Adverse Environmental Influences Research Articles

Gene–environment interactions predict cortisol responses after acute stress: Implications for the etiology of depression

Growing evidence suggests that the serotonin transporter polymorphism (5-HTTLPR) interacts with adverse environmental influences to produce an increased risk for the development of depression while the underlying mechanisms of this association remain largely unexplored. As one potential intermediate phenotype, we investigated alterations of hypothalamic-pituitary-adrenal (HPA) axis responses to stress in individuals with no history of psychopathology depending on both 5-HTTLPR and stressful life events. Healthy male adults (N=100) were genotyped and completed a questionnaire on severe stressful life events (Life Events Checklist). To test for gene-by-environment interactions on endocrine stress reactivity, subjects were exposed to a standardized laboratory stress task (Public Speaking). Saliva cortisol levels were obtained at 6 time points prior to the stressor and during an extended recovery period. Subjects homozygous for the s-allele with a significant history of stressful life events exhibited markedly elevated cortisol secretions in response to the stressor compared to all other groups, indicating a significant gene-by-environment interaction on endocrine stress reactivity. No main effect of either 5-HTTLPR (biallelic and triallelic) or stressful life events on cortisol secretion patterns appeared. This is the first study reporting that 5-HTTLPR and stressful life events interact to predict endocrine stress reactivity in a non-clinical sample. Our results underpin the potential moderating role of HPA-axis hyper-reactivity as a premorbid risk factor to increase the vulnerability for depression in subjects with low serotonin transporter efficiency and a history of severe life events.

Indices of fetal development derived from heart rate patterns

Background The fetal precursors of mental and cardiovascular disease caused by adverse prenatal environmental influences and manifesting in later age are an important issue of developmental medicine. However the number of measurable functional parameters of a fetus is limited. Evaluation of key parameters involving fetal autonomic control could permit an earlier detection of developmental problems and improved therapeutic strategies. Thus far, however, even the maturation of normal autonomic control has not been sufficiently assessed. Aim The objective of the present work is to describe normal fetal maturation based on indices of autonomic heart rate modulation. Study design Heart beat interval series were magnetocardiographically recorded with 1 kHz sampling rate over 30 min in 78 normal fetuses, gestational age (GA) 23–40 weeks. Indices considered were: number of accelerations (AC) and decelerations (DC), RMSSD, SDNN, and short-term/long-term autonomic information flows (AIF_NN, AIF_fVLF). These were measured from the entire 30 min data sets and from activity-specific subsets (10 min). Results In the 30 min recordings: the number of AC increased, number of DC decreased, rMSSD and SDNN increased and AIF_fVLF increased with GA, but AIF_NN remained constant. In the 10 min subsets: SDNN increased in the active state but remained constant in the quiet state and AIF_NN decreased with GA in the quiet state. Conclusion Heart rate patterns from 30 min biomagnetic recordings may provide new indices with which to assess the normal and abnormal maturation of fetal autonomic control and to identify risk of possible disorders in later life.

Cohort profile: The Hertfordshire Ageing Study (HAS)

We have previously described the discovery of a unique set of infant records collected in Hertfordshire between 1911 and 1948.1 The historical data for births between 1911 and 1930 were linked to the NHS central register and showed that small size at birth and during infancy was associated with increased risk of cardiovascular mortality in men and women.2,3 These were the first studies based on individual data to suggest that adverse environmental influences acting in utero and during infancy might increase the risk of cardiovascular disease mortality in later life. Detailed physiological investigations of surviving men and women born in Hertfordshire between 1920 and 1930 and still living there in the early 1990s were subsequently conducted and allowed investigation of morbidity. Studies based on men and women resident in East Hertfordshire demonstrated that small size at birth and during infancy was associated with increased risk of developing coronary heart disease

The value of FeNO measurement in asthma management: the motion for Yes, it's NO – or, the wrong end of the Stick!

The utility of measurements of exhaled nitric oxide (FeNO) will likely depend on context, being most helpful in moderate and severe asthma, rather than mild asthmatics and community based studies. Atopy on its own is a cause of elevation in FeNO. Adult and paediatric studies have clearly established that measurement of some aspect of airway inflammation is part of state of the art management of asthma, but it is as yet unclear which of several techniques is most useful. The relationship between FeNO and sputum eosinophils is relatively loose, but this does not preclude it being a useful test in clinical practice. In fact, there are only poor correlations between sputum, proximal mucosal, and distal eosinophils, and the importance of these different compartments is unclear. A low FeNO in the setting of supposedly poorly controlled asthma should cast doubt on the diagnosis. We certainly cannot treat an isolated elevation in FeNO, which may be due to a simple viral cold, or constitutional. If FeNO is elevated, particularly if asthma is uncontrolled, it suggests an imbalance between anti-inflammatory therapy and pro-inflammatory environmental influences. Inadequate anti-inflammatory therapy may be due to the prescribed dose being too low; the drug delivery device not being used correctly; or the medication not being taken. Adverse pro-inflammatory environmental influences driving up FeNO include IgE and non-IgE mediated allergen sensitivity in the home, and even in the child's school. Novel technology allows home monitoring of FeNO, but the role of these devices is less clear. Although more data is needed properly to define the role of FeNO measurements in clinical practice, there is sufficient data already published to conclude that 'inflammometry' is an important part of asthma management at the more severe end of the spectrum, and that FeNO measurements are probably the most useful at the moment.

Meeting Report: Looking Hard at Early Exposures

Children’s health was the focus of almost 30 different sessions at the International Conference on Environmental Epidemiology and Exposure, held 2–6 September 2006 in Paris. Exposure to environmental toxicants early in life, and even parental exposure prior to conception, may lead to metabolic effects, cardiovascular disease, and reproductive problems later in life, said researchers speaking at the meeting. According to Germaine Buck Louis, an epidemiologist from the National Institute of Child Health and Human Development, there is scientific evidence to support a relationship between maternal and paternal exposures prior to conception and testicular dysgenesis syndrome, a collection of adverse effects in testes, as well as the less well-studied ovarian dysgenesis. Said Buck Louis, “Periconception is a vital stage for research on exposures.” George Davey-Smith, a researcher in the University of Bristol Department of Social Medicine, told plenary attendees that prenatal and early-life exposures to environmental factors such as infectious agents and tobacco smoke have been associated with effects on blood pressure, insulin resistance (possibly leading to obesity), and cardiovascular disease in adults. Smith says that so-called predictive adaptive responses—developmental “programming” in response to adverse environmental cues—may underlie some of these associations. Evolutionarily, these responses are intended prepare the developing organism for a life of hardship. For example, a mother’s poor nutrition during pregnancy may “predict” a life of nutritional hardship for her fetus. The resulting changes in fetal metabolic and cardiovascular development can prove maladaptive if the child is not, in fact, nutritionally deprived; the result can be metabolic syndrome. In a particularly packed session on children’s health and environmental chemicals, Brenda Eskenazi, a professor of epidemiology at the University of California, Berkeley, presented the as yet unpublished, compiled results of studies from three NIEHS/EPA Children’s Environmental Health Centers (UC-Berkeley, Columbia University, and Mount Sinai Medical Center) that showed similar associations between exposure to organophosphate pesticides and neurodevelopmental effects. Said Eskenazi, “The children’s centers have begun to come of age, and we can now reap the benefits of harmonizing the methods for our longitudinal birth cohort studies. It demonstrates the importance of conducting similar studies in different populations.” Promotion of research on how adverse environmental exposures affect children is the primary goal of a new society announced at the Paris meeting. The International Society for Children’s Health and the Environment is dedicated to protecting children from adverse environmental influences—chemical, physical, biological, and social—through research, training, policy making, clinical care, and education. The society also seeks to promote children’s health by enhancing the quality of their environments. Bruce Lanphear, director of the Children’s Environmental Health Center at Cincinnati Children’s Hospital Medical Center, is a founding member of the new society. He said, “It has become increasingly clear that children are particularly vulnerable to numerous environmental hazards. This society is being formed to combine and enhance our efforts to protect children from these hazards.” The society is currently recruiting members. Protection of children’s health is part of the basis for a joint declaration by scientists of the International Society for Environmental Epidemiology and the European Respiratory Society, presented at the meeting, which calls for European Union authorities to strengthen proposed air quality directives. Bert Brunekreef, a professor of environmental epidemiology at the University of Utrecht, said, “It is now widely recognized that the [current] levels are not completely or sufficiently protective of public health.” He added that the proposals “lack teeth” because they do not include mandatory requirements for reduction of fine particle pollution, which is associated with increases in asthma attacks and decreased pulmonary function in children. The European Commission is expected to review the proposed directives on 13 October 2006.

Psychogenese in der Schizophrenieauffassung von Manfred Bleuler

In chapter 6 of his major work The Schizophrenic Disorders: Long-Term Patient and Family Studies (1972) Manfred Bleuler discusses in detail the role of psychotraumatic experiences in the genesis of schizophrenic disorders, clearly mentioning that there is no understanding of schizophrenic psychosis without considering the genetic component. According to Manfred Bleuler, (1) the better you know a schizophrenic patient, the more understandable the content of his psychotic experience against the background of his life course becomes; (2) there are clear relationships between life circumstances and the beginning of the illness as well as between social and psychological stresses and exacerbations of the disorder; (3) psychotherapeutic efforts in the treatment of schizophrenic patients are not without success; (4) certain schizophrenic symptoms appear as a reaction to adverse environmental influences (e.g. hospitalism). There are no specific schizophrenogenic traumatic events. All factors, viewed as specific psychological causes of schizophrenia, turned out to be unspecific factors which could have contributed to other psychic disorders as well or which could even remain without any consequences. All psychotraumatic experiences which have been identified in the history of schizophrenic patients have also been found in the history of individuals who have never suffered from a schizophrenic breakdown. Harmful and troublesome environmental effects have to concur with a special constitutional vulnerability to ensue in a schizophrenic disorder. Most frequently, they are long-lasting and undramatic events rather than sudden dramatic experiences. Generally, what is good for a healthy subject is also good for a schizophrenic patient, and everything which damages someone healthy also damages the schizophrenic patient. However, whereas healthy individuals can cope, the schizophrenic patient cannot, because of his primary vulnerability. Disadvantageous are: uncertainty, tension, overstimulation, complicated and difficult-to-survey environment, large groups and a frequent fluctuation of personal exchange, unpredictability, lability, devaluation, lack of understanding, distress, indifference and rejection, lack of explanations, denial of differences of opinion, unclear and equivocal situations, equivocal and not clearly communicated expectations, overprotection, role rigidity, emotional closeness, contradictory orders and comments, irrationality. Advantageous are: security, rest, tranquillity, adequate amount of stimulation, simple and clear environment, small groups and few changes in staff, calculable environment, constancy and continuity, valuation, trust, understanding and appreciation, warmth, explanations, communicating differences of opinions, transparency, unequivocal statements and expectations, responsibility, role flexibility, emotional openness, clear orders and commands, rationality.

Youth Development, Community Engagement, and Reducing Risk Behavior

This article examines behaviors and attitudes associated with the "Youth Development Model," widely cited as a means of promoting resistance among young people to adverse environmental influences. Focusing on tobacco use as an example of high-risk behavior, the research reported here (1) tests the statistical independence of individual Youth Development Model dimensions, and (2) assesses their relationships to tobacco-related attitudes and behavior. The "engagement" dimension, reflecting strong ties of youths with the broader community, most clearly distinguishes risk reduction interventions based on the Youth Development Model. Two exploratory studies indicate that, among dimensions associated with this model, engagement is the least readily measurable and the least consistent and robust as a predictor of tobacco-related attitudes and behavior. Editors' Strategic Implications: The authors present an important challenge to the increasingly prevalent Youth Development Model. The results of the two studies call for a better conceptual and operational understanding of engagement, which must precede its successful application in reducing risky behavior among young people.

Effects of Endocrine Disrupting Chemicals on Male Reproductive Function-Epidemiological Views-

Numerous medical studies have recently focused on the adverse trends in human male reproductive health including possible decline in semen quality and increasing incidences of reproductive anomalies such as testicular cancer, cryptorchidism and hypospadias, which have been reported from many counties during past decades. We have no sufficient evidence on the basis of which we could determine whether human male reproductive health is really declining and whether endocrine disrupting chemicals are responsible for this observed decline. However, Skakkebaek's group has currently proposed a hypothesis that the male reproductive problems are symptoms of one underlying entity, the testicular dysgenesis syndrome (TDS), which may be increasingly common due to adverse environmental influences. According to this hypothesis, TDS is a result of the disruption of embryonal programming and gonadal development during the fetal stage and the recent rise in the prevalence of TDS may be causally linked to endocrine disrupting chemicals affecting genetically susceptible individuals. This review aims to give a brief overview of the suspected adverse trend in human male reproductive health and current data associated with TDS.

Cohort Profile: The Hertfordshire Cohort Study

How did the study come about? Ecological studies conducted in the 1980s demonstrated a close geographic correlation between death rates from coronary heart disease during the years 1968–78 in different parts of England and Wales and the infant mortality rate in these areas 60 years earlier.1 These studies suggested that adverse environmental influences acting in utero and during infancy might increase the risk of cardiovascular disease in later life. However, this hypothesis required investigation using more robust epidemiological techniques. To yield results within a relatively short space of time, a cohort study was needed which linked information about the early environment of individuals born at least 60 years earlier to their health outcomes in later life. As part of a nationwide search of archives, staff working at the MRC Environmental Epidemiology Unit (MRC EEU), University of Southampton, discovered a large set of records maintained in Hertfordshire during the early 20th century.

Asthma research: The real action is in children

Many adult diseases have their roots in infancy or even prenatally. If events that initiate these diseases, as opposed to those that propagate the disease state, are to be understood, then the difficult area of how ethically to research problems in infancy must be tackled. Furthermore, the predisposition to archetypally 'pure' adult problems such as chronic obstructive pulmonary disease, may lie antenatally, the effects being masked until the lung starts to age. An additional factor is that the success of paediatricians, for example in ensuring the survival of extremely premature, low birth weight infants leads to adult survivors with potentially a whole new morbidity. The first prerequisite to making progress is a sound understanding of the development of the normal lung and how adverse environmental and genetic influences, such as exposure to environmental tobacco smoke and maternal atopy, respectively, may affect growth. This paper focuses on three key areas: the implications of different pre-school wheezing phenotypes for adult disease; the importance of very early life events in cystic fibrosis; and the long term consequences of chronic lung disease of prematurity. Finally, the ethical principles that must underpin future research in pre-school children is discussed, as well as the means we might use to further our understanding of the relevant early disease processes.

Separation-Induced Receptor Changes in the Hippocampus and Amygdala ofOctodon degus: Influence of Maternal Vocalizations

Relatively little is known about the basic mechanisms that play a role in the vulnerability of the developing brain toward adverse environmental influences. Our study in the South American rodent Octodon degus revealed that repeated brief separation from the parents and exposure to an unfamiliar environment induces in the hippocampal formation of male and female pups an upregulation of D1 and 5-HT1A receptor density in the stratum radiatum and stratum lacunosum moleculare of the CA1 region. In the CA3 region, only the 5-HT1A receptors were upregulated; no changes were observed for D1 receptors in this region. GABA(A) receptor density in the hippocampus and amygdala was downregulated (nonsignificant trend) after parental separation. The acoustic presence of the mother during parental separation suppressed the D1 and 5-HT1A receptor upregulation in some regions of the hippocampus; no such suppressing influence was observed for the GABA(A) receptors. In the basomedial amygdala, the maternal calls enhanced the separation-induced 5-HT1A receptor upregulation in the male pups, whereas in the female pups the separation-induced receptor densities were not only suppressed by the maternal call but further downregulated, compared with the control group. These results demonstrate that early adverse emotional experience alters aminergic function within the hippocampus and amygdala and that the mother's voice, a powerful emotional signal, can modulate these effects in the developing limbic system.

Mother’s voice “buffers” separation-induced receptor changes in the prefrontal cortex of octodon degus

Although the potential vulnerability of the postnatally developing brain toward adverse environmental influences is generally recognized, relatively little is known about the basic mechanisms involved. The plasticity and adaptability of the postnatally developing brain in response to adverse emotional experiences was analyzed in the South American Octodon degus. Our study revealed that repeated brief separation from the parents and exposure to an unfamiliar environment induces an up-regulation of dopamine (D1) and 5-hydroxytrytamine (5HT1 A)-receptor density in the precentral medial, anterior cingulate, prelimbic and infralimbic cortices in female pups. No significant changes of gamma aminobutyric acid (GABA A) receptor density were found in deprived animals of both genders. The acoustic presence of the mother during parental separation suppressed the D1-receptor up-regulation as well as the 5-HT1 A-receptor up-regulation, again only in the female pups. These results demonstrate that that early adverse emotional experience alters aminergic function within the prefrontal cortex in the female but not the male brain. The mother’s voice, a powerful emotional signal, can protect the developing cortex from separation-induced receptor changes.

Prevalence of Leptospirosis Antibodies in the European Hare (Lepus europaeus Pall.) in the District of Břeclav

home Acta Veterinaria Brno Journal of the University of Veterinary Sciences Brno, Czech Republic Search:

Genetic and environmental risk factors for the onset of drug use and problems in adoptees

Applying survival analysis methodology to age-of-onset data from an adoption study ( N=196), we present evidence that risks for both drug use and drug problems (DSM abuse or dependence) are elevated when combined antisocial personality (ASP) and substance abuse is present in the same biological parent. It is increased not only in comparison to adoptees with no known biological risk, but also when compared to adoptees with a biological background for only substance problems or only ASP. Neither of these later groups showed a statistically higher risk when compared with controls. Among adoptees with recurrent drug use, adolescent aggressivity is also elevated when the combined substance abuse/ASP biological diathesis is present. Statistical control for aggressivity diminished but did not eliminate the predictive significance of the combined biological diathesis for drug problems. We also verify, using more refined methodology, our previous reports of gender and adverse adoptive environmental influences on drug-related outcomes in these subjects. We could not document a biology–environment interaction, but power to do so was rather low. We argue that the observed biological associations are broadly consistent with generalization to other substances of an alcoholism phenotype similar to Cloninger's Type II or Babor's Type B.

Impact of exposure to endocrine disrupters in utero and in childhood on adult reproduction.

Recent reports have demonstrated a decline in human male reproductive health: high and probably increasing prevalence of cryptorchidism and hypospadias, low and probably decreasing semen quality, a rising incidence of testicular cancer and a growing demand for assisted reproduction. These changes seem to be interrelated and may be symptoms of a common underlying entity, the testicular dysgenesis syndrome, with foundations in fetal life due to adverse environmental influences. Wildlife experience and animal studies have provided evidence that fetal or perinatal exposure to endocrine disrupters results in disturbed sexual differentiation and urogenital malformations followed by decreased reproductive health in adult life. This chapter reviews existing evidence for a connection between (i) exposure to endocrine disrupters in fetal life and childhood and (ii) adult reproductive health in humans. This topic is not only relevant to basic scientists but also to clinical endocrinologists, who should also be encouraged to participate in research concerning this problem.

Evaluation of Factors that Influence School Readiness Among Nursery School Children in Enugu

The preschool child is often confronted with adverse environmental influences that may affect his/her development and hence his readiness for schooling. The factors that affect school readiness were evaluated in 532 nursery school pupils using a proforma on perinatal problems and gross motor development of the pupils. Their nutritional status, neurodevelopment status, and their performance on the Draw-A-Person Test were assessed. Sixty (11.3 per cent) of the 532 children were unready for schooling. Factors that are responsible for this included malnutrition, adverse perinatal period and a younger age at school entry. The need for the establishment of the preschool health unit in the Local Government as well as routine medical examination of nursery school pupils is emphasized. Nigerian Journal of Paediatrics 2002; 29: 34-39.

Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects

Numerous reports have recently focused on various aspects of adverse trends in male reproductive health, such as the rising incidence of testicular cancer; low and probably declining semen quality; high and possibly increasing frequencies of undescended testis and hypospadias; and an apparently growing demand for assisted reproduction. Due to specialization in medicine and different ages at presentation of symptoms, reproductive problems used to be analysed separately by various professional groups, e.g. paediatric endocrinologists, urologists, andrologists and oncologists. This article summarizes existing evidence supporting a new concept that poor semen quality, testis cancer, undescended testis and hypospadias are symptoms of one underlying entity, the testicular dysgenesis syndrome (TDS), which may be increasingly common due to adverse environmental influences. Experimental and epidemiological studies suggest that TDS is a result of disruption of embryonal programming and gonadal development during fetal life. Therefore, we recommend that future epidemiological studies on trends in male reproductive health should not focus on one symptom only, but be more comprehensive and take all aspects of TDS into account. Otherwise, important biological information may be lost.

Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects.

Numerous reports have recently focused on various aspects of adverse trends in male reproductive health, such as the rising incidence of testicular cancer; low and probably declining semen quality; high and possibly increasing frequencies of undescended testis and hypospadias; and an apparently growing demand for assisted reproduction. Due to specialization in medicine and different ages at presentation of symptoms, reproductive problems used to be analysed separately by various professional groups, e.g. paediatric endocrinologists, urologists, andrologists and oncologists. This article summarizes existing evidence supporting a new concept that poor semen quality, testis cancer, undescended testis and hypospadias are symptoms of one underlying entity, the testicular dysgenesis syndrome (TDS), which may be increasingly common due to adverse environmental influences. Experimental and epidemiological studies suggest that TDS is a result of disruption of embryonal programming and gonadal development during fetal life. Therefore, we recommend that future epidemiological studies on trends in male reproductive health should not focus on one symptom only, but be more comprehensive and take all aspects of TDS into account. Otherwise, important biological information may be lost.

Critical growth phases for adult shortness in Hong Kong Chinese.

This study was designed to explore whether the influence of subnormal growth in fetal, infancy, childhood and pubertal phases on adult short stature was the same when comparing privileged and underprivileged populations. Data came from two longitudinal growth studies: 1) Hong Kong Chinese children who were born in 1967 (n = 132), and 2) the comparatively more privileged Swedish children who were born in 1973-1975 (n = 2,850). 68% of Hong Kong Chinese children had two or more growth phases subnormal, much higher than the 12.4% for Swedish children. 42.4% of Hong Kong Chinese were short at final height, much higher than the 2.2% for Swedish children. Subnormal growth in any growth phase was associated with an increased risk of adult short stature in both series (p<0.01). After adjustment for mid-parental height, the place of residence (Hong Kong/Sweden) was not significant for adult shortness (p>0.05) in the pooled data. The impact of subnormal growth in any phase on adult shortness is similar in privileged and underprivileged populations. The much higher prevalence of subnormal growth and consequently adult short stature in developing countries is likely mainly attributable to adverse extrinsic or environmental influences.

The lung of the marmoset ( Callithrix jacchus): ultrastructure and morphometric data

Owing to its small size (body weight 300–400 g), its modest demands on animal husbandry, and in particular its relatively long life-span (up to 12 years) the common marmoset (cotton ear marmoset: Callithrix jacchus (Cj)) might be a useful animal model to study the adaptive capacity to different energetic demands, adverse environmental influences such as air pollution, and aging of the lung. In order to describe the gas exchange apparatus of healthy marmosets as a basis for further pulmonary research, the lungs of three young adult animals have been analysed both qualitatively and quantitatively (by morphometry) at the light and electronmicroscopic level. Qualitatively, there is a general similarity in the architecture and structure of lung parenchyma between marmosets and other mammals. Quantitatively, the alveolar surface area was found to be 7662±1647 cm 2. Capillary surface area and volume were 6000±1549 cm 2, and 1.01±0.34 ml, respectively. The harmonic mean thickness of the air-blood barrier was 0.517±0.117 μm. These morphometric parameters allowed to estimate the diffusing capacity for oxygen at 0.0299±0.0134 ml O 2 (sec mmHg) −1. In comparison with mammals of similar body size (rats, quinea pigs) it appears that the marmoset has a higher gas exchanging capacity of the lung, which might reflect the ‘athletic’ activity of this small primate. An incidental finding worth mentioning is the individual variability of septal structures due to variations in capillary blood volume and hematocrit. The distinction between such functional variations and subtle pathologic alterations of lung tissue requires a morphometric analysis at the electron-microscopic level.