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.

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.

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.

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.

The experience and even existence of cognitive deficits in the postpartum period is uncertain, with only a few scientific studies, reporting inconsistent results. Here we investigate cognition in 86 women (43 first-time mothers one year postpartum, and 43 non-mothers). Mothers and non-mothers showed no significant differences on measures of objective cognition (verbal memory, working memory, processing speed or theory of mind). Despite the absence of objective differences, mothers self-reported significantly worse subjective memory than non-mothers. To interpret the difference between objective and subjective measures of memory, we investigated relationships between subjective memory, objective memory, and wellbeing. Mothers, but not non-mothers, showed a positive correlation between subjective and objective measures of memory, indicating mothers are in-tune with their memory performance. Mothers also demonstrated a positive relationship between subjective memory and wellbeing (sleep, anxiety and depression), where better wellbeing correlated with higher subjective memory. This relationship was not apparent in non-mothers. The results suggest that poorer sleep, higher anxiety and higher depression are related to reports of poorer self-reported memory in mothers. Our results add to our growing understanding of maternal cognition at one year postpartum, with no evidence of cognitive differences between mothers and non-mothers.

Pregnancy is associated with neural and behavioral plasticity, systemic inflammation, and oxidative stress. Yet, the impact of systemic inflammation and oxidative stress on maternal neural and behavioral plasticity during pregnancy are unclear. We hypothesized that the maternal hippocampal CA1, a brain region associated with cognition, would be protected from pregnancy-associated systemic elevations in inflammation and oxidative stress, mediating stable peripartum cognitive performance. Cognitive performance was tested using novel object recognition (recollective memory), Morris water maze (spatial memory), and open field (anxiety-like) behavior tasks in female Sprague-Dawley rats of varying reproductive states [non-pregnant (nulliparous), pregnant (near term), and two months post-pregnancy (primiparous); n = 7-8/group]. Plasma and CA1 proinflammatory cytokines were measured using a MILLIPLEX(R) magnetic bead assay. Plasma oxidative stress was measured via advanced oxidation protein products (AOPP) assay. CA1 markers of oxidative stress, neuronal activity, and apoptosis were quantified via western blotting. Our results demonstrate CA1 oxidative stress-associated markers were elevated in pregnant compared to nulliparous rats (p [≤] 0.017) but were equivalent levels in pregnant and primiparous rats. In contrast, reproductive state did not impact CA1 inflammatory cytokines, neuronal activity, or apoptosis. Likewise, there was no effect of reproductive state on recollective or spatial memory. Even so, spatial learning was impaired (p [≤] 0.007) while anxiety-like behavior (p [≤] 0.034) was reduced in primiparous rats. Overall, our data suggest maternal hippocampal CA1 is protected from systemic inflammation but vulnerable to peripartum oxidative stress. Thus, peripartum oxidative stress elevations, such as in pregnancy complications, may contribute to peripartum neural and behavioral plasticity.

Neuroprotective properties of estrogen have poorly translated to reduced neurodegeneration in clinical trials of systemic estrogen replacement therapy. To more directly assess biological processes associated with brain estrogen (estrone, estradiol) levels, we recruited 81 women (42 non-white) and 28 men (13 non-white) for cerebrospinal fluid (CSF) proteomic and volumetric brain analysis. In these mostly post-menopausal women, we found low CSF estrogen levels to only modest correlate with their corresponding plasma levels. Aptamer-based proteomic analysis of CSF markers for inflammation, proteolysis, and DNA/RNA regulation revealed higher CSF estrogen to associate with changes involved in recruitment or activation of neutrophils, monocytes, and complement-related proteins in a race-dependent fashion. Parallel MRI analysis correlated higher CSF estrogen with smaller volumes of the brain somatosensory and posterior-medial networks without influence from cognition or neurodegeneration. These outcomes were only partially associated with plasma estrogens, reinforcing the need for improved CSF estrogen analysis to elucidate brain-specific effects.

Considerable evidence supports sex differences in episodic memory, which may translate to heightened vulnerability to stress- and trauma-related disorders in women. The hormones estradiol and oxytocin both affect episodic memory, but possible underlying hormonal interactions have not been systemically tested in humans. To this end, healthy women (n = 111) and men (n = 115) received estradiol gel (2 mg) or placebo before the administration of intranasal oxytocin (24 IU) or placebo in a randomized, placebo-controlled, parallel-group functional magnetic resonance imaging (fMRI) study. In the fMRI session, participants viewed positive, neutral, and negative scenes. A surprise recognition task was conducted three days later. Under placebo, women showed a significantly better recognition memory and increased hippocampal responses to subsequently remembered items independent of the emotional valence compared to men. The separate treatments with either hormone significantly diminished this mnemonic sex difference and reversed the hippocampal activation pattern. However, the combined treatments led to a memory performance comparable to that of the placebo group. Collectively, the results suggest that both hormones play a crucial role in modulating sex differences in episodic memory. Furthermore, possible antagonistic interactions between estradiol and oxytocin could explain previously observed opposing hormonal effects in women and men.

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.

BackgroundSingle measurements of salivary and plasmatic oxytocin are used as indicators of the physiology of the oxytocin system. However, questions remain about whether they are sufficiently stable to provide valid biomarkers of the physiology of the oxytocin system, and whether salivary oxytocin can accurately index its plasmatic concentrations. MethodsUsing radioimmunoassay, we measured baseline plasmatic and/or salivary oxytocin from two independent datasets. Dataset A comprised 17 healthy men sampled on four occasions approximately at weekly intervals. We administered exogenous oxytocin intravenously and intranasally in a triple dummy, within-subject, placebo-controlled design and compared baseline levels and the effects of routes of administration. Dataset B comprised baseline plasmatic oxytocin measurements from 20 healthy men sampled on two separate occasions. Additionally, in dataset A, we tested whether salivary oxytocin can predict plasmatic oxytocin at baseline and after intranasal and intravenous oxytocin administration. ResultsSingle measurements of plasmatic and salivary oxytocin showed poor reliability across visits in both datasets. Intranasal administration of exogenous oxytocin increases salivary oxytocin, but intravenous administration of a considerable dose does not produce any changes. Saliva and plasma oxytocin did not correlate at baseline or after administration of exogenous oxytocin. ConclusionsOur findings question the use of single measurements of baseline oxytocin concentrations in saliva and plasma as valid biomarkers of the physiology of the oxytocin system in humans. Salivary oxytocin is a weak surrogate for plasmatic oxytocin. The increases in salivary oxytocin observed after intranasal oxytocin most likely reflect unabsorbed peptide and should not be used to predict treatment effects.

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.

Adolescence is a vulnerable period for the emergence of mental health problems. Adrenarche, an early stage of pubertal development marked by rising adrenal androgens, particularly dehydroepiandrosterone (DHEA), may influence emotional and behavioral development. However, longitudinal evidence linking preadolescent endocrine influences to adolescent psychopathology remains limited. Using data from the Adolescent Brain Cognitive Development (ABCD) Study (Nmax=10,562), we analyzed whether salivary DHEA during preadolescence predicted later externalizing and internalizing symptoms during adolescence. To create a more robust estimate for hormonal levels in preadolescence, hormone concentrations were averaged across baseline and 1-year follow-up (age range=8.9-12.4 years). Outcomes were measured via the Child Behavior Checklist (CBCL) at the 2-, 3-, and 4-year follow-ups (age range=10.6-15.8 years). Sex-stratified linear mixed models were employed, adjusting for age, race/ethnicity, BMI and physical activity. In males, higher DHEA levels were linked to fewer externalizing symptoms across all follow-ups (e.g., {beta}=-0.07 SD change of CBCL per SD-change of log-transformed DHEA levels (95% CI [-0.10, -0.04] at 3-year) and to fewer internalizing symptoms at 3-year and 4-year follow-ups. The effect of preadolescent DHEA in males translated into a reduced probability of externalizing symptoms crossing borderline or clinical thresholds at each follow-up (e.g., adjusted Risk Ratio=0.76 to reach clinical threshold for CBCL externalizing per SD increase in log-transformed DHEA; 95% CI [0.62, 0.98] at 3-year). In females, no hormone-symptom associations emerged. Interestingly, sex-by-DHEA interaction effects increased with age for both symptom domains. These findings suggest that preadolescent adrenal endocrine influences may play a role in thedevelopment of sex-specific vulnerability during adolescence. Future studies should consider adrenarche as a sensitive period for hormonal effects on mental health.

In rodents and nonhuman primates, sex hormones are powerful modulators of dopamine neurotransmission. Yet little is known about hormonal regulation of the dopamine system in the human brain. Using Positron Emission Tomography (PET), we address this gap by comparing hormonal contraceptive users and non-users across multiple aspects of dopamine function: dopamine synthesis capacity via the PET radioligand 6-[18F]fluoro-m-tyrosine ([18F]FMT), baseline D2/3 receptor binding potential using [11C]raclopride, and dopamine release using methylphenidate-paired [11C]raclopride. Participants consisted of 36 healthy women (n=21 naturally cycling; n=15 hormonal contraceptive users), and men (n=20) as a comparison group. A behavioral index of cognitive flexibility was assessed prior to PET imaging. Hormonal contraceptive users exhibited greater dopamine synthesis capacity than naturally cycling participants, particularly in dorsal caudate, and greater cognitive flexibility. Further, across individuals the magnitude of striatal DA synthesis capacity was associated with cognitive flexibility. No group differences were observed in D2/3 receptor binding or dopamine release. Analyses by sex alone may obscure underlying differences in DA synthesis tied to womens hormone status. Hormonal contraception (in the form of pill, shot, implant, ring or IUD) is used by ~400 million women worldwide, yet few studies have examined whether chronic hormonal manipulations impact basic properties of the dopamine system. Findings from this study begin to address this critical gap in womens health.

Adolescence is a critical developmental period marked by significant physiological, psychological, and behavioural changes. Sex-specific biological factors can play a major role in their progression. Liquid chromatography - tandem mass spectrometry proteomic analysis was used to measure the plasma proteome abundances in 197 adolescents (11-16 years old) from the WALNUTs cohort. Orthogonal partial least squares discriminant analysis (OPLS-DA) revealed clear sex-based proteomic distinctions, with 76 proteins significantly differing between males and females after correcting for age and BMI. Gene Ontology enrichment analysis of these proteins highlighted pathways related to cell adhesion and extracellular matrix organization reflecting sex-specific developmental trajectories during puberty. Bioinformatic analysis revealed 37 proteins significantly associated with the total score of the Strengths and Difficulties Questionnaire (SDQ), with additional sex-specific associations emerging in subgroup analyses. Plasma protein abundancies in males exhibited stronger correlations with SDQ externalizing subscale scores, while in females the associations with the internalizing score were more prominent, consistent with known behavioural sex differences. Immune response and blood coagulation pathways were implicated in these associations, particularly in females, while no significant pathway enrichment was observed for males. These findings highlight both shared and sex-specific proteomic features associated with the SDQ scores in adolescents, emphasising the need to consider sex differences in proteomic studies. The results provide a critical step toward identifying biomarkers and pathways underlying sex-specific psychological and developmental processes in adolescence.

Parental rejection in captive primates represents severe early-life stress, yet intergenerational effects remain poorly characterised. We investigated spontaneous rejection in owl monkeys (Aotus nancymaae) across two generations using demographic records (n=1,372), behavioural observations (n=65), and blood miRNA profiling (n=47). Rejected individuals showed 51% reduced lifespan, decreased probability of reaching reproductive age, and increased morbidity throughout life. Critically, well-reared offspring of rejected parents exhibited similar reductions in survival to reproductive age and lifespan. Rejected adults displayed heightened fearfulness and aggression with reduced paternal care; offspring showed decreased locomotion and altered stress responses. Blood miRNA analysis revealed significant upregulation of mml-miR-30a-5p in female offspring-a miRNA associated with early-life stress and behavioural disorders in humans. These findings demonstrate intergenerational transmission of rejection effects on fitness and behaviour, with preliminary evidence suggesting epigenetic mechanisms are associated with this transmission, though multiple pathways likely operate.

Chronic stress involves both subjective appraisal and multisystem biological activation, yet these dimensions do not always converge. In a preventive medicine cohort of 1,383 adults, we investigated dissociations between perceived stress and allostatic load (AL) to identify stress phenotypes, with a particular focus on a latent profile characterized by high AL despite low perceived stress. Participants completed a comprehensive preventive health assessment and a 34-item perceived stress questionnaire (ZPSS), and AL was computed across five physiological domains. Using predefined thresholds, we delineated four stress profiles: homeostatic (low AL/low ZPSS), prodromal (low AL/high ZPSS), decompensated (high AL/high ZPSS), and a latent profile (high AL/low ZPSS). Nearly half the cohort exhibited elevated biological or psychological stress, and 14% belonged to the latent profile. These individuals showed significant multisystem dysregulation despite low perceived stress and reported the highest emotional expressivity, suggesting preserved emotional functioning despite physiological strain. Several mechanisms may underlie this dissociation, including expressive buffering, partial psychological habituation, and residual "biological scars from past stress exposures. Together, these findings reveal a substantial burden of silent physiological stress in ostensibly healthy adults and highlight the need for longitudinal and multimodal approaches to identify pre-symptomatic states and guide early, emotion-informed preventive interventions.

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.

BackgroundAdverse cardiovascular events during pregnancy (e.g., pre-eclampsia) occur at higher rates among individuals with pre-pregnancy overweight or obesity (body mass index [BMI][&ge;]25kg/m2) and have been associated with postpartum depression. However, it is unclear whether cardiovascular health (CVH), defined more holistically than the absence of cardiovascular conditions in pregnancy, relates to postpartum psychological functioning. The present study examined whether changes in CVH during the perinatal period predicted postpartum psychological functioning among individuals with pre-pregnancy BMI[&ge;]25kg/m2. MethodsIndividuals (N=226; Mage=28.43{+/-}5.4 years; MBMI=34.17{+/-}7.15kg/m2) were recruited when their pregnancies were 12-20 weeks gestation (M=15.64{+/-}2.45 weeks) for a longitudinal study of health and well-being. Participants completed the Center for Epidemiological Studies Depression Scale (CES-D) and Perceived Stress Scale (PSS) and reported on CVH behaviors (dietary intake, physical activity, nicotine exposure, and sleep) at baseline and at 6-months postpartum. BMI and CVH behaviors were coded according to the American Heart Associations Lifes Essential 8 to create a CVH score at both timepoints. Linear regression analyses were performed to examine whether change in CVH related to postpartum CES-D and PSS scores. Because sleep was only measured in a subset of participants (n=114), analyses were conducted with and without sleep included. Baseline CVH, CES-D and PSS scores, and demographic factors were included as covariates in all models. ResultsImproved CVH was associated with lower postpartum CES-D ({beta}=-0.18, p<0.01) and PSS ({beta}=-0.13, p=0.02) scores when excluding sleep. Compared to those whose CVH improved by >1SD from pregnancy to 6-months postpartum, individuals whose CVH worsened by >1SD scored 6.42 points higher on the CESD (MCESD=15.25{+/-}10.92 vs. 8.52{+/-}6.90) and 6.12 points higher on the PSS (MPSS=24.45{+/-}8.29 vs. 17.83{+/-}8.70). However, when including sleep, these relationships were no longer significant (ps>0.4). ConclusionsImprovements in CVH from early pregnancy to 6-months postpartum were associated with lower postpartum depressive symptoms and perceived stress. However, these relationships were no longer significant when including sleep in the CVH metric, potentially due to the large reduction in sample size. These data suggest that intervening during pregnancy to promote CVH may improve postpartum psychological functioning among high-risk individuals.

BackgroundHigher stress during pregnancy associates with negative outcomes and elevated inflammation. The gut microbiota reflects the environment, lifestyle, and the perinatal period. The gut microbiota, alongside host immune responses, has the potential to aid in identifying when stress is excessive. MethodsTwo U.S. cohorts, of 84 pregnant individuals, composed of urban women of color and suburban white women, completed the Perceived Stress Scale-10 (PSS-10) and provided fecal and blood samples at two time points. Confirmatory Factor Analysis assessed the robustness of a two-factor PSS-10 (Emotional Distress and Self-Efficacy) in the two cohorts. Gut microbiota composition was measured by 16S rRNA amplicon sequencing and the immune system activity was assessed with a panel of 21 T-cell related cytokines and chemokines. ResultsEmotional Distress levels were higher in the suburban compared to the urban cohort, but levels of Self-Efficacy were similar. Emotional Distress and Self-Efficacy levels were associated with distinct taxonomical signatures and the gut microbiota data improved the prediction of Self-Efficacy levels compared with models based on socio-demographic characteristics alone. Integration of self-reported symptoms, microbial and immune information revealed a possible mediation effect of Bacteroides uniformis between the immune system (through CXCL11) and Self-Efficacy. ConclusionsThe study identified links between distinct taxonomical and immunological signatures with perceived stress. The data is congruent with a model where gut microbiome and immune factors may modulate neural plasticity resulting in increased Self-Efficacy during pregnancy. The predictive value of these peripheral markers merit further study.

ObjectiveThe neurotrophic protein brain-derived neurotrophic factor (BDNF) plays a pivotal role in brain function and is affected by acute and chronic stress. We here investigate the patterns of BDNF and cortisol stress reactivity and recovery under the standardized stress protocol of the TSST and the effect of perceived chronic stress on the basal BDNF levels in healthy young men. MethodsTwenty-nine lean young men underwent the Trier Social Stress Test (TSST) and a resting condition. Serum BDNF and cortisol were measured before and repeatedly after both conditions. The perception of chronic stress was assessed by the Trier Inventory for Chronic Stress (TICS). ResultsAfter the TSST, there was a significant increase over time for BDNF and cortisol. Stronger increase in cortisol in response to stress was linked to an accelerated BDNF decline after stress. Basal resting levels of BDNF was significantly predicted by chronic stress perception. ConclusionsThe increased BDNF level following psychosocial stress suggest a stress-induced neuroprotective mechanism. The presumed interplay between BDNF and the HPA-axis indicates an antagonistic relationship of cortisol on BDNF recovery post-stress. Chronically elevated high cortisol levels, as present in chronic stress, could thereby contribute to reduced neurogenesis, and an increased risk of neurodegenerative conditions in persons suffering from chronic stress. HighlightsO_LIAcute psychosocial stress increases serum BDNF and cortisol C_LIO_LIStress-induced cortisol secretion may accelerate the decline of BDNF after stress. C_LIO_LIChronic stress is linked to lower basal serum BDNF levels C_LI