Publications by authors named "Darlene A Kertes"

22 Publications

  • Page 1 of 1

Dehydroepiandrosterone at birth: Response to stress and relation to demographic, pregnancy and delivery factors.

J Neuroendocrinol 2020 10 1;32(10):e12906. Epub 2020 Oct 1.

Department of Psychology, University of Florida, Gainesville, FL, USA.

Enhanced production of dehydroepiandrosterone (DHEA) by the foetal hypothalamic-pituitary-adrenal (HPA) axis enables maturational events critical for labour induction and neonatal adaptation. Despite knowledge of the interconnected nature of maternal and foetal physiology and dramatic changes in DHEA production after birth, few studies have examined DHEA levels in newborns and none have examined DHEA's response to acute stress. Understanding normative patterns of early DHEA activity is needed to accurately assess functioning of the biological stress system with relevance for health and development. The present study analysed DHEA concentrations and change after stress among 93 newborns and associations with pregnancy, delivery and demographic risk factors. Three saliva samples, collected prior to and following a blood draw stressor, were used to determine baseline and stress reactive DHEA levels. Mothers self-reported on health behaviours during pregnancy. Data on obstetric factors were obtained from medical records. DHEA levels declined from pre- to post-stressor assessments. Results also showed that post-stressor DHEA change was significantly associated with administration of medications used to treat pain and accelerate labour. However, there was no significant variation in DHEA pre-stress levels or change after stress as a function of time after birth. By capturing DHEA levels after birth, the present study provides a window into prenatal health of the HPA system. The study also advances knowledge of DHEA in newborns by providing data on reference levels and important covariates. This information on basic adrenal physiology provides a foundation that can be expanded on to enhance understanding of early hypothalamic-pituitary-adrenal axis activity.
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http://dx.doi.org/10.1111/jne.12906DOI Listing
October 2020

The impact of maternal stress on infant alpha-amylase is buffered by high infant regulation and low infant negative reactivity.

Dev Psychobiol 2019 12 19;61(8):1204-1213. Epub 2019 Apr 19.

Department of Psychology, University of Florida, Gainesville, Florida.

This study examined the main and interactive effects of maternal perceived stress and infant temperament-surgency, negative affectivity, and orienting/regulation-on infant salivary alpha-amylase (sAA) responses to stress. Saliva samples were collected prior to and following two naturalistic stressors: maternal separation conducted at 9 months and blood draw/immunizations conducted at 12 months. sAA area under the curve (AUC) was computed to determine response of the sympathetic nervous system to each stressor. Results revealed significant interactions of maternal stress and infant negative affectivity and orienting/regulation with sAA AUC. Relations between maternal stress and infant sAA AUC were stronger among infants with higher levels of negative affectivity and lower levels of orienting/regulation. These results highlight the need to examine both infant characteristics and environmental factors when investigating the development of stress response systems.
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http://dx.doi.org/10.1002/dev.21858DOI Listing
December 2019

Associations between Maternal Psychosocial Stress, DNA Methylation, and Newborn Birth Weight Identified by Investigating Methylation at Individual, Regional, and Genome Levels.

Hum Biol 2019 Apr;91(2):117-131

Department of Anthropology, University of Florida, Gainesville, Florida, USA.

Stress is known to affect health throughout life and into future generations, but the underlying molecular mechanisms are unknown. We tested the hypothesis that maternal psychosocial stress influences DNA methylation (DNAm), which in turn impacts newborn health outcomes. Specifically, we analyzed DNAm at individual, regional, and genome-wide levels to test for associations with maternal stress and newborn birth weight. Maternal venous blood and newborn cord blood ( = 24 and 22, respectively) were assayed for methylation at ∼450,000 CpG sites. Methylation was analyzed by examining CpG sites individually in an epigenome-wide association study (EWAS), as regional groups using variably methylated region (VMR) analysis in maternal blood only, and through the epigenome-wide measures using genome-wide mean methylation (GMM), Horvath's epigenetic clock, and mitotic age. These methylation measures were tested for association with three measures of maternal stress (maternal war trauma, chronic stress, and experience of sexual violence) and one health outcome (newborn birth weight). We observed that maternal experiences of war trauma, chronic stress, and sexual assault were each associated with decreased newborn birth weight ( < 1.95 × 10 in all cases). Testing individual CpG sites using EWAS, we observed no associations between DNAm and any measure of maternal stress or newborn birth weight in either maternal or cord blood, after Bonferroni multiple testing correction. However, the top-ranked CpG site in maternal blood that associated with maternal chronic stress and sexual violence before multiple testing correction is located near the gene. Testing at a regional level, we found increased methylation of a VMR in maternal blood near that was associated with chronic stress and sexual violence after Bonferroni multiple testing correction ( = 1.95 × 10 and 8.3 × 10, respectively). At the epigenomic level, cord blood GMM was associated with significantly higher levels of war trauma ( = 0.025) and was suggestively associated with sexual violence ( = 0.053). The other two epigenome-wide measures were not associated with maternal stress or newborn birth weight in either tissue type. Despite our small sample size, we identified associations even after conservative multiple testing correction. Specifically, we found associations between DNAm and the three measures of maternal stress across both tissues; specifically, a VMR in maternal blood and GMM in cord blood were both associated with different measures of maternal stress. The association of cord blood GMM, but not maternal blood GMM, with maternal stress may suggest different responses to stress in mother and newborn. It is noteworthy that we found associations only when CpG sites were analyzed in aggregate, either as VMRs or as a broad summary measure of GMM.
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http://dx.doi.org/10.13110/humanbiology.91.2.04DOI Listing
April 2019

Protective Factors Buffer Life Stress and Behavioral Health Outcomes among High-Risk Youth.

J Abnorm Child Psychol 2019 08;47(8):1289-1301

Department of Psychology, University of Florida, Gainesville, FL, 32611-2250, USA.

This study investigated internalizing problems, externalizing problems, and polydrug use among African-American youth residing in high-poverty neighborhoods, and tested the potential protective effects of religiosity, parental monitoring, and neighborhood collective efficacy on life stress and behavioral health outcomes (N = 576; 307 females; Mage = 16 years, SD = 1.44 years). A cumulative risk index reflected the combined effects of past year exposure to stressful life events, racial discrimination, and exposure to violence along with poor neighborhood ecology. Structural equation modeling revealed that cumulative risk significantly predicted internalizing problems, externalizing problems, and polydrug use. Interaction tests showed that the association of cumulative risk with internalizing problems was buffered by adolescent religiosity and neighborhood collective efficacy. The association of cumulative risk with externalizing problems was buffered by parental monitoring and collective efficacy. Adolescent sex further moderated these effects. The findings of the present study collectively highlight potential for protective factors to buffer effects of cumulative risk on behavioral health outcomes among youth residing in high-risk neighborhoods.
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http://dx.doi.org/10.1007/s10802-019-00515-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6616218PMC
August 2019

Children's Relationship With Their Pet Dogs and Genotype Predict Child-Pet Interaction in an Experimental Setting.

Front Psychol 2018 5;9:1472. Epub 2018 Sep 5.

Department of Psychology, University of Florida, Gainesville, FL, United States.

Human-animal interaction (HAI) research has increasingly documented the important role of pet dogs in children's lives. The quality of interaction between children and their pet dogs, however, is likely influenced by individual differences among children as well as their perceived relationship with their pet dog. Ninety-seven children aged 7-12 years and their pet dogs participated in a laboratory protocol during which the child solicited interaction with their dog, from which time petting and gazing were recorded. Children reported on their perceived relationship with the pet dog via interview. Children provided saliva samples, from which a polymorphism in the oxytocin receptor, rs53576, which has long been implicated in social behavior, was genotyped. The results showed that genotype and children's perceived antagonism with the pet dog predicted the amount of petting, but not gazing, between children and their pet dogs. This research adds to the growing body of HAI research by documenting individual differences that may influence children's interactions with animals, which is key to research related to pet ownership and understanding factors that may impact therapeutic interventions involving HAI.
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http://dx.doi.org/10.3389/fpsyg.2018.01472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134068PMC
September 2018

Putting a finger on the problem: Finger stick blood draw and immunization at the well-child exam elicit a cortisol response to stress among one-year-old children.

Psychoneuroendocrinology 2018 07 22;93:103-106. Epub 2018 Apr 22.

Department of Pediatrics, University of Florida, Gainesville, FL, USA.

Research examining stress reactivity of the hypothalamic-pituitary-adrenocortical (HPA) axis in young children has historically been hampered by a lack of reliable methods to invoke a cortisol stress response. This report details an effective method of eliciting a cortisol rise in one-year-old children (N = 83) by modifying and combining two naturalistic stressors previously used with infants and children. Salivary cortisol levels were collected from children before and after a finger stick blood draw and immunizations performed during their one year well-child checkup at their pediatrician's office. Results indicated that the stressor was successful at eliciting a significant cortisol response. An extensive set of potential demographic and clinical confounds were also assessed in order to identify methodological considerations important in studies of infant cortisol. The stress paradigm presented here provides a promising alternative for studies of infant HPA activity to enable investigators to more effectively evaluate early functioning of the biological stress system during this developmentally important life stage.
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http://dx.doi.org/10.1016/j.psyneuen.2018.04.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7075369PMC
July 2018

DNA methylation of methylation complex genes in relation to stress and genome-wide methylation in mother-newborn dyads.

Am J Phys Anthropol 2018 01 13;165(1):173-182. Epub 2017 Oct 13.

University of Florida, Gainesville, Florida 32611.

Objectives: Early life stress is known to have enduring biological effects, particularly with respect to health. Epigenetic modifications, such as DNA methylation, are a possible mechanism to mediate the biological effect of stress. We previously found correlations between maternal stress, newborn birthweight, and genome-wide measures of DNA methylation. Here we investigate ten genes related to the methylation/demethylation complex in order to better understand the impact of stress on health.

Materials And Methods: DNA methylation and genetic variants at methylation/demethylation genes were assayed. Mean methylation measures were constructed for each gene and tested, in addition to genetic variants, for association with maternal stress measures based on interview and survey data (chronic stress and war trauma), maternal venous, and newborn cord genome-wide mean methylation (GMM), and birthweight.

Results: After cell type correction, we found multiple pairwise associations between war trauma, maternal GMM, maternal methylation at DNMT1, DNMT3A, TET3, and MBD2, and birthweight.

Conclusions: The association of maternal GMM and maternal methylation at DNMT1, DNMT3A, TET3, and MBD2 is consistent with the role of these genes in establishing, maintaining and altering genome-wide methylation patterns, in some cases in response to stress. DNMT1 produces one of the primary enzymes that reproduces methylation patterns during DNA replication. DNMT3A and TET3 have been implicated in genome-wide hypomethylation in response to glucocorticoid hormones. Although we cannot determine the directionality of the genic and genome-wide changes in methylation, our results suggest that altered methylation of specific methylation genes may be part of the molecular mechanism underlying the human biological response to stress.
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http://dx.doi.org/10.1002/ajpa.23341DOI Listing
January 2018

methylation in mothers and newborns is associated with maternal exposure to war trauma.

Clin Epigenetics 2017 30;9:68. Epub 2017 Jun 30.

Department of Anthropology and University of Florida Genetics Institute, University of Florida, Gainesville, FL USA.

Background: The gene codes for brain-derived neurotrophic factor, a growth factor involved in neural development, cell differentiation, and synaptic plasticity. Present in both the brain and periphery, BDNF plays critical roles throughout the body and is essential for placental and fetal development. Rodent studies show that early life stress, including prenatal stress, broadly alters methylation, with presumed changes in gene expression. No studies have assessed prenatal exposure to maternal traumatic stress and methylation in humans. This study examined associations of prenatal exposure to maternal stress and methylation at CpG sites across the gene.

Results: Among 24 mothers and newborns in the eastern Democratic Republic of Congo, a region with extreme conflict and violence to women, maternal experiences of war trauma and chronic stress were associated with methylation in umbilical cord blood, placental tissue, and maternal venous blood. Associations of maternal stress and methylation showed high tissue specificity. The majority of significant associations were observed in putative transcription factor binding regions.

Conclusions: This is the first study in humans to examine methylation in relation to prenatal exposure to maternal stress in three tissues simultaneously and the first in any mammalian species to report associations of prenatal stress and methylation in placental tissue. The findings add to the growing body of evidence highlighting the importance of considering epigenetic effects when examining the impacts of trauma and stress, not only for adults but also for offspring exposed via effects transmitted before birth.
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http://dx.doi.org/10.1186/s13148-017-0367-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493129PMC
April 2018

Effect of Pet Dogs on Children's Perceived Stress and Cortisol Stress Response.

Soc Dev 2017 May 28;26(2):382-401. Epub 2016 Jul 28.

University of Florida.

The present study tested whether pet dogs have stress-buffering effects for children during a validated laboratory-based protocol, the Trier Social Stress Test for Children (TSST-C). Participants were 101 children aged 7-12 years with their primary caregivers and pet dogs. Children were randomly assigned in the TSST-C to a pet present condition or one of two comparison conditions: parent present or no support figure present. Baseline, response, and recovery indices of perceived stress and cortisol levels were computed based on children's self-reported feelings of stress and salivary cortisol. Results indicated that in the alone (no social support) condition, children showed the expected rise for both perceived stress and cortisol response to stress. Pet dog presence significantly buffered the perceived stress response in comparison to children in the alone and parent present conditions. No main condition effect was observed for cortisol; however, for children experiencing the stressor with their pet present, lower cortisol response to stress was associated with more child-initiated petting and less dog proximity-seeking behavior. The results support the notion that pet dogs can provide socio-emotional benefits for children via stress buffering.
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http://dx.doi.org/10.1111/sode.12203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5400290PMC
May 2017

Behavioral and Self-report Measures Influencing Children's Reported Attachment to Their Dog.

Anthrozoos 2016 8;29(1):137-150. Epub 2016 Mar 8.

Department of Psychology, Arizona State University, Tempe, AZ.

Despite the prevalence of dogs as family pets and increased scientific interest in canine behavior, few studies have investigated characteristics of the child or dog that influence the child-dog relationship. In the present study, we explored how behavioral and self-report measures influence a child's reported feelings of attachment to their dog, as assessed by the Lexington Attachment to Pets Scale (LAPS). We tested specifically whether children (= 99; Age: 10.25 years, SD= 1.31 years) reported stronger attachment to dogs that were perceived as being more supportive (measured by a modified version of the Network of Relationships Inventory), to dogs that are more successful in following the child's pointing gesture in a standard two-object choice test, or to dogs that solicited more petting in a sociability assessment. In addition, we assessed whether children's attachment security to their parent, and whether being responsible for the care of their dog, influenced reported feelings of attachment to the dog. Overall, perceived support provided by the dog was highly predictive of all subscales of the LAPS. The dog's success in following the child's pointing gesture and lower rates of petting during the sociability assessment were associated with higher ratings on the general attachment subscale of the LAPS, but not of other subscales of the LAPS. Caring for the dog did not predict the child's reported attachment to dog, but did predict the dog's behavior on the point following task and petting during the sociability task. If the child cared for the dog, the dog was more likely to be successful on the pointing task and more likely to be petted. These results indicate a dyadic relationship in which the child's care for the dog is associated with the dog's behavior on the behavioral tasks, which in turn is related to the child's reported feelings of attachment. The direction of influence and nature of this dyad will be a fruitful area for future research.
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http://dx.doi.org/10.1080/08927936.2015.1088683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5214578PMC
March 2016

Cortisol and DHEA in development and psychopathology.

Horm Behav 2017 03 12;89:69-85. Epub 2016 Dec 12.

Department of Psychology, University of Florida, Gainesville, FL 32611, USA; University of Florida Genetics Institute, University of Florida, Gainesville, FL 32611, USA. Electronic address:

Dehydroepiandrosterone (DHEA) and cortisol are the most abundant hormones of the human fetal and adult adrenals released as end products of a tightly coordinated endocrine response to stress. Together, they mediate short- and long-term stress responses and enable physiological and behavioral adjustments necessary for maintaining homeostasis. Detrimental effects of chronic or repeated elevations in cortisol on behavioral and emotional health are well documented. Evidence for actions of DHEA that offset or oppose those of cortisol has stimulated interest in examining their levels as a ratio, as an alternate index of adrenocortical activity and the net effects of cortisol. Such research necessitates a thorough understanding of the co-actions of these hormones on physiological functioning and in association with developmental outcomes. This review addresses the state of the science in understanding the role of DHEA, cortisol, and their ratio in typical development and developmental psychopathology. A rationale for studying DHEA and cortisol in concert is supported by physiological data on the coordinated synthesis and release of these hormones in the adrenal and by their opposing physiological actions. We then present evidence that researching cortisol and DHEA necessitates a developmental perspective. Age-related changes in DHEA and cortisol are described from the perinatal period through adolescence, along with observed associations of these hormones with developmental psychopathology. Along the way, we identify several major knowledge gaps in the role of DHEA in modulating cortisol in typical development and developmental psychopathology with implications for future research.
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http://dx.doi.org/10.1016/j.yhbeh.2016.11.018DOI Listing
March 2017

Risk and protective factors for comorbid internalizing and externalizing problems among economically disadvantaged African American youth.

Dev Psychopathol 2017 08 19;29(3):1043-1056. Epub 2016 Oct 19.

University of Florida.

Comorbidity of internalizing and externalizing problems and its risk and protective factors have not been well incorporated into developmental research, especially among racial minority youth from high-poverty neighborhoods. The present study identified a latent comorbid factor as well as specific factors underlying internalizing and externalizing problems among 592 African American adolescents living in economically disadvantaged neighborhoods (291 male; M age = 15.9 years, SD = 1.43 years). Stressful life events and racial discrimination were associated with higher comorbid problems, whereas stressful life events and exposure to violence were associated with higher specific externalizing problems. Collective efficacy was associated with both lower specific externalizing problems and lower comorbid problems. Moreover, high collective efficacy buffered the risk effects of stressful life events and racial discrimination on comorbid problems. Our results demonstrated the advantages of latent variable modeling to understanding comorbidity by articulating impacts of risk factors on comorbid and specific components underlying internalizing and externalizing problems. They also highlighted the protective effect of collective efficacy in mitigating risks for these problems. These findings broadly call for more studies on comorbidities in developmental psychopathology among youth from diverse sociocultural backgrounds.
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http://dx.doi.org/10.1017/S0954579416001012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5763553PMC
August 2017

Effect of Environmental Risk and Externalizing Comorbidity on Internalizing Problems Among Economically Disadvantaged African American Youth.

J Res Adolesc 2016 Sep 8;26(3):552-566. Epub 2015 Jul 8.

Department of Psychology, University of Florida.

This study examined effects of racial discrimination, community violence, and stressful life events on internalizing problems among African American youth from high poverty neighborhoods ( = 607; 293 boys; age = 16.0 years, = 1.44 years). Mediated effects via externalizing problems on these relations were also examined, given the high comorbidity rate between internalizing and externalizing problems. Externalizing problems partially mediated the effect of stressful life events on internalizing problems and fully mediated the effect of racial discrimination for boys but not for girls. Exposure to violence had a significant indirect effect on internalizing problems via externalizing problems. The findings call for greater attention to internalizing problems among African American youth and pathways to internalizing problems via externalizing problems.
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http://dx.doi.org/10.1111/jora.12213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5006957PMC
September 2016

Prenatal Maternal Stress Predicts Methylation of Genes Regulating the Hypothalamic-Pituitary-Adrenocortical System in Mothers and Newborns in the Democratic Republic of Congo.

Child Dev 2016 Jan-Feb;87(1):61-72

University of Florida.

Exposure to stress early in life permanently shapes activity of the hypothalamic-pituitary-adrenocortical (HPA) axis and the brain. Prenatally, glucocorticoids pass through the placenta to the fetus with postnatal impacts on brain development, birth weight (BW), and HPA axis functioning. Little is known about the biological mechanisms by which prenatal stress affects postnatal functioning. This study addresses this gap by examining the effect of chronic stress and traumatic war-related stress on epigenetic changes in four key genes regulating the HPA axis in neonatal cord blood, placenta, and maternal blood: CRH, CRHBP, NR3C1, and FKBP5. Participants were 24 mother-newborn dyads in the conflict-ridden region of the eastern Democratic Republic of Congo. BW data were collected at delivery and maternal interviews were conducted to assess culturally relevant chronic and war-related stressors. Chronic stress and war trauma had widespread effects on HPA axis gene methylation, with significant effects observed at transcription factor binding (TFB) sites in all target genes tested. Some changes in methylation were unique to chronic or war stress, whereas others were observed across both stressor types. Moreover, stress exposures impacted maternal and fetal tissues differently, supporting theoretical models that stress impacts vary according to life phase. Methylation in several NR3C1 and CRH CpG sites, all located at TFB sites, was associated with BW. These findings suggest that prenatal stress exposure impacts development via epigenetic changes in HPA axis genes.
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http://dx.doi.org/10.1111/cdev.12487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4733886PMC
December 2016

Genes involved in stress response and alcohol use among high-risk African American youth.

Subst Abus 2016 Jul-Sep;37(3):450-458

a Department of Human and Molecular Genetics , School of Medicine, Virginia Commonwealth University , Richmond , Virginia , USA.

Background: Genetic and environmental factors influence substance use behaviors in youth. One of the known environmental risk factors is exposure to life stressors. The aim of this project is to study the interaction between NR3C1 and CRHBP, genes thought to be involved in stress pathways, exposure to stressful life events, and adolescent alcohol use/misuse.

Methods: The sample included 541 African American individuals (ages 13-18) from the Genes, Environment, and Neighborhood Initiative, a subset of the Mobile Youth Survey sample from whom DNA and more extensive phenotypic data were collected. Participants were selected from high-poverty neighborhoods in Mobile, Alabama, with potential exposure to a variety of extreme life stressors.

Results: A measure of stressful life events was significantly predictive of alcohol use/misuse. In addition, this association was significantly dependent upon the number of putative risk variants at rs1715749, a single-nucleotide polymorphism (SNP) in CRHBP (P ≤ .006). There was no significant interaction between NR3C1 and stressful life events with respect to alcohol use/misuse, after taking into account multiple testing.

Conclusions: These findings suggest that CRHBP variants are potentially relevant for adolescent alcohol use/misuse among African American youth populations being reared within the context of stressful life events and warrant replication.
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http://dx.doi.org/10.1080/08897077.2015.1134756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5007209PMC
January 2018

Latent state trait modeling of children's cortisol at two points of the diurnal cycle.

Psychoneuroendocrinology 2012 Feb 12;37(2):249-55. Epub 2011 Jul 12.

Department of Psychology, University of Florida, P.O. Box 112250, Gainesville, FL 32611-2250, USA.

One challenge in examining stable individual differences in basal activity of the HPA axis is controlling for internally or externally based situational factors that lead to day-to-day variation in ambulatory cortisol. Disturbed basal activity is of particular interest in studies with children, for whom a dysregulated HPA axis may play an etiologic role in emotional or health outcomes. The purpose of this study was to determine whether trait vs. situationally specific sources of variation can be identified at different points of the diurnal cycle in children and if so, whether state and trait components vary according to time of measurement. Early morning and late evening salivary cortisol was collected from 164 children aged 7 to 11 years. Samples were collected 30 min after wake-up and 30 min before bedtime on 3 weekdays. State, trait, and error components of cortisol levels were assessed using a latent state trait model. Possible influences of sampling day and outlier treatment on parameter estimates were examined. The results showed that a latent trait factor superimposed on state residuals and measurement error was identified for both early morning and late evening cortisol. Model fit was excellent and criteria for invariance tests were met. Trait factors accounted for 41% and 57% of the variance in morning and evening cortisol, respectively. These findings suggest cortisol attributed to trait factors can be identified and are of substantial magnitude at both the peak and nadir of the diurnal cycle. Latent state trait modeling is a potentially useful tool in understanding the role of stable individual differences in cortisol levels for development and health.
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http://dx.doi.org/10.1016/j.psyneuen.2011.06.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3241873PMC
February 2012

Neurotransmitter and neuromodulator genes associated with a history of depressive symptoms in individuals with alcohol dependence.

Alcohol Clin Exp Res 2011 Mar 8;35(3):496-505. Epub 2010 Dec 8.

Department of Psychology, University of Florida, Gainesville, 32611-2250, USA.

Background: Depressive symptoms are common among individuals with alcohol use disorders and impact treatment outcome. Substantial overlap exists among the neurobiological systems proposed in the pathophysiology of depressive and alcohol use disorders; however, specific genetic effects contributing to risk for depressive comorbidity remain poorly understood.

Methods: This study examines the association of depressive symptom scores for lifetime depression (the sum of DSM-IV major depression co-endorsed criteria for lifetime depression) with markers in 120 candidate genes in 554 alcohol-dependent individuals. The candidate genes code for molecules involved in dopamine, serotonin, glutamate, gamma-aminobutyric acid (GABA), and opioid neurotransmission, cell signaling, pharmacokinetics, stress biology, and behavioral control. Analyses were conducted at the single marker level with experimentwise permutation to control for multiple testing.

Results: Results revealed nominal associations for markers in 20 genes. Following experimentwise permutation, markers in the corticotropin-releasing hormone-binding protein (CRHBP) the μ-opioid receptor (OPRM1) and the β1 subunit of GABA A (GABA(A)) receptors (GABRB1) met or exceeded the significance threshold. None of the markers associated with depressive symptom scores were significantly associated with alcohol dependence symptom scores.

Conclusion: These findings suggest potential risk genes for depressive symptoms in alcohol-dependent individuals.
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http://dx.doi.org/10.1111/j.1530-0277.2010.01366.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3116055PMC
March 2011

Inhibited temperament and parent emotional availability differentially predict young children's cortisol responses to novel social and nonsocial events.

Dev Psychobiol 2009 Nov;51(7):521-32

Department of Psychology, University of Florida, Gainesville, FL 32611-2250, USA.

Preschool-aged children (n = 274) were examined in the laboratory to assess behavioral and cortisol responses to nonsocial and social threat. Parents also responded to scales on the Children's Behavior Questionnaire reflecting exuberant approach to novel/risky activities (reversed scored) and shyness. Multi-method measures of Nonsocial and Social Inhibition were computed. Parents and children were observed engaging in a series of interactive tasks and the Emotional Availability scales were scored for parental sensitivity, nonintrusiveness, nonhostility, and structuring. These scores were factored to yield one measure of Parenting Quality. Analyses revealed that Nonsocial and Social Inhibition could be distinguished and that associations with cortisol response were stressor specific. Moderation analyses revealed that parenting quality buffered cortisol elevations for extremely socially, but not nonsocially inhibited children. These findings are consistent with evidence that sensitive, supportive parenting is an important buffer of the HPA axis response to threat in infants and toddlers, and extends this finding to the preschool period.
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http://dx.doi.org/10.1002/dev.20390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5870881PMC
November 2009

Identifying atypical cortisol patterns in young children: The benefits of group-based trajectory modeling.

Psychoneuroendocrinology 2009 Jan 5;34(1):50-61. Epub 2008 Oct 5.

Institute of Child Development, University of Minnesota, 51 East River Road, Minneapolis, MN 55455, USA.

The introduction of growth curve modeling into the field of neuroendocrinology has enabled researchers to examine mean patterns of change in unbalanced and/or incomplete repeated measures data. However, growth curve modeling assumes population homogeneity, or that all individuals follow roughly the same pattern of change, with differences expressed as deviation around the mean curve. Group-based trajectory modeling, in contrast, is designed for heterogeneous populations and as a result is able to identify atypical patterns of change over time that may exist within a population. To illustrate the strengths and weaknesses of each technique, we apply both to a sample of diurnal cortisol data measured at home in young children (N=106, 46 male, M age=3.81 years, S.D.=0.24). We find three distinct trajectories of cortisol and demonstrate that the members of these trajectories are measurably different in terms of cortisol levels across context and time and in terms of the relationship between behavioral problems and parenting. At the same time, our growth curve analysis finds differential response patterns for high vs. low internalizing children with high vs. low parenting quality. We discuss these results in terms of their implications for the proper application of each method.
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http://dx.doi.org/10.1016/j.psyneuen.2008.08.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2741322PMC
January 2009

Early deprivation and home basal cortisol levels: a study of internationally adopted children.

Dev Psychopathol 2008 ;20(2):473-91

Institute of Child Development, 51 East River Road, University of Minnesota, Minneapolis, MN 55455, USA.

Animal studies reveal that early deprivation impairs regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis, potentially increasing vulnerability to stressors throughout life. To examine early deprivation effects on basal HPA axis activity in humans, basal cortisol levels were examined in 164 internationally adopted children who had experienced varying degrees of preadoption deprivation. Duration of institutional care, age at adoption, and parent ratings of preadoption neglect indexed a latent factor of Deprived Care. Adoption measures of height and weight standardized to World Health Organisation norms indexed a latent factor of Growth Delay that was viewed as another reflection of deprivation. Cortisol samples were collected 3.3-11.6 years postadoption (Md = 7.3 years) at home on 3 days approximately 30 min after wakeup and before bedtime. Both early a.m. levels and the decrease in cortisol across the day were examined. A structural equation model revealed that preadoption Deprived Care predicted Growth Delay at adoption and Growth Delay predicted higher morning cortisol levels and a larger diurnal cortisol decrease.
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http://dx.doi.org/10.1017/S0954579408000230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5863229PMC
August 2008

Developmental changes in baseline cortisol activity in early childhood: relations with napping and effortful control.

Dev Psychobiol 2004 Nov;45(3):125-33

Department of Human Development, Cornell University, Ithaca, NY 14853, USA.

Development of the hypothalamic-pituitary-adrenocortical (HPA) axis was examined using salivary cortisol levels assessed at wake-up, midmorning, midafternoon, and bedtime in 77 children aged 12, 18, 24, 30, and 36 months, in a cross-sectional design. Hierarchical linear modeling (HLM) analyses were used to characterize cortisol production across the day and to examine age-related differences. Using area(s) under the curve (AUC), cortisol levels were higher among the 12-, 18-, and 24-month children than among the 30- and 36-month children. For all five age groups, cortisol levels were highest at wake-up and lowest at bedtime. Significant decreases were noted between wake-up and midmorning, and between midafternoon and bedtime. Unlike adults, midafternoon cortisol levels were not significantly lower than midmorning levels. Over this age period, children napped less and scored increasingly higher on parent reports of effortful control. Among the 30- and 36-month children, shorter naps were associated with more adultlike decreases in cortisol levels from midmorning to midafternoon. Considering all of the age groups together, effortful control correlated negatively with cortisol levels after controlling for age. These results suggest that circadian regulation of the HPA axis continues to mature into the third year in humans, and that its maturation corresponds to aspects of behavioral development.
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http://dx.doi.org/10.1002/dev.20026DOI Listing
November 2004

Evening activities as a potential confound in research on the adrenocortical system in children.

Child Dev 2004 Jan-Feb;75(1):193-204

Institute of Child Development, University of Minnesota. Minneapolis, MN 55455, USA.

The relation among children's evening activities, behavioral characteristics, and activity of the hypothalamic-pituitary-adrenocortical axis was assessed in normally developing children ages 7 to 10 years. Salivary cortisol at bedtime was compared on evenings when children had structured activities outside of the home with unstructured evenings at home in relation to parental reports of children's behavioral characteristics. Participating in evening activities, particularly sport activities, was associated with small increases in bedtime cortisol levels in boys but not in girls. Differences in cortisol on activity versus no-activity nights were negatively related to children's social isolation. These results show that in studies with children, nights on which participants engage in sport activities should be avoided when collecting ambulatory measures of salivary cortisol concentrations.
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http://dx.doi.org/10.1111/j.1467-8624.2004.00663.xDOI Listing
July 2004