Pascale Voelker

Parenting quality interacts with genetic variation in dopamine receptor D4 to influence temperament in early childhood.

We examined the influence of a common allelic variation in the dopamine receptor D4 (DRD4) gene and caregiver quality on temperament in early childhood. Children 18-21 months of age were genotyped for the DRD4 48 base pair tandem repeat polymorphism, which has been implicated in the development of attention, sensation seeking, and attention-deficit/hyperactivity disorder. The children also interacted with their caregiver for 10 min in a laboratory setting, and these videotaped interactions were coded for parenting quality using an observational rating procedure. The presence of the DRD4 7-repeat allele was associated with differences in the influence of parenting on a measure of temperamental sensation seeking constructed from caregiver reports on childrens activity level, impulsivity, and high-intensity pleasure. Children with the 7-repeat allele were influenced by parenting quality, with lower quality parenting associated with higher levels of sensation seeking; children without the 7-repeat allele were uninfluenced by parenting quality. Differences between alleles were not related to the childs self-regulation as assessed by the effortful control measure. Previous studies have indicated that the 7-repeat allele is under positive selective pressure, and our results are consistent with the hypothesis that the DRD4 7-repeat allele increased childrens sensitivity to environmental factors such as parenting. This study shows that genes influence the relation between parenting and temperament in ways that are important to normal development and psychopathology.

Control Networks and Neuromodulators of Early Development.

In adults, most cognitive and emotional self-regulation is carried out by a network of brain regions, including the anterior cingulate, insula, and areas of the basal ganglia, related to executive attention. We propose that during infancy, control systems depend primarily upon a brain network involved in orienting to sensory events that includes areas of the parietal lobe and frontal eye fields. Studies of human adults and alert monkeys have shown that the brain network involved in orienting to sensory events is moderated primarily by the nicotinic cholinergic system arising in the nucleus basalis. The executive attention network is primarily moderated by dopaminergic input from the ventral tegmental area. A change from cholinergic to dopaminergic modulation would be a consequence of this switch of control networks and may be important in understanding early development. We trace the attentional, emotional, and behavioral changes in early development related to this developmental change in regulative networks and their modulators.

Developing Attention: Behavioral and Brain Mechanisms

Brain networks underlying attention are present even during infancy and are critical for the developing ability of children to control their emotions and thoughts. For adults, individual differences in the efficiency of attentional networks have been related to neuromodulators and to genetic variations. We have examined the development of attentional networks and child temperament in a longitudinal study from infancy (7 months) to middle childhood (7 years). Early temperamental differences among infants, including smiling and laughter and vocal reactivity, are related to self-regulation abilities at 7 years. However, genetic variations related to adult executive attention, while present in childhood, are poor predictors of later control, in part because individual genetic variationmay have many small effects and in part because their influence occurs in interaction with caregiver behavior and other environmental influences. While brain areas involved in attention are present during infancy, their connectivity changes and leads to improvement in control of behavior. It is also possible to influence control mechanisms through training later in life. The relation between maturation and learning may allow advances in our understanding of human brain development.

Variations in catechol-O-methyltransferase gene interact with parenting to influence attention in early development

Attention influences many aspects of cognitive development. Variations in the catechol-O-methyltransferase (COMT) gene, known to affect dopamine neurotransmission, have frequently been found to influence attention in adults and older children. In this paper we examined 2 year old children and found that variation in the COMT gene influenced attention in a task involving looking to a sequence of visual stimuli. Because the influence of another dopamine-related gene (DRD4) has been shown to interact with parenting quality at this age, we explored parenting in relation to variations in the COMT gene. Variations in COMT interacted with parenting quality to influence our attention measure. The Val(108/158)Met polymorphism of COMT is commonly used to determine allelic groups, but recently haplotypes of several polymorphisms within this gene have been shown to be more strongly associated with perceived pain. Since attention and pain both involve the activation of the anterior cingulate gyrus in imaging studies, we compared the Val(108/158)Met influence with the COMT haplotypes and found the latter to be more predictive of attention. Our results confirm that important aspects of cognitive development including attention depend on the interaction of genes and early environment.

Genetic variation influences on the early development of reactive emotions and their regulation by attention

Introduction. Individual differences in temperament and attention provide an important link between normal and pathological development. Previous studies suggest that during infancy, orienting of attention is associated with higher levels of positive affect and lower levels of negative affect. For older children and adults, self-regulation, as measured by ratings of effortful control, is consistently associated with lower levels of negative affect such as sadness and distress. Methods. In the current paper we use a longitudinal study of children at ages 6–7 months (Time 1) and 18–20 months (Time 2) to examine how variations in candidate genes relate to emotional and self-regulatory aspects of temperament. Results. In accord with previous findings, parent ratings of orienting were positively related to positive affect only during infancy. Genetic variation in COMT was related to positive affect at Time l but not Time 2. Negative affect at both Time 1 and Time 2 was related to genetic variation in SNAP25. Genetic variation in CHRNA4 was related to Effortful Control at Time 2. Conclusions. These findings lend support to the early modulation of emotion by aspects of orienting (Time 1) and executive attention (Time 2), and indicate that emotional reactivity and its regulation are modulated by different genes.

The dopamine receptor D4 gene 7-repeat allele interacts with parenting quality to predict effortful control in four-year-old children

The dopamine receptor D4 gene (DRD4) 7-repeat allele has been found to interact with environmental factors such as parenting in children and peer attitudes in adults to influence aspects of behavior such as risk taking. We previously found that in toddlers, lower-quality parenting in combination with the 7-repeat allele of the DRD4 gene was associated with greater parent-reported Sensation Seeking (SS), but was unrelated to Effortful Control (EC). We now report findings from a followup assessment with the same sample of children showing that parenting quality interacts with the presence of the 7-repeat allele to predict EC in 3-to 4-year-old children. The change in these patterns of results may reflect the increased role of the executive attention network in older children and adults. However, due to the small sample size (N = 52) and the novelty of the results, these findings should be treated with caution and considered preliminary until they are replicated in an independent sample.

How changes in white matter might underlie improved reaction time due to practice

ABSTRACT Why does training on a task reduce the reaction time for performing it? New research points to changes in white matter pathways as one likely mechanism. These pathways connect remote brain areas involved in performing the task. Genetic variations may be involved in individual differences in the extent of this improvement. If white matter change is involved in improved reaction time with training, it may point the way toward understanding where and how generalization occurs. We examine the hypothesis that brain pathways shared by different tasks may result in improved performance of cognitive tasks remote from the training.

Methylation polymorphism influences practice effects in children during attention tasks

ABSTRACT Epigenetic mechanisms mediate the influence of experience on gene expression. Methylation is a principal method for inducing epigenetic effects on DNA. In this paper, we examine alleles of the methylenetetrahydrofolate reductase (MTHFR) gene that vary enzyme activity, altering the availability of the methyl donor and thus changing the efficiency of methylation. We hypothesized that alleles of the MTHFR gene would influence behavior in an attention-related task in conjunction with genes known to influence attention. We found that seven-year-old children homozygous for the C allele of MTHFR in interaction with the catechol O-methyltransferase (COMT) gene showed greater improvement in overall reaction time (RT) and in conflict resolution with practice on the Attention Network Test (ANT). This finding indicates that methylation may operate on or through genes that influence executive network operation. However, MTHFR T allele carriers showed faster overall RT and conflict resolution. Some children showed an initial improvement in ANT RT followed by a decline in performance, and we found that alleles of the dopamine beta-hydroxylase (DBH) gene were related to this performance decline. These results suggest a genetic dissociation between improvement while learning a skill and reduction in performance with continued practice.

Developing brain networks of attention.

Purpose of review Attention is a primary cognitive function critical for perception, language, and memory. We provide an update on brain networks related to attention, their development, training, and pathologies. Recent findings An executive attention network, also called the cingulo-opercular network, allows voluntary control of behavior in accordance with goals. Individual differences among children in self-regulation have been measured by a higher order factor called effortful control, which is related to the executive network and to the size of the anterior cingulate cortex. Summary Brain networks of attention arise in infancy and are related to individual differences, including pathology during childhood. Methods of training attention may improve performance and ameliorate pathology.

Influence of the SLC6A3-DAT1 Gene on Multifaceted Measures of Self-regulation in Preschool Children

Development of self-regulation, the capacity to voluntarily modulate thoughts, emotions and actions is strongly related to the maturation of the dopamine-mediated executive attention network (EAN). The attention control processes associated with the EAN greatly overlap with efficiency of the executive functions and are correlated with measures of effortful control. Regulation of dopamine levels within the EAN, particularly in the basal ganglia is carried out by the action of dopamine transporters. In humans, the SLC6A3/DAT1 gene carries out the synthesis of the DAT protein. The 10-repeat allele has been associated with an enhanced expression of the gene and has been related to ADHD symptoms. Little is known about the impact of DAT1 variations on childrens capacity to self-regulate in contexts that impose particular demands of regulatory control such as the school or home. This study defines a multi-domain phenotype of self-regulation and examines whether variations of the DAT1 gene accounts for individual differences in performance in 4–5 year old children. Results show that presence of the 10r allele is related to a diminished ability to exert voluntary regulation of reactivity. These findings shed light on the neurobiological mechanisms underlying individual differences in self-regulation during childhood.