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Genetic Variants and the Cortisol Response in Children: An Exploratory Study.

ABSTRACT: OBJECTIVE:We examined genomic variation potentially associated with the cortisol stress response in children having a painful medical procedure. DESIGN:Children 4-10 years old having a peripheral intravenous line inserted provided saliva samples for evaluation of the cortisol response as a biological measure of distress: two on the day of the procedure and two at home on a nonstressful day for comparison values. Children and biological parents also provided samples for genotyping of variants with known or suspected association with the cortisol stress response. Analysis included child-only association and family-based transmission disequilibrium tests (TDTs). RESULTS:Genotype and phenotype data on the cortisol stress response were available from 326 children for child-only association analyses and 376 complete family trios for TDTs. Children were 50% female, an average of 7.5 years old, and mostly (83%) White/non-Hispanic. We identified four single-nucleotide polymorphisms (SNPs) potentially associated with the cortisol stress response: rs1176744 ( HTR3B), rs10062367 ( CRHBP), rs634479 ( OPRM1), and rs8030107 ( NTRK3). Family-based analysis identified a two-SNP haplotype in HTR1B suggestive for association with the cortisol response (rs6296, rs11568817). Allelic TDTs identified rs7897947 ( NFKB2) as potentially related to cortisol response. CONCLUSIONS:Findings provide preliminary evidence for genes potentially important in cortisol response to an acute stressor in children in the serotonin, dopamine, and brain-derived neurotrophic factor pathways, the hypothalamic-pituitary-adrenal axis, and the inflammatory response. Combined with analyses of related phenotypes and clinical data, these results could help identify patients at increased risk of adverse responses to painful medical procedures who might benefit from tailored interventions.

SUBMITTER: Ersig AL

PROVIDER: S-EPMC6700893 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Genetic Variants and the Cortisol Response in Children: An Exploratory Study.

Ersig Anne L AL Schutte Debra L DL Standley Jennifer J Leslie Elizabeth J EJ Zimmerman Bridget B Hanrahan Kirsten K Murray Jeffrey C JC McCarthy Ann Marie AM

Biological research for nursing 20190130 2

<h4>Objective</h4>We examined genomic variation potentially associated with the cortisol stress response in children having a painful medical procedure.<h4>Design</h4>Children 4-10 years old having a peripheral intravenous line inserted provided saliva samples for evaluation of the cortisol response as a biological measure of distress: two on the day of the procedure and two at home on a nonstressful day for comparison values. Children and biological parents also provided samples for genotyping ...[more]

PMID: 30700110

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Project description:Background:Watermelon, a rich source of lycopene, has garnered attention for cardioprotective effects including cholesterol reduction and promotion of redox balance. It is unknown whether 100% watermelon juice may represent a food-first approach to confer cardioprotective benefits of lycopene. Objectives:This study examined influences of 100% watermelon juice on serum lycopene, lipids, and antioxidant capacity. Secondly, the study explored genetic influences on lycopene metabolism and bioavailability. Methods:A placebo-controlled, randomized, double-blind, crossover trial with postmenopausal women (n = 16, mean ± SD age: 60 ± 4.1 y) assessed effects of 100% watermelon juice on mechanistic and clinical outcomes influencing vascular function. Participants maintained low-lycopene diets for a 1-wk run-in period and throughout the study. Morning and evening consumption of 100% watermelon juice provided a daily dose of 14.4 ± 0.34 mg lycopene. Study arms of 4 wk were separated by a 2-wk washout period. Saliva was collected for genetic analysis of single nucleotide polymorphisms, and fasting blood samples were taken pre- and post-study arms. Statistical analyses included mixed models, linear regression, and nonparametric tests. Results:Serum lycopene exhibited a significant treatment effect (P = 0.002) along with notable interindividual responses; however, significant improvements in serum lipids or antioxidant capacity were not observed. Genetic variant rs6564851 in the ?-carotene 15,15'-oxygenase-1 (BCO1) gene was associated with changes in lycopene such that TT homozygotes exhibited a significantly greater increase (? ± SE: 13.4 ± 1.6, P = 1.4 × 10-06). Conclusions:Watermelon juice supplementation did not result in improvements in serum lipids or antioxidant capacity; however, results support findings in which watermelon juice significantly, yet differentially, increased circulating lycopene. Genetics appears to explain some of the variability. Given that dose has been shown to overcome individual responsiveness to lycopene interventions, future investigations with varying doses of lycopene-rich foods would be strengthened by genotyping so as to establish personalized nutrition recommendations.This trial was registered at clinicaltrials.gov as NCT03626168.

Project description:Abnormal hypothalamic-pituitary-adrenal (HPA) axis function, as indexed by elevated diurnal cortisol levels and/or a blunted cortisol awakening response (CAR), has been observed among patients with first episode psychosis and associated with neurocognitive deficits in this population. However, the extent to which these features precede illness onset is unclear. The current study aimed to determine whether children who are at putatively elevated risk for psychosis because they present multiple antecedents of schizophrenia (ASz), and high-risk children with a family history of illness (FHx), are characterized by abnormal cortisol levels when compared with their typically developing (TD) peers. A further aim was to investigate the extent to which cortisol levels are associated with psychosocial stress and neurocognitive function. Thirty-three ASz children, 22 FHx children, and 40 TD children were identified at age 9-12 years using a novel community-based screening procedure or as relatives of individuals with schizophrenia. All participants were antipsychotic-naive and not currently seeking treatment for their symptoms. At age 11-14 years, participants provided salivary cortisol samples and completed psychosocial stress measures and tests of memory and executive function. Results indicated that FHx children, but not ASz children, were characterized by a blunted CAR relative to their TD peers (effect size=-0.73, p=0.01) that was not explained by psychosocial stress exposure or by distress relating to these experiences. Neither FHx nor ASz children were characterized by elevated diurnal cortisol. Among both FHx and ASz children, more pronounced HPA axis function abnormalities (i.e., higher diurnal cortisol levels and greater blunting of the CAR) were associated with poorer performance on tests of verbal memory and executive function. These findings support the notion that at least some HPA axis abnormalities described in psychosis precede illness onset, rather than being a subsequent epiphenomenon. We speculate that the blunted CAR may constitute an early (potentially genetically mediated) marker of psychosis vulnerability, whilst elevated diurnal cortisol levels may emerge only proximally to disease onset.

Dataset Information

Genetic Variants and the Cortisol Response in Children: An Exploratory Study.

Publications

Genetic Variants and the Cortisol Response in Children: An Exploratory Study.

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