region- and tissue-matched replication, harmonized stress phenotyping with cell-type adjustment, and meta-analysis-friendly, open reporting.
Cortisol, stress, and cognition in military subpopulations: A systematic review and meta-analysis.
Crabb KE, Clay M, Pham U … +2 more , Chinn LK, Grigorenko EL
Psychoneuroendocrinology · 2026 Jan · PMID 41232232 · Publisher ↗
This systematic review and meta-analysis investigated the role of cortisol in the relationship between acute stress and cognitive performance in military subpopulations. Given the high operational demands placed on milit...
This systematic review and meta-analysis investigated the role of cortisol in the relationship between acute stress and cognitive performance in military subpopulations. Given the high operational demands placed on military personnel, understanding the neurobiological mechanisms that support or impair cognition under stress may provide critical insight into managing the effects of this relationship. A comprehensive literature search identified 18 studies (n = 572) assessing cortisol levels and cognitive performance in military personnel exposed to acute stressors. Cortisol was not a consistent moderator of stress-related cognitive changes in military personnel, highlighting the complexity of neuroendocrine influences on cognition in general, and in this subpopulation in particular. Findings suggest that cognitive domain and methodological characteristics meaningfully shape outcomes.
Diurnal cortisol trajectories from mid-pregnancy to one year after birth.
van Kessel B, Rinne GR, Okun ML … +3 more , Coussons-Read M, Dunkel Schetter C, Ross KM
Psychoneuroendocrinology · 2026 Jan · PMID 41223680 · Full text
BACKGROUND: The hypothalamic-pituitary-adrenal (HPA) axis is involved in the regulation of pregnancy and postpartum recovery. Diurnal cortisol indices, specifically cortisol awakening response (CAR), area under the curve...
BACKGROUND: The hypothalamic-pituitary-adrenal (HPA) axis is involved in the regulation of pregnancy and postpartum recovery. Diurnal cortisol indices, specifically cortisol awakening response (CAR), area under the curve (AUCg), and slope, are ways to study HPA axis activity. Whether these indices show within-person changes during the perinatal period is not clear, nor do we know how maternal sociodemographic, health, or prenatal medical conditions are associated with within-person diurnal cortisol index trajectories. The purpose of this study is to investigate within-person changes in three diurnal cortisol indices from mid-pregnancy to one year postpartum, and test whether sociodemographic, pregnancy, or health factors moderate these changes. METHODS: A sample of 172 pregnant women provided saliva samples at six time points from mid-pregnancy to one year after birth. At each time point, they provided samples on two days (wake, 30 + wake, noon, pm). The samples were assayed for cortisol. CAR, slope and AUCg indices were calculated. Piecewise growth curve models tested for within-person changes during pregnancy and postpartum on each index with sociodemographic, pregnancy and health variables included in the models. RESULTS: Within-person trajectories were observed only for AUCg during pregnancy, linear: b = -0.51, p = .012; quadratic: b = -0.45, p = .009, such that AUCg increased from mid to late pregnancy. No significant within-person changes in CAR or slope were observed in pregnancy or after birth. Hispanic women demonstrated increasing CAR in the postpartum year, whereas the opposite was observed for non-Hispanic women. Longer gestation was associated with increasing AUCg after birth. CONCLUSION: AUCg increased from mid-to-late pregnancy, consistent with prior research. Maternal ethnicity and gestational length moderated diurnal cortisol index trajectories during the postpartum period only.
Hippocampal prolactin receptor long-form signaling contributes to prenatal stress-induced depression-like behavior.
Yao D, Li J, Lu Y … +7 more , Sun A, Pang X, Yi Q, Zhu Z, Song D, Lu Y, Li H
Psychoneuroendocrinology · 2026 Jan · PMID 41223679 · Publisher ↗
Prenatal stress (PS) is a well-established risk factor for depression-like behaviors in adolescent offspring. The prolactin receptor long-form (PRLR-LF), which has been implicated in depression pathogenesis, activates th...
Prenatal stress (PS) is a well-established risk factor for depression-like behaviors in adolescent offspring. The prolactin receptor long-form (PRLR-LF), which has been implicated in depression pathogenesis, activates the downstream Janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) signaling cascade. Immunoprecipitation assays demonstrated that nuclear STAT5 physically interacts with the glucocorticoid receptor (GR), forming a transcriptional repressor complex that attenuates GR-dependent gene expression. Given the critical role of hippocampal GR in stress responses and depression, we hypothesized that the PRLR-LF-JAK2/STAT5-GR pathway in the hippocampus mediates depression-like behavior in prenatally stressed offspring. We established a prenatal restraint stress model and assessed depression-like behavior using sucrose preference and forced swim tests. To establish causality, we genetically modulated PRLR-LF expression through hippocampal microinjection of AAV-mediated overexpression or knockdown constructs in 21-day-old offspring. The results show that PS significantly upregulated hippocampal PRLR-LF expression and JAK2/STAT5 phosphorylation while downregulating GR expression and nuclear translocation--effects observed exclusively in female offspring. PRLR-LF knockdown in PS-exposed females attenuated depression-like behavior, normalizing JAK2/STAT5 activation and GR dysfunction. Conversely, PRLR-LF overexpression in control females induced depression-like behavior and replicated GR suppression in the hippocampus. These results demonstrate that the hippocampal PRLR-LF-JAK2/STAT5-GR pathway drives sex-specific vulnerability to PS-induced depression in adolescent offspring, offering a mechanistic target for therapeutic intervention.
Glucocorticoid metabolism: A scientific lifetime in and beyond psychoneuroendocrinology.
Seckl J
Psychoneuroendocrinology · 2026 Jan · PMID 41223678 · Publisher ↗
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Allostatic load and biological aging among middle aged adults.
Teferi HM, Shelton RC, Conneely KN … +7 more , De Vivo I, Factor-Litvak P, Kezios KL, Cirillo PM, Cohn BA, Link BG, Suglia SF
Psychoneuroendocrinology · 2026 Jan · PMID 41223677 · Publisher ↗
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Early life adversity and physical health implications in adulthood: The Multi-Ethnic Study of Atherosclerosis.
Merkin SS, Sheridan MA, Markovic D … +2 more , Sachs BC, Seeman TE
Psychoneuroendocrinology · 2026 Jan · PMID 41218336 · Publisher ↗
INTRODUCTION: Several biological processes have been implicated in explaining the association between exposure to early life adversity (ELA) and poor health outcomes later in life, but most studies have classified ELA in...
INTRODUCTION: Several biological processes have been implicated in explaining the association between exposure to early life adversity (ELA) and poor health outcomes later in life, but most studies have classified ELA in terms of a simple count of adverse childhood events (ACEs). Few studies have also considered how race/ethnicity might modify these associations. OBJECTIVES: To determine to what extent different dimensions of ELA (threat and deprivation) influence cardiometabolic and inflammatory dysregulation in adulthood by race/ethnic groups. METHODS: Participants in MESA, ages 45-84, were recruited from 2000 to 2002. Information regarding ELA was collected at the 2020 follow up call. Measures of inflammation (C-Reactive Protein, CRP) and cardiometabolic dysfunction (index of risk and prevalence of metabolic syndrome) were assessed at the MESA baseline exam (mid- to later life for participants); cardiovascular disease events were ascertained throughout the 20 year follow-up period. Logistic and linear regression models were fit for the relevant outcomes and adjusted for age, sex, nativity, MESA site, parental education, education, income, levels of optimism and pessimism. RESULTS: These findings suggest some modest associations between reported experiences of ELA related to threat and deprivation and elevated CRP, metabolic dysfunction and increased risk of CVD, however these associations varied by type of ELA and by race/ethnic groups. Unexpectedly, we also found some indirect associations between reported types of ELA and lower risk of those same health outcomes. CONCLUSIONS: The inconsistent trends across race/ethnic groups, ELA dimensions and health outcomes highlight the need for a dimensional approach in classifying experiences of ELA, and suggest potential cultural differences in reporting ELA in adulthood.
Associations between mental health indicators and genital immune biomarkers among recent survivors of forced sex: A case-control analysis.
Anderson KM, Stockman JK, Capozzi E … +6 more , Meyers-Pantele SA, Karris MY, Mejia FC, Meyer E, Nasr MA, Ghosh M
Psychoneuroendocrinology · 2026 Jan · PMID 41202393 · Publisher ↗
Sexual violence against women remains pervasive and is associated with HIV risk through sexual violence-related immune dysregulation. We sought to test the associations between mental health indicators and genital immune...
Sexual violence against women remains pervasive and is associated with HIV risk through sexual violence-related immune dysregulation. We sought to test the associations between mental health indicators and genital immune biomarkers among female survivors of recent sexual violence. Data were drawn from a case-control study of women in San Diego, California who had experienced recent forced or consensual vaginal penetration. Successive adjusted linear regressions models with interaction terms were employed to test moderation of the associations between mental health indicators (perceived stress, depression, PTSD symptoms, and resilience) and inflammatory (interleukin [IL]-1α, IL-1β, IL-6, IL-8, tumor necrosis factor-alpha [TNF-α], macrophage inflammatory protein-3α [MIP3α]), anti-inflammatory/anti-HIV (secretory leukocyte protease inhibitor (SLPI), elafin, and human β-defensin 2 [HBD2]) biomarkers, and percent HIV inhibition, by case/control status. Subsequently, stratified or non-stratified regressions were reported. Overall, participants (n = 64) identified as Hispanic (42.1 %), White (34.4 %), and Black (25.0 %), with a median age of 22 (IQR:18-26). Case participants had higher perceived stress, depression, PTSD symptoms, TNF-α, and SLPI. Analyses indicate differential relationships between cases and controls relating to IL1-α, IL-6, and IL-8, overall suggesting dysregulation of the immune response in cases compared to controls. Results point to a mechanism by which HIV/STI risk can increase in recent sexual violence survivors experiencing PTSD symptoms. Responsively, we suggest biological and behavioral intervention to limit lasting impacts of related trauma.
Everyday discrimination frequency, intersectional attributions, and C-reactive Protein for Black midlife women who experience discrimination.
Volpe VV, Mejía-Bradford SC, Collins AN
Psychoneuroendocrinology · 2026 Jan · PMID 41202392 · Publisher ↗
Discrimination is a chronic psychosocial stressor that elevates the inflammation response. If chronically activated, this elevation may contribute to health risks such as cardiovascular disease and obesity among Black wo...
Discrimination is a chronic psychosocial stressor that elevates the inflammation response. If chronically activated, this elevation may contribute to health risks such as cardiovascular disease and obesity among Black women, who disproportionately experience discrimination at the intersection of racism and sexism. We used cross-sectional data from the Study of Women's Health Across the Nation to examine how both discrimination frequency and discrimination attributions (single gender, single race, or the intersection of gender and race) relate to levels of the inflammatory biomarker C-reactive protein (CRP) among Black midlife women (n = 209, M = 52.67). Midlife represents a critical period for the emergence of cardiometabolic disease, making it an important developmental stage for understanding how discrimination shapes inflammation and health. Participants reported experiencing relatively frequent discrimination during one visit of the study. CRP levels were assayed from blood samples. Using the Detroit Area Study Everyday Discrimination Scale, women reported the frequency with which they experienced discrimination and selected all attributions for that experience from a list of potential social identity statuses. From these responses, we derived single-race, single-gender, and intersectional race-and-gender attribution categories. Linear regression analyses revealed that discrimination frequency was not significantly associated with CRP (p = .424). There was no difference in CRP levels between those who made a single race attribution and those who made an intersectional attribution. Black women who made a single attribution to gender had higher CRP levels compared to those who made an intersectional attribution (β =.14, 95 % CI [.21, 7.01], p = .038). Attributions of discrimination to gender but not, at least in some part, to race may increase health risks for Black midlife women if inflammation is chronically elevated. More research on the content of intersectional attributions of discrimination, above and beyond the frequency of exposure, is needed.
The inner dynamics of positive human-animal interactions: Investigating the roles of oxytocin, opioids, dopamine, serotonin and the proteome.
Schmitt O, Truong S, Otten W … +6 more , Volkmann H, Greiner J, Dolezal M, Hummel K, Rocchi A, Rault JL
Psychoneuroendocrinology · 2026 Jan · PMID 41197290 · Publisher ↗
Research on the neuroendocrine basis of positive interactions has predominantly focused on oxytocin (OT), although dopamine (DA) and opioids also play crucial roles. Furthermore, these neurotransmitters are known to inte...
Research on the neuroendocrine basis of positive interactions has predominantly focused on oxytocin (OT), although dopamine (DA) and opioids also play crucial roles. Furthermore, these neurotransmitters are known to interact with each other but have seldom been studied concurrently. In this study, we quantified longitudinal changes in these neurotransmitters using a within-subject, 2 × 2 factorial design by varying human familiarity (familiar versus unfamiliar) and contact type (positive contacts versus ignoring) for 10 min human-pig interaction sessions. We obtained cerebrospinal fluid samples from 10 pigs through a spinal catheter 65 and 5 min before the test and at 10, 30, 60, 120 and 240 min after the start of the test. Samples at various timepoints were analysed for OT, DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), β-endorphin opioids concentrations, and using proteomics to explore novel protein candidates. Additionally, the duration and frequency of physical contacts initiated by the pig toward the human were coded from videos. The test condition (human familiarity × contact type) had a significant effect on the concentration of β-endorphin (F = 4.45; P = 0.04) and 5-HIAA (F = 5.02; P = 0.03), and tended to affect the concentration of OT (F = 3.19; P = 0.08) and DOPAC (F = 3.31; P = 0.07), but pairwise comparisons were not significant or showed complex changes. Specifically, OT was highest when the unfamiliar humans ignored the pig compared to when they delivered positive contacts (t = 3.31; P = 0.008), and β-endorphin tended to be higher after interacting with the familiar human compared to the unfamiliar humans (60 min post-test; t = 3.3; P = 0.055). There were only minor differences in the pigs' behaviour, suggesting that pigs seemed to perceive all test conditions as positive. Nevertheless, β-endorphin and OT appear to relate to different aspects of the interactions, possibly familiarity vs. novelty respectively.
Exposure to community violence and cortisol reactivity: An exploratory analysis of the role of coping.
Gresham B, Sackett CE, Karras EI … +1 more , Gunnar MR
Psychoneuroendocrinology · 2026 Jan · PMID 41192238 · Publisher ↗
Research suggests exposure to community violence may "get under the skin" to impact hypothalamic-pituitary-adrenocortical (HPA) axis functioning. Less is known about protective factors, such as coping, that may mitigate...
Research suggests exposure to community violence may "get under the skin" to impact hypothalamic-pituitary-adrenocortical (HPA) axis functioning. Less is known about protective factors, such as coping, that may mitigate the risk conferred by exposure to violence (ETV) on physiological functioning. A widespread and better understanding of factors influencing the relationship between ETV and negative outcomes is critical to mitigate the enduring effects of community violence exposure. Thus, we investigated 1) the association between ETV and HPA axis reactivity and 2) whether coping styles moderated this association. We recruited 148 first-generation college students aged 18-25 from across the United States. Participants completed self-report questionnaires regarding their demographics, ETV, and coping strategies and completed an online version of the Trier Social Stress Test (i.e., TSST-OL). Multilevel modeling adjusting for peak latency was used to predict cortisol reactivity across the TSST-OL from ETV, coping, and their two-way interactions. There was no direct association between ETV and cortisol reactivity, however, the interaction between ETV and avoidant coping was significant. ETV was associated with larger cortisol responses among those reporting average or high levels of avoidant coping but was not associated with cortisol responding for those reporting low avoidant coping. This exploratory study suggests avoidant coping may amplify the impact of ETV on stress responses to social evaluation among young adults.
Fetal Dehydroepiandrosterone from Hair Samples at Birth Predicts Language Development.
Reimann-Ayiköz M, Preiß J, Reisenberger E … +6 more , Florea C, Angerer M, Schabus M, Roehm D, Schaadt G, Männel C
Psychoneuroendocrinology · 2026 Jan · PMID 41192237 · Publisher ↗
OBJECTIVE: Sex hormones testosterone and estradiol have been related to children's language development. Expanding the focus on dehydroepiandrosterone (DHEA), which has not yet been considered as a biological marker of l...
OBJECTIVE: Sex hormones testosterone and estradiol have been related to children's language development. Expanding the focus on dehydroepiandrosterone (DHEA), which has not yet been considered as a biological marker of language ability, may provide novel insights, as emerging evidence suggests that fetal DHEA plays a critical role in the organization of the neonatal brain, potentially shaping later language development. The present study investigated whether fetal DHEA, compared to fetal testosterone, is associated with infant language development. DESIGN AND METHODS: DHEA and testosterone concentrations were measured in newborn hair strands (n = 63) collected two weeks after birth, capturing fetal long-term hormone secretions during the third trimester of pregnancy. At six months of age, children's language abilities were assessed using the German version of the Bayley Scales of Infant Development. RESULTS: Multiple linear regression analysis revealed fetal DHEA levels to be significantly associated with language abilities at six months of age in boys only, with lower DHEA levels corresponding to higher language scores. Control analyses assessing general cognitive abilities showed no association of fetal DHEA levels with infant cognitive function. Testosterone levels were not associated with language. CONCLUSIONS: The current study identifies fetal DHEA levels extracted from newborn hair samples as a potential biological factor influencing infant language development in boys.
Consummatory deficits in close social reward predict inflammation-induced depressed mood.
Boyle CC, Rahal D, Meinert J … +4 more , Ko V, Olmstead R, Eisenberger NI, Irwin MR
Psychoneuroendocrinology · 2026 Jan · PMID 41192236 · Full text
BACKGROUND: Inflammation is implicated in the etiology of depression, but not all individuals develop mood symptoms when exposed to inflammatory states. Identifying psychological predictors of this vulnerability is criti...
BACKGROUND: Inflammation is implicated in the etiology of depression, but not all individuals develop mood symptoms when exposed to inflammatory states. Identifying psychological predictors of this vulnerability is critical for advancing mechanistic models of depression. Deficits in global reward processing predict risk for depression, but reward processing involves both temporal dimensions (e.g., anticipatory vs. consummatory pleasure) and experiential domains (e.g., social vs. non-social). It remains unknown whether specific aspects of reward experience predict greater affective sensitivity to inflammation. This study examined whether lower in-the-moment and anticipated enjoyment across multiple reward domains in daily life predicted greater increases in depressed mood following an experimental inflammatory challenge. METHODS: Secondary analyses were completed on data from healthy female adults (n = 40; age 25-44) who were enrolled in a double-blind, randomized, placebo-controlled trial in which participants were randomly assigned to receive either low-dose endotoxin (n = 18) or placebo (n = 22) and reported on depressed mood pre- and post-infusion. Prior to the challenge, participants completed a 7-day ecological momentary assessment (EMA) protocol, rating anticipated and in-the-moment enjoyment five times daily across three reward domains: close social interactions, general social interactions, and non-social experiences. RESULTS: Linear mixed models were used to generate person-level estimates of EMA reward ratings. Endotoxin induced increases in depressed mood (p = .001), and this effect was moderated by enjoyment of close social interactions; lower enjoyment was associated with greater depressed mood responses to endotoxin (p = .004). Results were similar when adjusting for baseline levels of depressive symptoms. Enjoyment of general social interactions and non-social rewards, as well as anticipated enjoyment across all reward domains, did not moderate depressed mood responses to the inflammatory challenge (p's > .05). DISCUSSION: These preliminary results suggest that reduced enjoyment of close social interactions uniquely predicts vulnerability to inflammation-induced depressed mood in female adults. Interventions targeting close social relationships and strategies for savoring social experiences may play a critical role in preventing inflammation-related depression.
The relationship between childhood autistic traits and diurnal cortisol activity in adolescence.
Roberts E, Francesconi M, Flouri E
Psychoneuroendocrinology · 2026 Jan · PMID 41176904 · Publisher ↗
BACKGROUND: Autistic adolescents experience higher levels of stress compared to non-autistic adolescents. Chronic stress is associated with dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which can be mea...
BACKGROUND: Autistic adolescents experience higher levels of stress compared to non-autistic adolescents. Chronic stress is associated with dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which can be measured by cortisol levels. Previous studies investigating cortisol activity in autistic adolescents are predominantly cross-sectional, have small sample sizes, exclude females, and include those with a clinical diagnosis of autism. The currently study sought to prospectively examine whether the severity and persistence of autistic traits in childhood is associated with cortisol activity in adolescence in a population-representative cohort. METHODS: Data from 915 participants from the Avon Longitudinal Study of Parents and Children (ALSPAC) were used. Bivariate correlations were calculated between autistic traits (using the Social Communication Disorders Checklist) at ages 8, 11 and 14 years and four cortisol activity indices at age 15 years (diurnal cortisol slope, cortisol awakening response (CAR), total morning cortisol, and daily total cortisol output). Regression analyses investigated the effect of autistic traits on cortisol activity, before and after adjustment for confounders. RESULTS: Being likely autistic (i.e., demonstrating severe and persistent autistic traits across ages 8-14 years) was associated with increased CAR, even after adjustment for confounders. No associations were observed between autistic traits and diurnal cortisol slope, total morning cortisol, or total daily cortisol output. CONCLUSION: The observation that autistic traits are associated with CAR, but not other cortisol activity indicators, suggests this may not reflect a generalised HPA axis dysfunction in autistic youth, but a heightened situational response during periods of transition and increased anticipatory stress.
Sex-dependent behavioral responses and phenotypic traits of Pcsk9 knockout mice in anxiety- and depression-like paradigms.
Nasini S, Barzon B, Tidei S … +4 more , Rossi I, Lupo MG, Ferri N, Comai S
Psychoneuroendocrinology · 2026 Jan · PMID 41176903 · Publisher ↗
Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) regulates plasma LDL cholesterol by promoting the degradation of LDL receptors. Beyond lipid metabolism, PCSK9 has been implicated in neuropsychiatric conditions, inc...
Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) regulates plasma LDL cholesterol by promoting the degradation of LDL receptors. Beyond lipid metabolism, PCSK9 has been implicated in neuropsychiatric conditions, including depression and anxiety, potentially through mechanisms involving inflammation, insulin resistance, and hormonal regulation. This preclinical study investigated the effects of Pcsk9 deficiency on anxiety- and depression-like behaviors in male and female C57BL/6 mice, with additional analysis of corticosterone levels and the estrous cycle in females, taking advantage of the Pcsk9 knock-out (Pcsk9 KO) mouse model. Regardless of sex, Pcsk9 KO mice showed increased anxiety-like behavior, with reduced time and fewer entries into the open arms of the Elevated Plus Maze (p < 0.0001), and less time in the light compartment of the Light-Dark Box Test (p < 0.001). Exploratory behavior was greater in females than in males across genotypes. In the Open Field Test, Pcsk9 KO females traveled shorter distances and at lower speeds than WT females (p < 0.01), while within Pcsk9 KO mice only, males were more active than females (p < 0.05). In both sexes, Pcsk9 KO mice showed increased immobility in the Tail Suspension and Forced Swim Tests (p < 0.05), and elevated grooming in the Splash Test (p < 0.05). Estrous cycle analysis revealed that Pcsk9 KO females spent more time in estrus (p < 0.0001) and less (p = 0.0083) in diestrus than WT females, suggesting altered hormonal regulation. However, corticosterone levels did not significantly differ between groups. These findings indicate that, in a murine model of Pcsk9 deficiency, this loss may associate with sex-dependent emotional dysregulation, thus supporting further preclinical and clinical investigations into its neuropychiatric relevance.
Sex-specific factors and APOEε4 genotype alter functional connectivity at middle age.
Lee BH, McGovern AJ, Lieblich SE … +4 more , Mitchell SV, Yin J, Epp JR, Galea LAM
Psychoneuroendocrinology · 2026 Jan · PMID 41160972 · Publisher ↗
Cognitive aging is influenced by sex and sex-specific factors. Indeed, research has shown that parity (pregnancy and parenthood) uniquely alters biomarkers of brain health in middle age depending on Alzheimer's disease (...
Cognitive aging is influenced by sex and sex-specific factors. Indeed, research has shown that parity (pregnancy and parenthood) uniquely alters biomarkers of brain health in middle age depending on Alzheimer's disease (AD) risk. This study investigated functional connectivity changes and network dynamics at middle age based on parity and APOEε4 genotype, the top genetic risk factor for late-onset sporadic AD risk. Neural activation was assessed in middle-aged wildtype and hAPOEε4 rats that were either nulliparous (0 litters) or primiparous (1 litter), by quantifying expression of the immediate early gene, zif268, across 19 brain regions implicated in memory and AD. Primiparous hAPOEε4 rats exhibited widespread reductions in neural activation, particularly in the dorsal striatum, nucleus accumbens, frontal cortex, and retrosplenial cortex. Network analyses further revealed that primiparous wildtype rats had the most cohesive and efficient functional connectivity networks. Activation of hippocampal new neurons in conjunction with the dorsal striatum, frontal cortex, and retrosplenial cortex dynamically predicted cognitive performance depending on parity and hAPOEε4 genotype. These findings underscore the importance of considering sex-specific factors in aging and AD research.
Peripheral cytokine dysregulation, microglial dysfunction in adolescent major depressive disorder: Neuroimmune crosstalk implications.
Shen X, Ji W, Zheng H … +5 more , Yu B, Wan Y, Cai H, Dai H, Zhong H
Psychoneuroendocrinology · 2026 Jan · PMID 41138684 · Publisher ↗
BACKGROUND: Major depressive disorder (MDD) exhibits a high prevalence among adolescents; however, its pathogenesis remains unclear. This study aimed to investigate the relationship between cytokine dysregulation and mic...
BACKGROUND: Major depressive disorder (MDD) exhibits a high prevalence among adolescents; however, its pathogenesis remains unclear. This study aimed to investigate the relationship between cytokine dysregulation and microglial dysfunction in adolescents with MDD (regardless of disease onset or duration) during the course of the disorder. METHODS: This study included 60 adolescent patients with MDD and 25 healthy controls (HCs). Peripheral blood levels of nine target cytokines-including interleukins (IL-1α, IL-1β, IL-6, IL-17A, IL-18), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), granulocyte colony-stimulating factor (G-CSF), and macrophage colony-stimulating factor (M-CSF)-were measured using ultrasensitive multiplex electrochemiluminescence assays. To better understand the potential changes in microglial cells of adolescents with MDD, the human microglial cell line HMC3 was treated with 3-hydroxykynurenine (3-HK), a key neurotoxic metabolite of the kynurenine pathway (KP), and the effects of 3-HK on microglial cells were subsequently evaluated. RESULTS: After multiple test correction using the Holm method, compared with the HCs, adolescents with MDD exhibited a significant increase in the level of the peripheral pro-inflammatory cytokine IL-1α. Moreover, the levels of IL-1β, IL-6, IL-17A, and IL-18 showed an upward trend, while the levels of TNF-α and IFN-γ showed a downward trend, yet none of these trends reached statistical significance. In addition, G-CSF levels were significantly decreased, while M-CSF levels were significantly increased. In vitro experiments, 3-HK significantly reduced the viability of human microglial cells. Further experiments demonstrated that 3-HK induced microglial pyroptosis in a concentration-dependent manner via the mitochondrial pathway, leading to the release of the pro-inflammatory cytokine IL-1β. CONCLUSION: Dysregulation of cytokines may lead to excessive activation of microglia, resulting in increased release of the neurotoxic KP metabolite 3-HK. This suppresses microglial proliferation and induces microglial cell death, including pyroptosis, accompanied by the release of pro-inflammatory cytokines.
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