Jacob F. Orlebeke

The Young Netherlands Twin Register (YNTR): Longitudinal Twin and Family Studies in Over 70,000 Children

The Netherlands Twin Register (NTR) began in 1987 with data collection in twins and their families, including families with newborn twins and triplets. Twenty-five years later, the NTR has collected at least one survey for 70,784 children, born after 1985. For the majority of twins, longitudinal data collection has been done by age-specific surveys. Shortly after giving birth, mothers receive a first survey with items on pregnancy and birth. At age 2, a survey on growth and achievement of milestones is sent. At ages 3, 7, 9/10, and 12 parents and teachers receive a series of surveys that are targeted at the development of emotional and behavior problems. From age 14 years onward, adolescent twins and their siblings report on their behavior problems, health, and lifestyle. When the twins are 18 years and older, parents are also invited to take part in survey studies. In sub-groups of different ages, in-depth phenotyping was done for IQ, electroencephalography , MRI, growth, hormones, neuropsychological assessments, and cardiovascular measures. DNA and biological samples have also been collected and large numbers of twin pairs and parents have been genotyped for zygosity by either micro-satellites or sets of short nucleotide polymorphisms and repeat polymorphisms in candidate genes. Subject recruitment and data collection is still ongoing and the longitudinal database is growing. Data collection by record linkage in the Netherlands is beginning and we expect these combined longitudinal data to provide increased insights into the genetic etiology of development of mental and physical health in children and adolescents.

Is there an effect of prenatal testosterone on aggression and other behavioral traits? A study comparing same-sex and opposite-sex twin girls

Men and women differ in temperament and personality traits, such as aggression and sensation seeking. The sex hormone testosterone could play a role in the origin of these differences, but it remains unclear how and when testosterone could have these effects. One way to investigate the prenatal exposure effect of testosterone is to compare opposite-sex (OS) and same-sex (SS) female twins. It has been suggested that OS twin girls are exposed prenatally to elevated testosterone levels and that this may result in some masculinization of their personality and behavior. We measured sexually dimorphic traits and circulating testosterone levels in 13-year-old OS (n = 74) and SS (n = 55) twins. Testosterone levels showed a clear circadian rhythm, with higher levels in the morning than in the afternoon. Testosterone was higher in boys than girls, but similar in OS and SS twin girls. Testosterone was not in any way systematically related to the different personality traits. However, a sex difference in aggression proneness was observed, and OS girls showed a more masculine pattern of aggression proneness than the SS girls. It is argued that it is unlikely that this difference is due to social factors, such as a gender-specific upbringing.

The Dutch Twin Register: Growth data on Weight and Height

As part of a longitudinal developmental study of newborn and young Dutch twins, data on weight and height are collected. Birth weight and height are available for 3275 pairs; data on growth, for 1390 pairs.

Cardiovascular response to mental stress in offspring of hypertensive parents: The Dutch Hypertension and Offspring Study

Objective: To compare blood pressure-regulating mechanisms during mental stress in two groups of offspring with contrasting risk for hypertension. Design: Cardiovascular reactivity to two different types of mental stressors was studied in adolescents and young adults with two hypertensive or two normotensive parents. The two tasks used were intended to evoke either a predominantly adrenergic cardiac response (a memory search task) or a predominantly vascular response (a reaction-time task with visual search and tone avoidance). Methods: Blood pressure and heart rate were recorded at rest and during stress. To study adaptations of the cardiovascular system to mental stress, cardiac output, total peripheral resistance and indices of vagal and sympathetic influences on the heart were measured. Results: The reactivity of systolic blood pressure (SBP) to the memory search task was significantly higher in offspring of hypertensive parents, which resulted in a longer recovery after the task. In contrast, during the reaction-time task, offspring of hypertensive parents had a significantly enhanced reactivity of peripheral resistance, but no differences in heart rate or blood pressure response were observed. No differences between the two groups were found in sympathetic or vagal activity during either task measured by the ratio of pre-ejection time and left ventricular ejection time, and respiratory sinus arrhythmia, respectively. Conclusion: Apart from a higher reactivity of SBP during the memory search task, no other indications supporting the presence of hyperadrenergic activation of the heart in early primary hypertension were found. On the contrary, the results of the present study support the hypothesis that blood pressure responses in prehypertensive subjects are characterized by enhanced vasoconstriction rather than by increased cardiac output.

FREQUENCY OF PARENTAL REPORT OF PROBLEM BEHAVIOR IN CHILDREN DECREASES WITH INCREASING MATERNAL AGE AT DELIVERY

Child behavior problems were assessed in 1377 3-yr.-old twin pairs with the Child Behavior Check List from Achenbach (translated into Dutch language by Verhulst). The association between problem scores and maternal age at delivery of the twins was analyzed with statistical control for several potential confounding variables: birth weight of twins, maternal smoking during pregnancy, being breast or bottle fed and socioeconomic status. After controlling for all available confounding covariates, a significant linear effect for maternal age was left. Especially Externalizing behavior problems as well as the separate categories that constitute Externalizing, i.e., Aggressive, Oppositional, and Overactive, appeared to decrease continuously with increasing maternal age. This was true for both boys and girls as well as for first and secondborn twins. Evidence in support of a biological explanation of the association between maternal age and child behavior problems, is presented.

Epidemiological and birth weight characteristics of triplets: a study from the Dutch twin register

From 112 triplet sets, born in The Netherlands from the end of 1986 to the beginning of 1991 and registered in the Dutch Twin Register, several details such as birth weight, gestational age, zygosity, and etiology were assessed by questionnaire, which was filled out by the mother. For 33 triplet sets, zygosity was also assessed by blood typing. Maternal smoking during pregnancy was also noted. Results show a very strong increase in number of triplets caused by artificial fertility enhancing techniques and consequently a shift in the relative contribution of zygosity types to the total number of triplets. Birth weight is predominantly influenced by gestational age. Other effects on birth weight are controlled for possible confounding with gestational age. First born triplets weigh more than later born triplets; boys weigh more than girls; nearly 25% of all individual triplets weigh less than 1500 g, i.e. belong to the category very low birth weight (VLBW); regular maternal smoking produces a 14% birth weight reduction; ovulation induction seems to decrease the sex ratio, i.e. hormonal treatment with ovulation inducing substances increases the probability of female offspring.

Elevated sinistrality in transsexuals

On the basis of both Geschwind andBehans (1984) theory—that at least part of the genesis of left-handedne ss can be ascribed to overexposure to testosterone during fetal development—andDorners (1980;Dorneretal., 1991) theory—that transsexuality emerges from prenatal over- or underexposure to androgens infemale-to-male (FTM) andmale-to-female (MTF) transsexuals, respectively—it was predicted that thefrequency of left-handedne ss in FTM transsexuals would be higher than in the general population. In MTF transsexuals, by contrast, thefrequency of left-handedne ss was expected to be lower or the same as in the general population. Results showed that the prevalence of left- handedness in both FTM and MTF transsexuals is nearly two times higher than in the general population. The generally higher prevalence of left-handedne ss among trans- sexuals, combined with the absence of the predicted sex difference, indicates that either Dorners theory on the etiology of transsexuality or Geschwinds model of the genesis of left-handedness, or both, need to be revised.

Adrenaline and the relationship between neurosomatism, aerobic fitness and mental task performance

The influence of neurotic instability as manifested by functional somatic complaints (neurosomatism) and aerobic fitness on responses to mental stress and to intravenous adrenaline infusions were investigated in 44 university students. Adrenaline-induced changes from resting levels in state anxiety and somatic anxiety were significantly more pronounced in high than in low neurosomatic subjects and all anxiety ratings were generally negatively related to aerobic fitness. Cardiovascular reactivity was induced by mental stress and by adrenaline infusions, but was not altered by neurosomatism. In individuals assumed to be characterized by a susceptibility to adrenergic effects, interference of adrenaline-induced arousal with cognitive performance may not occur. In contrast, a further increase in performance may occur when adrenaline is infused. Performance measures correlated negatively with anxiety during the baseline task and the placebo task, but this negative relation was absent during the adrenaline infusion and was replaced by positive relations between performance and aerobic power. The complex relations between bodily symptoms of anxiety, aerobic fitness and mental stress are discussed.

Effect of maternal smoking on birth weight of twins: a study from the Dutch Twin Register

Since twins weigh about 20% less than singletons at birth, maternal smoking may be a more severe risk for them than for singletons. Therefore, the effect of maternal smoking during pregnancy on birth weight was investigated in a group of 5376 twins. All necessary information was collected by a questionnaire filled out by the mother of the twins. Gestational age explains more than 75% of the variance in birth weight. Other effects were tested with gestational age as a covariate. Apart from zygosity (DZ twins weigh more than MZ twins), birth order (first born twins weigh more than second born twins) and sex (boys weigh more than girls), there was a very significant birth weight reducing effect (more than 8%) maternal smoking as well as a significant influence of maternal age (young mothers give birth to smaller children). There were no interactions with maternal smoking.

The psychophysiological effects of adrenaline infusions as a function of trait anxiety and aerobic fitness

Abstract This study compares changes in anxiety and cardiovascular variables elicited by intravenously infused adrenaline in 45 male university students who were selected on the basis of their trait anxiety. During the infusion cognitive anxiety, somatic anxiety, systolic blood pressure and heart rate increased and diastolic blood pressure and pre-ejection period decreased, dose-dependently. High trait anxiety was associated with higher levels of adrenaline-induced anxiety. Across all subjects, adrenaline-induced anxiety was inversely related to aerobic fitness. Emotional and cardiovascular reactivity was similar in low- and high-anxious subjects, but high autonomic instability may be associated with enhanced emotional reactivity to infused adrenaline. Thus, anxiety in the central nervous system can be elicited by a peripheral stimulant such as adrenaline, but controlling for physical fitness and autonomic lability may be necessary.