Relation between stressful life events,neuropeptides and cytokines: results from the LISA birth cohort study

Stressful life events evidently have an impact on development of allergic diseases, but the mechanism linking stress to pathological changes of immune system function is still not fully understood. The aim of our study was to investigate the relationship between stressful life events, neuropeptide and cytokine concentrations in children. Within the LISAplus (Life style-Immune system-Allergy) study, blood samples from children of 6 yr of age were analysed for concentration of the neuropeptides vasoactive intestinal peptide (VIP), somatostatin (SOM), substance P (SP) and the Th1/Th2 cytokines interferon-γ (IFN-γ) and interleukin (IL)-4. Life events such as severe disease or death of a family member, unemployment or divorce of the parents were assessed with a questionnaire filled in by the parents. For 234 children, blood analysis and questionnaire data regarding life events were available. Children with separated/divorced parents showed high VIP levels and high concentrations of the Th2 cytokine IL-4 in their blood. Severe diseases and death of a family member were neither associated with neuropeptide levels nor with cytokine concentrations. Unemployment of the parents was associated with decreased IFN-γ concentrations in children’s blood but not with neuropeptide levels, whereas children experiencing concomitant severe disease and death of a family member had reduced SP blood levels. The neuropeptide VIP might be a mediator between stressful life events and immune regulation contributing to the Th2 shifted immune response in children with separated/divorced parents. Unemployment of the parents was associated with immune regulation in children on the basis of a still unknown mechanism whereas reduced SP levels seem to have no effect on immune regulation.     

Prevention of essential hypertension in minority populations

The precursors of essential hypertension (EH) begin in childhood. If the etiology of the evolution of EH were discovered, interventions may be developed to lead to the primary prevention of EH. In particular, one ethnic group, African-Americans (Blacks), are at increased risk of development of EH in adulthood. Hemodynamic changes in response to stressors are termed measures of cardiovascular reactivity (CVR). Ethnic difference in CVR are known to exist; are these markers or mechanisms of EH evolution? Investigations are underway to discover the mechanism(s) of the excessive vasoconstriction which appears to be characteristic of the CVR responses in Blacks. These may lead to the pharmacologic, or non-pharmacologic, interventions which may be initiated in childhood and prevent EH in adults.     

运动后心率恢复的研究进展

摘要：心率恢复（HRR）指数显示运动停止后心率下降的速度,运动后HRR异常是预测心血管疾病及其主要心血管事件发生的有效独立危险因子。HRR减慢指运动后心率下降不足,与交感神经功能缺陷和（或）迷走神经激活有关。临床主要用于评价冠心病、心衰、高血压、糖尿病、代谢综合征与肥胖、睡眠呼吸暂停综合征、风湿免疫病、慢性阻塞性肺病与肺动脉高压等儿童的心脏自主神经功能。研究表明有望通过药物治疗与运动训练等提高自主神经功能的干预措施改善异常的HRR。     

Modes of cardiovascular regulation during middle childhood.

Obtaining meaningful baseline measures of children's cardiovascular activity (CVA) has been difficult because of constraints inherent to laboratory procedures that are used to assess individual differences in response to stress. To circumvent these problems, we performed repeated baseline measures of pulse rate (PR) and blood pressure for 174 children (aged 7-10 yr) in their natural school setting throughout 2 1-week periods. In addition, experimental assessments of cardiovascular reactivity (CVR) were conducted after each baseline period while children participated in a challenging cognitive task. Multivariate analyses of physiological indices revealed three primary styles of cardiovascular functioning. Two of them, characterizing children either with high PR and low blood pressure or conversely with low PR and high blood pressure, have already been described in the research literature. However, analyses also revealed a third group of children (48% of the subjects) who had both low PR and low blood pressure. Findings indicate developmental differences in cardiovascular regulation and highlight the need to consider both variations in baseline CVA as well as in CVR when examining children's physiological adaptation in everyday settings.     

Stressful life events and asthma in adolescents

Recent studies suggest that psychosocial factors may contribute to asthma. We examined associations of stressful life events with asthma prevalence and morbidity among Chicago adolescents. Self-reported asthma, measures of asthma morbidity, and 15 life events were collected from 2026 seventh to ninth grade students from 34 Chicago Catholic schools as part of the International Study of Allergies and Asthma in Childhood in 1994–95. Life events were reported by 77% of adolescents and overall asthma prevalence was 15.5%. Stressful life events in adolescents were significantly related to both asthma and asthma morbidity. Odds of asthma was 1.44 (95% confidence interval [CI] = 1.07, 1.95) for those reporting two to three stressful events and 1.92 (95% CI = 1.41, 2.62) for subjects endorsing more than three stressful events. In adolescents with asthma, number of asthma symptoms (odds ratio [OR] for increase in one event = 1.16, 95% CI = 1.07, 1.27), asthma-related school absenteeism (OR = 1.17, 95% CI = 1.04, 1.32), physician visits for asthma (OR = 1.16, 95% CI = 1.04, 1.29), and hospitalization for asthma (OR = 1.20, 95% CI = 1.001, 1.44) were significantly associated with the number of stressful events, independent of home exposure to cigarette smoke and dampness, use of inhaled substances, and sociodemographic factors. While these results are not sufficient to assign causality in the relationship between stress and asthma, they are supported by a number of other studies and by plausible biologic mechanisms. Assessing and addressing the effects of stressful life events may be helpful in managing asthma in inner city adolescents.     

Relationships Between Adolescent Stress,Depressive Symptoms,and Sexual Risk Behavior in Young Adulthood: A Structural Equation Modeling Analysis

IntroductionThis study examined longitudinal associations between stressful life events and depressive symptoms, assessed during two time points of adolescence, and sexual risk behavior, assessed during young adulthood.MethodsStructural equation modeling was conducted with three waves of data from the National Longitudinal Study of Adolescent to Adult Health.ResultsAnalyses revealed bidirectional relationships between stressful life events and depressive symptoms during the two time points of adolescence. Adolescent depressive symptoms indirectly affected young adult sexual risk behavior through adolescent stressful life events. Adolescent stressful life events during late adolescence were directly associated with young adult sexual risk behavior.DiscussionFindings highlight the need to screen for both depression and stressful life events during adolescence, to identify at-risk adolescents and deliver tailored interventions to prevent sexual risk behavior during young adulthood.     

Life Events, Social Support and the Risk of Sudden Infant Death Syndrome

The effects of a lack of maternal social support and stressful life events on the risk of Sudden Infant Death Syndrome (SIDS) were examined by case-control design: 390 cases and 1592 control infants. A seven item index of mother's social support was used. A possible 21 life events experienced by each family were summed and then put into one of three categories: 0-2, 3-5, and 6 or more life events. Similar levels of maternal social support were found for both groups. SIDS families experienced significantly more stressful life events than control families, but once social factors had been taken into account this association was lost.     

Obesity, metabolic syndrome, and cardiovascular disease

Early childhood overweight and obesity have alarmingly increased over the years. Adulthood obesity is a well demonstrated significant independent predictor of cardiovascular risk (CVR) and/or mortality, which predisposes to the major components of metabolic syndrome (MS). Evidence of MS in obese children has been also reported associated with biochemical and inflammatory factors that affect vascular physiologic function. Assessment of vascular function can be measured noninvasively in children allowing early detection of endothelial dysfunction and severe increase of arterial stiffness before clinical manifestations of atherosclerosis. Impairment of endothelial function related to the severity of obesity and to the degree of insulin resistance is considered as a condition that confers a premature atherogenicity status and is linked to adult conventional cardiovascular risk factors. Adipose tissue factors that interfere with insulin action and endothelial cell function have also been identified as major precursors of CVR factors. The metabolic and cardiovascular consequences of childhood obesity are well demonstrated and have a major impact on the development of atherosclerosis and lifetime CVR. The development of programs involving both diet and exercise for children with overt overweight/obesity appears to be essential to improve vascular function and metabolic disorders. Such interventions should be complemented by a primary prevention against childhood obesity.     

Risk factors for preschool depression: the mediating role of early stressful life events

BACKGROUND: Family history of mood disorders and stressful life events are both established risk factors for childhood depression. However, the role of mediators in risk trajectories, which are potential targets for intervention, remains understudied. To date, there have been no investigations of mediating relationships between risk factors and very early onset depression, a developmental period during which intervention may be more effective. The current study used regression analyses to examine the relationships between family history of mood disorders and stressful life events as risk factors for depression in a preschool sample. METHOD: Preschoolers 3.0 to 5.6 years of age participated in a comprehensive mental health assessment. Caregivers were interviewed about their children using a structured diagnostic measure to derive DSM-IV major depressive disorder (MDD) diagnoses and dimensional depression severity scores. Family history of psychiatric disorders and preschoolers' stressful life events was obtained. RESULTS: Both family history and stressful life events predicted depression severity scores 6 months later. Analyses examining the influence of family history of mood disorders and stressful life events on preschoolers' depression severity demonstrated that stressful life events mediated the relationship between family history and preschoolers' depression. CONCLUSIONS: Findings outline the key role of exposure to early stressful life events as a mediator of familial mood disorder risk in preschool onset depression. This finding in a preschool sample provides support for the hypothesis that psychosocial factors may have increased importance as mediators of risk in younger age groups. Findings suggest that psychosocial factors should be considered key targets for early intervention in depression.     

Stressful family life events and nonspecific somatic complaints in school children.

The relationship between stressful family life events and somatic complaints in 477 school children was studied. There was a significant association between life events and somatic complaints, with a general trend for somatic complaints to increase in almost direct proportion to the number of family life events. Overall occurrence of these nonspecific symptoms was more in girls. The somatic complaints were significantly more in children from nuclear families and of illiterate or poorly educated mothers. No significant association was observed between somatic complaints and number of children in the family or socio-economic status. Assessment of psychodevelopmental tasks and family environment during routine check up of children by the school health teams and their appropriate training in this field should be stressed upon.     

Are sibling relationships protective? A longitudinal study

BACKGROUND: Although the protective effects of familial and parental support have been studied extensively in the child psychopathology literature, few studies have explored the protective quality of positive sibling relationships. METHODS: A two-wave longitudinal design was used to examine the protective effect of positive sibling relationships on child adjustment for children experiencing stressful life events. Mothers reported on stressful life events and child adjustment. Older siblings assessed the quality of relationship between themselves and target children. RESULTS: Sibling affection moderated the relationship between stressful life events and internalizing symptomatology but not the relationship between stressful life events and externalizing symptomatology. Notably, the protective effect of sibling affection was evident regardless of mother-child relationship quality. CONCLUSIONS: Positive sibling relationships are an important source of support for children experiencing stressful life events. Implications for intervention are discussed.     

5HTT genotype moderates the influence of early institutional deprivation on emotional problems in adolescence: evidence from the English and Romanian Adoptee (ERA) study

Background: A common polymorphism in the serotonin transporter gene (SLC6A4, 5HTT) has been repeatedly shown to moderate the influence of childhood adversity and stressful life events on the development of psychopathology. Using data from the English and Romanian Adoptee Study, a prospective‐longitudinal study of individuals (n = 125) exposed to severe early institutional deprivation (ID), we tested whether the effect of ID on adolescent emotional problems is moderated by 5HTT genotype and stressful life events in adolescence. Methods: Emotional problems were assessed using questionnaire data (age 11), and on the basis of the CAPA diagnostic interview (age 15). Additionally, the number of stressful life events was measured. Results: There was a significant effect for genotype (p = .003) and a gene × environment interaction (p = .008) that was independent of age at testing. Carriers of the s/l and s/s genotype who experienced severe ID showed the highest emotional problem scores, while l/l homozygotes in the severe ID group showed the lowest overall levels. Furthermore, s/s carriers in the severe ID group who experienced a high number of stressful life events between 11 and 15 years had the largest increases in emotional problem scores, while a low number of stressful life events was associated with the largest decrease (4‐way interaction: p = .05). Conclusions: The effects of severe early ID on emotional problems in adolescence are moderated by 5HTT genotype, and influenced by stressful life events in adolescence.     

Health-compromising behaviors: why do adolescents smoke or drink?: identifying underlying risk and protective factors

OBJECTIVES: To better understand the motivation for adolescent smoking and drinking and to identify the underlying risk and protective factors associated with these behaviors among adolescents. DESIGN: Cross-sectional, school-based survey of students in grades 5 through 12. PARTICIPANTS: A nationally representative sample of 2574 boys and 2939 girls in grades 7 through 12 from 297 public, private, and parochial schools across the United States who participated in The Commonwealth Fund Survey of the Health of Adolescent Girls and Boys in 1997. MAIN OUTCOME MEASURES: Sex-specific adjusted relative risks (RRs) and 95% confidence intervals (CIs) comparing self-reported regular smokers and regular drinkers by risk and protective factors with adolescents reporting none of these behaviors. RESULTS: Adolescent boys and girls were equally likely to be regular smokers (11.2%). The prevalence rate of regular drinking was only slightly higher for boys (22.4%) than it was for girls (19.3%). The rates of both health-risk behaviors were significantly higher for those reporting risk factors, and the strengths of associations varied by sex. Sex differences also emerged in motivation for engaging in these behaviors. When we adjusted for demographic characteristics, exposure to childhood abuse (RR, 4.1; 95% CI, 2.4-7.0) and stressful life events (RR, 2.4; 95% CI, 1.1-5.4) were strongly associated with increased risk for boys' regular smoking. Similar associations were found for regular drinking. For girls, a history of abuse (RR, 1.8; 95% CI, 1.1-2.8), violence within the family (RR, 2.2; 95% CI, 1.6-3.2), depressive symptoms (RR, 1.6; 95% CI, 1.0-2.4), and stressful life events (RR, 3.1; 95% CI, 1.8-5.6) were significantly associated with increased risk for regular smoking. Similar associations were again found for regular drinking. Parental support was protective against both health-risk behaviors for both sexes. Participation in extracurricular activities was associated with lower risk for regular smoking for boys (RR, 0.4; 95% CI, 0.2-0.7) and for girls (RR, 0.3; 95% CI, 0.2-0.5); however, there was no significant association between drinking behavior and participation in activities. CONCLUSIONS: The increased risk for regular smoking and regular drinking among adolescents with a history of abuse, family violence, depressive symptoms, and stressful life events suggests that routine screening for abuse, violence, and other family experiences should be an essential component of adolescent health care visits. Effective prevention programs to reduce smoking and drinking among adolescents should recognize that health-risk behaviors may be associated with other negative life experiences and that the strength of these associations differs by sex.     

Perceptions of stressful life events in Northern Irish school children: a longitudinal study

BACKGROUND: Adults' perceptions of stressful life events have been acknowledged as important moderators of the stress adjustment relationship. Until recently, however, there has been a lack of research on children's perceptions of negative life events. This study assesses children's own perceptions of the stressfulness of negative familial, academic and social events as well as events related to the political conflict in Northern Ireland. METHOD: Developmental changes in children's perceptions of events are traced over time. One hundred and sixty 8-year-old children completed a self-report measure of the perceived stressfulness of a range of negative life events. The sample was drawn from schools in the Greater Belfast area to include children of both genders, primary religious affiliations in Northern Ireland (i.e., Protestant and Roman Catholic) and of varying socio-economic status. Three years later, 113 of these children, then aged 11, were traced through the school system and completed the same measure. RESULTS: Children's perceptions of stressful events are related to a host of social factors. Girls viewed many negative events as more stressful than their male counterparts. Roman Catholic and Protestant children differed in their perceptions of conflict-related events. Perceptions of various types of negative experiences were differentially related to socio-economic status and age. CONCLUSION: Personal, social and situational factors differentially determine children's perceptions of negative life experiences.     

Krankheiten nach Nierentransplantation

Kidney transplantation is the therapy of choice in children with end-stage renal disease. There are myriad problems that can arise after renal transplantation, and they are individually very variable. Recurrence of the original underlying disease is of concern in focal segmental glomerulosclerosis, in other forms of glomerulonephritis, and in primary hyperoxaluria. The progression of extrarenal manifestations such as hepatic fibrosis with the development of portal hypertension is observed in autosomal recessive polycystic kidney disease. Liver involvement in nephronophthisis is also clinically significant. Long-term side effects of steroids can be stressful and demand that the medication be tapered off. Nephrotoxic side-effects of calcineurin inhibitors can require an individually tailored drug combination strategy. EBV-associated lymphoproliferation is a consequence of exaggerated immune suppression. In many patients creeping creatinine build-up is ongoing. The most important risk factors for life expectancy are cardiovascular complications of chronic renal insufficiency and of medicamentous treatment.     

Functional somatic complaints in adolescents: relationship to negative life events, self-concept, and family characteristics

While recurrent somatic complaints are commonly encountered in children and adolescents, occult organic disease is rarely found in patients with these complaints. Recent studies have confirmed the clinical impression that a relationship exists between functional somatic complaints and negative life events in adolescents. Our goal was to investigate additional psychosocial characteristics that may be associated with functional complaints. One hundred fifteen adolescents coming for the first time to an adolescent medicine clinic completed standard measures of negative life events, psychophysiologic symptoms, self-esteem, peer social comparison, and family functioning before an independent evaluation by a physician. Patients with functional somatic complaints (chest pain, recurrent abdominal pain, limb pain, and hyperventilation syndrome) reported significantly more negative life events, lower self-esteem, more psychophysiologic symptoms and a lower self-evaluation than did patients coming for physical examination or routine health maintenance. Functional somatic complaints in adolescents may be associated with poor psychosocial adjustment and reaction to negative life events. In addition to ruling out organic disease, physicians dealing with these patients should evaluate other areas, including stressful life events, peer relations, and self-esteem.     

Change in psychopathology in referred children: the role of life events and perceived stress

Background: This study examined the relation between stress and change in emotional and behavioural problems in children and adolescents referred for mental health services. Method: At three waves across four years, children and their parents (N = 310, mean age at the first wave = 11.26 years, SD = 3.18) reported emotional and behavioural problems, as well as stressful life events (parent report) and perceived stress (child report). Results: Major life events before referral were associated with higher levels of parent‐reported internalising and externalising problems at referral. Life events after referral were associated with a slower recovery from internalising problems. The associations between stressful life events and the course of parent‐ and self‐reported problems were mediated by children’s subjective feelings of stress. Conclusion: Stressful life events appear to interfere with recovery from internalising problems in the years after referral through increasing the experience of stress in daily life.     

Long‐term effects of a home‐visiting intervention for depressed mothers and their infants

Background: Whereas preventive interventions for depressed mothers and their infants have yielded positive short‐term outcomes, few studies have examined their long‐term effectiveness. The present follow‐up of a randomised controlled trial (RCT) is one of the first to examine the longer‐term effects of an intervention for mothers with postpartum depression and their infants at school‐age. In early infancy, the intervention was found effective in improving mother–infant interaction and the child’s attachment to its mother. Methods: Twenty‐nine mother–child pairs who completed the intervention are compared with 29 untreated mother–child dyads as to the quality of maternal interactive behaviour and the child outcomes of attachment security to the mother, self‐esteem, ego‐resiliency, verbal intelligence, prosocial behaviour, school adjustment, and behaviour problems at age 5 (M = 68 months). Results: In the total sample no lasting treatment benefits were found, but in families reporting a higher number of stressful life events, children in the intervention group had fewer externalising behaviour problems as rated by their mothers than children in the control group. Conclusions: In the context of multiple stressful life events the intervention served as a buffer by preventing the development of externalising problems in the child. The results warrant cautious interpretation because of the relatively small sample size and differential attrition revealing the mothers that completed the follow‐up assessment to have improved less on maternal sensitivity following the intervention than the mothers who did not participate in the follow‐up.     

Maternal trait anxiety, depression and life event stress in pregnancy: relationships with infant temperament

AIMS: To assess whether links exist between maternal trait anxiety (STAI), perceived life event (LE) stress and depression (Edinburgh scale) and infant temperament. STUDY DESIGN AND SUBJECTS: Women in the third trimester of pregnancy returned psychological self-report questionnaires; infant temperament was evaluated at 4 and 6 months by maternal and paternal report, while depression (concurrent Edinburgh scale) was also assessed at four and six months. As data were returned inconsistently at 4 and 6 months, we combined these two time points for simplicity of reporting and optimisation of numbers. RESULTS: Univariate logistic regressions on 970 subjects indicated that the pregnancy STAI (>40) scores were associated with 2.56- and 1.57-fold increases (maternal and paternal, respectively), in the odds of "difficult" infant temperament at 4 or 6 months. Concurrent Edinburgh scores (OR of 3.06 and 2.64 for maternal reports, respectively) were also predictive of infant temperament. Age, education, income, marital status, obstetric complications, infant gender and prematurity were not predictive of infant temperament. In stepwise multiple logistic regression analyses, the antenatal trait STAI (odds ratio 1.96) significantly predicted maternal reports of "difficult" temperament at 4 or 6 months independent of both antenatal and postnatal depression scores. There were similar trends for paternal reports of "difficult" temperament but these were not significant. Antenatal depression and perceived LE stress were not predictive of temperament. Finally, women (N=14) reporting domestic violence (DV) in pregnancy had highly significant increased Edinburgh and STAI scores. CONCLUSIONS: Maternal trait anxiety was predictive of "difficult" infant temperament, independent of "concurrent" depression and key sociodemographic and obstetric risk factors. These findings, while needing replication using objective measures of infant temperament, suggest that antenatal psychological interventions aimed at minimising anxiety may optimize infant temperament outcomes. There may be some benefit in shaping specific interventions to women reporting specific risk factors such as DV or past abuse.     

Restricted autonomic flexibility in children with social phobia

Background: Psychophysiological hyperresponsiveness to social‐evaluative stress plays a key role in current theories of social phobia (SP). Owing to the early onset of this disorder, the study of children with SP can help to improve etiological models. However, research to date has failed to clarify whether children with SP are physiologically hyperresponsive to stress or not. In addition, the existence of elevated pre‐stressor baseline group differences complicates the interpretation of acute stress responses and therefore poses a challenge for this line of research. Drawing on current models of autonomic control to explain the relationship between baseline and stress responding in SP children and healthy controls (HC), we acquired a broad set of autonomic measures in our study. Method: To index baseline and stress reactivity and to assess autonomic flexibility, we assessed a comprehensive array of sympathetic and parasympathetic measures in SP children (aged 8 to 12 years; n = 30) and healthy control children (HC, n = 26), while exposing them to the Trier Social Stress Test for Children (TSST‐C). Results: At baseline, the SP children showed higher levels of sympathetic (heart rate, electrodermal activity) and lower levels of parasympathetic (respiratory sinus arrhythmia, RSA) activation when compared to the HC children. During the TSST‐C, the SP children showed similar HR responses but a limited RSA reactivity and a slower HR recovery relative to the HC children. Conclusion: Our study extends previous research by showing elevated baseline arousal and comparable stress responding in SP children relative to HC children. In addition, based on the autonomic flexibility model, we provide a potential explanation for the null findings of previous studies during stress. The pattern of elevated baseline heart rates and reduced RSA point to restricted autonomic flexibility in children with SP.