Adult Stress Research Articles

Dysregulated HPA axis during postnatal developmental stages in the BTBR T+ Itpr3tf/J mouse: A model of autism spectrum disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder. Some children with ASD show enhanced cortisol response to stress. BTBR T+ Itpr3tf/J (BTBR) mice, an ASD model, display behavior consistent with the three diagnostic categories of ASD and exhibit an exaggerated response to stress in adulthood. However, it remains unclear how basal corticosterone levels change and how the hypothalamic-pituitary-adrenal axis responds to stress during the early life stages in BTBR mice. In this study, we found that basal corticosterone levels showed characteristic changes, peaking at weaning during postnatal development in both BTBR and control C57BL/6J (B6J) mice. Furthermore, we observed higher corticosterone and corticotropin-releasing hormone levels in BTBR mice than in B6J mice following acute stress exposure during weaning; however, adrenocorticotropic hormone levels were lower in BTBR mice. Glucocorticoid receptor mRNA expression levels in the hippocampus and lateral septum after stress were higher in BTBR mice than in B6J mice. This study documented changes in corticosterone levels at baseline during postnatal development in mice and showed that BTBR mice exhibited disrupted stress responses at weaning.

Developmental Thermal Conditioning Regulates Oxidative State and Beak Coloration in Response to Thermal Stressors in Adulthood

Developmental Thermal Conditioning Regulates Oxidative State and Beak Coloration in Response to Thermal Stressors in Adulthood

Triangulation for causal loop diagrams: constructing biopsychosocial models using group model building, literature review, and causal discovery

AbstractThe complex nature of many health problems necessitates the use of systems thinking tools like causal loop diagrams (CLDs) to visualize the underlying causal network and facilitate computational simulations of potential interventions. However, the construction of CLDs is limited by the constraints and biases of specific sources of evidence. To address this, we propose a triangulation approach that integrates expert and theory-driven group model building, literature review, and data-driven causal discovery. We demonstrate the utility of this triangulation approach using a case example focused on the trajectory of depressive symptoms in response to a stressor in healthy adults. After triangulation with causal discovery, the CLD exhibited (1) greater comprehensiveness, encompassing multiple research fields; (2) a modified feedback structure; and (3) increased transparency regarding the uncertainty of evidence in the model structure. These findings suggest that triangulation can produce higher-quality CLDs, potentially advancing our understanding of complex diseases.

Examining childhood and adulthood stressors as risk factors for gestational diabetes mellitus in working pregnant individuals: A prospective cohort study

AimsThis study aimed to examine the individual and joint associations of adverse childhood experiences (ACEs) and maternal work and non-work related stressors with the risk of gestational diabetes mellitus (GDM). MethodsWorking pregnant individuals (n = 1163) from a United States (U.S.) prospective cohort conducted in South Carolina between 2016 and 2021 were included in the study. ACEs were assessed at study enrollment before 20 gestational weeks (GW), while maternal stressors were assessed in late pregnancy and GDM diagnosis occurred between 24 and 30 GW. Multivariable logistic regressions were performed to assess associations of ACEs and maternal stressors with GDM. ResultsChildhood abuse, an ACE subdomain, was associated with an elevated but statistically insignificant risk of GDM (adjusted OR = 1.47; 95 % CI: 0.85–2.53). Only maternal work stressors were associated with an increased risk of GDM (adjusted OR = 2.11; 95 % CI: 1.17–3.79) and the association became much stronger among those with childhood abuse experiences (adjusted OR = 3.80; 95 % CI:1.68–8.60). ConclusionAmong U.S. working pregnant individuals, having work stressors during pregnancy was associated with an elevated risk of developing GDM, particularly among those who had childhood experience of abuse.

Chronic stress in adulthood results in microvascular dysfunction and subsequent depressive-like behavior

Depression is a prevalent mental disorder characterized by unknown pathogenesis and challenging treatment. Recent meta-analyses reveal an association between cardiovascular risk factors and an elevated risk of depression. Despite this, the precise role of vascular injury in depression development remains unclear. In this investigation, we assess vascular system function in three established animal models of depression— chronic unpredictable mild stress (CUMS), chronic social defeat stress (CSDS) and maternal separation (MS)—utilizing ultrasonography and laser Doppler measurement. All three model animals exhibit anhedonia and despair-like behavior. However, significant microvascular dysfunction (not macrovascular) is observed in animals subjected to CUMS and CSDS models, while such dysfunction is absent in the MS model. Statistical analysis further indicates that microcirculation dysfunction is not only associated with depression-like behavior but is also intricately involved in the development of depression in the CUMS and CSDS models. Furthermore, our study has proved for the first time that endothelial nitric oxide synthase-deficient (eNOS+/−) mice, which is a classic model of vascular endothelial injury, showed depression-like behavior which occurred two months later than microvascular dysfunction. Notably, the mitigation of microvascular dysfunction successfully reverses depression-like behavior in eNOS+/− mice by enhancing nitric oxide production. In conclusion, this study unveils the pivotal role of microvascular dysfunction in the onset of depression induced by chronic stress in adulthood and proposes that modulating microvascular function may serve as a potential intervention in the treatment of depression.

Early-Life Milk αS1-Casein Allergy Induces the Activation of Astrocytes in Mice and Leads to Stress Vulnerability in Adulthood.

In recent years, the incidence of food allergies in children has been increasing annually, significantly affecting the quality of life for patients and their families. It has long been suspected that childhood allergies might potentially lead to behavioral and psychological issues in adulthood, but the specific connection remains unclear. In this study, we established a model of young mice allergic to milk αS1-casein, conducted behavioral tests, and employed transcriptomics, immunohistochemistry, Golgi staining, and fecal microbiota transplantation to explore the link between early life allergies and adult psychological problems. The results showed that early life milk protein allergy significantly increased intestinal epithelial permeability in mice, leading to the translocation of gut microbiota metabolites. This process subsequently activated astrocyte lysosomes via SLC15a3, making astrocytes more susceptible. This susceptibility caused mice with early life milk protein allergy to have more activated astrocytes and excessive dendritic spine phagocytosis (normal group: 5.4 ± 1.26 spines/10 μm, allergy group: 3.2 ± 0.92 spines/10 μm) under acute stress in adulthood, leading to anxiety and depressive behaviors.

The relationship between alcohol bingeing in the gestational period of wistar rats and the development of schizophrenia in the offspring adult life

The incidence of schizophrenia in young adulthood may be associated with intrauterine factors, such as gestational alcohol consumption. This study investigated the relationship between a single high dose of alcohol during pregnancy in Wistar rats and the development of schizophrenia in the adult life of the offspring. On the 11th day of gestation, pregnant rats received either water or alcohol via intragastric gavage. Male and female offspring were subjected to behavioral tests at 30 days of age according to the maternal group. At 60 days of age, offspring received intraperitoneal injections of ketamine (ket) or saline (SAL). After the final ketamine administration, the adult offspring underwent behavioral tests, and their brain structures were removed for biochemical analysis. Alcohol binge drinking during pregnancy induces hyperlocomotion in both young female and male offspring, with males of alcohol-exposed mothers showing reduced social interactions. In adult offspring, ketamine induced hyperlocomotion; however, only females in the alcohol + ket group exhibited increased locomotor activity, and a decrease in the time to first contact was observed in the alcohol group. Cognitive impairment was exclusively observed in male animals in the alcohol group. Increased serotonin and dopamine levels were observed in male rats in the alcohol + ket group. Biochemical alterations indicate the effects of intrauterine alcohol exposure associated with ketamine in adult animals. These behavioral and biochemical changes suggest that the impact of prenatal stressors such as alcohol persists throughout the animals’ lives and may be exacerbated by a second stressor in adulthood, such as ketamine.

Sex-Specific Impacts of Early Life Sleep Disruption: Ethanol Seeking, Social Interaction, and Anxiety Are Differentially Altered in Adolescent Prairie Voles.

Early life sleep is important for neuronal development. Using the highly social prairie vole rodent model, we have previously reported that early life sleep disruption (ELSD) during the preweaning period results in interference with social bonding and increases ethanol consumption following a stressor in adulthood. Furthermore, ELSD increases parvalbumin expression and reduces glutamatergic neurotransmission in cortical regions in adult prairie voles. To understand the impact of ELSD on the lifespan, an examination of an earlier time in life is necessary. The aim of the present study was to examine behavioral outcomes of ELSD on adolescent prairie voles. Given the known effects of ELSD on development of neuronal systems involved in mood and social motivation, we hypothesized that anxiety, risk, and reward-related behaviors would be impacted by ELSD in adolescent prairie voles. We report that both male and female adolescent prairie voles that experienced ELSD showed heightened anxiety-like behavior compared to age-matched controls (CONs) as measured by a light-dark box. Additionally, both male and female ELSD voles showed reductions in both ethanol preference and consumption, and affiliative behavior compared to CONs. These results suggest that adolescent prairie voles of both sexes experience heightened anxiety-like behavior and reduced reward-seeking behaviors after ELSD. These results further suggest that early life sleep is critically important for neurotypical behaviors in adolescence.

Microglia: The Drunken Gardeners of Early Adversity.

Early life adversity (ELA) is a heterogeneous group of negative childhood experiences that can lead to abnormal brain development and more severe psychiatric, neurological, and medical conditions in adulthood. According to the immune hypothesis, ELA leads to an abnormal immune response characterized by high levels of inflammatory cytokines. This abnormal immune response contributes to more severe negative health outcomes and a refractory response to treatment in individuals with a history of ELA. Here, we examine this hypothesis in the context of recent rodent studies that focus on the impact of ELA on microglia, the resident immune cells in the brain. We review recent progress in our ability to mechanistically link molecular alterations in microglial function during a critical period of development with changes in synaptic connectivity, cognition, and stress reactivity later in life. We also examine recent research showing that ELA induces long-term alterations in microglial inflammatory response to "secondary hits" such as traumatic brain injury, substance use, and exposure to additional stress in adulthood. We conclude with a discussion on future directions and unresolved questions regarding the signals that modify microglial function and the clinical significance of rodent studies for humans.

Impact of stress during adolescence on general and work-related stress in early adulthood: A prospective cohort study

Impact of stress during adolescence on general and work-related stress in early adulthood: A prospective cohort study

Future time perspective and depression, anxiety, and stress in adulthood

ABSTRACT Background and objective Research has shown that perceptions of future time as limited are associated with more depressive symptoms. However, there is limited research on which dimensions of future time perspective (FTP: opportunity, extension, constraint) are associated with depression, anxiety, and stress, and whether these findings vary across age. Design and methods Data came from a cross-sectional study in a nonclinical U.S. sample (N = 793, 48.0% male; 48.7% female; age: M = 50 years, range: 19–85 years), and local structural equation modeling was used to examine the moderating role of age as a continuous variable rather than artificial age groups. Results For all dimensions of FTP, the perception of the future as limited was moderately to strongly associated with higher depression, anxiety and stress levels. More importantly, the association between the perceived constraint dimension and depression, anxiety, and stress was twice as large at younger ages than at older ages. Conclusion These findings indicate that perceived constraint is primarily a strong risk factor for or indicator of negative wellbeing in young adulthood, whereas perceived limited opportunity and extension are potential risk factors or indicators across the entire adulthood.

Juvenile/Peripubertal Exposure to Omega-3 and Environmental Enrichment Differentially Affects CORT Secretion and Adulthood Stress Coping, Sociability, and CA3 Glucocorticoid Receptor Expression in Male and Female Rats.

In adult rats, omega-3 supplementation through fish oil (FO) and environmental enrichment (EE) have shown beneficial effects on cognition and stress regulation. This study assessed sex-specific effects of FO and EE during adolescence, a period critical for brain maturation, on adulthood coping mechanisms, sociability, and glucocorticoid regulation. An amount of 64 Wistar rats [n = 32/sex; postnatal day (PND) 23] were assigned to supplementation of control soybean oil (CSO) or menhaden fish oil (FO; 0.3 mL/100 g) from PND28 to 47 and exposed to EE or regular cage (RC) housing from PND28 to 58, with their blood corticosterone (CORT) levels being assessed weekly. As adults, exposure to repeated forced swim tests (FSTs; PND90-91) enabled analysis of coping responses, while socioemotional and memory responses were evaluated using the OFT, EPM, SIT, and Y maze tests (PND92-94). Immunohistochemistry determined hippocampal CA1/CA3 glucocorticoid receptor (GR) expression (PND95). CORT secretion gradually increased as the supplementation period elapsed in female rats, while changes were minimal in males. Coping strategies in the FST differed between sexes, particularly in FO-fed rats, where females and males, respectively, favoured floating and tail support to minimise energy consumption and maintain immobility. In the SIT, FO/EE promoted sociability in females, while a CSO diet favoured social recognition in males. Reduced CA3 GR-ir expression was found in FO/RC and CSO/EE rat groups, supporting stress resilience and memory consolidation. Our findings support environment and dietary conditions to exert a sex-specific impact on biobehavioural responses.

Early life thermal conditioning alters heat-shock protein expression in response to an adult thermal stressor.

Developmental environmental stressors can have instructive effects on an organism's phenotype. This developmental plasticity can prepare organisms for potentially stressful future environments, circumventing detrimental effects on fitness. However, the physiological mechanisms underlying such adaptive plasticity are understudied, especially in vertebrates. We hypothesized that captive male zebra finches (Taeniopygia castanotis) exposed to a mild heat conditioning during development would acquire a persisting thermotolerance, and exhibit increased heat-shock protein (HSP) levels associated with a decrease in oxidative damage when exposed to a high-intensity stressor in adulthood. To test this, we exposed male finches to a prolonged mild heat conditioning (38°C) or control (22°C) treatment as juveniles. Then in a 2 × 2 factorial manner, these finches were exposed to a high heat stressor (42°C) or control (22°C) treatment as adults. Following the adult treatment, we collected testes and liver tissue and measured HSP70, HSP90, and HSP60 protein levels. In the testes, finches exhibited lower levels of HSP90 and HSP60 when exposed to the high heat stressor in adulthood if they were exposed to the mild heat conditioning as juveniles. In the liver, finches exposed to the high heat stressor in adulthood had reduced HSP90 and HSP60 levels, regardless of whether they were conditioned as juveniles. In some cases, elevated testes HSP60 levels were associated with increased liver oxidative damage and diminishment of a condition-dependent trait, indicating potential stress-induced tradeoffs. Our results indicate that a mild conditioning during development can have persisting effects on HSP expression and acquired thermotolerance.

Early-Life Resource Scarcity in Mice Does Not Alter Adult Corticosterone or Preovulatory Luteinizing Hormone Surge Responses to Acute Psychosocial Stress.

Early-life stressors can affect reproductive development and change responses to adult stress. We tested if resource scarcity in the form of limited bedding and nesting (LBN) from postnatal days (PND) 4 to 11 delayed sexual maturation in male and female mice and/or altered the response to an acute, layered, psychosocial stress (ALPS) in adulthood. Contrary to the hypotheses, age and mass at puberty were unaffected by the present application of LBN. Under basal conditions and after ALPS, corticosterone concentrations in males, diestrous females, and proestrous females reared in standard (STD) or LBN environments were similar. ALPS disrupts the luteinizing hormone (LH) surge in most mice when applied on the morning of proestrus; this effect was not changed by resource scarcity. In this study, the paucity of effects in the offspring may relate to a milder response of CBA dams to the paradigm. While LBN dams exited the nest more often and their offspring were smaller than STD-reared offspring on PND11, dam corticosterone concentrations were similar on PND11. To test if ALPS disrupts the LH surge by blunting the increase in excitatory GABAergic input to gonadotropin-releasing hormone (GnRH) neurons on the afternoon of proestrus, we conducted whole-cell voltage-clamp recordings. The frequency of GABAergic postsynaptic currents in GnRH neurons was not altered by LBN, ALPS, or their interaction. It remains possible that ALPS acts at afferents of GnRH neurons, changes response of GnRH neurons to input, and/or alters pituitary responsiveness to GnRH and that a more pronounced resource scarcity would affect the parameters studied.

Associations between adversity in the family of origin and hair cortisol concentration in adulthood.

The current study examined associations between parental adversities as experienced in adolescence and hair cortisol concentration (HCC) 26 years later (n = 47). Specifically, bivariate correlations and linear regressions were used to examine harsh parenting as well as parental economic pressure, emotional distress, and body mass index (BMI) when their adolescent was between 15 and 16 years old (parent average age 43). HCC was measured when the adolescent was an adult (average 42 years old), at a similar age to when their parent(s) first participated in the study. We also assessed their economic pressure, emotional distress, obesity, and perceived stress in adulthood. For results across generations, parental economic pressure experienced during adolescence was significantly related to HCC when these adolescents were adults. None of the adult economic pressure, emotional distress, BMI, and perceived stress variables were associated with their HCC. Interestingly, there were significant associations among adult perceived stress, economic pressure, emotional distress, and obesity. Thus, the association between parental economic pressure and adult HCC is independent of adult adversities. Results highlight early economic adversity as a possible childhood stressor that has implications throughout the life course.

Perceived Stress and Life Stressors in Adults with and without Fibromyalgia.

Chronic medical conditions (i.e., chronic widespread pain) may contribute to accelerated/accentuated aging, such that middle-aged individuals with comorbidities may actually show increased declines in physical, cognitive, and mental health compared to normal aging adults. We examined perceived stress, life stressors, and depression in adults with and without fibromyalgia, a chronic pain condition. Ninety-four participants (52% with fibromyalgia, 78% female) aged 50 to 93 were administered the Perceived Stress Scale, Social Readjustment Rating Scale, and Beck Depression Inventory. Hierarchical regression analyses were conducted: the predictor variables were age, gender, fibromyalgia status, depression, and fibromyalgia-depression interaction. The interaction term significantly predicted perceived stress, but not life stressors. Depression significantly predicted stress for Social Readjustment Rating Scale measures after controlling for covariates. Significant associations were found between perceived stress and life stressors in all participants. In addition, those with fibromyalgia were significantly more likely to report higher levels of stress above standardized scores on both the Perceived Stress Scale and the Social Readjustment Rating Scale. Finally, depressive symptoms played a more significant role than fibromyalgia status in predicting life stressors. Conclusions: These findings emphasize the importance of assessing different types of stress and stressors in individuals with chronic widespread pain and/or depression in mid-life and beyond to better treat individuals with these conditions.

Differences in Digital Stress in Early Adulthood in Terms of Personality Types Extraversion and Neuroticism

Differences in Digital Stress in Early Adulthood in Terms of Personality Types Extraversion and Neuroticism

Exposure to elevated glucocorticoid during development primes altered transcriptional responses to acute stress in adulthood

Early life stress (ELS) is a major risk factor for developing psychiatric disorders, with glucocorticoids (GCs) implicated in mediating its effects in shaping adult phenotypes. In this process, exposure to high levels of developmental GC (hdGC) is thought to induce molecular changes that prime differential adult responses. However, identities of molecules targeted by hdGC exposure are not completely known. Here, we describe lifelong molecular consequences of hdGC exposure using a newly developed zebrafish double-hit stress model, which shows altered behaviors and stress hypersensitivity in adulthood. We identify a set of primed genes displaying altered expression only upon acute stress in hdGC-exposed adult fish brains. Interestingly, this gene set is enriched in risk factors for psychiatric disorders in humans. Lastly, we identify altered epigenetic regulatory elements following hdGC exposure. Thus, our study provides comprehensive datasets delineating potential molecular targets mediating the impact of hdGC exposure on adult responses.

Did childhood adversity increase the vulnerability of university students to the negative mental health impact of the COVID-19 pandemic?

Objective To examine a potential synergistic effect of history of childhood adversity and COVID-19 pandemic exposure on the association with mental health concerns in undergraduate students. Participants: We used U-Flourish Survey data from 2019 (pre-pandemic) and 2020 (during-pandemic) first-year cohorts (n = 3,149) identified at entry to a major Canadian University. Methods Interactions between childhood adversity (physical and sexual abuse, and peer bullying) and COVID-19 pandemic exposure regarding mental health concern (depressive and anxiety symptoms, suicidality, and non-suicidal self-harm) were examined on an additive scale. Results We found a positive additive interaction between physical abuse and pandemic exposure in relation to suicidality (combined effect was greater than additive effect (risk difference 0.54 vs. 0.36)). Conversely, less than additive interactions between peer bullying and pandemic regarding depression and anxiety were observed. Conclusions Childhood adversities have diverse reactions to adult stressor depending on the nature of the childhood adversity and the mental health outcomes.

War-Related Life Course Stress and Late-Life Subjective Age in Northern Vietnam.

The role of early life stressors in subjective aging is weakly understood, especially in low- to middle-income countries. This paper investigated how early life stressors encountered in armed conflict influence subjective age among Vietnamese older adults who experienced war over decades of their early life. We analyzed survey data from the 2018 Vietnam Health and Aging Study involving 2,447 Vietnamese older adults who encountered diverse war-related stressors in early adulthood. The analytical sample (N = 2,341) included 50.9% women and 49.1% men, with an average age of 69.8. 41.1% are military veterans. We conducted survey-adjusted multinomial logistic regression analyses with mediation to predict the probability of feeling younger or older than one's chronological age. We examined how childhood adversity (i.e., childhood hunger and low parental SES) and wartime stressors (i.e., war-related violence, malevolent environment, and military service) influenced late-life subjective age, both directly and as mediated by late-life mental, functional, and physical health. We found significant associations between early adulthood war-related stressors and subjective age. Formal military service significantly lessened the relative risk of feeling subjectively old, and more plentiful wartime violence exposures significantly increased the risk of feeling younger than one's chronological age. Violence exposure's effects were both direct and indirect through functional and mental health. Conversely, greater exposure to wartime malevolent conditions (e.g., shortages of clean water and evacuations) and multiple episodes of severe hunger in childhood increased the risk of feeling older, effects both direct and mediated by late-life functional and mental health. Results suggest wartime stressors, especially war's malevolent environments and severe childhood hunger, experienced in many conflict-affected populations globally, have the potential to subjectively "age" survivors. Yet, not all war exposures are equal, and some may yield psychological and socioeconomic resources that support healthy aging.