Biomedical subjects

E J de Geus

Publications and source records attributed to E J de Geus.

At least 19 recordsLinked to original sources

PubMed2003

The association between birth weight and plasma fibrinogen is abolished after the elimination of genetic influences.

Low birth weight is associated with an increased risk of atherothrombosis, which may be related in part to the association between low birth weight and high plasma fibrinogen. The association between birth weight and fibrinogen may be explained by intrauterine, socio-economic or genetic factors. We examined birth weight and fibrinogen in 52 dizygotic and 56 adolescent monozygotic (genetically identical) twin pairs. The dizygotic but not the monozygotic twins with the lowest birth weight from each pair had a fibrinogen level that was higher compared with their co-twins with the highest birth weight [dizygotic twins: 2.62 +/- 0.46 g L(-1) vs. 2.50 +/- 0.41 g L(-1) (P = 0.04); monozygotic twins: 2.42 +/- 0.45 g L(-1) vs. 2.49 +/- 0.39 g L(-1) (P = 0.2)]. These findings suggest that the association between birth weight and plasma fibrinogen is abolished after the elimination of genetic influences and therefore that this association has genetic causes. Improvement of intrauterine nutrition may not lower fibrinogen levels in later life.

Adolescent↗

PubMed2001

Genetic correlation between the P300 event-related brain potential and the EEG power spectrum.

Previous studies have demonstrated moderate heritability of the P300 component of event-related brain potentials (ERPs) and high heritability of background electroencephalogram (EEG) power spectrum. However, it is unclear whether EEG and ERPs are influenced by common or independent genetic factors. This study examined phenotypic and genetic correlations between EEG spectral power and P300 amplitude using data from 206 Dutch twin pairs, age 16 years. Multivariate genetic models (Cholesky decomposition) were fitted to the observed twin covariances using Mx software. In males, genetic correlations between P300 and EEG power measures were high (0.54-0.74); 30% of the total P300 variance could be explained by genetic factors influencing EEG delta power and 26% by P300-specific genetic factors (total heritability 56%). In females, 45% of P300 variance could be attributed to familial influences that were shared with the EEG. However, it was not possible to distinguish between the genetic versus shared environmental factors, consistent with previous analysis of P300 in this sample (van Beijsterveldt et al., 1998). The results suggest that a substantial proportion of genetic influences on P300 amplitude can be explained by strong heritability of slow EEG rhythms contributing to P300.

Adolescent↗

PubMed2001

Are smarter brains running faster? Heritability of alpha peak frequency, IQ, and their interrelation.

It has often been proposed that faster central nervous system (CNS) processing amounts to a smarter brain. One way to index speed of CNS processing is through the assessment of brain oscillations via electroencephalogram (EEG) recordings. The dominant frequency (peak frequency) with which neuronal feedback loops in an adult human brain oscillate in a relaxed state is around 10 cycles/sec, but large individual differences exist in peak frequencies. Earlier studies have found high peak frequencies to be associated with higher intelligence. In the present study, data from 271 extended twin families (688 participants) were collected as part of a large, ongoing project on the genetics of adult brain function and cognition. IQ was assessed with the Dutch version of the Wechsler Adult Intelligence Scale (WAIS-IIIR), from which four dimensions were calculated (verbal comprehension, working memory, perceptual organization, and processing speed). Individual peak frequencies were picked according to the method described by Klimesch (1999) and averaged 9.9 Hz (SD 1.01). Structural equation modeling indicated that both peak frequency and the dimensions of IQ were highly heritable (range, 66% to 83%). A large part of the genetic variance in alpha peak frequency as well as in working memory and processing speed was due to nonadditive factors. There was no evidence of a genetic correlation between alpha peak frequency and any of the four WAIS dimensions: Smarter brains do not seem to run faster.

Adult↗

PubMed2001

Perceptual speed and IQ are associated through common genetic factors.

Individual differences in inspection time explain about 20% of IQ test variance. To determine whether the association between inspection time and IQ is mediated by common genes or by a common environmental factor, inspection time and IQ were assessed in an extended twin design. Data from 688 participants from 271 families were collected as part of a large ongoing project on the genetics of adult brain function and cognition. The sample consisted of a young adult cohort (mean age 26.2 years) and an older adult cohort (mean age 50.4 years). IQ was assessed with the Dutch version of the WAIS-3R. Inspection time was measured in the so-called II-paradigm, in which a subject is asked to decide which leg of the II-figure is longest at varying display times of the II-figure. The number of correct inspections per second (i.e., the reciprocal of inspection time) was used to index perceptual speed. For Verbal IQ and Performance IQ, heritabilities were 85% and 69%, respectively. For perceptual speed, 46% of the total variance was explained by genetic variance. No differences in heritability estimates across age cohorts or sexes were found. Across the whole sample, a significant phenotypic correlation was found between perceptual speed and Verbal IQ (0.19) and between perceptual speed and Performance IQ (0.27). These correlations were entirely due to a common genetic factor that accounted for 10% of the genetic variance in verbal IQ and for 22% of the genetic variance in performance IQ. This factor is hypothesized to reflect the influence of genetic factors that determine axonal myelination in the central nervous system.

Adult↗

PubMed2001

Longitudinal genetic analysis of EEG coherence in young twins.

During middle childhood, continuous changes occur in electroencephalogram (EEG) coherence, an index of cortico-cortical connectivity of the brain. In the gradual development of EEG coher ence, occasional "growth spurts" are observed which coincide with periods of discontinuous development in cognition. Discontinuous development may reflect changes in the genetic architecture of a trait over time, for instance, by the emergence of new genetic factors. To examine stability and change in genetic and environmental influences on EEG coherence from ages 5 to 7 years, intrahemispheric EEG coherences from 14 connections were collected twice in 209 twin pairs. Overall, heritabilities (h2) were moderate to high for all EEG coherences at both ages (average: 58%). For occipito-cortical connections in the right hemisphere, h2 increased with age due to a decrease in environmental variance. For prefronto-cortical connections in the left hemisphere, h2 decreased with age due to a decrease in genetic variance. New genetic factors at age 7 were found for prefronto-parietal coherence, and centro-occipital and parieto-occipital EEG coherences in both hemispheres and, in the left hemisphere, for prefronto-frontal EEG coherences. Mean genetic correlation for these cortico-cortical connections over time was 0.72, indicating that at least part of the genetic influences is age-specific. We argue that this is convincing evidence for the existence of stage-wise brain maturation from years 5 to 7, and that growth spurts in EEG coherence may be part of the biological basis for discontinuous cognitive development at that age range.

Brain Mapping↗

PubMed2001

Genetics of brain function and cognition.

There is overwhelming evidence for the existence of substantial genetic influences on individual differences in general and specific cognitive abilities, especially in adults. The actual localization and identification of genes underlying variation in cognitive abilities and intelligence has only just started, however. Successes are currently limited to neurological mutations with rather severe cognitive effects. The current approaches to trace genes responsible for variation in the normal ranges of cognitive ability consist of large scale linkage and association studies. These are hampered by the usual problems of low statistical power to detect quantitative trait loci (QTLs) of small effect. One strategy to boost the power of genomic searches is to employ endophenotypes of cognition derived from the booming field of cognitive neuroscience. This special issue of Behavior Genetics reports on one of the first genome-wide association studies for general IQ. A second paper summarizes candidate genes for cognition, based on animal studies. A series of papers then introduces two additional levels of analysis in the "black box" between genes and cognitive ability: (1) behavioral measures of information-processing speed (inspection time, reaction time, rapid naming) and working memory capacity (performance on on single or dual tasks of verbal and spatio-visual working memory), and (2) electrophyiosological derived measures of brain function (e.g., event-related potentials). The obvious way to assess the reliability and validity of these endophenotypes and their usefulness in the search for cognitive ability genes is through the examination of their genetic architecture in twin family studies. Papers in this special issue show that much of the association between intelligence and speed-of-information processing/brain function is due to a common gene or set of genes, and thereby demonstrate the usefulness of considering these measures in gene-hunting studies for IQ.

Brain↗

PubMed2001

Stability of genetic and environmental influences on P300 amplitude: a longitudinal study in adolescent twins.

This study examined the stability of genetic and environmental influences on individual differences in P300 amplitude during adolescence. The P300 component is an event-related brain potential (ERP) that has attracted much attention as a biological marker for disturbed cognitive processing in psychopathology. Understanding the genetics of this biological marker may contribute to understanding the genetics of the associated psychopathologies. In a group of 213 adolescent twin pairs, the P300 component was measured twice, the first time at age 16 and the second time 18 months later. A large part of the variance of the P300 amplitude could be explained by familial factors, with estimates ranging from 30% to 81%. Whether the familial resemblance was due to genetic or shared environmental factors depended on sex. For males, genetic factors explained familial resemblance in P300 amplitude, but for females such resemblance was likely due to shared environmental factors. The phenotypic stability of the P300 amplitude from 16 to 18 years was high in both sexes, and stability could be attributed largely to the same familial factors. There was no evidence that new familial influences emerged at age 18.

Adolescent↗

PubMed2001

Effects of medication use on health state in postictal migraineurs.

We investigated whether headache-free patients with migraine report a lower health state compared with healthy controls, and whether health state is differently affected during the postattack period after using sumatriptan versus habitual nonvasoactive medication. Mood, health state, and personality questionnaires were administered once during an interictal period and twice within 30 hours after different migraine attacks treated with sumatriptan or habitual nonvasoactive medication. Twenty migraineurs without aura, 10 migraineurs with aura, and 30 matched and headache-free controls participated in this study. During an interictal period, patients with migraine reported more problems regarding social activities and pain compared with healthy controls. During the postictal period, mood (fatigue and emotional state) was negatively affected by an attack that was treated with habitual medication, whereas health state (physical pain, social activities, current pain) was similar to the migraine-free period. Sumatriptan treatment had beneficial effects on aspects of health state and mood during the postictal period.

Adult↗

PubMed2001

Interictal and postictal contingent negative variation in migraine without aura.

Cortical hyperexcitability is thought to explain the more enhanced contingent negative variation (CNV) amplitudes and impaired CNV habituation that have been found during the interictal period in migraine without aura. These CNV characteristics have been shown to normalize to the level of healthy controls during an attack. This study aimed to replicate the interictal findings, and additionally examine whether migraineurs show reduced CNV amplitudes during the postattack period. Of 12 patients with migraine without aura and their sex- and age-matched healthy controls, CNV characteristics were recorded once in an interictal period, once during the postattack period within 30 hours after an attack that was treated with sumatriptan, and once after an attack that was treated with habitual nonvasoactive medication (counterbalanced). The present results did not confirm the enhanced CNV early and late wave amplitudes or impaired habituation, and cortical hyperexcitability that have previously been reported in the interictal period in patients with migraine without aura. During the postattack period, a decrease in CNV early and late amplitudes was found but only after sumatriptan use. This reduction in CNV amplitudes was most prominent over the frontal cortex and could reflect cortical hypoexcitability, possibly related to a suppression of central catecholaminergic activity by sumatriptan.

Adult↗

PubMed2001

Quantitative genetic modeling of variation in human brain morphology.

The degree to which individual variation in brain structure in humans is genetically or environmentally determined is as yet not well understood. We studied the brains of 54 monozygotic (33 male, 21 female) and 58 dizygotic (17 male, 20 female, 21 opposite sex) pairs of twins and 34 of their full siblings (19 male, 15 female) by means of high resolution magnetic resonance imaging scans. Structural equation modeling was used to quantify the genetic and environmental contributions to phenotypic (co)variance in whole brain, gray and white matter volume of the cerebrum, lateral ventricle volume and associated variables such as intracranial volume and height. Because the cerebral cortex makes up more that two-thirds of the brain mass and almost three-quarters of its synapses, our data predominantly concerns the telencephalon. Genetic factors accounted for most of the individual differences in whole brain (90%), gray (82%) and white (88%) matter volume. Individual differences in lateral ventricle volume were best explained by a model containing common (58%) and unique (42%) environmental factors, indicating genes to be of no or minor influence. In our sample, genetic or environmental influences were not different for males and females. The same genes influenced brain volumes and intracranial volume and almost completely explained their high phenotypic correlation. Genes influencing gray and white matter overlapped to a large extent and completely determined their phenotypic correlation. The high heritability estimates that were found indicate that brain volumes may be useful as intermediate phenotypes in behavioral genetic research.

Adult↗

PubMed2001

Ambulatory heart rate is underestimated when measured by an ambulatory blood pressure device.

OBJECTIVE: To test the validity of ambulatory heart rate (HR) assessment with a cuff ambulatory blood pressure (ABP) monitor. DESIGN: Cross-instrument comparison of HR measured intermittently by a cuff ABP monitor (SpaceLabs, Redmond, Washington, USA), with HR derived from continuous electrocardiogram (ECG) recordings (1) in a controlled laboratory experiment and (2) during long-term recording in a true naturalistic setting. PARTICIPANTS: Six normotensive subjects participated in the laboratory study. A total of 109 male white-collar workers underwent ambulatory monitoring, of which 30 were mildly hypertensive. METHODS: Four different laboratory conditions (postures: lying, sitting, standing, walking), repeated twice, were used to assess the short-term effects of cuff inflation on the HR. To test the actual ambulatory validity, participants simultaneously wore a continuous HR recorder and the ABP monitor from early morning to late evening on 2 workdays and one non-workday. Diary and vertical accelerometery information was used to obtain periods of fixed posture and (physical) activity across which HR from both devices was compared. RESULTS: Laboratory results showed that the ABP device reliably detected HR during blood pressure measurement, but that this HR was systematically lower than the HR directly before and after the blood pressure measurement. The ambulatory study confirmed this systematic underestimation of the ongoing HR, but additionally showed that its amount increased when subjects went from sitting to standing to light physical activity (2.9; 4.3 and 9.1 bpm (beats/min), respectively). In spite of this activity-dependent underestimation of HR, the correlation of continuous ECG and intermittent ABP-derived HR was high (median r= 0.81). Also, underestimation was not different for normotensives and mild hypertensives. CONCLUSIONS: A direct effect of cuff inflation leads to the underestimation of ongoing HR during cuff-based ABP measurement. Additional underestimation of HR occurs during periods with physical activity, probably due to behavioural freezing during blood pressure measurements. HR underestimation was not affected by hypertensive state. When its limitations are taken into account, ABP-derived ambulatory HR can be considered a reliable and valid measure.

Adult↗

PubMed2001

Comparing blood pressure of twins and their singleton siblings: being a twin does not affect adult blood pressure.

The hypothesis was tested that monozygotic (MZ) and dizygotic (DZ) twins, with their lower average birth weight, have higher adult blood pressure than their singleton brothers or sisters. From the Netherlands Twin Registry, 261 twin families were recruited from a young adult and an older adult cohort with mean ages of 26.2 and 50.4 respectively. These families yielded 204 MZ twins with 71 singleton siblings and 271 DZ twins with 103 of their singleton siblings. Anti-hypertensive medication use of these 649 participants was assessed twice with a two-year interval. Resting blood pressure was measured thrice during a standardized laboratory protocol. In spite of a significant difference in birth weight (1036 gram), no differences were found in anti-hypertensive medication use at both time points between twins and singletons nor between their resting laboratory diastolic or systolic blood pressure. These results applied to each gender and to both age cohorts. Limiting the analyses to matched twin-sibling pairs of the same families and taking current weight and height into account did not change the results; no evidence was found for a twin-singleton difference. It was concluded that estimates of genetic and environmental contributions to blood pressure deriving from twin studies do not appear to be biased and may be generalized to singletons. Our results suggest that the lower birth weight in twins does not reflect the intrauterine disadvantage described by the Barker hypothesis.

Adult↗

PubMed2001

Intra-uterine and genetic influences on the relationship between size at birth and height in later life: analysis in twins.

Epidemiological studies have consistently shown a positive association between size at birth (i.e. birth weight or birth length) and height in children, adolescents and adults. To examine whether this association is explained by genetic or nongenetic (intra-uterine) factors, we investigated birth weight, birth length and height in 60 dizygotic and 68 monozygotic adolescent twin pairs still living with their parents. Birth weight of the twins was obtained from their mothers. Height was measured in a standardised way. The mean age was 17+/-1.7 years for the dizygotic twins and 16+/-1.8 years for the monozygotic twins. Both dizygotic and monozygotic twins with the lowest birth weight from each pair had a height that was lower compared to their co-twins with the highest birth weight (dizygotic twins: 172.2+/-7.9 vs. 173.8+/-9.4 cm [p = 0.05]; monozygotic twins: 171.1+/-9.4 vs. 171.8+/-9.5 cm [p = 0.01]). Similarly, both dizygotic and monozygotic twins with the shortest birth length from each pair had a height that was lower compared to their co-twins with the longest birth length (dizygotic twins: 172.3+/-7.9 vs. 174.9plus minus9.7 cm [p < 0.05]; monozygotic twins: 168.9+/-10.6 vs. 169.9+/-10.2 cm [p < 0.01]). In addition, intra-pair differences in birth weight and birth length were significantly associated with differences in height in both dizygotic twins (regression coefficient: 4.3 cm/kg [95% confidence interval: 1.0 to 7.5] and 0.96 cm/cm [0.17 to 1.74], respectively) and monozygotic twins (2.8 cm/kg [1.4 to 4.1] and 0.73 cm/cm [0.40 to 1.06], respectively). These associations were stronger in dizygotic than in monozygotic twins, but this difference was not statistically significant (for birth weight p = 0.4; and for birth length p = 0.6). However, genetic model fitting indicated that models incorporating a genetic source of the covariance gave a better description of the observed association of birth weight and length with height in later life than models not incorporating this genetic source. The results were similar for data on adult height after 12 years of follow-up in a subgroup of these twin pairs. These data suggest that the association between size at birth and height in later life is influenced by non-genetic intra-uterine and by genetic factors.

Adolescent↗

PubMed2001

Differential effects of active versus passive coping on secretory immunity.

This study examined the acute immunological effects of two laboratory stressors, expected to evoke distinct patterns of cardiac autonomic activity; namely an "active coping" time-paced memory test, and a "passive coping" stressful video showing surgical operations. We measured salivary S-IgA, IgA-subclasses (IgA1, IgA2), and secretory component (SC). SC is responsible for the transport of S-IgA across the epithelium, and thus a rate-determining step in S-IgA secretion. Thirty-two male undergraduates were subjected to both stressors and a control video (a didactic television program). The memory test induced a typical "fight-flight" response, characterized by increases in heart rate and blood pressure in association with a decrease in cardiac preejection period (PEP) and vagal tone. The surgical video produced a "conservation-withdrawal"-like response, characterized by an enhanced vagal tone, a decrease in heart rate, and a moderate sympathetic coactivation (as indicated by a shortened PEP and an increased systolic pressure). The memory test induced an increase in the concentration and, to a lesser extent, in the output of S-IgA, IgA], and SC. The output of IgA2 was not significantly affected. For the surgical video, a different pattern emerged: During stressor exposure S-IgA remained unaffected, against the background of a small increase in SC output. However, 10 min after the surgical video S-IgA levels had decreased. This decrease in S-IgA was paralleled by a decrease in IgA1, but not IgA2. We conclude that acute stress can have both enhancing and suppressive effects on secretory immunity, the IgA1 subclass in particular. The mechanisms that underlie these divergent responses may include stressor-specific patterns of autonomic activation.

Adaptation, Psychological↗

PubMed2000

Multivariate genetic analysis of brain structure in an extended twin design.

The hunt for genes influencing behavior may be aided by the study of intermediate phenotypes for several reasons. First, intermediate phenotypes may be influenced by only a few genes, which facilitates their detection. Second, many intermediate phenotypes can be measured on a continuous quantitative scale and thus can be assessed in affected and unaffected individuals. Continuous measures increase the statistical power to detect genetic effects (Neale et al., 1994), and allow studies to be designed to collect data from informative subjects such as extreme concordant or discordant pairs. Intermediate phenotypes for discrete traits, such as psychiatric disorders, can be neurotransmitter levels, brain function, or structure. In this paper we conduct a multivariate analysis of data from 111 twin pairs and 34 additional siblings on cerebellar volume, intracranial space, and body height. The analysis is carried out on the raw data and specifies a model for the mean and the covariance structure. Results suggest that cerebellar volume and intracranial space vary with age and sex. Brain volumes tend to decrease slightly with age, and males generally have a larger brain volume than females. The remaining phenotypic variance of cerebellar volume is largely genetic (88%). These genetic factors partly overlap with the genetic factors that explain variance in intracranial space and body height. The applied method is presented as a general approach for the analysis of intermediate phenotypes in which the effects of correlated variables on the observed scores are modeled through multivariate analysis.

Adult↗

PubMed2000

Effects of work stress on ambulatory blood pressure, heart rate, and heart rate variability.

Work stress has repeatedly been associated with an increased risk for cardiovascular disease. This study tested whether this relationship could be explained by exaggerated cardiovascular reactivity to work or impaired recovery in leisure time. Vagal tone was assessed as a possible determinant of these work stress effects. Participants included 109 male white-collar workers (age, 47.2+/-5. 3) who were monitored on 2 workdays and 1 nonworkday for ambulatory blood pressure, heart rate, and heart rate variability. Chronic work stress was defined according to Siegrist's model as (1) high imbalance, a combination of high effort and low reward at work, or (2) high overcommitment, an exhaustive work-related coping style indexing the inability to unwind. All findings were adjusted for possible differences in posture and physical activity between the work stress groups. High imbalance was associated with a higher heart rate during work and directly after work, a higher systolic blood pressure during work and leisure time, and a lower 24-hour vagal tone on all 3 measurement days. Overcommitment was not associated with an unfavorable ambulatory profile. Logistic regression analysis revealed that heart rate [odds ratio 1-SD increase 1.95 (95% CI, 1.02 to 3.77)] and vagal tone [odds ratio 1-SD decrease 2.67 (95% CI, 1.24 to 5.75)] were independently associated with incident mild hypertension. Surprisingly, the values during sleep were more predictive for mild hypertension than the values during work. The results from the present study suggest that the detrimental effects of work stress are partly mediated by increased heart rate reactivity to a stressful workday, an increase in systolic blood pressure level, and lower vagal tone.

Adult↗

PubMed2000

Netherlands twin family study of anxious depression (NETSAD).

In a longitudinal study of Dutch adolescent and young adult twins, their parents and their siblings, questionnaire data were collected on depression, anxiety and correlated personality traits, such as neuroticism. Data were collected by mailed surveys in 1991, 1993, 1995 and 1997. A total of 13,717 individuals from 3344 families were included in the study. To localise quantitative trait loci (QTLs) involved in anxiety and depression, the survey data were used to select the most informative families for a genome-wide search. For each individual a genetic factor score was computed, based on a genetic multivariate analysis of anxiety, depression, neuroticism and somatic anxiety. A family was selected if at least two siblings (or DZ twins) had extreme factor scores. Both discordant (high-low) and concordant (high-high and low-low) pairs were included in the selected sample. Once an extreme sibling pair was selected, all family members (parents and additional siblings of the selected pair) who had at least once returned a questionnaire booklet were asked to provide a DNA sample. In total, 2724 individuals from 563 families (1007 parents and 1717 offspring) were approached and 1975 individuals from 479 families (643 patients and 1332 offspring) complied by returning a buccal swab for DNA isolation. All offspring from selected families were asked to participate in a psychiatric interview and in a 24-hour ambulatory assessment of cardiovascular parameters and cortisol. The interview consisted of the WHO-Composite International Diagnostic Interview and was administered to 1253 offspring. In this paper we describe the genetic-epidemiological analyses of the survey data on anxiety, somatic anxiety, neuroticism and depression. We detail how these data were used to select families for the QTL study and discuss strategies that may help elucidate the molecular pathways leading from genes to anxious depression.

Adolescent↗

PubMed1999

Interictal and postictal cognitive changes in migraine.

The question whether symptom-free migraine patients show cognitive impairments compared to matched control subjects is addressed, and also whether migraine patients show transient cognitive impairments induced by an attack. The Neuropsychological Evaluation System (NES2) was administered once in an interictal period and twice within 30 h after different migraine attacks. Since cognitive impairments could be related to attack duration or severity, cognitive performance was compared during a postictal period after sumatriptan use and during a postictal period after habitual nonvasoactive medication use. Twenty migraineurs without aura, 10 migraineurs with aura, and 30 matched headache-free controls participated in the study. During a headache-free period, migraineurs without aura responded as quickly as controls, while migraineurs with aura were slower than controls during all tasks specifically requiring selective attention. These effects were not aggravated by a preceding migraine attack, irrespective of medication use and attack duration.

Adult↗