Psychoneuroendocrinology最新文献

Background

While peripheral markers of endogenous oxytocin and glucocorticoid release are widely employed in psychological and behavioural research, there remains uncertainty regarding the effectiveness of saliva and urine samples in accurately capturing fluctuating hormone levels in response to relevant stimuli. In addition, it is unclear whether and under which conditions, urinary concentrations correlate with salivary levels of oxytocin and cortisol.

Methods

In the present study, two groups of healthy adult male and female participants (N=43) provided heart rate, saliva, and urine samples before and after exercising at different durations and intensities (3 ×10 min of running vs. 60 min of running). Effects of age, gender, cycle phase, and previous running experience were considered in the statistical analyses. Concentrations of oxytocin and cortisol were analysed in both saliva, and urine using validated assays.

Results

Runners of both groups had significantly increased oxytocin concentrations in urine and saliva after running than before. Oxytocin in saliva was elevated after 10 min and peaked after 30 min of running. Only participants of the long-running group showed an increase in urinary cortisol concentrations following exercise (and only after 90 min of stimulus onset), and neither group had a significant increase in salivary cortisol levels. Oxytocin rise in urine and saliva from basal to post-run was strongly and significantly correlated, as was cortisol rise from basal to post-rest, but no correlations between absolute hormone concentrations were found for oxytocin.

Conclusions

Our results show that both urine and saliva are useful body fluids that can provide meaningful results when measuring oxytocin and cortisol concentrations after a physical stimulus. While temporal resolution may be better with salivary sampling as higher sampling frequency is possible, signal strength and robustness were better in urinary samples. Importantly, we report a strong correlation between the magnitude of change in oxytocin and cortisol concentrations in urine and saliva following physical exercise, but no correlations between absolute oxytocin concentrations in the two substrates.

Background

Genetic copy number variants (CNVs; i.e., a deletion or duplication) at the 22q11.2 locus confer increased risk of neuropsychiatric disorders and immune dysfunction. Inflammatory profiles of 22q11.2 CNV carriers can shed light on gene-immune relationships that may be related to neuropsychiatric symptoms. However, little is known about inflammation and its relationship to clinical phenotypes in 22q11.2 CNV carriers. Here, we investigate differences in peripheral inflammatory markers in 22q11.2 CNV carriers and explore their relationship with psychosis risk symptoms and sleep disturbance.

Methods

Blood samples and clinical assessments were collected from 22q11.2 deletion (22qDel) carriers (n=45), 22q11.2 duplication (22qDup) carriers (n=29), and typically developing (TD) control participants (n=92). Blood plasma levels of pro-inflammatory cytokines, including interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), and anti-inflammatory cytokine interleukin-10 (IL-10) were measured using a MesoScale Discovery multiplex immunoassay. Plasma levels of C-reactive protein (CRP) were measured using Enzyme-linked Immunosorbent Assay (ELISA). Linear mixed effects models controlling for age, sex, and body mass index were used to: a) examine group differences in inflammatory markers between 22qDel, 22qDup, and TD controls, b) test differences in inflammatory markers between 22qDel carriers with psychosis risk symptoms (22qDelPS+) and those without (22qDelPS-), and c) conduct an exploratory analysis testing the effect of sleep disturbance on inflammation in 22qDel and 22qDup carriers. A false discovery rate correction was used to correct for multiple comparisons.

Results

22qDup carriers exhibited significantly elevated levels of IL-8 relative to TD controls (q<0.001) and marginally elevated IL-8 levels relative to 22qDel carriers (q=0.08). There were no other significant differences in inflammatory markers between the three groups (q>0.13). 22qDelPS+ exhibited increased levels of IL-8 relative to both 22qDelPS- (q=0.02) and TD controls (p=0.002). There were no relationships between sleep and inflammatory markers that survived FDR correction (q>0.14).

Conclusion

Our results suggest that CNVs at the 22q11.2 locus may have differential effects on inflammatory processes related to IL-8, a key mediator of inflammation produced by macrophages and microglia. Further, these IL-8-mediated inflammatory processes may be related to psychosis risk symptoms in 22qDel carriers. Additional research is required to understand the mechanisms contributing to these differential levels of IL-8 between 22q11.2 CNV carriers and IL-8’s association with psychosis risk.

Dementia spousal caregivers are at risk for adverse mental and physical health outcomes. Caregiver burden, anticipatory grief, and proinflammatory cytokine production may contribute to depressive symptoms among caregivers. People who report childhood trauma are more likely to have exaggerated stress responses that may also contribute to depressive symptoms in adulthood. This study aimed to test whether the relationship between whole-blood cytokine production and depressive symptoms is strongest in caregivers who report high levels of childhood trauma.

Methods

A sample of 103 dementia spousal caregivers provided self-report data on demographics, health information, caregiver burden, anticipatory grief, and depressive symptoms. We also determined lipopolysaccharide-induced whole-blood cytokine production as the primary measure of immune cell reactivity. We measured interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) and converted z-scores of each cytokine into a composite panel. We regressed depressive symptoms on proinflammatory cytokine production, caregiver burden, and anticipatory grief, adjusting for demographic and health-related covariates.

Results

Whole-blood cytokine production and childhood trauma were associated with depressive symptoms. Childhood trauma moderated the relationship between whole-blood cytokine production and depressive symptoms. Whole-blood cytokine production was only associated with depressive symptoms at mean and high levels of childhood trauma, but not at low levels of childhood trauma. The main effects of burden and anticipatory grief on depressive symptoms were strongest for caregivers reporting high levels of childhood trauma.

Discussion

Childhood trauma has lasting impacts on psychosocial experiences later in life and has effects that may confer susceptibility to inflammation-related depression. Our findings contribute to ongoing efforts to identify risk factors for adverse mental health in dementia spousal caregivers.

Intro

Prenatal exposure to synthetic glucocorticoids may increase the risk of emotional symptoms in childhood partly by reducing fetal growth. We explored if physiological levels of prenatal maternal cortisol were associated with internalising problems in boys and girls and if this was mediated by birth weight.

Methods

Mother-child dyads from the prospective Odense Child Cohort (n=1162) were included if maternal serum cortisol (3rd trimester), offspring birth weight, and Child Behaviour Checklist (CBCL) assessments in preschool age were available. Crude and adjusted associations between cortisol and internalising problems were determined in linear mixed models stratified by offspring sex. Covariates included parental psychiatric history, parity, maternal age, education, smoking during pregnancy, and gestational age at birth. In the presence of significant associations, we evaluated the potential mediating role of birth weight.

Results

The study sample included 601 boys and 561 girls and internalising problems were assessed at mean ages 2.3 (±0.4) and 5 (±0.5) years. In the crude analysis, cortisol was positively associated with internalising problems in boys (p-value 0.017) and in girls (p-value < 0.0001). In the adjusted analyses, there was no statistically significant association between cortisol and offspring internalising problems in boys or girls (all p-values > 0.15). There was no mediation by birth weight.

Discussion

Maternal serum cortisol was positively associated with offspring internalising problems in boys and girls, but there was no association following adjustment for potential confounders and no mediation through birth weight. Maternal third-trimester cortisol levels do not predict preschool offspring internalising problems in our study.

Objective

Previous research has suggested beneficial effects of music in reducing stress levels. However, there is no consistent conclusion demonstrating that music can contribute to stress recovery, primarily due to limitations in stress measurement, and inconsistent methodology within existing studies. Our study explores whether relaxing music, especially when self-selected, outperforms non-music acoustic, and silence conditions, fostering both subjective and biological stress recovery.

Methods

One hundred and five healthy female participants underwent the Trier Social Stress Test (TSST) before being randomly allocated to one of four conditions: condition 1 (n = 25) listened to researcher-selected relaxing music; condition 2 (n = 27) listened to self-selected relaxing music; condition 3 (n = 26) listened to the sound of rippling water; and condition 4 (n = 27) remained in silence. Stress parameters were repeatedly measured nine times before and after the TSST. Saliva samples were collected for cortisol and saliva alpha-amylase (sAA) analysis, Movisens equipment was used to measure heart rate (HR) and skin conductance levels (SCL), and Visual Analogue Scales (VAS) were used for subjective stress measurement.

Results

The examination of SCL, and VAS scores revealed no significant changes following the four relaxation interventions. Although sAA displayed a significant main effect of condition, post hoc tests did not pinpoint specific differences. HR recovery patterns varied among the four relaxation interventions, with the sound of rippling water condition exhibiting a later significant decrease compared to the other conditions. Exploratory analyses revealed that cortisol levels continued increase in all conditions during intervention phase except the researcher-selected music condition.

Conclusions

The subjective and biological stress markers did not exhibit better recovery after the music stimulus, except for a tendency in the researcher-selected music condition to mitigate the continued increase in cortisol levels after the stress test. Our study provides the first evidence comparing the impact of researcher- and participant-selected music with silence and a non-music acoustic stimulus, on both subjective and biological stress recovery. Our findings contribute to a more nuanced understanding of the impact of music on stress recovery.

Hair and nail cortisol is increasingly studied as a physiologic proxy for chronic stress response. Glucocorticoid use is an expected confounder for cortisol measurement, yet there remains little evidence of whether external cortisol use should be subject to exclusion in study subjects. In a group of 209 youth (15–22 year-olds), we analyzed hair and fingernail cortisol concentrations. We assessed topical, nasal, oral, and injectable glucocorticoid use via a questionnaire. Extensively validated methods were used for hair and nail cortisol extraction and measurements. The median value of hair cortisol was 10.2 pg/mg (n=200), and the median value of nail cortisol was 7.06 pg/mg (n=203). Topical glucocorticoid use significantly increased hair and nail cortisol concentrations (p<0.005). Hair and nail cortisol concentrations were positively associated (p<0.0001, n=194). Spearman correlation coefficients demonstrated that the positive correlation between hair and nail cortisol values was higher in participants who used external glucocorticoids. Topical glucocorticoids moderated the association between hair and nail cortisol values (p=0.006). Based on these findings, we recommend that the assessment of topical glucocorticoid use must be performed when collecting hair/nail samples and that subjects reporting glucocorticoid use should be excluded from all future hair and nail cortisol studies; also, all outliers must be excluded to account for glucocorticoid medication underreporting and yet-unknown confounders.

Osteocalcin is a bone-derived hormone implicated in the acute stress response and recently linked to adult depression. Yet it is unclear whether osteocalcin is a biomarker of other forms of psychopathology and whether osteocalcin-psychopathology associations emerge during developmentally sensitive periods earlier in life. Thus, in the current pilot study we examined salivary osteocalcin and psychiatric symptoms and disorders among 48 early adolescents during a period of stress. A logistic regression indicated lower osteocalcin was associated with meeting criteria for a psychiatric disorder, OR = 0.43, 95 % CI [.002,.924], and showed moderate-to-large cross-sectional associations with a range of elevated psychopathology symptoms, Bs ≥ |-3.44|, ps ≤.034. Multilevel linear growth models indicated that low osteocalcin prospectively predicted an even greater range of psychopathology symptoms at one-year follow-up as well as increases in some symptoms over time, Bs ≥ |-1.83|, ps ≤.021. Findings introduce osteocalcin as a biomarker of diverse forms of psychopathology in youth. Osteocalcin is a potential transdiagnostic mechanism through which dysregulated responses to stress could cause or exacerbate various types of psychopathology, highlighting a promising target for clinical assessment and early intervention.

Objective

Cognitive impairment, especially impaired social cognition, is largely responsible for the deterioration of the social life of patients with schizophrenia (SZ). Oxytocin (OT) is a neuropeptide that offers promising therapy for SZ. This study aimed to explore whether OT could affect dizocilpine (MK801)-induced cognitive impairment and to investigate the effect of exogenous OT on the endogenous OT system in the hippocampus.

Methods

The SZ mouse model was established by repeated administration of dizocilpine [MK801, 0.6 mg/kg, intraperitoneal (i.p.)], and then OT (6–60 μg/kg, intranasal) or risperidone (0.3 mg/kg, i.p.) was administered to explore the effect of OT on cognitive impairment.

Results

OT at a dose of 6 μg/kg alleviated MK801-induced hyperactivity, sociability impairment, and spatial memory impairment. OT at a dose of 20 or 60 μg/kg attenuated the hyperactivity and social novelty impairment. In MK801-injected mice, the compensatory upregulation of OT mRNA in the hippocampus was reversed by three OT doses, whereas 60 μg/kg OT reversed the compensatory upregulation of CD38 protein expression.

Conclusion

OT alleviated cognitive impairment in the SZ mouse model to varying degrees, reversing the compensatory upregulation of OT signaling in the hippocampus.