Associations between Social Adversity and Biomarkers of Inflammation, Stress, and Aging in Children.

BACKGROUND: Prior work has found relationships between childhood social adversity and biomarkers of stress, but knowledge gaps remain. To help address these gaps, we explored associations between social adversity and biomarkers of inflammation (interleukin-1ß [IL-1ß], IL-6, IL-8, tumor necrosis factor-alpha [TNF-α], and salivary cytokine hierarchical "clusters" based on the three interleukins), neuroendocrine function (cortisol, cortisone, dehydroepiandrosterone, testosterone, and progesterone), neuromodulation (N-arachidonoylethanolamine, stearoylethanolamine, oleoylethanolamide, and palmitoylethanolamide), and epigenetic aging (Pediatric-Buccal-Epigenetic clock). METHODS: We collected biomarker samples of children ages 0-17 recruited from an acute care pediatrics clinic and examined their associations with caregiver-endorsed education, income, social risk factors, and cumulative adversity. We calculated regression-adjusted means for each biomarker and compared associations with social factors using Wald tests. We used logistic regression to predict being in the highest cytokine cluster based on social predictors. RESULTS: Our final sample included 537 children but varied based on each biomarker. Cumulative social adversity was significantly associated with having higher levels of all inflammatory markers and with cortisol, displaying a U-shaped distribution. There were no significant relationships between cumulative social adversity and cortisone, neuromodulation biomarkers or epigenetic aging. CONCLUSION: Our findings support prior work suggesting that social stress exposures contribute to increased inflammation in children. IMPACT: Our study is one of the largest studies examining associations between childhood social adversity and biomarkers of inflammation, neuroendocrine function, neuromodulation, and epigenetic aging. It is one of the largest studies to link childhood social adversity to biomarkers of inflammation, and the first of which we are aware to link cumulative social adversity to cytokine clusters. It is also one of the largest studies to examine associations between steroids and epigenetic aging among children, and one of the only studies of which we are aware to examine associations between social adversity and endocannabinoids among children. CLINICAL TRIAL REGISTRATION: NCT02746393.

Impact of parental socioeconomic status on offspring's mental health: protocol for a longitudinal community-based study.

INTRODUCTION: Socioeconomic status (SES) affects physical and mental health and cognitive functioning. The association between SES changes (SES mobility) and health has ethical and political implications in that the pernicious effects of inequality and the differential impact on social classes of economic and social policies. There is a lack of research conducted to explore the intergenerational transmission of parental SES changes on the offspring's mental health and cognitive functioning. We aim to fill this gap and identify roles of parental SES changes in offspring's mental health and cognitive outcomes. METHODS AND ANALYSIS: This study will be based on a longitudinal cohort from the most populous municipality in the Canadian province of Quebec. Participants and their biological offspring will be invited to this study. For those with informed consent, we will collect their information on mental health, psychiatric disorders, cognitive functioning and early life experiences for offspring. Latent class growth analysis will be used to identify parental SES mobility groups. Multivariate regression analyses will be used to explore the roles of early life stress, parental SES mobility and their interactions in psychiatric disorders and cognitive functioning. Subgroup analyses (males and females) are also planned. ETHICS AND DISSEMINATION: This study has been given ethical approval by the Research Ethics Board of the Douglas Mental Health University Institute (IUSMD-18/17). Each participant will provide informed consent on participation. We will disseminate research findings through publication in peer-reviewed academic journals and presentations at conferences. Lay summaries of major research findings will also be shared annually with our partners in the health system and community agencies located in the catchment area.

Effects of Antenatal Maternal Depressive Symptoms and Socio-Economic Status on Neonatal Brain Development are Modulated by Genetic Risk.

This study included 168 and 85 mother-infant dyads from Asian and United States of America cohorts to examine whether a genomic profile risk score for major depressive disorder (GPRSMDD) moderates the association between antenatal maternal depressive symptoms (or socio-economic status, SES) and fetal neurodevelopment, and to identify candidate biological processes underlying such association. Both cohorts showed a significant interaction between antenatal maternal depressive symptoms and infant GPRSMDD on the right amygdala volume. The Asian cohort also showed such interaction on the right hippocampal volume and shape, thickness of the orbitofrontal and ventromedial prefrontal cortex. Likewise, a significant interaction between SES and infant GPRSMDD was on the right amygdala and hippocampal volumes and shapes. After controlling for each other, the interaction effect of antenatal maternal depressive symptoms and GPRSMDD was mainly shown on the right amygdala, while the interaction effect of SES and GPRSMDD was mainly shown on the right hippocampus. Bioinformatic analyses suggested neurotransmitter/neurotrophic signaling, SNAp REceptor complex, and glutamate receptor activity as common biological processes underlying the influence of antenatal maternal depressive symptoms on fetal cortico-limbic development. These findings suggest gene-environment interdependence in the fetal development of brain regions implicated in cognitive-emotional function. Candidate biological mechanisms involve a range of brain region-specific signaling pathways that converge on common processes of synaptic development.

Cortisol awakening response and subsequent depression: prospective longitudinal study.

BACKGROUND: Some studies have found an association between elevated cortisol and subsequent depression, but findings are inconsistent. The cortisol awakening response may be a more stable measure of hypothalamic-pituitary-adrenal function and potentially of stress reactivity. AIMS: To investigate whether salivary cortisol, particularly the cortisol awakening response, is associated with subsequent depression in a large population cohort. METHOD: Young people (aged 15 years, n = 841) from the Avon Longitudinal Study of Parents and Children (ALSPAC) collected salivary cortisol at four time points for 3 school days. Logistic regression was used to calculate odds ratios for developing depression meeting ICD-10 criteria at 18 years. RESULTS: We found no evidence for an association between salivary cortisol and subsequent depression. Odds ratios for the cortisol awakening response were 1.24 per standard deviation (95% CI 0.93-1.66, P = 0.14) before and 1.12 (95% CI 0.73-1.72, P = 0.61) after adjustment for confounding factors. There was no evidence that the other cortisol measures, including cortisol at each time point, diurnal drop and area under the curve, were associated with subsequent depression. CONCLUSIONS: Our findings do not support the hypothesis that elevated salivary cortisol increases the short-term risk of subsequent depressive illness. The results suggest that if an association does exist, it is small and unlikely to be of clinical significance.

Maternal prenatal anxiety and downregulation of placental 11ß-HSD2.

BACKGROUND: Raised maternal anxiety during pregnancy is associated with increased risk of adverse neurodevelopmental outcomes for her child. The mechanisms underlying this are not known but animal studies suggest prenatal stress may alter the function of the placenta. Here we determined whether maternal prenatal anxiety was associated with a downregulation of placental 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2), the enzyme which metabolises cortisol. METHODS: We recruited mothers the day before delivery by elective caesarean, and gave them the Spielberger Trait and State anxiety and Edinburgh Depression self-rating scales. Placentae were collected and aliquots stored for later analysis. RESULTS: Prenatal Trait anxiety was negatively correlated with placental 11ß-HSD2 mRNA expression (r=-0.40, p<0.01, n=56). Results were similar with male and female fetuses (r=-0.39, p=0.04, n=28; r=-0.40, p=0.03, n=28) respectively. Results were also significant with State anxiety (r=-0.27, p=0.05, n=56) but somewhat weaker for depression (r=-0.20, p=0.13, n=56). Preliminary analyses on a subset of cases (n=25) suggested parallel results for enzyme activity. CONCLUSIONS: These findings provide evidence for an association between prenatal maternal mood and downregulation of placental 11ß-HSD2. Results are consistent with raised maternal anxiety being associated with increased fetal exposure to maternal cortisol, and support the hypothesis that this may be one mechanism underlying fetal programming by prenatal stress.