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 children's 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 child's 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 children's 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.

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 show 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.

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.

Attention influences many aspects of cognitive development. Variations in the 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 do a better job in reflecting 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.

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 (EC) which is related to 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.

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 (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.

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