Abstract
Background: Early life nutrition may affect individuals' susceptibility to adult non-communicable diseases (NCD). Psychological stress is a well-recognised NCD risk factor. Recent evidence suggests that impaired foetal nutrition alters neuro-endocrine pathways, and hypothalamic-pituitary-adrenal axis feedback systems, resulting in abnormal stress responses, and NCD risk. This study aims to examine adolescent cortisol and cardiovascular stress responses in relation to maternal nutrition and contemporaneous NCD risk markers. Methods: The study sample will be drawn from three well-established birth cohorts in India; the Parthenon cohort, Mysore (N=550, age~20y), the SARAS KIDS prenatal intervention cohort, Mumbai (N=300, age~10-12y) and the Pune Rural Intervention in Young Adults/ PRIYA cohort, Pune (N=100, age~22y). We will perform the 'Trier Social Stress Test (TSST)', a well-accepted stress-test module which involves participants performing 5-minutes each of public speaking and mental arithmetic tasks in front of unfamiliar 'judges' (stressor). Repeated measures of salivary cortisol and autonomic cardiovascular outcomes relative to the stressor will be assessed. Measures of psychological stress, cognitive function, blood pressure, glucose-insulin metabolism and depression will be carried out. Mechanistic studies including DNA methylation in gluco-corticoid receptor ( NR3C1) and 11β-HSD2 gene loci and neuroimaging will be carried out in a subsample. Qualitative interviews and focus group discussions in a subsample of the Parthenon cohort will explore the perception of stress and stressors among the youth. We will convert repeated measures into time-weighted averages before analysis. We will carry out multivariable regression analysis to test the associations. We will further refine the analyses using the mixed-model regression and conditional analyses for the association with repeated measures. Ethics and dissemination: This study has been approved by the research ethics committee of CSI Holdsworth Memorial Hospital, Mysore. The findings will be disseminated locally and at international meetings, and reports will be submitted to open access peer reviewed journals.
Highlights
Psychological stress is an unpleasant subjective experience, caused by an awareness of situational demands exceeding an individual’s adaptive capacity[1]. It has been identified as an important lifestyle risk factor for adult non-communicable disease (NCD)[2]
It is suggested that repeated psychological stress induces dysregulated HPA axis activity and autonomic cardiovascular control, reflected in either exaggerated or blunted responses of these systems to acute stress
The current study proposes to build on the previous evidence to understand the life course factors that predict adolescent stress responses
Summary
Psychological stress is an unpleasant subjective experience, caused by an awareness of situational demands exceeding an individual’s adaptive capacity[1]. Test the persistence of the association of birth weight, and maternal GDM and micronutrient status with cortisol and autonomic cardiovascular responses to acute stress in adolescents. We will test the hypothesis that current micronutrient supplementation is associated with improved cortisol and cardiovascular responses to stress in young adults exposed to maternal nutritional deficiencies. Metanalysis: We will do metanalyses of data from Mysore, Mumbai and Pune components of the study on the association of stress responses with 1) maternal nutritional status and 2) offspring NCD risk markers. Pune: As there are no earlier studies on the effect of current nutritional intervention on stress responses, we based the sample size for this study on the findings from comparison of effect size between the offspring of B12 deficient and normal B12 status mother. Qualitative interviews have been carried out among 5 adolescents/young adults
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