Psychoneuroendocrinology最新文献

Background

Epigenetic modifications, including DNA methylation (DNAm), can play a role in the biological embedding of early-life adversity (ELA) through serotonergic mechanisms. The current study examines methylation of the CpG island in the promoter region of the stress-responsive serotonin transporter gene (SLC6A4) and is the first to jointly assess how it is influenced by ELA severity, timing, and type—specifically, deprivation and threat.

Methods

We use data from 627 Youth Emotion Project study participants, recruited from two US high schools. Using adjusted linear regressions, we analyze DNA collected in early adulthood from 410 participants and ELA based on interviewer-rated responses from concurrent Childhood Trauma Interviews, adjusting for survey-measured covariates.

Results

ELA robustly predicted mean CpG island SLC6A4 DNAm percent across 71 CpG sites. Each additional major-severity ELA event was associated with a 0.121-percentage-point increase (p<0.001), equating to a 0.177 standard deviation (sd) higher DNAm level (95 % CI: 0.080, 0.274) with each 1-sd higher adversity score. When modeled separately, both childhood and adolescent ELA predicted SLC6A4 DNAm. When modeled jointly, adolescent ELA was most strongly predictive, and child adversity remained significantly associated with DNAm through indirect associations via adolescent adversity. Additionally, the ELA-SLC6A4 DNAm association may vary by adversity type. Across separate models for childhood and adolescent exposures, deprivation coefficients are positive and statistically significant. Meanwhile, threat coefficients are positive and not significantly significant but do not statistically differ from deprivation coefficients. In models including all ELA dimensions, one major adolescent deprivation event is associated with a 0.222-percentage-point increased SLC6A4 DNAm (p<0.05), or a 1-sd higher deprivation score with a 0.157-sd increased DNAm.

Conclusion

Results further implicate epigenetic modification on serotonergic neurotransmission via DNAm in the downstream sequelae of ELA—particularly adolescent deprivation—and support preventive interventions in adolescence to mitigate biological embedding.

While hormonal contraceptives (HCs) like oral contraceptive pills (OCs) and intrauterine devices (IUDs) can reportedly influence mood, the evidence is mixed, and the mechanisms remain unclear. Emotion reactivity and regulation processes may be hormone-sensitive and underlie these mood changes. This study sought to investigate the role of the menstrual cycle and HC use in emotion regulation using ERP measures during an emotion regulation paradigm. Participants with a natural cycle (NC) were measured in the mid-follicular and mid-luteal phase (within-subject design, n = 26), and compared with OC (n = 36) and IUD (n = 25) users. The centroparietal late positive potential (LPP) reflected negative emotion reactivity and its modulation by cognitive reappraisal served as a marker for emotion regulation processing. NC participants had a lower LPP amplitude in the mid-luteal compared to the mid-follicular phase. Reactivity to negative emotional stimuli decreased over time in the mid-luteal phase, whereas the HC groups showed sustained LPP activation. Reappraisal led only to significant LPP changes in the mid-follicular phase, and not in the mid-luteal phase or HC groups. Our results showed a specific left frontal activity (FR-LPP) in the contrast that reflected emotion regulation processing. This activity was highest in the mid-follicular phase, and was significantly different from the OC users but not from the IUD group. Higher self-reported PMS symptoms were associated with stronger effects on the reduced mid-luteal LPP activity and with lower FR-LPP amplitude in the mid-follicular phase. No effect of OC phase (active pill use versus pill pause) was found. These findings add insights into the neurophysiological underpinnings of hormone-related mood changes and demonstrate the importance of considering hormonal status and PMS symptoms in emotion research.

Severe Mental Illness (SMI) is often associated with metabolic alteration and/or metabolic syndrome, which may determine an increased mortality due to a further increased cardiovascular risk. The relationship with metabolic syndrome is often bidirectional, resulting in a pathoplastic effect of these dysmetabolisms. Among the several hormones involved, insulin appears to play a key role, albeit not entirely clear. The aim of our real-world cross-sectional observational study is to investigate a set of metabolic biomarkers of illness relapse/recurrence/onset in a cohort of 310 adult SMI inpatients consecutively admitted to the Psychiatry Clinic of the Azienda Ospedaliero Universitaria of Marche, in Ancona (Italy), between February 2021 and February 2024. According to the stepwise multivariate regression model, a higher number of acute episodes per year was positively predicted by the age of illness onset, the lifetime number of suicidal attempts and fasting insulinemia and negatively by the participant’s age. A second stepwise multivariate regression model using only the metabolic characteristics as independent variables, found that a higher number of acute episodes per year was predicted positively by the fasting insulinemia and red blood cells and negatively by the abdominal circumference. Overall, our findings could provide practical implications for the treatment and management of SMI patients, emphasizing the importance of monitoring and managing metabolic factors, particularly insulinemia, metabolic syndrome and insulin resistance. Finally, insulinemia could potentially act as metabolic biomarker of illness relapse, though more larger and longitudinal studies should be carried out to confirm these results.

Appetite hormones may play a significant role in neuronal excitability and synaptic plasticity and may also affect brain function development. This study aimed to explore the role of appetite hormones in attention deficit/hyperactivity disorder (ADHD), including aspects of pathophysiology, pharmacotherapy, and side effects. We recruited 119 patients with ADHD who were undergoing methylphenidate treatment (ADHD+MPH), 77 unmedicated ADHD patients (ADHD-MPH), and 87 healthy controls. Blood samples were collected from all participants to examine serum levels of orexin A, ghrelin, leptin, and adiponectin. Behavioral symptoms were assessed using the Swanson, Nolan, and Pelham Rating Scale, and visual and auditory attention were evaluated using computerized neuropsychological tests. The side effects of methylphenidate treatment were measured using Barkley's Side Effects Rating Scale. Orexin levels in the control group were significantly higher than in the ADHD-MPH (p=0.037) and ADHD+MPH (p<0.001) groups; additionally, orexin levels in the ADHD-MPH group were significantly higher than in the ADHD+MPH group (p=0.032). Leptin levels in both the ADHD+MPH (p=0.011) and ADHD-MPH (p=0.011) groups were significantly lower than in the control group. Ghrelin levels were positively associated with auditory attention across all ADHD groups (p=0.015). Furthermore, ghrelin levels were positively correlated with methylphenidate dosage (p=0.024), and negatively correlated with methylphenidate side effects (p=0.044) in the ADHD+MPH group. These findings provide further insight into the relationships between appetite hormones, pharmacotherapy, and ADHD. Orexin A and leptin are associated with the etiology of ADHD, while orexin A and ghrelin play important roles in attention deficits and methylphenidate usage in ADHD.

Poor maternal diet and psychosocial stress represent two environmental factors that can significantly impact maternal health during pregnancy. While various mouse models have been developed to study the relationship between maternal and offspring health and behaviour, few incorporate multiple sources of stress that mirror the complexity of human experiences. Maternal high-fat diet (HF) models in rodents are well-established, whereas use of psychosocial stress interventions in female mice are still emerging. The social instability stress (SIS) paradigm, serves as a chronic and unpredictable form of social stress. To evaluate the combined effects of a poor maternal diet and intermittent social stress on maternal health and behaviour, we developed a novel maternal stress model using adult female C57Bl/6 mice. We observed that all HF+ mice demonstrated rapid weight gain, elevated fasting blood glucose levels and impaired glucose tolerance independent of the presence (+) or absence (-) of SIS. Behavioural testing output revealed anxiety-like behaviours remained similar across all groups prior to pregnancy. However, integrated anxiety z-scores revealed a mixed anxious profile amongst HF+/SIS+ females prior to pregnancy. HF+/SIS+ females also did not show reduced plasma ACTH and corticosterone levels that were observed in our other HF+ and HF- stress groups after SIS exposure. Further, HF+/SIS+ females demonstrated significant postpartum maternal neglect, resulting in fewer numbers of live offspring. These findings suggest that prolonged maternal HF diet consumption, coupled with previous exposure to SIS, places a significant burden on the maternal stress response system, resulting in reduced parental investment and negative postpartum behaviour towards offspring.

Purpose

Few longitudinal studies have investigated the mediating role of inflammation during childhood in associations between prenatal maternal stress and adolescent mental health. The objective of this study was to examine the associations between prenatal maternal stress, concentrations of immune markers at age 9, and symptoms of generalized anxiety disorder (GAD) and depression during adolescence.

Methods

This study included 3723 mother-child pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC). Prenatal maternal stress was examined using 55 items measured during pregnancy. Inflammation was assessed using serum concentrations of interleukin-6 (IL-6) and C-reactive protein (CRP) when children were 9 years old. GAD and depression were assessed when children were 16 and 18 years of age, respectively. Analyses comprised of structural equation models.

Results

Prenatal maternal stress was associated with higher concentrations of IL-6 in childhood, and with greater symptoms of depression and GAD in adolescence. However, we did not observe associations between prenatal maternal stress and CRP; also, CRP and IL-6 were not associated with depression and GAD. There was no evidence that CRP and IL-6 mediated the associations between prenatal maternal stress and either GAD or depression.

Conclusions

Prenatal maternal stress is associated with IL-6 levels in childhood, and with GAD and depression during adolescence. Future studies should examine immune activity at multiple points during development in relation to mental health into adulthood to determine whether inflammation at different points during development could increase risk for mental health problems among children whose mothers experienced significant stressors during pregnancy.

Difficulties in fear regulation can sometimes result in maladaptive fear responses. To better understand how to improve fear regulation, it is important to determine how known factors, such as sex hormone status and stress, might interact to influence fear memory. Research has shown that women with high estradiol levels (mid-cycle) and men exhibit better extinction retention compared to women with low estradiol levels (women in the early follicular cycle or using oral contraceptives). Stress has also been demonstrated to affect both the learning and retention of extinction. Despite documented interactions between stress and sex hormones, their combined effects have not been thoroughly studied. This study aims to examine the impact of stress as a function of sex hormone status on extinction learning and retention.

A total of 168 non-clinical participants were studied, including men (n = 46), women using oral contraceptives (n = 38), women in the early follicular phase (n = 40), and women in mid-cycle (n = 44). On Day 1, fear acquisition training was performed. On day 2, prior to extinction training, half of the participants were exposed to a psychosocial stressor, while the other half performed a non-stressful control task. On day 3, extinction retention was tested. Fear was quantified using skin conductance responses, while stress hormones were quantified through saliva samples.

Exposure to stress prior to extinction training did not affect extinction learning, regardless of sex hormone status. In contrast, pre-extinction stress exposure had different effects on extinction retention depending on hormone status. Stressed men showed impairment in extinction retention compared to controls, while the experimental condition had no effect on naturally cycling women. Regardless of stress exposure, early follicular women exhibited a deficit in fear regulation, while mid-cycle women showed effective fear regulation. Among women using oral contraceptives, the stress group demonstrated better extinction retention compared to the control group.

These results demonstrate the importance of considering sex hormone status and stress exposure during extinction learning, as both components may modulate extinction retention. These results could help identifying hormonal conditions that may enhance the effectiveness of extinction-based psychological therapies used in the treatment of fear-related disorders.

Stress-related disorders are commonly associated with abnormalities in hypothalamic-pituitary-adrenal (HPA) axis activity. Preliminary studies with cortisol administration in the aftermath of trauma suggest that this HPA axis hormone can potentially prevent maladaptive behavioral and biological stress responses. However, the efficacy of glucocorticoid administration during the peripuberty period has not been tested yet, although this lifetime is a critical time window in brain development and is highly sensitive to the harmful effects of stress. To further examine the short and long-lasting impact of glucocorticoids treatment given during the post-peripubertal stress period, the present study utilized a rat model of peripubertal stress-induced psychopathology and animals were subjected to a battery of tests to assess anxiety-like behaviors, exploratory behavior and reactivity to novelty at late adolescence and sociability, anhedonia and stress coping behaviors at adulthood. All the experiments were performed in males and females to evaluate the potential behavioral sex differences. Overall, our results demonstrated that rats exposed to peripubertal stress show decreased sociability in adulthood without differences in anxiety and depression-like behaviors. Moreover, this study shows that the administration of corticosterone after stress exposure at peripuberty does not prevent stress-induced behavioral alterations. However, we observed that some stress-induced behavioural alterations and corticosterone responses are sex-specific. Thus, the data obtained highlight that delineating sex differences in stress-related studies may ultimately contribute to the development of effective therapeutic interventions for each sex.