Psychoneuroendocrinology

Cell-free mitochondrial DNA (cf-mtDNA) has emerged as a dynamic molecular signal responsive to psychological stress and a potential biomarker of stress-related physiological adaptations. While previous work has established the acute stress reactivity of cf-mtDNA in saliva, little is known about its diurnal regulation. In this intensive-sampling study, we characterized the diurnal dynamics of saliva cf-mtDNA across one weekday and one weekend day in healthy adults (N = 25, 52% female, 826 samples). Saliva was collected at awakening, during the first hour post-awakening, and at hourly intervals throughout the day. Using a quantitative PCR-based assay, we observed a robust cf-mtDNA awakening response, with concentrations peaking approximately 45 minutes after waking (2.5-fold change, Cohens d = 0.90), followed by a second peak at 180 minutes post-awakening (5.7-fold change, d = 1.70) and relatively stable levels thereafter. Saliva cf-mtDNA closely tracked cell-free nuclear DNA (cf-nDNA) across time points (rS = .85), suggesting shared release mechanisms. Diurnal cf-mtDNA showed limited correspondence with cortisol and other hormones in saliva. Psychosocial stress indicators--including daily hassles, lack of social support, negative emotional affect, trait anxiety, fatigue, and depressive symptoms--were associated with higher awakening cf-mtDNA levels, a diminished awakening response, and lower diurnal variability. These findings suggest that saliva cf-mtDNA exhibits a diurnal rhythm and is sensitive to psychosocial stress exposure. By establishing its diurnal patterns and individual-level variability, this study advances saliva cf-mtDNA as a promising non-invasive biomarker to dynamically capture stress-related mitochondrial signaling.

Suffering the stress of others (termed empathic stress or stress contagion) may affect an individuals health and well-being. To understand the underlying hormonal processes of empathic stress, N = 108 opposite-sex dyads were tested, with one dyad partner passively observing the other undergo a standardized psychosocial laboratory stressor. A positive link between oxytocin release and empathic stress responding was hypothesized, while a negative relationship was expected for testosterone release. Associations of observer oxytocin and testosterone levels with two components of empathic stress were examined: stress resonance (i.e., synchronized observer - target responses) and vicarious stress (observer responses independent of target stress). During the passive observation of a stressed target, saliva oxytocin and testosterone levels increased by 16.64% and 23.00%, respectively, followed by a drop back to baseline levels. Supporting our hypotheses, increased observer oxytocin reactivity was linked to greater stress resonance in HF-HRV reactivity, while in low oxytocin responders, this association was reversed. Also, testosterone reactivity was negatively linked to stress resonance in heart rate activity. However, testosterone also showed a positive association with vicarious cortisol activity, which resembles the response pattern seen in first-hand stress exposure. We conclude that stress resonance may be the more empathy-dependent component of the empathic stress construct, aligning with previous work on the implication of oxytocin and testosterone in empathy. To draw further conclusions about the role of oxytocin and testosterone in empathic stress responding, future studies including a control group and stimulation of hormones are called for.

BackgroundBorderline personality disorder (BPD) involves emotional instability and stress sensitivity linked to oxytocinergic and HPA-axis dysregulation. This study examined oxytocin and cortisol responses to acute psychosocial stress and the modulatory effects of SSRIs and hormonal contraception. Methods93 female participants (45 with BPD with/without SSRIs and 48 healthy controls) underwent the Trier Social Stress Test. Linear and generalized linear mixed-effects models were applied to assess time, group, and hormonal contraception effects, and their interactions. ResultsDuring the stress task, both BPD groups reported significantly higher subjective anxiety and anger than controls. All participants showed increased salivary oxytocin (OXT) during stress anticipation, but post-task trajectories diverged: BPD participants without SSRIs exhibited a sharp OXT decline, whereas those on SSRIs mirrored the stable trajectory of controls. Hormonal contraception reversed the OXT decline in untreated BPD participants, resulting in a progressive increase during recovery. Cortisol (CORT) analyses revealed hyporeactivity in BPD participants without SSRIs, a pattern unaffected by hormonal contraception. A significant three-way interaction indicated that higher OXT levels were associated with higher CORT concentrations during late recovery specifically in the BPD SSRI group, a relationship that was marginal in untreated patients and absent in controls. ConclusionsOur findings confirm that neuroendocrine dysregulation in BPD is context-dependent and sensitive to pharmacological modulation. The ability of SSRIs and hormonal contraception to influence stress-response patterns, despite limited efficacy on core symptoms, highlights the importance of controlling for medication and hormonal status in future BPD biomarker research.

Interleukin-17A (IL-17A) has been implicated in stress- and pain-related inflammation, yet evidence for acute IL-17A stress response in humans remains scarce. This study examined whether the Maastricht Acute Stress Test (MAST) induces changes in circulating IL-17A and how IL-17A dynamics relate to cortisol and subjective stress/pain. Forty-six healthy adults (mean age: 30.50, SD = 12.86 years; 54% female) completed the standardized MAST. Serum IL-17A and cortisol were assessed repeatedly across baseline and recovery. Stress- and pain-related ratings (VAS) and trait questionnaires (e.g., chronic stress, psychological distress, resilience) were completed. There was a significant increase over time in IL-17A and cortisol following the MAST, with an 36 % increase of IL-17A level measured at 105 min post-stressor and cortisol peaking at 10 min post-stressor. IL-17A indices (baseline and AUCi) showed no meaningful associations with cortisol, subjective stress/pain, or psychological traits, whereas cortisol response (AUCi) correlated positively with perceived acute stress and pain. Overall, the MAST produced clear IL-17A and cortisol responses that appeared dissociable in healthy individuals. Future studies should include broader inflammatory panels and clinical or high-stress samples to clarify conditions under which IL-17A covaries with HPA-axis activity and subjective experience.

Acute stress affects cognitive processes, including our perception of time, yet few studies have examined how HPA axis activation specifically modulates time perception. This study provides the first systematic examination of how psychosocial stress influences temporal versus spatial reproduction using the Trier Social Stress Test (TSST), investigating underlying epigenetic mechanisms. Forty-four healthy adults (21 men; mean age 21.96 {+/-} 3.03) completed temporal and spatial reproduction tasks before and after TSST, with salivary cortisol sampling and DNA methylation analysis of four dopamine-related genes (COMT, DRD2, SLC6A3, TH). The TSST successfully elevated cortisol and state anxiety, confirming effective HPA axis activation. Critically, stress selectively reduced temporal underestimation. Despite their shared neurocognitive mechanisms, spatial processing remained unchanged. This demonstrates that HPA-mediated stress enhances interval timing. Men demonstrated greater stress-induced improvement in temporal accuracy than women, while neither sex showed significant spatial changes, independent of cortisol reactivity differences. The results are discussed in the context of dopaminergic models of temporal processing. Exploratory epigenetic analyses revealed a DRD2 methylation x cortisol response interaction for temporal tasks, with higher methylation associated with greater stress-induced improvement among high cortisol responders. However, sensitivity analysis indicated these interactions were driven by participants with extreme methylation values, limiting generalizability of epigenetic results. These findings demonstrate that acute psychosocial stress selectively enhances temporal accuracy, potentially through cortisol-dopamine interactions in corticostriatal timing circuits. This work opens avenues for investigating stress-timing mechanisms and cortisol-dopamine interactions in timing circuits, and provides preliminary evidence for epigenetic moderation.

BackgroundChildhood maltreatment exposure (CME) increases the risk of adverse long-term health consequences for the exposed individual. Animal studies suggest that CME may also influence the health and behaviour in the next generation offspring through CME-driven epigenetic changes in the paternal germ line. The contribution of paternal early life stress on the health of the next generation in humans is not fully elucidated. MethodsIn this study, we measured paternal CME using the Trauma and Distress Scale (TADS) questionnaire and mapped sperm-borne sncRNAs expression by small RNA sequencing (small RNA-seq) and DNA methylation (DNAme) in spermatozoa by reduced-representation bisulfite sequencing (RRBS-seq) in males from the FinnBrain Birth Cohort Study. The study design was a (nested) case-control study, high-TADS (TADS [≥] 39, n = 25 for DNAme and n = 14 for small RNA-seq) and low-TADS (TADS [≤] 10, n = 30 for DNAme and n = 16 for small RNA-seq)). Groups were compared to identify specific epigenetic signatures associated with TADS levels in the spermatozoa of participants. ResultsCompared to the control group, high CME was associated with altered sperm sncRNA expression and DNAme profiles. Particularly, we identified several tRNA-derived small RNAs (tsRNAs) and miRNAs with markedly changed levels in males with high CME. DNA methylation analysis identified several genomic regions with differentially methylated CpGs between groups. Notably, we identified two epigenetic marks related to brain development with distinct profiles between CME and controls, the miRNA hsa-mir-34c-5p and differential methylation of the region in proximity of FSCN1. ConclusionsThis study provides further evidence that early life stress influences the paternal germ line epigenome and supports a possible contribution in the development of the central nervous system of the next generation.

The Developmental Origins of Health and Disease (DOHaD) theory hypothesized that environmental exposures during early life (particularly the in-utero period) can permanently influence health and vulnerability to disease in later life. This intriguing concept has been the subject matter of great interest in recent research, as much vital development of fetal neuronal networks and brain cell division happens in fetal life. Fetal programming, suggests that the in-utero environment is now increasingly believed to have a great impact on long term health and pattern of disease development in later life. There is also some evidence to show transgenerational epigenetic programming of genes. Various biological mechanisms are likely to be involved in fetal programming, epigenetic modifications being just one of them. This systematic study aims to review currently available primary research data to assess the significance of maternal stress in epigenetic modification affecting fetal neurodevelopment as assessed from fetal or maternal tissue sampling. RationaleMost studies have focused on impact by a particular type of stress. While some studies have studied long term outcomes, into psychiatric and intellectual follow up in adults, few have actually researched the direct effect of maternal stress or trauma on the fetus, and even fewer have documented direct sampling of genetic markers as a result of the same. There is a significant knowledge gap on how to link or classify the epigenetic impact of various kinds of maternal stress on fetal development. This systematic review hopes to evaluate the available evidence that may help us better understand the significance various types of maternal stress during pregnancy and of its diverse epigenetic influence on the developing fetus. ObjectiveTo assess and review the current available research in evaluating the role of epigenetics of the influence of maternal stress during human pregnancy on the neurodevelopment of the developing fetus as evidenced by tissue analysis. MethodsA systematic review was conducted on available literature from online databases and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020 checklist. A comprehensive search strategy was developed. Only Observational and interventional studies, which were primary research studies were included in assessing epigenetic markers derived from fetal or maternal tissue in conditions of maternal stress during pregnancy and were analyzed. We retrieved 492 papers most relevant to the query, mostly from PubMed, Semantic search tools and Journals. Both authors rigorously studied and summarized the abstracts to exclude the studies that did not meet the outlined criteria, even though well planned comprehensive studies were found, which lacked key inclusion criteria. Each study was further analysed for specific type of stress, gestational age (temporal characteristics), tissue sample analysed. Forty studies were shortlisted after screening and selected for the review, based on the inclusion criteria. Only human studies, that use validated psychological or physiological measures to assess maternal stress and analyze epigenetic markers in fetal or maternal tissue were included and also must specify the gestational timing of stress exposure. Only observational, cohort, or case-control primary studies that clearly defines and categorizes the type of stress (psychological, physical, or environmental) were included. Non-human studies, or Duplicate publications and studies that were missing key information related to the question asked were excluded. Studies were screened by the two reviewers independently. Risk of bias was assessed using RoB 2.0 tool. Data was analyzed and tabulated descriptively, using the data extraction tool designed for the study. Data extraction table is attached at the end of the article Missing data were not analysed. ResultsThis systematic review of literature spanning at least 40 independent primary studies, involving around 19,400 mothers indicated that different maternal stress types yield distinct epigenetic signatures in tissues linked to fetal development. Factors such as chronic psychological stress, traumatic exposure and symptoms of anxiety or depression are each associated with specific patterns of DNA methylation. Stress response genes, especially NR3C1, FKBP5 and HSD11B2, consistently show altered methylation. One investigation of maternal smoking documented global DNA methylation changes in fetal brain tissue, whereas most studies examined placenta, cord blood, or buccal cells. In early gestations, it was found that maternal depression, perceived stress, and adverse life events relate to altered methylation of NR3C2, MEST, and other markers enriched for neurodevelopmental functions. In contrast, maternal stress during later trimesters was associated with changes in NR3C1, FKBP5, BDNF, and related genes, sometimes also exhibiting sex-specific effects. Traumatic and especially war-related stress yields robust increases in NR3C1 methylation that may persist into later life. These findings support that the type and timing of maternal stress selectively drives epigenetic modifications in gene networks critical to neuroendocrine function and neural development. ConclusionThe timing and type of maternal stress determines which specific genes undergo methylation changes in feto maternal tissue, with early and late gestational periods showing distinct epigenetic signatures. Although several key similarities were noted, there were some conflicting results, which may be attributable to limited sample size or heterogeneity between studies. Further research with more robust standardization and more large scale randomized studies is needed to validate the exact mechanism and impact on epigenetics due to maternal stress.

Quarantines prevent infectious disease spread during primate transport, fostering acclimatisation. Environmental stress can lead to altered physiology, health risks, and epigenetic changes in other primates. We analysed Peruvian Saguinus fuscicollis and Saimiri macrodon, immobilised for 10 months in quarantine during the COVID-19 crisis, and compared them to wild counterparts to determine effects of quarantine as a stressor in New World monkeys. MethodsBoth quarantine and wild samples were collected from two riverine islands near the city of Iquitos, situated in the Peruvian Amazon (Island Muyuy and Padre Island). Cortisol levels in hair were quantified using ELISA (n=37; quarantine n=16; wild=21), and global DNA methylation levels were assessed for epigenetic comparison in dried blood spots (n=45; Quarantine: n=23; Wild: n=22), also utilising ELISA. Two-way ANOVA was employed to explore the effect of quarantine on cortisol and DNA methylation, considering the effect of species, and sex differences on these measurements. ResultsCortisol analysis revealed a significant association between quarantine and elevated cortisol secretion when testing both species together and independently, with a greater difference between quarantine and wild for Saguinus fuscicollis. Quarantine was associated with global DNA hypomethylation when testing both species together, however, independent ANOVAs show there was no effect of quarantine on Saguinus fuscicollis, and a marginal significant effect of quarantine on Saimiri macrodon. DiscussionNew World monkey species displayed hormonal and epigenetic dysregulation 10-months after starting quarantine period, suggesting long-term physiological and genomic stress as a response to captivity. Species specific differences in stress adaptability might mediate observed effects.

The cortisol awakening response (CAR) marks the transition from rest to wake phase by a sharp increase in cortisol levels upon awakening in the morning. This increase may assist in cognitive and behavioral awakening, but its function is not fully understood yet. In this pilot study we aimed to provide first data on the influence of immune system activity on the CAR. Thereby, a within-subject analysis approach was applied to avoid confounding by between-subject bias and improve inference of the results. Three healthy subjects collected their overnight urine for analysis of neopterin (Th1 immune activation marker) and sampled saliva at 0, 30, and 45 minutes after awakening in the morning for cortisol determination and CAR estimation. Additionally, subjects wore an EEG-headband overnight for objective determination of the awakening timepoint. Random-effects models were computed to estimate the effect of overnight neopterin on the CAR. There was a significant positive effect of overnight neopterin levels on the CAR, indicating that overnight Th1 immune activation may predict the dynamic increase of cortisol in the morning, with higher immune levels leading to a stronger CAR. These results provide first evidence for the immunological awakening hypothesis and a potential role of the CAR in the maintenance of circadian immune rhythms, but given the small number of participants, findings should be interpreted as exploratory.

Acute stress triggers the release of stress hormones such as cortisol, increasing stress reactivity and aiding post-stress recovery. Rodent studies revealed that stress reactivity is modulated by the gut microbiota, and few interventional studies have provided evidence for an effect on human cortisol dynamics. However, it remains unclear whether stress reactivity is related to interindividual variations in gut microbial composition and to ones capacity to produce microbial metabolites such as short-chain fatty acids (SCFAs). To close this gap, we analyzed data from 74 healthy human adults who completed the study in the laboratory and were either exposed to a well-established, standardized intervention that induced acute stress or to a non-stressful control condition (n = 35/39 per stress/control group). Stool samples were obtained at baseline, and the gut microbiota were characterized through 16S rRNA gene amplicon sequencing. Cortisol changes were assessed from repeated saliva sampling, paralleled by measurements of subjectively experienced stress. We found that higher gut microbial alpha diversity was associated with higher cortisol and subjective stress reactivity across individuals of the stress group, but not in controls. Cortisol stress reactivity was also associated with the relative abundance of bacterial taxa inferred to encode metabolic pathways for the production of butyrate and propionate, two key SCFAs. The results are the first to highlight the link between gut microbial diversity, inferred SCFA production capacity, and the acute stress response in healthy adults, underscoring the microbiotas potential to flexibly modulate human psychophysiology in the aftermath of stress.

Study questionis fetal exposure to paracetamol associated with markers of ovarian function in infancy? Summary answerMild to moderate doses of prenatal paracetamol exposure, assessed by detailed maternal reports and urinary measurements, is associated with ovarian morphology and activity as well as reduced size of estrogen-responsive tissues in infant girls. What is known alreadyMaternal use of paracetamol is widespread. Across multiple independent animal studies, fetal exposure consistently impairs the formation of primordial ovarian follicles, causing subfertility and premature estropause in female offspring. Study design, size, durationThe Copenhagen Analgesic study (COPANA) is a single center, prospective, observational cohort study conducted at the Copenhagen University Hospital - Rigshospitalet, Denmark (March 2020 to November 2022). Participants/materials, setting, methods;O_ST_ABSCOPANA cohortC_ST_ABS3425 eligible participants. In total, 685 healthy, singleton pregnant women of Caucasian origin were enrolled in the first trimester of pregnancy, 302 girls examined at follow up. Exclusion criteria: maternal diabetes or thyroid disease, pre- or post-term delivery, or severe infant illness. Exposure: pregnant women reported paracetamol use biweekly and provided first-trimester urinary samples which were analyzed for paracetamol levels (LC-MS/MS) and adjusted for urinary osmolarity (n = 299). Girls were classified by timing of exposure: early fetal life (<17 weeks, n = 92), mid-late fetal life ([&ge;]17 weeks, n = 67), or unexposed controls (n = 143). A subgroup of girls was exposed exclusively in early fetal life (n = 22). Independent confirmatory cohort1210 girls followed from infancy to adolescence. Exposure: maternal self-reported any use of paracetamol during pregnancy reported in early third trimester (yes/no). Main results and the role of chanceEarly fetal exposure was associated with reduced ovarian volume (-0.11 cm3, 95% CI -0.19 to -0.03) and uterine volume (-0.16 cm3, -0.32 to -0.01), whereas mid-late fetal exposure was associated with fewer ovarian follicles (-1.05, -1.71 to -0.39) compared to unexposed girls. AMH levels were lower in girls exposed exclusively in early fetal life (-0.45 SDS, -0.87 to -0.03) compared to unexposed girls. Maternal urinary paracetamol concentrations were inversely associated with ovarian and uterine volume as well as breast tissue diameter. In an independent cohort, fetal paracetamol exposure was associated with reduced uterine volume at puberty (-4.11 cm3, -7.29 to -0.92) and smaller ovarian volume in adolescence (-2.76 cm3, -4.82 to -0.70). Limitations, reasons for cautionThe design of the study allows evaluation of exposure- outcome associations, while causality is strengthened by experimental models demonstrating comparable effects. Residual confounding by indication cannot be completely excluded, although results were robust after accounting for fever and other maternal factors. The analytic design of the current study limited our ability to evaluate whether frequency or patterns of paracetamol use influenced the observed associations. Wider implications of the findingsThe consistency of findings across different assessment measures and cohorts, in combination with parallel evidence from animal studies, suggests potential long-term implications for female reproductive health. Study funding/competing interest(s)This research was supported by Rigshospitalets Research Council under grant (E-22717-21), Laege Sofus Carl Emil Friis og hustru Doris Friis Legat (F-23936-01), Aase og Ejnar Danielsens Foundation (20-10-0367), Helsefonden (20-B-0388), Axel Muusfeldt Foundation (2020-0385) and The Danish Centre for Endocrine Disrupting Substances (CeHoS) (2022-23219). The authors have nothing to declare. Trial registration numberClinicalTrials.gov ID: NCT0436922

Cisgender women report higher stress than cisgender men, potentially due to psychosocial and biological factors, including sex hormone levels. Gender-affirming hormone therapy (GAHT) alters hormone levels, but its impact on perceived stress remains unclear. This study examined changes in perceived stress after 3 and 12 months of GAHT and potential differences between feminizing (FHT) and masculinizing hormone therapy (MHT). Data were drawn from two prospective cohort studies (ENIGI and RESTED) in the Netherlands, Belgium, and Israel. A total of 442 individuals (median age 23 years, IQR 20.5 to 28.0) completed the 10-item Perceived Stress Scale (PSS) before starting GAHT and after 3 and 12 months. Linear mixed models assessed changes after starting GAHT and differences between FHT and MHT groups. Baseline perceived stress levels did not significantly differ between groups (0.15, p = 0.84). No significant changes in perceived stress were observed after 3 or 12 months, nor were there significant differences in changes between FHT and MHT (-1.0, p = 0.21; 0.25, p = 0.76). Improvements in well-being during GAHT may not reduce perceived stress, potentially due to ongoing gender minority stressors. Future research should explore stressors and coping mechanisms to identify strategies for reducing perceived stress during GAHT.

Studies have shown that paternal stress prior to conception can influence the innate behaviours of their offspring. The evolutionary impacts of such intergenerational effects are therefore of considerable interest. Our group previously showed that glucocorticoid treatment of adult male mouse breeders prior to conception leads to increased anxiety-related behaviours in male offspring. Here, we aimed to understand the transgenerational effects of paternal stress exposure on the social behaviour of progeny and its potential influence on reproductive success. We assessed social parameters including social reward, male attractiveness and social dominance, in the offspring (F1) and grand-offspring (F2). We report that paternal corticosterone-treatment was associated with increased display of subordination towards other male mice. Those mice were unexpectedly more attractive to female mice while expressing reduced levels of the key rodent pheromone Darcin, contrary to its conventional purpose. We investigated the epigenetic regulation of major urinary protein (Mup) expression by performing the first Oxford Nanopore direct methylation of sperm DNA in a mouse model of stress, but found no differences in Mup genes that could be attributed to corticosterone-treatment. Furthermore, no overt differences of the prefrontal cortex transcriptome were found in F1 offspring, implying that peripheral mechanisms are likely contributing to the phenotypic differences. Interestingly, no phenotypic differences were observed in the F2 grand-offspring. Overall, our findings highlight the potential of moderate paternal stress to affect intergenerational (mal)adaptive responses, informing future studies of adaptiveness in rodents, humans and other species.

The present study analyzes the impact of naturalistic stress and emotions on saliva cell-free mitochondrial DNA (cf-mtDNA) in daily life across two independent cohorts with different temporal resolutions. Study 1 examined the interaction between daily stress and major depressive disorder (MDD) on cf-mtDNA in young adults (n= 18, 8 MDD, 10 controls) across four days. For individuals with MDD, stress exposure was associated with a 68% reduction in cf-mtDNA. A higher number or greater severity of stressors also reduced cf-mtDNA by 24 to 27%. Study 2 extended this framework by implementing a finer temporal resolution, measuring saliva and affective states every hour, up to 20 times per day for 2 days (n = 25). Negative emotions, including stress and frustration, were associated with reductions in cf-mtDNA of 15%, whereas positive emotions, such as happiness and calm, predicted increases of up to 28%. The strength and direction of the effects were person- and context-dependent. These findings suggest that cf-mtDNA does not exhibit a uniform stress response in daily life. Instead, it reflects dynamic signaling shaped by timing, emotional context, and diagnostic status. Accordingly, cf-mtDNA should be conceptualized as a dynamic biobehavioral signal rather than a static indicator of between-person differences.

BackgroundPeer victimization (PV) in adolescence--verbal, social, and physical aggression--may disrupt normative developmental processes and is associated with psychosocial difficulties. Although previous research has established associations between early adversity and altered attention and cognitive-affective processing, the specific mechanisms of information-processing through which adolescent PV may affect later social functioning remain unclear. MethodsWe conducted a counterfactual multimethod study in a sample of young adults (age 22; n = 191; 47.1% female), comparing individuals with and without a history of PV between ages 11-20. Specifically we employed: (1) an eye tracking task using a free-viewing paradigm to assess spontaneous threat-related attention; (2) a longitudinal analysis of changes in hostile attribution and reactive aggression using baseline data collected prior to PV exposure and follow-up data in young adulthood; and (3) a morph-based task assessing facial emotion discrimination capabilities between happy and angry expressions. ResultsRelative to controls, victims exhibited a vigilance-avoidance attentional pattern and blunted affective responses; they showed reduced initial gaze allocation, repeated returns to angry faces, and a tendency to rate more angry faces as neutral. Over adolescence, a flatter decline in hostile attribution and a steeper drop in reactive aggression led to elevated hostile attribution and reduced reactive aggression. ConclusionsThese results suggest a victim profile characterized by impaired attentional processing with biased social threat perception, a more hostile view of the social world, and blunted affect. Our study offers preliminary evidence that adolescent PV may induce enduring changes in social information processing, with implications for maladaptive social cognition and increased risk for psychopathology.

Biomarker research in psychopathology increasingly employs high-dimensional omics approaches. Yet, proteomics based on human hair remain largely unexplored, despite its potential to efficiently capture stable biological signals accumulated over weeks to months. This study leveraged machine learning to investigate the potential of the hair proteome--all detectable peptides and proteins--as a biomarker source for stress-associated psychopathology. We analyzed protein profiles from hair segments of women with non-suicidal self-injury disorder (n = 36) and healthy controls (n = 32). Of 1114 identified proteins, 611 were sufficiently abundant for analyses. Partial Least Squares Discriminant Analysis achieved stable 84.4% cross-validated accuracy for classification of clinical groups (p < .001), outperforming models based on data-derived clusters (60%), stress-related proteins (73%), and simulated hair cortisol from meta-analytic effect sizes (53-59%). Predicted class probabilities strongly correlated with clinical symptoms and well-being (r > .60). Key predictive proteins were linked to pain perception, oxidative stress, and cholesterol homeostasis. Approximately 15% of proteins differed significantly between groups, with the strongest candidates related to ribosomal function--an emerging target in depression. These findings establish hair proteomics as a promising, non-invasive biomarker source for psychiatric research, warranting validation in larger cohorts and exploration of clinical applications in risk assessment and personalized interventions.

To attract mating partners, female mammals communicate their reproductive status through one or multiple sensory modalities, providing redundant or complementary information. Chimpanzees (Pan troglodytes) are an excellent model for studying multimodal communication. Exaggerated sexual swellings of females serve as a visual proxy for ovulation but increased male mating interest during maximum swelling suggests that olfactory cues may pinpoint fertility more accurately than the swelling alone. Here, we combined gas chromatography-mass spectrometry, hormonal analyses, and bioassays to examine (1) whether chemical composition of female anogenital odours changes during the fertile period, and (2) whether males are able to detect these changes. Our results suggest that, in addition to prominent olfactory changes associated with swelling stages, chemical cues provide complementary information regarding the timing of the fertile window. These changes, however, are minor compared to those related to swelling stages. Male behavioural responsiveness in bioassays was too low to draw conclusions regarding their ability to detect these subtle shifts when presented with a chemical cue only. Overall, our findings support the existence of a multimodal fertility cue in chimpanzees, wherein visual signals are complemented by subtle olfactory changes indicating the timing of the fertile period.

Chronic adolescent stress has been shown to cause increased adverse effects in response to an immune stressor later in life including the development of anxiety and PTSD. Following stress, the production of inflammatory cytokines including IL-1{beta} and TNF is expected to increase in response to an immune challenge such as LPS. Male and female mice underwent fifteen consecutive days of predatory stress. Chronic adolescent stress was shown to increase both anxiety-like behavior (F(1, 28) = 19.82, p = 0.0001) and TNF levels within the periphery (F(1, 19) = 4.748, p = 0.0421).

BackgroundThe Michigan Freshman Study on Stress and Resilience aims to identify factors that predict the emergence of depression and/or anxiety symptoms in college freshmen. We previously showed that a combination of psychiatric instruments (Affect Score) strongly predicts who will develop such symptoms during the freshman year. Here, we ask: a) Can we replicate the predictive power of the Affect Score in an independent cohort? and b) Can the neuroendocrine profile during the Trier Social Stress Test (TSST) serve as an additional predictor? MethodsA new cohort of subjects (N= 357) was used for Affect Score replication. The TSST study involved 337 subjects (Females 184, Males 153). Self-report questionnaires at the start of the year were used to derive the Affect Score. GAD-7 and PHQ-9 were used to monitor anxiety and depression, respectively. TSST measures involved plasma ACTH and Cortisol and heart rate monitoring. ResultsThe Affect Score proved to be a highly replicable predictor of future depression and anxiety. In the TSST, subjects not currently depressed but who developed depression at another timepoint during the year showed a higher and delayed peak of the CORT response. Female subjects not currently anxious but who developed anxiety at another timepoint had an elevated CORT response throughout the TSST. This hyperresponsiveness was not correlated with Affect Score and was an independent predictor of anxiety. Present addressMichigan Neuroscience Institute, University of Michigan, A. Alfred Taubman Biomedical Science Research Building, Rm 2009, Ann Arbor, MI, 48109-9901, USA Author ContributionsHK performed research, analyzed data, wrote the paper; CAT designed research, performed research, wrote the paper; VM-W designed research, performed research; LG, FL, AO, KA and LW performed research; CS coded and analyzed data; JFL designed research; SJW Jr designed research; HA designed research, wrote the paper. FundingThis work was supported by the Office of Naval Research (ONR) Grant N00014-09-1-0598, N00014-12-1-0366 and N00014-19-1-2149, the Pritzker Neuropsychiatric Disorders Research Consortium Fund, LLC and the Hope for Depression Research Foundation. This project was also supported by Grant Number P30DK020572 (MDRC) from the National Institute of Diabetes and Digestive and Kidney Diseases. Competing interestsThe authors declare no competing interests. ConclusionsThe Affect Score is a powerful predictor of depression and anxiety in college freshmen. The combination of Affect Score and TSST is strongly predictive of anxiety in females.

Acute stress activates the immune system, leading to the release of pro-inflammatory cytokines, such as interleukin-6 (IL-6). Chronic alcohol consumption alters the physiological stress systems and is associated with increased chronic inflammation. However, it remains unclear how IL-6 responds to acute stress in individuals with alcohol use disorder (AUD). Forty patients with AUD during early abstinence and 37 healthy controls (HC) completed two study visits. On one day, an acute stress induction task was performed, and on the other, a non-stressful control task, with the order of tasks being balanced. Plasma IL-6 and C-reactive protein (CRP) were measured as inflammatory markers at baseline and changes in IL-6 were assessed 90 minutes after the experimental manipulation. Patients with AUD showed significantly elevated baseline IL-6 and CRP compared to HC. In HC, inflammatory parameters were positively correlated with age and BMI, whereas in patients with AUD, they were correlated with the amount of consumed alcohol. IL-6 responses to the stress intervention did not differ between groups. Increases in IL-6 were observed on stress and control days and were larger when samples were collected via an indwelling catheter than with a butterfly needle. These findings suggest that heavy chronic alcohol use may mask the typical associations between inflammatory markers and physiological factors. However, IL-6 responses to acute stress do not differ between AUD and HC, despite increased baseline inflammation. Furthermore, the results indicate that blood collection methods can influence IL-6 measurements and highlight the importance of methodological considerations.