Psychoneuroendocrinology [JOURNAL]
Sun
200 papers
Sex-specific links between stress regulation in early life and anxiety in middle childhood.
Galbally M, Vukusic S, Lewis A … +4 more , van IJzendoorn MH, van Rossum EFC, Power J, de Kloet ER
Psychoneuroendocrinology · 2026 Jun · PMID 42258972 · Publisher ↗
Anxiety disorders become more prevalent in females from middle childhood onwards. Yet it is likely that predictors for developing these disorders occur earlier, with emerging evidence of sex differences. We examined whet...
Anxiety disorders become more prevalent in females from middle childhood onwards. Yet it is likely that predictors for developing these disorders occur earlier, with emerging evidence of sex differences. We examined whether early life predictors, including maternal depression, placental cortisol bioavailability, and infant cortisol reactivity, predict sex differences in anxiety disorders at age 8. Data are from 149 mothers recruited in the Mercy Pregnancy and Emotional Wellbeing Study (MPEWS) before 20 weeks' gestation and their children followed to 8 years. Maternal measures included the Structured Clinical Interview for DSM-IV, the Edinburgh Postnatal Depression Scale, State-Trait Anxiety Inventory, Childhood Trauma Questionnaire, Parenting Stress Index, and antenatal hair cortisol. At birth, placental 11β-HSD2 mRNA levels were used to inferpotential fetal cortisol exposure. Child measures included salivary cortisol reactivity at 12 months. At age 8, the Diagnostic Interview Schedule for Children and the Child Behavior Checklist were administered. The results show that at age 8, associations were sex-specific: (i) Among females but not males, higher infant 12-month cortisol reactivity and lower placental 11β-HSD2 mRNA were associated with anxiety disorders. (ii) Maternal antenatal antidepressant use was associated with a lower risk of anxiety symptoms in 8-year-old females. (iii) For male children, concurrent maternal depressive symptoms at 8 years were the only significant association with anxiety. In conclusion, our findings identify the possible predictors of sex differences in the early life development for differential susceptibility to later anxiety disorders.
Personality nuances and inflammation: A coordinated analysis of six samples.
Stephan Y, Sutin AR, Mõttus R … +2 more , Luchetti M, Terracciano A
Psychoneuroendocrinology · 2026 Jun · PMID 42250395 · Full text
Five-Factor personality domains are associated with inflammatory markers across adulthood. Personality nuances, the most specific personality characteristics at the bottom of the personality hierarchy that are typically...
Five-Factor personality domains are associated with inflammatory markers across adulthood. Personality nuances, the most specific personality characteristics at the bottom of the personality hierarchy that are typically measured by individual questionnaire items, may provide more information on which specific characteristics of traits are related to inflammation. Using six cohort studies (total N > 19,000, age range: 25-104 years) that measured nuances using items from the Midlife Development Inventory (MIDI), this study examined the association between personality nuances and two inflammatory markers: c-reactive protein (CRP) and interleukin-6 (IL-6). Across most samples and a meta-analysis, the extraversion item lively and the conscientiousness items organized and hardworking were related to lower levels of CRP and IL-6. The extraversion item active was the strongest item-level correlate of lower CRP in the meta-analysis and across most samples. Domain-level analyses indicated that higher conscientiousness was associated with lower CRP and IL-6, whereas higher extraversion was associated with lower CRP. Neuroticism, openness, and agreeableness domains and items were mostly unrelated to inflammatory markers. The associations between the items active and hardworking and inflammatory markers persisted in most samples controlling for their respective extraversion and conscientiousness domains. Item-level analyses provide more detailed insights into the specific personality nuances connected to inflammation, showing that the active component of extraversion, rather than components related to sociability, are associated with inflammation.
Low levels of organization and consistency in the home in middle childhood predicts cortisol levels and internalizing symptoms 12 years later among the offspring of parents with bipolar disorder.
Ellenbogen MA, Serravalle L, Hodgins S … +2 more , Walker CD, Walker EF
Psychoneuroendocrinology · 2026 May · PMID 42247738 · Publisher ↗
The offspring of parents with bipolar disorder (OBD) are at high risk for developing affective disorders. Low levels of organization and consistency in the home (parenting structure) is associated with increased behavior...
The offspring of parents with bipolar disorder (OBD) are at high risk for developing affective disorders. Low levels of organization and consistency in the home (parenting structure) is associated with increased behavioral problems and hypothalamic-pituitary-adrenal (HPA) reactivity in the OBD and thus may be an important developmental risk factor. We also examined whether the cortisol response following awakening (CAR) is increased in the OBD who developed an affective disorder relative to OBD with no affective disorder. The sample (19.3 ± 3.4 years) consisted of 68 OBD and 64 offspring (61 female) of parents with no affective disorder (controls). As predicted, offspring who developed an affective disorder had higher CAR than OBD who did not have an affective disorder (Cohen's d= 0.423) and controls (Cohen's d= 0.468). Bootstrapping serial mediation analyses revealed that parenting structure in middle childhood and the CAR in offspring significantly mediated the relationship between risk status and offspring depressive and anxiety symptoms 12 years later (CI:.01,.66). Low parenting structure in the OBD leads to changes in the HPA axis that increases the risk of developing symptoms of an affective disorder. Suboptimal childrearing may have enduring consequences on mental health outcomes in the OBD.
From PCOS to PMOS: Beyond ovarian morphology to neuroendocrine networks.
Yildiz BO
Psychoneuroendocrinology · 2026 Jun · PMID 42242037 · Publisher ↗
Abstract loading — click title to view on PubMed.
Elevated hair cortisol concentrations in trauma-exposed adolescents who engage in nonsuicidal self-injury.
Goreis A, Pfeffer B, Klinger D … +13 more , Oehlke SM, Macura S, Kafka JX, Müller NM, Prillinger K, Zesch HE, Kapusiz I, Felnhofer A, Feneberg AC, Nater UM, Skoluda N, Plener PL, Kothgassner OD
Psychoneuroendocrinology · 2026 Jun · PMID 42242036 · Publisher ↗
BACKGROUND: Nonsuicidal self-injury (NSSI) is common in trauma-exposed adolescents and has been linked to dysregulation of stress-response systems, including the hypothalamic-pituitary-adrenal (HPA) axis. Most existing e...
BACKGROUND: Nonsuicidal self-injury (NSSI) is common in trauma-exposed adolescents and has been linked to dysregulation of stress-response systems, including the hypothalamic-pituitary-adrenal (HPA) axis. Most existing evidence is based on short-term cortisol measures, whereas hair cortisol concentrations index cumulative HPA axis activity over several months. We therefore investigated hair cortisol concentrations in trauma-exposed adolescents by comparing those with and without recent NSSI. METHODS: Fifty trauma-exposed adolescents (mean age = 16.02 years; 68% identified as female, 26% as male, and 6% as gender-diverse; 72% were assigned female at birth and 28% male at birth) were recruited. Recent NSSI within the past three months and trauma symptom severity were assessed using clinical interviews. Proximal 3-cm hair segments were analyzed to index cumulative cortisol secretion over the corresponding three-month period. Group differences in hair cortisol concentrations were examined using t-tests on log-transformed values, with additional analyses adjusting for dimensional trauma symptom severity. RESULTS: Trauma-exposed adolescents with recent NSSI (n = 23) showed higher hair cortisol concentrations than those without NSSI (n = 27; p = .006, Hedges' g = 0.86). These group differences remained significant after adjusting for trauma symptom severity, which was not significantly associated with hair cortisol concentrations. CONCLUSIONS: In trauma-exposed adolescents, recent NSSI was associated with elevated cumulative HPA axis activity, indexed by higher hair cortisol concentrations. This finding highlights the relevance of long-term stress-system functioning in adolescents who engage in NSSI and underscores the importance of considering cumulative, rather than solely acute, indices of HPA axis activity in clinical research.
Beyond comfort: Basic environmental enrichment accelerates sexual development in mouse pups.
Luque EM, Cantarelli VI, Carlini VP … +4 more , Torres PJ, Ramírez ND, Ponzio MF, Martini AC
Psychoneuroendocrinology · 2026 Jun · PMID 42242035 · Publisher ↗
Most studies on environmental enrichment utilize 'super-enrichment' protocols, which are challenging to implement routinely in animal facilities; furthermore, few explore the effects of environmental enrichment on offspr...
Most studies on environmental enrichment utilize 'super-enrichment' protocols, which are challenging to implement routinely in animal facilities; furthermore, few explore the effects of environmental enrichment on offspring development and fertility. The objectives of this study were to investigate the effects of standard housing (S) or basic environmental enrichment (EE) conditions across two experiments: 1) reproduction and fertility of adult male and female mice; and 2) physical, neurobiological, and sexual development of the offspring (F1) from S and EE dams (as well as from dams enriched only starting from mating -EEc-) including their fertility in adulthood. EEc group was included to distinguish F1 outcomes resulting from enrichment since birth versus those resulting from mother's pre-reproductive enrichment. Standard conditions involved group housing in polypropylene cages with wood shavings. For EE, paper strips and PVC tubes were added. Experiment 1 showed no differences in reproduction or fertility between S and EE mice, nor in reproductive endocrinology or corticosterone levels. Experiment 2 revealed that, independent of body weight, EE-and to a lesser extent, EEc-significantly accelerated F1 sexual maturation and incisors eruption. No differences were observed in F1 female fertility. In F1 males, mild but significant alterations in sperm quality were recorded, though these were insufficient to affect fertility. Worsening in sperm quality was possibly secondary to the significantly increased anxiety and aggressiveness observed in EE males, despite no differences in plasma corticosterone. In conclusion, basic EE accelerated postnatal development in mice, which could, in the long term, improve facility productivity.
Naringin ameliorates depressive-like behaviors in offspring rats induced by prenatal stress identified with metabolomic and network pharmacology analysis.
Ma Y, Shi Y, Liu W … +11 more , Dong Y, Xu K, Zhao H, Zhou X, Li Y, Yang J, Liu J, Ma X, Lu Y, Li H, Zhu Z
Psychoneuroendocrinology · 2026 Aug · PMID 42229082 · Publisher ↗
OBJECTIVE: The present research aimed to evaluate naringin (NRG) in alleviating depressive-like behaviors in offspring rats induced by prenatal stress (PS), and to explore key metabolites and pathways. METHODS: A PS rat...
OBJECTIVE: The present research aimed to evaluate naringin (NRG) in alleviating depressive-like behaviors in offspring rats induced by prenatal stress (PS), and to explore key metabolites and pathways. METHODS: A PS rat model was established. The antidepressant effects of NRG were evaluated using the sucrose preference test and forced swimming test. Untargeted metabolomics combined with network pharmacology was employed to identify key metabolic pathways and molecular targets in the prefrontal cortex (PFC) and hippocampal (HIP) tissues. Key neurotransmitter levels (5‑HT, 5‑HIAA, GABA, glutamic acid) were measured by ELISA. RESULTS: PS induced depressive-like behaviors in offspring, NRG administration significantly ameliorated depressive-like behavior. Metabolomics analysis identified 61 and 46 significantly altered metabolites in the PFC and HIP following PS respectively. NRG modulated 66 metabolites in the PFC and 49 in the HIP. Network pharmacology identified 107 potential antidepressant targets for NRG. Integration of network pharmacology and metabolomic analyses highlighted 7 key targets. Metabolic pathway analysis revealed that NRG primarily influences two pathways in the PFC and four pathways in the HIP. ELISA further confirmed that NRG reversed PS-induced reductions in 5‑HT and GABA levels, normalized the 5‑HT/5‑HIAA ratio, and restored the GABA/glutamate balance in both PFC and HIP. Molecular docking suggested favorable binding affinities between NRG and all identified key targets. CONCLUSION: NRG ameliorated PS-induced depressive-like behaviors, potentially by modulating metabolic network disruptions in the PFC and HIP. These findings support its potential as an antidepressant candidate, although confirmation in female offspring, brain pharmacokinetic profiling, and direct target validation are warranted.
Salivary cortisol reactivity to social rejection in a simulated video conference: Findings from the O-Cam paradigm.
Kuehl LK, Lamberg E, Salzmann S … +1 more , Euteneuer F
Psychoneuroendocrinology · 2026 Aug · PMID 42224818 · Publisher ↗
Social rejection represents a social stressor with well-documented psychological effects, yet biological stress responses have been examined mostly with paradigms of limited ecological validity. This study investigated p...
Social rejection represents a social stressor with well-documented psychological effects, yet biological stress responses have been examined mostly with paradigms of limited ecological validity. This study investigated psychobiological reactions to social rejection using the O-Cam paradigm, a simulated video-conference designed to mirror contemporary social interactions with higher ecological validity. Eighty-four participants were randomly assigned to experience either social rejection or social inclusion during a prerecorded web-conference with two peers. Following the interaction, participants reported on fundamental need depletion and negative affect, and provided salivary cortisol samples at baseline, immediately post-interaction, and at three follow-up time points across 45 min. As expected, participants in the rejection condition showed significantly higher fundamental need depletion and stronger negative affect than those in the inclusion condition, confirming the psychological effectiveness of the O-Cam manipulation. In contrast, no overall group differences emerged in cortisol trajectories. However, exploratory moderation analyses revealed sex-specific patterns. Women exhibited higher cortisol levels immediately after rejection compared to social inclusion, potentially reflecting a modulatory effect of rejection (vs. inclusion). Men, in contrast, showed similar acute cortisol increases across both conditions in adjusted analyses and even higher levels following inclusion in unadjusted analyses, suggesting a more generalized stress response possibly related to performance-oriented appraisal. These findings provide important insights into cortisol reactivity using the O-Cam paradigm and highlight the importance of considering sex and gender when examining psychobiological processes in the context of social rejection and inclusion.
The association between telomere length and expression of DNA repair genes as a biological trace of cumulative lifetime stress.
Keppler H, Mavioglu RN, Behnke A … +8 more , Gola H, Hitzler M, Fieres J, Christmann M, Bürkle A, Moreno-Villanueva M, Kolassa IT, Mack M
Psychoneuroendocrinology · 2026 Aug · PMID 42224817 · Publisher ↗
Compromised DNA integrity, including telomere attrition, has been linked to traumatic stress and early adversity. We investigated whether cumulative lifetime stress exposure is associated with telomere length and express...
Compromised DNA integrity, including telomere attrition, has been linked to traumatic stress and early adversity. We investigated whether cumulative lifetime stress exposure is associated with telomere length and expression of key DNA repair genes, poly (ADP-ribose) polymerase 1 (PARP1) and X-ray repair cross complementing 1 (XRCC1), across two independent cohorts. In 65 postpartum women (cohort 1), childhood maltreatment (CM) and lifetime trauma exposure (LTE) were assessed using the Childhood Trauma Questionnaire and the Posttraumatic Diagnostic Scale event checklist. In 49 refugees and immigrants (cohort 2), trauma exposure was assessed using the Clinician-Administered PTSD Scale and the Vivo Checklist of War, Detention and Torture Events. Telomere length and gene expression were quantified in peripheral blood mononuclear cells using cohort-specific standard methods. In cohort 1, shorter telomeres were associated with higher PARP1 expression specifically in women with both CM and LTE, but not in those with lower cumulative stress exposure. Given the limited variance in stress exposure in this sample, we examined whether this pattern generalizes to a cohort with substantially higher and more heterogeneous trauma exposure. In cohort 2, shorter telomeres were consistently associated with higher expression of both PARP1 and XRCC1. These converging findings across independent cohorts suggest that cumulative lifetime stress exposure may be linked to altered DNA repair activity in the context of telomere maintenance, consistent with a model of stress-related allostatic load. While interpretation is limited by small sample sizes and methodological differences between cohorts, future studies in larger, longitudinal, and methodologically harmonized samples are needed to clarify underlying mechanisms and directionality.
Association between cortisol and cardiovascular reactivity varied in child maltreatment.
Zhang L, Lü W
Psychoneuroendocrinology · 2026 Aug · PMID 42214945 · Publisher ↗
Dysregulation of physiological stress systems, including the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS), is considered the pathway that links child maltreatment with psychopathology....
Dysregulation of physiological stress systems, including the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS), is considered the pathway that links child maltreatment with psychopathology. However, how child maltreatment is linked with the coordination of the HPA axis and ANS stress responses remains unclear, particularly during the critical developmental period such as adolescence. This study investigated the association between the HPA axis indexed by cortisol and the ANS indexed by cardiovascular stress responses among adolescents with and without child maltreatment. The Childhood Trauma Questionnaire was administered to 116 adolescents (59 in the child maltreatment group and 57 in the comparison group), who took part in the Trier Social Stress Test during which their cortisol, heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) reactivity were collected. Results showed that after controlling for age, sex, body mass index, and socioeconomic status, a symmetry between the HPA axis and ANS stress response marked by significantly positive relationships between cortisol reactivity and SBP and DBP reactivity was found in the comparison group, while an asymmetry between the HPA axis and ANS stress response marked by a negative association between cortisol reactivity and DBP reactivity and a null association between cortisol reactivity and SBP reactivity was observed in the child maltreatment group. These findings suggest that child maltreatment disrupts the symmetry between the HPA axis and ANS stress response in adolescents.
The cortisol awakening response (CAR) of elite athletes is elevated before a competition, but no interaction with sport type.
Jiménez M, Lopez-Lluch G, Barón-López FJ … +5 more , Benítez-Porres J, Gallardo-Pérez J, Rivilla-Arias, Crewther BT, Mehta P
Psychoneuroendocrinology · 2026 Aug · PMID 42208408 · Publisher ↗
The cortisol awakening response (CAR) is thought to represent an anticipatory mechanism to prepare for upcoming demands. In sport, competition increases in the CAR have been reported, although findings remain inconsisten...
The cortisol awakening response (CAR) is thought to represent an anticipatory mechanism to prepare for upcoming demands. In sport, competition increases in the CAR have been reported, although findings remain inconsistent. A study on amateur athletes identified a divergent CAR between individual-sport (IS) and team-sport (TS) athletes, thereby highlighting sport type as a confounding factor. Our aim was to determine whether competition-related changes in the CAR are robust in elite athletes and whether sport type moderates this response. Using a within-subject crossover design, 190 elite athletes (58 women) from seven sports (soccer, field hockey, handball, badminton, athletics, swimming, and judo) provided saliva samples upon awakening (T0) and 30 min after awakening (T30) on both a competition day and a rest day. The CAR was quantified as a change score (T30 - T0) based on log-transformed and raw values. Both sets of analyses revealed a significant trial effect (p < 0.001). The CAR was greater on competition days (back-transformed mean = 82.1%, 4.81 ng/mL raw units) than on resting days (mean = 24.7%, 0.99 ng/mL), representing large effect size differences. No significant effect of sport type, nor a trial × sport type interaction, was detected. In conclusion, we observed a robust elevation in CAR on competition mornings in elite athletes, compatible with anticipatory processes and potential training-related influences. In contrast to findings in amateur athletes, the CAR did not differ between IS and TS athletes, suggesting a relatively consistent CAR pattern across sports played at the elite level.
Losing face? Facial activity during evaluative stress is characterized by rigidity, tension and unpredictability.
Blasberg JU, Thaler J, Engert V
Psychoneuroendocrinology · 2026 Aug · PMID 42208407 · Publisher ↗
Psychosocial stress detection via cost-effective means could prove a useful tool in the diagnosis of long-term stress experience and subsequent prevention of stress-related health disorders. Facial expressions are both p...
Psychosocial stress detection via cost-effective means could prove a useful tool in the diagnosis of long-term stress experience and subsequent prevention of stress-related health disorders. Facial expressions are both part of and a relay for complex affective states, such as acute stress. In the current post-hoc study we investigated differences in facial activity between participants under acute psychosocial stress and in a stress-free control task. N = 126 adults either completed the Trier Social Stress Test (TSST) or a stress-free placebo TSST while being video recorded. Stress group participants also provided multiple samples of salivary cortisol, heart rate, heart rate variability and subjective stress. Facial activity was indexed via action unit (AU) activity on a frame-by-frame basis. We found that stress group participants showed significantly less facial activity across AU04 (brow lowerer), AU06 (cheek raiser), AU07 (eyelid tightener) and AU12 (lip corner puller) during the talk but not during the math block of the TSST. These group differences were not further explained by participant sex. These findings were corroborated by dynamic structural equation modeling of facial activity. Physiological and psychological stress reactivity, however, was not revealed to covary with facial behavior during evaluative stress. In conclusion, this study is another step towards stress detection via easy-to-implement and cost-effective means.
Maternal exposure to childhood maltreatment is linked to alterations in the trajectories of steroid hormones during pregnancy.
Salo V, Lahti-Pulkkinen M, Seikku T … +11 more , Girchenko P, Airikka A, Tukiainen T, Heinonen K, Phelan E, Lee P, Denham SG, Simpson JP, Reynolds RM, Homer NZM, Räikkönen K
Psychoneuroendocrinology · 2026 Aug · PMID 42208406 · Publisher ↗
BACKGROUND: Evidence suggests that the mental health effects of maternal exposure to childhood maltreatment may be transmitted to the next generation, possibly via alterations in maternal stress-sensitive endocrine funct...
BACKGROUND: Evidence suggests that the mental health effects of maternal exposure to childhood maltreatment may be transmitted to the next generation, possibly via alterations in maternal stress-sensitive endocrine functioning during gestation, with potential implications for fetal programming. However, empirical evidence supporting this mechanism remains limited. METHODS: We investigated whether maternal exposure to childhood maltreatment, assessed using the Childhood Trauma Questionnaire, was associated with the levels of 15 steroid hormones and the trajectories of 18 steroid hormones and their substrate-to-product ratios, serving as proxies of metabolizing enzyme activity during pregnancy. Maternal morning plasma samples were collected in mid pregnancy (median 20.29, Interquartile Range [IQR] 19.57-21.14) from 563 mothers, and across early (median 13.0, IQR 12.57-13.43), mid (median 19.29, IQR 19.0 - 19.71), and late (median 27.0, IQR 26.57-27.50) pregnancy from 188 mothers. RESULTS: Mothers with moderate-to-severe compared with none-to-low childhood maltreatment had significantly higher mid-pregnancy levels of aldosterone. They also had significantly higher increases in the levels of corticosterone, aldosterone, 11-deoxycortisol, cortisol, cortisone, androstenedione, and testosterone, and in the corticosterone/11-dehydrocorticosterone ratio from early to late pregnancy. These associations were not explained by mother-, child-, and study design-related covariates. CONCLUSIONS: These findings show that maternal exposure to childhood maltreatment may alter maternal steroid hormone functioning during gestation, potentially contributing to its intergenerational programming effects. The results highlight potential targets for prevention to mitigate the intergenerational transmission of these effects.
Oxytocin moderates father-infant dynamics during triadic family interaction: A dynamic structural equation modeling approach.
Ouyang J, León GA, Rinne GR … +1 more , Saxbe DE
Psychoneuroendocrinology · 2026 Aug · PMID 42176421 · Publisher ↗
BACKGROUND: Touch is a primary way parents communicate and bond with infants. Oxytocin, a neuropeptide that promotes bonding and regulates social responsiveness, may shape how parents touch their infants. However, most r...
BACKGROUND: Touch is a primary way parents communicate and bond with infants. Oxytocin, a neuropeptide that promotes bonding and regulates social responsiveness, may shape how parents touch their infants. However, most research has focused on maternal touch in dyadic interactions, leaving fathers and triadic family processes understudied. This study examined second-by-second links between parental touch and infant affect during triadic play with mothers, fathers, and infants. METHODS: Sixty-nine families from a longitudinal transition-to-parenthood study were observed during a four-minute triadic free-play task when the infant was six months old (M = 28.7 weeks, SD = 2.3 weeks). Parental touch and infant affect were observationally coded using the Triadic Coding System. Plasma oxytocin was assayed from blood samples taken from parents after the interaction task at the same lab visit. Dynamic structural equation modeling (DSEM) was used to test time-lagged associations between infant affect and parental touch, and whether these links were moderated by parental oxytocin. RESULTS: Both mothers and fathers showed strong moment-to-moment stability in the intensity of their touch. Parental touch and infant positive affect were bidirectionally associated across time, forming a positive feedback loop. Paternal post-interaction plasma oxytocin (hereafter, oxytocin) moderated these dynamics: fathers who responded to infant positive affect with more vigorous touch showed higher oxytocin levels. No moderation was found for maternal oxytocin. These results only emerged when examining extracted oxytocin, considered the gold standard for reliability. CONCLUSIONS: Findings highlight real-time coordination between parental touch and infant affect and suggest oxytocin may relate to fathers' moment-to-moment responsiveness to infant cues during triadic family interaction.
Association of internet addiction symptoms with hair cortisol and hair testosterone concentrations.
Tsumura H, Izawa S
Psychoneuroendocrinology · 2026 Aug · PMID 42176420 · Publisher ↗
Internet addiction (IA) has been consistently shown to be closely associated with stress; however, studies on physiological stress in IA have yielded mixed findings regarding the relationship between IA and cortisol. In...
Internet addiction (IA) has been consistently shown to be closely associated with stress; however, studies on physiological stress in IA have yielded mixed findings regarding the relationship between IA and cortisol. In addition, the role of testosterone-another hormone potentially relevant to addiction-has been scarcely examined in IA. The present study investigated associations between IA symptom severity and long-term basal secretion of cortisol and testosterone using hair-based hormone measures. A total of 155 Japanese undergraduate and graduate students (94 females, mean age = 21.1 years, standard deviation = 4.1 years) participated in the study. IA symptom severity was assessed using the Japanese version of the Internet Addiction Test (Osada, 2013; Young, 1998). Hair cortisol and hair testosterone concentrations, reflecting cumulative hormone secretion over the preceding three months, were quantified using enzyme-linked immunosorbent assays. A multivariate linear regression analysis revealed that hair cortisol concentrations were negatively associated with IAT scores, whereas hair testosterone concentrations were not. These results suggest that IA symptom severity may be linked to altered long-term activity of the hypothalamic-pituitary-adrenal axis. By jointly examining cortisol and testosterone, the present findings extend previous research that has largely focused on single hormonal systems.
Salivary cortisol reactivity to stress in pregnancy: A scoping review.
Celestin GF, Restrepo M, Daugherty M … +4 more , Costello LA, Aran Ö, Espinola-Coombs P, Reid BM
Psychoneuroendocrinology · 2026 Jul · PMID 42172732 · Full text
OBJECTIVE(S): Cortisol reactivity to acute experimental stressors indexes hypothalamic-pituitary-adrenal (HPA) axis responsivity under challenge, a dimension of stress physiology that is particularly consequential during...
OBJECTIVE(S): Cortisol reactivity to acute experimental stressors indexes hypothalamic-pituitary-adrenal (HPA) axis responsivity under challenge, a dimension of stress physiology that is particularly consequential during pregnancy, when neuroendocrine adaptations alter how the stress system functions. No scoping review has characterized this literature. The present study mapped evidence on salivary cortisol reactivity to acute experimental stressors during pregnancy, with attention to experimental paradigms, mental health, psychological stress, gestational timing, and demographic characteristics. METHOD: A systematic search yielded 1234 records, of which 33 empirical studies representing 2418 pregnant participants met inclusion criteria. Data were extracted and charted using a standardized framework. Cortisol data were digitized from published figures where necessary for descriptive visualization. RESULTS: Fewer than half of studies (39.4%) found significant cortisol responses to the administered stressor. Social stressors elicited significant responses more consistently than non-social stressors (47.4% vs. 33.3%). Associations between cortisol reactivity and depressive symptomatology were found in less than half of tests, with all significant associations in the positive direction. Substantial heterogeneity in sampling timing, pre-testing protocols, and operationalization of reactivity was observed across studies. There was limited ability to compare cortisol reactivity across racial and ethnic identity, socioeconomic variables, or gestational age. CONCLUSIONS: This scoping review of salivary cortisol reactivity during pregnancy reveals a growing literature marked by substantial methodological heterogeneity that limits cross-study synthesis. Social-evaluative stressors are recommended to improve HPA axis activation in pregnancy. Future research should prioritize diverse populations, trimester-specific reporting, and standardized cortisol reporting (means, standard deviations, sampling times) at each time point relative to stressor onset.
The glucagon-like peptide-1 receptor agonist, Ex4, reduces intromission in sexually experienced male mice.
Shevchouk O, Edvardsson CE, Ericson M … +2 more , Westberg L, Jerlhag E
Psychoneuroendocrinology · 2026 Jul · PMID 42166808 · Publisher ↗
The physiological effects of glucagon-like peptide-1 (GLP-1) are vast, including food and glucose homeostasis. As the half-life is short, both short-acting, exendin-4 (Ex4) and long-acting, liraglutide and dulaglutide, G...
The physiological effects of glucagon-like peptide-1 (GLP-1) are vast, including food and glucose homeostasis. As the half-life is short, both short-acting, exendin-4 (Ex4) and long-acting, liraglutide and dulaglutide, GLP-1 receptor (GLP-1R) agonists have been developed and are approved for type 2 diabetes and/or obesity. They have also been found to reduce behaviors linked to addictive drugs through involvement of mesolimbic brain regions such as the medial amygdala. Additionally, Ex4 reduces sexual interactions in sexually naïve male mice and experienced females. However, the effects of GLP-1, short- and long-acting GLP-1R agonists on sexual behaviors in sexually experienced males remain unknown. Therefore, we examined how GLP-1 and Ex4 affect sexual behavior in experienced male mice, influenced associated neurochemical changes in the medial amygdala, and evaluated the potential modulatory factors through social behaviors. Additionally, we assess whether long-acting GLP-1R agonists impacted similar behaviors as well as the levels of corticosterone and insulin. Ex4 reducced the number of intromissions and ejaculations in sexually experienced male mice without GLP-1 having an effect. Moreover, social behaviors were unaffected by short-acting GLP-1R agonists. In the medial amygdala of these male mice treated with Ex4, the levels of glutamate and other amino acids were lower. Conversely, liraglutide and dulaglutide did not modify sexual behaviors but enhanced time in the social zone, with no effect on corticosterone or insulin levels. Together, these studies suggest that GLP-1R activation modulates both sexual and social behaviors, but the outcome depends on which agonists have been used.
Sex-specific alterations of niacin flush pathway biomarkers in schizophrenia.
Hsieh KY, Chiu CW, Lin JJ … +10 more , Tseng HH, Huang CC, Wang TY, Chen PS, Yao CY, Jang FL, Chang WH, Lin CW, Kang YE, Lin SH
Psychoneuroendocrinology · 2026 Jul · PMID 42156190 · Publisher ↗
Attenuated niacin flush has been associated with schizophrenia (SZ), and six biomarkers within the niacin flush pathway have been identified as potential biomarkers for SZ, including niacin flush response, G-protein-coup...
Attenuated niacin flush has been associated with schizophrenia (SZ), and six biomarkers within the niacin flush pathway have been identified as potential biomarkers for SZ, including niacin flush response, G-protein-coupled receptor 109 A (GPR109A), prostaglandin E2 (PGE2), prostaglandin D2 receptor 1 (DP1), and PGE2 receptors (EP2 and EP4). However, sex differences may influence the discriminative performance of biomarker-based models. To examine this hypothesis, we recruited 182 patients with SZ and 111 healthy controls (HC) and constructed sex-specific classification models to evaluate the impact of sex on the predictive utility of these biomarkers. Additionally, the expression levels of two other PGE2 receptors, EP1 and EP3, were also measured, but neither showed statistically significant differences between SZ and HC. In females, PGE2 demonstrated promising discriminative ability, with a nested 10-fold cross-validated AUC of 0.92 and a Brier score of 0.10. In contrast, the contribution of PGE2 in males was negligible, resulting in lower model performance compared with that in females. In terms of AUC performance, EP4 also showed a similar but weaker effect to PGE2. Feature analysis indicated PGE2 contributed prominently to the discriminative model in females but had minimal impact in males. Decision curve analysis revealed a higher clinical benefit for the female-specific model, suggesting superior utility. These findings suggest the presence of sex-specific differences in inflammatory signaling associated with the niacin flush pathway in SZ. Incorporating sex-specific profiles may therefore help refine niacin flush pathway biomarkers into more robust tools for the personalized prediction of SZ.
Biological modulators of treatment outcome during psychiatric care: The interplay between inflammation and oxytocin.
Sedoff O, Brugnera A, Tasca GA … +3 more , Maoz H, Bloch Y, Tzur Bitan D
Psychoneuroendocrinology · 2026 Jul · PMID 42156189 · Publisher ↗
BACKGROUND: Although scientific advancements highlight the involvement of inflammatory processes in psychiatric disorders, few studies have explored how these processes relate to treatment outcomes. This study aimed to e...
BACKGROUND: Although scientific advancements highlight the involvement of inflammatory processes in psychiatric disorders, few studies have explored how these processes relate to treatment outcomes. This study aimed to examine whether inflammation is associated with reduced treatment outcomes in inpatient psychiatric care, and whether oxytocin (OT) - a neuropeptide known for its anti-inflammatory properties - may buffer these effects. METHODS: Patients (N = 72, 76% females) who received intranasal OT or placebo twice daily for four weeks adjacent to standard inpatient care were examined for their pre-treatment inflammation, using the neutrophil-to-lymphocyte ratio (NLR). Baseline Depressive symptoms, anxiety, suicidal ideation, and distress were assessed using self-report measures at pre and post-treatment. Multilevel models were utilized to test the predictive effects of baseline NLR on treatment outcomes and its interaction with OT administration. RESULTS: Higher pre-treatment NLR was associated with reduced improvement in trait anxiety (p = .02). A significant NLR × OT interaction emerged for depression (p = .005), indicating that OT administration did not significantly improve depression outcomes for patients with high baseline NLR (p = .35), but was associated with greater improvement among patients with low baseline NLR compared to placebo (p = .001). CONCLUSIONS: Inflammation is a potential biological factor shaping treatment outcome, however, OT administration benefits mostly those with low inflammation. Additional studies are needed to assess whether other anti-inflammatory agents may buffer its effects.
Differences in cortisol responding and post-stress affiliation among women who are naturally cycling, using oral contraceptives, and using IUDs.
Joslin MDM, Shields GS, Sibson A … +1 more , Makhanova A
Psychoneuroendocrinology · 2026 Jul · PMID 42134052 · Publisher ↗
Despite the pervasiveness of women's use of hormonal contraceptives, surprisingly little is known about the influence of HCs on psychological processes under stress. We examined how hormonal contraceptive use, including...
Despite the pervasiveness of women's use of hormonal contraceptives, surprisingly little is known about the influence of HCs on psychological processes under stress. We examined how hormonal contraceptive use, including use of oral contraceptives and hormonal intrauterine devices (IUDs), relates to physiological and affiliative responses under stress. Women (N=190) underwent the Trier Social Stress Test (TSST), provided saliva samples for assays of free cortisol and progesterone, and completed three measures of affiliation. Women using both oral contraceptives and hormonal IUDs showed blunted cortisol responses to the TSST relative to naturally cycling women. Although there were no group differences in women's self-reported extraversion at baseline (prior to the TSST), women using oral contraceptives, compared to the other three groups, showed less social affiliative behavior following the TSST across two dependent measures. There were no differences in affiliation between naturally cycling women in their follicular or luteal phase, failing to replicate past research. Importantly, differences in affiliation were unrelated to differences in cortisol responses. Results suggest that hormonal contraceptives may subtly alter multiple stress-responsive processes via independent mechanisms, and in ways that are consistent with past research demonstrating that some women who use hormonal contraceptives experience heightened risk of negative stress-related outcomes.
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