Biological and Contextual Correlates of Cortisol Reactivity in Early Childhood

Purpose: Individual differences in early-emerging vulnerability to mood and anxiety disorders have been linked to genetic and environmental influences, with psychophysiological reactivity potentially mediating this vulnerability. However, research seeking to identify influences on the development of psychophysiological reactivity, such as the Hypothalamic-Adrenal-Pituitary (HPA) axis, is still in an early stage, with most studies focusing on individual risks, even though such vulnerability is likely etiologically complex. Disentangling the interplay of biology and context in shaping HPA axis responses to stress, indexed via salivary cortisol reactivity, may ultimately aid in the development and application of targeted prevention and early intervention programs. Method: This study examined whether key biological and contextual variables, including specific genes (5-HTTLPR and BDNF val66met), parent psychopathology, poor parenting, and life stress, were related to cortisol reactivity to psychosocial stress in 409 preschool-aged children. Parenting was assessed using questionnaires and observational ratings, and stress and parent psychopathology were assessed using structured interviews. Cortisol reactivity was indexed using both area under the curve and multi-level modelling. Results: Maternal depression interacted with poor parenting and chronic stress to predict child cortisol reactivity. Specifically, evidence was found for dysregulated cortisol reactivity in children with a maternal depression history who were exposed to life stress, including hyperreactivity in the context of chronic stress and hyporeactivity in the context of poor parenting. In contrast, the cortisol reactivity of children with no maternal depression history was unrelated to these environmental influences. However, the pattern of findings differed depending on the index of cortisol reactivity being examined (AUC versus MLM). Paternal depression had a stronger influence on baseline or trait-like cortisol relative to cortisol reactivity. Conclusion: Findings suggest that children with a history of maternal depression and exposure to early stress may be at the greatest risk for HPA dysregulation, and that this risk is manifested differently depending on which type of early stress is experienced. Findings highlight a potential mechanism, cortisol stress reactivity, through which familial depression risk and the early environment influence children’s vulnerability. Results also speak to the importance of methodological factors when examining cortisol reactivity to stress

Associations between observed temperament in preschoolers and parent psychopathology

Parent history of psychopathology is an established marker of children\u27s own risk for later disorder and can therefore be used as a means of validating other risks, such as child temperament. While associations between children\u27s temperament and parent psychopathology have been reported, few studies have used observational measures of child temperament or examined trait interactions, particularly between children\u27s affective and regulatory traits such as effortful control (EC). In this bottom-up family study of 968 three-year-olds and their parents, we examined interactions between preschoolers\u27 observed positive and negative affectivity (NA) and EC as predictors of a known marker of psychopathology risk: parent history of disorder. Children with lower positive affectivity had an increased probability of paternal depression history in the context of higher child NA. In addition, children with lower EC and higher NA had an increased probability of maternal anxiety. Findings shed new light on the main effects and interactions that account for associations between child temperament and parent history of disorder, one of the best-established markers of an individual\u27s own risk for future disorder, implicating reactive and regulatory traits that merit special consideration in future longitudinal work. Copyright © 2017 John Wiley & Sons, Ltd

The serotonin transporter promoter polymorphism moderates the continuity of behavioral inhibition in early childhood.

Persistently elevated behavioral inhibition (BI) in children is a marker of vulnerability to psychopathology. However, little research has considered the joint influences of caregiver and child factors that may moderate the continuity of BI in early childhood, particularly genetic variants that may serve as markers of biological plasticity, such as the serotonin transporter linked polymorphic region (5-HTTLPR). We explored this issue in 371 preschoolers and their caregivers, examining whether parent characteristics (i.e., overinvolvement or anxiety disorder) and child 5-HTTLPR influenced the continuity of BI between ages 3 and 5. Measures were observational ratings of child BI, observational and questionnaire measures of parenting, and parent interviews for anxiety disorder history, and children were genotyped for the 5-HTTLPR. Parent factors did not moderate the association between age 3 and age 5 BI; however, child BI at age 3 interacted with children\u27s 5-HTTLPR variants to predict age 5 BI, such that children with at least one copy of the short allele exhibited less continuity of BI over time relative to children without this putative plasticity variant. Findings are consistent with previous work indicating the 5-HTTLPR short variant increases plasticity to contextual influences, thereby serving to decrease the continuity of BI in early childhood

Effortful control and parenting: Associations with HPA axis reactivity in early childhood

While activation of the hypothalamic-pituitary-adrenal (HPA) axis is an adaptive response to stress, excessive HPA axis reactivity may be an important marker of childhood vulnerability to psychopathology. Parenting, including parent affect during parent-child interactions, may play an important role in shaping the developing HPA system; however, the association of parent affect may be moderated by child factors, especially children\u27s emerging self-regulatory skills. We therefore tested the relationship between parent affectivity and 160 preschoolers\u27 cortisol reactivity during a laboratory visit, examining children\u27s effortful control (EC) as a moderator. Greater parent negative affectivity was related to greater initial and increasing cortisol over time, but only when children were low in EC. Higher parent positive affectivity was related to a higher baseline cortisol for children with low EC and lower baseline cortisol for children with high EC. Results indicate that children\u27s EC moderates the extent to which parent affect shapes stress reactive systems in early childhood. © 2013 Blackwell Publishing Ltd

Links between white matter microstructure and cortisol reactivity to stress in early childhood: evidence for moderation by parenting.

Activity of the hypothalamic-pituitary-adrenal axis (measured via cortisol reactivity) may be a biological marker of risk for depression and anxiety, possibly even early in development. However, the structural neural correlates of early cortisol reactivity are not well known, although these would potentially inform broader models of mechanisms of risk, especially if the early environment further shapes these relationships. Therefore, we examined links between white matter architecture and young girls\u27 cortisol reactivity and whether early caregiving moderated these links. We recruited 45 6-year-old girls based on whether they had previously shown high or low cortisol reactivity to a stress task at age 3. White matter integrity was assessed by calculating fractional anisotropy (FA) of diffusion-weighted magnetic resonance imaging scans. Parenting styles were measured via a standardized parent-child interaction task. Significant associations were found between FA in white matter regions adjacent to the left thalamus, the right anterior cingulate cortex, and the right superior frontal gyrus (all ps \u3c .001). Further, positive early caregiving moderated the effect of high cortisol reactivity on white matter FA (all ps ≤ .05), with high stress reactive girls who received greater parent positive affect showing white matter structure more similar to that of low stress reactive girls. Results show associations between white matter integrity of various limbic regions of the brain and early cortisol reactivity to stress and provide preliminary support for the notion that parenting may moderate associations

Catechol-O-methyltransferase gene val158met polymorphism and depressive symptoms during early childhood

Catechol-O-Methyltransferase (COMT) is a critical regulator of catecholamine levels in the brain. A functional polymorphism of the COMT gene, val158met, has been linked to internalizing symptoms (i.e., depression and anxiety) in adolescents and adults. We extended this research by investigating whether the val158met polymorphism was associated with childhood symptoms of depression and anxiety in two independent samples of young children (Ns=476 and 409). In both samples, preschool-aged children were genotyped for the COMT val158met polymorphism. Symptoms of psychopathology were assessed via parent interviews and primary caregiver reports. In both samples, children homozygous for the val allele had higher levels of depressive symptoms compared to children with at least one copy of the met allele. Our findings extend previous research in older participants by showing links between the COMT val158met polymorphism and internalizing symptoms in early childhood. © 2013 Wiley Periodicals, Inc

Value of percutaneous transluminal coronary angioplasty after unsuccessful intravenous streptokinase therapy in acute myocardial infarction

The effect of sequential high-dose intravenous streptokinase (SK) (1.5 million units) followed by emergency percutaneous transluminal coronary angioplasty (PTCA) on preserving left ventricular function was assessed prospectively in 34 patients with acute myocardial infarction (AMI). Intravenous SK therapy was initiated 2.6 +/- 1.3 hours (mean +/- standard deviation) after the onset of chest pain. Urgent coronary angiography showed persistent total occlusion in 13 patients, significant diameter stenosis (70 to 99%) in 18 patients and a widely patent artery (less than 50% stenosis) in 3 patients. Emergency PTCA was performed in 29 patients 5.0 +/- 2.1 hours after symptom onset. Successful recanalization was achieved in 33 of the 34 patients (97%) treated with sequential therapy. Repeat contrast ventriculograms recorded 7 to 10 days after intervention in 23 patients showed that the left ventricular ejection fraction increased from 53 +/- 12% to 59 +/- 13% (area-length method, p < 0.002). Regional wall motion of the infarcted segments improved from - 2.7 +/- 1.1 to - 1.5 +/- 1.7 SD/chord (centerline method, p < 0.003). In the subgroup of patients with an occluded artery on initial angiography (group A, N = 10), both global left ventricular ejection fraction (49 +/- 12% vs 59 +/- 12%, p < 0.002) and regional wall motion (-3.2 +/- 1.0 vs -1.9 +/- 1.7 SD/chord, p < 0.002) improved significantly. In contrast, no significant improvement was seen in patients with a patent artery on initial angiography (n = 13). Thus, sequential intravenous SK and emergency PTCA is efficacious in achieving coronary reperfusion and in improving both global and regional left ventricular function. When thrombolytic therapy fails, successful recanalization can be achieved by emergency PTCA, resulting in significant myocardial salvage.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26031/1/0000104.pd

Income and social rank influence UK children's behavioral problems : a longitudinal analysis

Children living in low‐income households face elevated risks of behavioral problems, but the impact of absolute and relative income to this risk remains unexplored. Using the U.K. Millennium Cohort Study data, longitudinal associations between Strengths and Difficulties Questionnaire scores and absolute household income, distance from the regional median and mean income, and regional income rank were examined in 3‐ to 12‐year‐olds (n = 16,532). Higher absolute household incomes were associated with lower behavioral problems, while higher income rank was associated with lower behavioral problems only at the highest absolute incomes. Higher absolute household incomes were associated with lower behavioral problems among children in working households, indicating compounding effects of income and socioeconomic advantages. Both absolute and relative incomes therefore appear to influence behavioral problems