心理学最新文献

Adolescence is a sensitive window for the maturation of hypothalamic-pituitary-adrenal (HPA) axis function; however, the timing and mechanisms underlying this transition remain unclear, particularly in females and in response to repeated homotypic stress. We measured corticosterone (CORT) release and glucocorticoid-related gene expression in postpubertal (P45) and adult (P75) male and female rats after acute or repeated restraint. In males, adolescents elicited higher CORT responses than adults did after acute stress, although both ages showed habituation to repeated restraint. In contrast, females exhibited adult-like CORT responses by P45 and no evidence of habituation. At the molecular level, adolescents of both sexes displayed distinct medial prefrontal cortex and ventral hippocampus expression profiles of glucocorticoid receptor (Nr3c1) and co-chaperones (Fkbp4, Fkbp5) relative to adults, though these effects were more pronounced in females, for whom there were also age- and stress-dependent changes in mineralocorticoid receptor (Nr3c2) expression. These findings suggest that while hormonal stress responses mature earlier in females than in males, sex-specific trajectories of molecular regulation continue to develop into late adolescence, potentially shaping long-term vulnerability to stress-related disorders.

Depression is one of the most common health concerns all around the globe. Valproic acid (VPA) is an anticonvulsant agent, with neuroprotective, anti-apoptotic, anti-inflammatory, and antidepressant effects in animal models. We carried out a systematic review of articles that reported the effect of VPA on stress-related depression in animal models. A search of databases was conducted with keywords related to valproic acid (VPA) and stress-induced depression. Data from the Forced Swimming Test (FST), Open Field Test (OFT), Novel Object Recognition (NOR), and Sucrose Preference Test (SPT) were extracted. Meta-analysis was conducted using Stata 14, and standardized mean differences (SMD) were calculated. Quality control and subgroup analysis were carried out. Meta-analysis of FST results obtained from 16 separate experiments showed that VPA had a strong effect in reducing the percentage immobility, signifying lower stress compared to the untreated group (SMD = -0.93; 95% CI = -1.66 to -0.21; p = 0.012). When administered via injection for four consecutive weeks, VPA at a dosage of 300 mg/kg/day significantly decreased depressive symptoms. Results from the vertical OFT in seven studies and the horizontal OFT in six studies indicated that VPA increased movement scores. SPT results in nine separate experiments showed that VPA significantly increased the animals' desire to drink sucrose water. Analysis of the NOR test demonstrated that VPA had no significant effects on the ability of animals to identify a new object. Our findings suggest that VPA can exert antidepressant-like effects in rat models of stress-induced depression, but heterogeneity and potential publication bias suggests caution is required.

Hair cortisol concentration (HCC) reflects long-term hypothalamic-pituitary-adrenal (HPA) axis activity and is a biomarker of chronic stress. Although HCC has been linked to mental health, less is known about how genetic susceptibility and early adversity jointly influence cortisol regulation, particularly in low- and middle-income countries (LMICs). This study examined whether harsh parenting predicts adolescent HCC and whether this association is moderated by genetic variation. Data were drawn from 1,823 participants in the 2004 Pelotas (Brazil) Birth Cohort, followed at ages 6, 11, and 15. Genetic data were obtained using the Illumina Global Screening Array v2, and HCC was measured at age 15 using ELISA. Harsh parenting was assessed using the Conflict Tactics Scales: Parent-Child Version, and cumulative exposure was analyzed using linear regression models. Gene-by-environment interaction analyses tested whether rs11621961 moderated the association between harsh parenting and HCC. Greater cumulative exposure to harsh parenting, particularly overall harsh parenting and corporal punishment, was associated with higher HCC at age 15. Evidence of G × E interaction indicated stronger associations among individuals carrying more copies of the T allele, suggesting a gene-dosage effect. These findings highlight how genetic susceptibility may amplify the physiological consequences of early-life stress in LMIC settings.

Posttraumatic stress disorder (PTSD) occurs after exposure to a traumatic event, leading to debilitating symptoms, including avoidance, hypervigilance, and functional impairment. There is a paucity of effective therapies to treat PTSD, partially due to the difficulty in identifying consistent underlying mechanisms. Using a modified single prolonged stress (mSPS) paradigm combined with single housing to induce both acute fear conditioning and chronic stress in mice, we developed a novel analysis method to robustly define a PTSD-like phenotype based on the criteria from the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V). Following mSPS exposure, C57BL/6NHsd mice underwent behavioral testing to examine each of the criteria of PTSD according to the DSM-V. Specific parameters with the largest effect sizes between mSPS and non-mSPS mice were chosen. Absolute z-scores were generated for each behavioral parameter, and mSPS mice whose z-scores were outside the 85th confidence interval for at least one parameter for each of the eight criteria were defined as susceptible; the remainder of the exposed mice were considered resilient. Finally, resilient mice were evaluated for anhedonia and hyperlocomotive behaviors. The results demonstrated that a PTSD-like phenotype can be robustly defined in mice based on all 8 DSM-V criteria. Importantly, 29.76% of mSPS mice were classified as susceptible, which is similar to the incidence observed in humans exposed to trauma. This novel behavioral analysis method may assist in better defining a PTSD-like phenotype, identifying a more robust population, which may help facilitate the discovery of the underlying mechanism(s) of PTSD and its association with other comorbidities.

Early Life Stress (ELS) increases the risk for mental health issues in humans, notably in major depression and anxiety disorders. ELS is frequently modeled in laboratory rodents by disrupting the early postnatal environment. Literature on ELS is expanding, yet studies on sex-specific differences remain mixed. We utilized a novel ELS protocol that subjected mouse pups of both sexes to maternal separation and removed pup-to-pup contact comfort during postnatal days 10 to 17. We hypothesized that this ELS protocol would induce depressive and anxiety-like phenotypes persisting into adulthood, with greater vulnerability in females. A second cohort reared under normal conditions until adulthood was subjected to forced swim, mimicking adult-onset stress (AS). ELS, AS, and control animals (reared under normal conditions) underwent open field, social interaction, and tail suspension tests. In open field, AS mice spent significantly less time in center than controls. Social interaction showed significant effects of treatment and sex, with stress exposure increasing familiar-mouse interaction time and reducing the sex difference observed in controls. Tail suspension testing revealed a significant decrease in latency to immobility for stress groups compared to controls. Total time immobile showed significant group and interaction effects, with stress groups showing more time immobile. Both social interaction and tail suspension revealed a sex difference in controls, eliminated in stress groups. This ELS protocol produces lasting alterations in adult social and coping-related behaviors and demonstrates multiple sex-specific outcomes.

Chronic fatigue after Epstein-Barr virus (EBV) infection is a significant health problem among adolescents, yet its underlying mechanisms remain unclear. This study investigated whether preinfection hair cortisol levels predict chronic fatigue following acute EBV infection and examined the associations between hair cortisol and concurrent fatigue during acute infection, six months postinfection, and in healthy controls. This study is part of the CEBA project (Chronic Fatigue following Acute Epstein-Barr Virus Infection in Adolescents). Hair samples for cortisol measurements were obtained from 192 adolescents aged 12-20 years during acute EBV infection and again six months later, and from 66 age- and sex-matched healthy controls. Fatigue was measured by the total score on the Chalder Fatigue Questionnaire. Group comparisons were performed using nonparametric tests, and associations were examined with linear regression analyses. Adolescents with EBV infection had significantly higher preinfection hair cortisol levels (median 5.12, IQR: 3.27-8.76) compared with healthy controls did (median 3.90, IQR: 2.61-6.19) and with their own levels six months later (median 3.74, IQR: 2.46-6.52). A trend toward a positive association between preinfection hair cortisol and fatigue during acute infection, became significantly negative six months later. No associations were found among controls. Preinfection hair cortisol concentration did not predict chronic fatigue six months after acute EBV infection. Elevated preinfection hair cortisol may reflect stress-related vulnerability to infection, and the shifted from a positive to a negative association over time, suggests that HPA-axis alterations are more likely a consequence rather than a cause of chronic fatigue.

Heat stress is a well-known stressor that causes heat illnesses. Heat stress causes significant cardiovascular changes needed for temperature control through vasodilation and sweating. Therefore, the objective was to assess photoplethysmogram (PPG)-derived pulse rate variability (PRV) characteristics for predicting heat stress in a preclinical model. Ten male Wistar rats (10-12 weeks old) were divided into control (n = 5) and experimental (n = 5) groups. The subjects were exposed to 38 ± 1 °C and 24 ± 1 °C for 30 minutes daily for five consecutive days. The rectal temperature, electrocardiogram (ECG), and PPG signals were recorded after the 5th day of exposure. Pulse rate variability (PRV) was analyzed using time-domain, frequency-domain, and nonlinear metrics derived from PPG signals. Pulse arrival time (PAT) was estimated from synchronized ECG-PPG recordings and used to compute pulse wave velocity (PWV). A Naive Bayes classifier was trained using selected PRV features to distinguish heat stress from control conditions. The core body temperature increased by 0.5 °C (p < 0.05) under elevated heat stress for five consecutive days. The results also indicated a reduction in PRV under heat stress, suggesting increased sympathetic and withdrawal of parasympathetic activity, highlighting the physiological alterations induced by heat stress. A slight increase in pulse wave velocity (PWV) was also observed, revealing minimal heat-related changes in arterial stiffness. Further, the PRV parameters-based Naive Bayes algorithm demonstrated an accuracy of 94.58% in the prediction of the heat stress event. The findings highlighted the withdrawal of parasympathetic activity and the potential of PPG-derived parameters as a modality for predicting heat stress events.

The pathophysiology of psychiatric disorders is complex and involves multiple biological systems. The allostatic load (AL) model offers a framework to capture this multisystem dysregulation by assessing biomarkers that reflect the activity of different physiological systems. This systematic review aimed to summarise current literature on the association between AL and psychiatric disorders. The databases Medline (Ovid), PsycINFO, Ovid Emcare, CINAHL, Cochrane, and Scopus were systematically searched from inception to July 2025. A total of twenty-eight studies were included in the systematic review, and sixteen were eligible for meta-analysis. We found that individuals with a psychiatric disorder demonstrated elevated AL compared to healthy controls (HCs). Furthermore, the meta-analyses revealed an overall standardised mean difference of the between-group meta-analysis, which demonstrated higher AL in individuals with schizophrenia and first-episode psychosis (SMD: 0.97; 95% CI: 0.76, 1.18; p < .0001) compared to HCs. In contrast, no significant difference in AL was observed for individuals with major depressive disorder (SMD: 0.07; 95% CI: -0.23; 0.37; p = 0.67). In conclusion, the AL model may offer a valuable tool for evaluating the impact of chronic stress across various biological systems. This approach can be applied to the early intervention of the core pathophysiology as well as systemic comorbidities that are common among those with psychiatric symptoms.