Henning Tiemeier

Adverse childhood experiences and the risk of premature mortality.

BACKGROUND Strong, graded relationships between exposure to childhood traumatic stressors and numerous negative health behaviors and outcomes, healthcare utilization, and overall health status inspired the question of whether these adverse childhood experiences (ACEs) are associated with premature death during adulthood. PURPOSE This study aims to determine whether ACEs are associated with an increased risk of premature death during adulthood. METHODS Baseline survey data on health behaviors, health status, and exposure to ACEs were collected from 17,337 adults aged >18 years during 1995-1997. The ACEs included abuse (emotional, physical, sexual); witnessing domestic violence; parental separation or divorce; and growing up in a household where members were mentally ill, substance abusers, or sent to prison. The ACE score (an integer count of the eight categories of ACEs) was used as a measure of cumulative exposure to traumatic stress during childhood. Deaths were identified during follow-up assessments (between baseline appointment date and December 31, 2006) using mortality records obtained from a search of the National Death Index. Expected years of life lost (YLL) and years of potential life lost (YPLL) were computed using standard methods. The relative risk of death from all causes at age < or =65 years and at age < or =75 years was estimated across the number of categories of ACEs using multivariable-adjusted Cox proportional hazards regression. Analysis was conducted during January-February 2009. RESULTS Overall, 1539 people died during follow-up; the crude death rate was 91.0 per 1000; the age-adjusted rate was 54.7 per 1000. People with six or more ACEs died nearly 20 years earlier on average than those without ACEs (60.6 years, 95% CI=56.2, 65.1, vs 79.1 years, 95% CI=78.4, 79.9). Average YLL per death was nearly three times greater among people with six or more ACEs (25.2 years) than those without ACEs (9.2 years). Roughly one third (n=526) of those who died during follow-up were aged < or =75 years at the time of death, accounting for 4792 YPLL. After multivariable adjustment, adults with six or more ACEs were 1.7 (95% CI=1.06, 2.83) times more likely to die when aged < or =75 years and 2.4 (95% CI=1.30, 4.39) times more likely to die when aged < or =65 years. CONCLUSIONS ACEs are associated with an increased risk of premature death, although a graded increase in the risk of premature death was not observed across the number of categories of ACEs. The increase in risk was only partly explained by documented ACE-related health and social problems, suggesting other possible mechanisms by which ACEs may contribute to premature death.

Maternal Thyroid Function during Early Pregnancy and Cognitive Functioning in Early Childhood: The Generation R Study

CONTEXT Thyroid hormones are essential for neurodevelopment from early pregnancy onward. Yet population-based data on the association between maternal thyroid function in early pregnancy and childrens cognitive development are sparse. OBJECTIVE Our objective was to study associations of maternal hypothyroxinemia and of early pregnancy maternal TSH and free T(4)(FT(4)) levels across the entire range with cognitive functioning in early childhood. DESIGN AND SETTING We conducted a population-based cohort in The Netherlands. PARTICIPANTS Participants included 3659 children and their mothers. MAIN MEASURES In pregnant women with normal TSH levels at 13 wk gestation (SD = 1.7), mild and severe maternal hypothyroxinemia were defined as FT(4) concentrations below the 10th and 5th percentile, respectively. Childrens expressive vocabulary at 18 months was reported by mothers using the MacArthur Communicative Development Inventory. At 30 months, mothers completed the Language Development Survey and the Parent Report of Childrens Abilities measuring verbal and nonverbal cognitive functioning. RESULTS Maternal TSH was not related to the cognitive outcomes. An increase in maternal FT(4) predicted a lower risk of expressive language delay at 30 months only. However, both mild and severe maternal hypothyroxinemia was associated with a higher risk of expressive language delay across all ages [odds ratio (OR) = 1.44; 95% confidence interval (CI) = 1.09-1.91; P = 0.010 and OR = 1.80; 95% CI = 1.24-2.61; P = 0.002, respectively]. Severe maternal hypothyroxinemia also predicted a higher risk of nonverbal cognitive delay (OR = 2.03; 95% CI = 1.22-3.39; P = 0.007). CONCLUSIONS Maternal hypothyroxinemia is a risk factor for cognitive delay in early childhood.

Cerebellum development during childhood and adolescence: a longitudinal morphometric MRI study.

In addition to its well-established role in balance, coordination, and other motor skills, the cerebellum is increasingly recognized as a prominent contributor to a wide array of cognitive and emotional functions. Many of these capacities undergo dramatic changes during childhood and adolescence. However, accurate characterization of co-occurring anatomical changes has been hindered by lack of longitudinal data and methodologic challenges in quantifying subdivisions of the cerebellum. In this study we apply an innovative image analysis technique to quantify total cerebellar volume and 11 subdivisions (i.e. anterior, superior posterior, and inferior posterior lobes, corpus medullare, and three vermal regions) from anatomic brain MRI scans from 25 healthy females and 25 healthy males aged 5-24 years, each of whom was scanned at least three times at approximately 2-year intervals. Total cerebellum volume followed an inverted U shaped developmental trajectory peaking at age 11.8 years in females and 15.6 years in males. Cerebellar volume was 10% to 13% larger in males depending on the age of comparison and the sexual dimorphism remained significant after covarying for total brain volume. Subdivisions of the cerebellum had distinctive developmental trajectories with more phylogenetically recent regions maturing particularly late. The cerebellums unique protracted developmental trajectories, sexual dimorphism, preferential vulnerability to environmental influences, and frequent implication in childhood onset disorders such as autism and ADHD make it a prime target for pediatric neuroimaging investigations.

The Generation R Study: Design and cohort profile

The Generation R Study is a population-based prospective cohort study from fetal life until young adulthood. The study is designed to identify early environmental and genetic causes of normal and abnormal growth, development and health from fetal life until young adulthood. The study focuses on four primary areas of research: (1) growth and physical development; (2) behavioral and cognitive development; (3) diseases in childhood; and (4) health and healthcare for pregnant women and children. In total, 9778 mothers with a delivery date from April 2002 until January 2006 were enrolled in the study. Of all eligible children at birth, 61% participate in the study. Data collection in the prenatal phase included physical examinations, questionnaires, fetal ultrasound examinations and biological samples. In addition, more detailed assessments are conducted in a subgroup of 1232 pregnant women and their children. The children form a prenatally recruited birth-cohort that will be followed until young adulthood. Eventually, results forthcoming from the Generation R Study have to contribute to the development of strategies for optimizing health and healthcare for pregnant women and children.

The Generation R Study Biobank: a resource for epidemiological studies in children and their parents

The Generation R Study is a population-based prospective cohort study from fetal life until young adulthood. The study is designed to identify early environmental and genetic causes of normal and abnormal growth, development and health from fetal life until young adulthood. In total, 9,778 mothers were enrolled in the study. Prenatal and postnatal data collection is conducted by physical examinations, questionnaires, interviews, ultrasound examinations and biological samples. Major efforts have been conducted for collecting biological specimens including DNA, blood for phenotypes and urine samples. In this paper, the collection, processing and storage of these biological specimens are described. Together with detailed phenotype measurements, these biological specimens form a unique resource for epidemiological studies focused on environmental exposures, genetic determinants and their interactions in relation to growth, health and development from fetal life onwards.

Urinary metabolite concentrations of organophosphorous pesticides, bisphenol A, and phthalates among pregnant women in Rotterdam, the Netherlands : The Generation R study

Concern about potential health impacts of low-level exposures to organophosphorus (OP) pesticides, bisphenol A (BPA), and phthalates among the general population is increasing. We measured levels of six dialkyl phosphate (DAP) metabolites of OP pesticides, a chlorpyrifos-specific metabolite (3,5,6-trichloro-2-pyridinol, TCPy), BPA, and 14 phthalate metabolites in urine samples of 100 pregnant women from the Generation R study, the Netherlands. The unadjusted and creatinine-adjusted concentrations were reported, and compared to National Health and Nutrition Examination Survey and other studies. In general, these metabolites were detectable in the urine of the women from the Generation R study and compared with other groups, they had relatively high-level exposures to OP pesticides and several phthalates but similar exposure to BPA. The median concentrations of total dimethyl (DM) metabolites was 264.0 n mol/g creatinine (Cr) and of total DAP was 316.0 n mol/g Cr. The median concentration of mono-ethyl phthalate (MEP) was 222.0 microg/g Cr; the median concentrations of mono-isobutyl phthalate (MiBP) and mono-n-butyl phthalate (MnBP) were above 50 microg/g Cr. The median concentrations of the three secondary metabolites of di-2-ethylhexyl phthalate (DEHP) were greater than 20 microg/g Cr. The data indicate that the Generation R study population provides a wide distribution of selected environmental exposures. Reasons for the relatively high levels and possible health effects need investigation.

Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group.

The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen’s d=−0.14, % difference=−1.24). This effect was driven by patients with recurrent MDD (Cohen’s d=−0.17, % difference=−1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen’s d=−0.20, % difference=−1.85) and a trend toward smaller amygdala (Cohen’s d=−0.11, % difference=−1.23) and larger lateral ventricles (Cohen’s d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.

Disagreement between subjective and actigraphic measures of sleep duration in a population-based study of elderly persons

Sleep duration is an important concept in epidemiological studies. It characterizes a night’s sleep or a person’s sleep pattern, and is associated with numerous health outcomes. In most large studies, sleep duration is assessed with questionnaires or sleep diaries. As an alternative, actigraphy may be used, as it objectively measures sleep parameters and is feasible in large studies. However, actigraphy and sleep diaries may not measure exactly the same phenomenon. Our study aims to determine disagreement between actigraphic and diary estimates of sleep duration, and to investigate possible determinants of this disagreement. This investigation was embedded in the population‐based Rotterdam Study. The study population consisted of 969 community‐dwelling participants aged 57–97 years. Participants wore an actigraph and kept a sleep diary for, on average, six consecutive nights. Both measures were used to determine total sleep time (TST). In 34% of the participants, the estimated TST in the sleep diaries deviated more than 1 h from actigraphically measured TST. The level of disagreement between diary and actigraphic measures decreased with subjective and actigraphic measures of sleep quality, and increased with male gender, poor cognitive function and functional disability. Actigraphically measured poor sleep was often accompanied by longer subjective estimates of TST, whereas subjectively poor sleepers tended to report shorter TST in their diaries than was measured with actigraphy. We recommend, whenever possible, to use multiple measures of sleep duration, to perform analyses with both, and to examine the consistency of the results over assessment methods.

Incidence and recurrence of late-life depression.

CONTEXT Depression is common in old age. Nevertheless, few incidence studies have established how often depression occurs in elderly persons with and without a history of depression. OBJECTIVES To determine the incidence and recurrence rates of depression in an elderly population. DESIGN, SETTING, AND PARTICIPANTS A cohort study of community-dwelling elderly persons aged 56 years or older residing in Rotterdam, the Netherlands, performed between September 1993 and October 2005 and encompassing baseline and 2 follow-up examinations as well as continuous procedures. The study population consisted of 5653 participants free of dementia. Depression was identified through standardized psychiatric examinations, monitoring of medical records, registration of antidepressant use, and self-reported histories of depression. We categorized the depression as depressive syndromes, including DSM-IV-defined major depression, or clinically relevant depressive symptoms. MAIN OUTCOME MEASURES Incidence and recurrence rates for depressive syndromes as well as for depressive syndromes and symptoms combined. In addition to overall rates, sex- and age-specific rates were calculated. RESULTS During the follow-up period of 8 years on average, 566 depressive syndromes and 1073 episodes of clinically relevant depressive symptoms occurred. For depressive syndromes, the incidence rate was 7.0 (95% confidence interval, 6.0-8.3) per 1000 person-years and the recurrence rate was 27.5 (95% confidence interval, 23.7-32.1) per 1000 person-years. The incidence and recurrence rates more than doubled when episodes of depressive symptoms were included. The recurrence rate of depressive syndromes was equal for women and men, but all other rates were almost twice as high for women compared with men. No rates seemed to change with age. CONCLUSIONS The incidence rate of depression in the elderly population is low except when episodes of clinically relevant depressive symptoms are accounted for. Most late-life depression occurs in persons with a history of depression. Moreover, the recurrence rate of depressive syndromes does not differ between men and women.

Children's eating behavior, feeding practices of parents and weight problems in early childhood: results from the population-based Generation R Study

BackgroundWeight problems that arise in the first years of life tend to persist. Behavioral research in this period can provide information on the modifiable etiology of unhealthy weight. The present study aimed to replicate findings from previous small-scale studies by examining whether different aspects of preschooler’s eating behavior and parental feeding practices are associated with body mass index (BMI) and weight status -including underweight, overweight and obesity- in a population sample of preschool children.MethodsCross-sectional data on the Child Eating Behaviour Questionnaire, Child Feeding Questionnaire and objectively measured BMI was available for 4987 four-year-olds participating in a population-based cohort in the Netherlands.ResultsThirteen percent of the preschoolers had underweight, 8% overweight, and 2% obesity. Higher levels of children’s Food Responsiveness, Enjoyment of Food and parental Restriction were associated with a higher mean BMI independent of measured confounders. Emotional Undereating, Satiety Responsiveness and Fussiness of children as well as parents’ Pressure to Eat were negatively related with children’s BMI. Similar trends were found with BMI categorized into underweight, normal weight, overweight and obesity. Part of the association between children’s eating behaviors and BMI was accounted for by parental feeding practices (changes in effect estimates: 20-43%), while children’s eating behaviors in turn explained part of the relation between parental feeding and child BMI (changes in effect estimates: 33-47%).ConclusionsThis study provides important information by showing how young children’s eating behaviors and parental feeding patterns differ between children with normal weight, underweight and overweight. The high prevalence of under- and overweight among preschoolers suggest prevention interventions targeting unhealthy weights should start early in life. Although longitudinal studies are necessary to ascertain causal directions, efforts to prevent or treat unhealthy child weight might benefit from a focus on changing the behaviors of both children and their parents.