Some pioneering papers have recently appeared in which the authors seek to dissect components of attention, perception, or affect in infants by associating cognitive and behavioral assessments to allelic variation. These studies are motivated by several considerations. First, there is the basic science interest in finding ways to dissociate components of cognition in infants. Traditionally, theories about the cognitive processing capacities of infants have been based largely on seeking confirmatory evidence from studies of their behaviour. However, over the past decade there has been burgeoning interest in using neuroimaging methods such ERP, NIRS and fMRI to constrain the range of plausible theories, and to discover unanticipated dissociations. Adding data on genetic variation into the mix will potentially provide even more powerful ways to dissociate components of the infant mind. A second consideration is that mappings between individual variation in genetics and behaviour may be more direct in infants than in adults. The reasoning behind this assertion is that with development increasingly complex interactions with environmental factors are likely to result in more diffuse dimensions of difference that will become harder to analyse and unpack. This suggestion is reminiscent of the endophenotype concept, in which relatively simple genetic architecture is thought likely to be revealed by focusing on underlying disease-relevant cognitive or neural systems. While the search for endophenotypes has arguably had mixed success, a speculation that remains to be tested is that genetic effects may be stronger and clearer when looking at precisely defined components of cognition or affect early in development, what we might refer to as developmental endophenotypes. Such an approach provides a strong motivation for the study of infants. A third reason for interest in genetic variation in babies is that it may be key for understanding mechanisms of risk and resilience. Common allelic variation is thought to be a factor in risk for autism and ADHD among other developmental disorders of uncertain etiology. For example, ADHD shows strong heritability in quantitative genetic studies and has been linked in meta-analytic investigations to a number of genetic polymorphisms, including the dopamine D4 and D5 receptor genes, the dopamine transporter gene and the serotonin transporter gene (Stergiakouli & Thapar 2010). This suggests that combinations of common and rare allelic variations may be risk factors for later adverse outcome. Conversely, other combinations may be protective or promote resilience to other genetic or environmental insult.
In this landmark study, Leppanen and colleagues associate genetic polymorphisms linked to the production of serotonin in the central nervous system to variations in attention skills in a group of typically developing infants (Leppanen et al. 2011). They find that babies with the T-carrier genotype of the TPH2 -703 G/T polymorphism had greater difficulty in shifting their attention from a central (foveal) stimulus to a target presented in the periphery than babies who are TPH2 G/G homozygotes. Although one of the simplest of attention paradigms, the ability to “disengage” attention from a central stimulus and orient to a peripheral one turns out to be a sensitive marker of typical developmental stages and atypicality. In typical development many babies go through a transient stage of “sticky fixation” in which they seem unable to make such shifts of attention, and aspects of this ability during infancy relate to performance on executive function tasks more than a year later. Similarly, a relative inability to shift gaze is associated with risk groups such as babies at-risk for a later diagnosis of autism (Zwaigenbaum et al. 2005), although the extent to which the measure could be used to predict atypical outcomes remains to be determined.
Another recent study indicates that polymorphisms in dopaminergic system genes also affect components of infant attention (Holmboe et al. 2010). This study investigated variants of four dopamine system genes on different aspects of attention and “executive function” as assessed by a related infant attention paradigm, the “freeze frame” task. The authors found that infants with the Met/Met variant of the COMT valine 158 methionine polymorphism were significantly less distractable (by peripheral targets) than the val/val genotype when in the presence of an engaging central stimulus. In addition, this effect was only present in infants that did not have two copies of the DAT1 10-repeat allele, suggesting an interaction between two dopaminergic genes in influencing this aspect of selective attention. Interestingly, in both studies the association with the polymorphisms in question were clearer in trials in which the central stimulus was more dynamic and colourful (Holmboe et al. 2010) or more affectively salient (Leppanen et al. 2011), suggesting that the degree of engagement in processing the central stimulus is critical for the associations observed. Exploring possible interactions between dopamine and serotonin related polymorphisms in early attentional development provides an exciting direction for future research.
In a secondary analysis, Leppanen and colleagues found that TPH2 genotype was indirectly associated with temperamental emotion regulation as assessed by the “soothability” scale of Rothbart’s Infant Behavior Questionnaire (IBQ). This finding adds to the evidence for the long posited link between attention skills and the self-regulation of emotion. A relation between serotonin and dopamine-related polymorphisms and the IBQ has also recently been reported by Holmboe and colleagues (Holmboe et al. In press). These authors assessed temperament using the IBQ in 90 infants and found an effect of the DRD4 gene on infant negative affect and an interaction between the DRD4 gene and a serotonin system polymorphism (5HTTLPR). These effects were stable from at least 4 to 9 months of age, suggesting developmental continuity, and the effects were most prominent for the ‘falling reactivity’ scale – an aspect of negative affectivity closely linked to emotional regulation.
Future challenges for using genetic variation to dissociate infant attention and temperament include trying to establish three-way relations between genetic polymorphisms, functional imaging, and measures of behaviour. The results from these studies have the potential to tell us much about the involvement of particular transmitter systems in controlling behaviour during development. However, even for tasks as apparently simple as shifting your attention from a central stimulus to a peripheral one it would be naïve to suppose that only one neurotransmitter system (and its related polymorphisms) will influence individual differences in a straightforward fashion. Instead, we should expect multiple neurotransmitter systems to be important, and the evidence reviewed above suggests that this is the case. Focusing on the early development of well-specified and basic cognitive and affective mechanisms may make the job of integrating neurophysiological and behavioural evidence with molecular genetics a more tractable problem.