Karla Holmboe

Neural Correlates of Eye Gaze Processing in the Infant Broader Autism Phenotype

BACKGROUND Studies of infant siblings of children diagnosed with autism have allowed for a prospective approach to study the emergence of autism in infancy and revealed early behavioral characteristics of the broader autism phenotype. In view of previous findings of atypical eye gaze processing in children and adults with autism, the aim of this study was to examine the early autism phenotype in infant siblings of children diagnosed with autism spectrum disorder (sib-ASD), focusing on the neural correlates of direct compared with averted gaze. METHODS A group of 19 sib-ASD was compared with 17 control infants with no family history of ASD (mean age=10 months) on their response to direct versus averted gaze in static stimuli. RESULTS Relative to the control group, the sib-ASD group showed prolonged latency of the occipital P400 event-related potentials component in response to direct gaze, but they did not differ in earlier components. Similarly, time-frequency analysis of high-frequency oscillatory activity in the gamma band showed group differences in response to direct gaze, where induced gamma activity was late and less persistent over the right temporal region in the sib-ASD group. CONCLUSION This study suggests that a broader autism phenotype, which includes an atypical response to direct gaze, is manifest early in infancy.

Polymorphisms in dopamine system genes are associated with individual differences in attention in infancy

Knowledge about the functional status of the frontal cortex in infancy is limited. This study investigated the effects of polymorphisms in four dopamine system genes on performance in a task developed to assess such functioning, the Freeze-Frame task, at 9 months of age. Polymorphisms in the catechol-O-methyltransferase (COMT) and the dopamine D4 receptor (DRD4) genes are likely to impact directly on the functioning of the frontal cortex, whereas polymorphisms in the dopamine D2 receptor (DRD2) and dopamine transporter (DAT1) genes might influence frontal cortex functioning indirectly via strong frontostriatal connections. A significant effect of the COMT valine(1)methionine (Val 158 Met) polymorphism was found. Infants with the Met/Met genotype were significantly less distractible than infants with the Val/Val genotype in Freeze-Frame trials presenting an engaging central stimulus. In addition, there was an interaction with the DAT1 3; variable number of tandem repeats polymorphism; the COMT effect was present only in infants who did not have two copies of the DAT1 10-repeat allele. These findings indicate that dopaminergic polymorphisms affect selective aspects of attention as early as infancy and further validate the Freeze-Frame task as a frontal cortex task.

Motor development in children at risk of autism: A follow-up study of infant siblings:

Recently, evidence of poor or atypical motor skills in autism spectrum disorder has led some to argue that motor impairment is a core feature of the condition. The current study uses a longitudinal prospective design to assess the development of motor skills of 20 children at increased risk of developing autism spectrum disorder, who were recruited and tested at 9 and 40 months of age, on the basis of having an older sibling diagnosed with the condition. All children completed a range of motor, face processing, IQ and diagnostic assessments at a follow-up visit (aged 5–7 years), providing a detailed profile of development in this group from a number of standardised, parental report and experimental measures. A higher proportion of children than expected demonstrated motor difficulties at the follow-up visit and those highlighted by parental report as having poor motor skills as infants and toddlers were also more likely to have lower face processing scores and elevated autism-related social symptoms at 5–7 years, despite having similar IQ levels. These data lend support to the argument that early motor difficulties may be a risk factor for later motor impairment as well as differences in social communication and cognition, traits that are related to autism spectrum disorder.

Dopamine D4 receptor and serotonin transporter gene effects on the longitudinal development of infant temperament

Existing studies of the effect on infant temperament of the 48 base pair variable number of tandem repeats polymorphism in exon 3 of the dopamine D4 receptor gene, DRD4 VNTR, and the serotonin transporter‐linked polymorphic region, 5‐HTTLPR, have provided contradictory results, and age seems to be an important factor. The present study investigated the effect of these two polymorphisms on the stability of infant temperament between 4 and 9 months of age. Furthermore, the effect of a recently discovered single nucleotide polymorphism which modulates the 5‐HTTLPR (rs25531) was investigated in relation to infant temperament. The study sample consisted of 90 infants, who were assessed by parental report at the two ages under consideration using the Revised Infant Behavior Questionnaire. It was found that infants carrying the 7‐repeat allele of the DRD4 VNTR had higher levels of Negative Affect. Furthermore, there was an interaction between DRD4 VNTR and 5‐HTTLPR genotype such that infants with the DRD4 VNTR 7‐repeat allele and the highest expressing 5‐HTTLPR genotype (LALA) had the highest level of Negative Affect. These effects were largely driven by scores on the Falling Reactivity scale. Genetic effects were stable across age. The results emphasize the need for developmental studies of genetic effects on temperament.

Social and attention factors during infancy and the later emergence of autism characteristics.

Characteristic features of autism include atypical social perception and social-communication skills, and atypical visual attention, alongside rigid and repetitive thinking and behavior. Debate has focused on whether the later emergence of atypical social skills is a consequence of attention problems early in life, or, conversely, whether early social deficits have knock-on consequences for the later development of attention skills. We investigated this question based on evidence from infants at familial risk for a later diagnosis of autism by virtue of being younger siblings of children with a diagnosis. Around 9months, at-risk siblings differed as a group from controls, both in measures of social perception and inhibitory control. We present preliminary data from an ongoing longitudinal research program, suggesting clear associations between some of these infant measures and autism-related characteristics at 3years. We discuss the findings in terms of the emergent nature of autism as a result of complex developmental interactions among brain networks.

Strong Genetic Influences on the Stability of Autistic Traits in Childhood

Objective Disorders on the autism spectrum, as well as autistic traits in the general population, have been found to be both highly stable across age and highly heritable at individual ages. However, little is known about the overlap in genetic and environmental influences on autistic traits across age and the contribution of such influences to trait stability itself. The present study investigated these questions in a general population sample of twins. Method More than 6,000 twin pairs were rated on an established scale of autistic traits by their parents at 8, 9, and 12 years of age and by their teachers at 9 and 12 years of age. Data were analyzed using structural equation modeling. Results The results indicated that, consistently across raters, not only were autistic traits stable, and moderately to highly heritable at individual ages, but there was also a high degree of overlap in genetic influences across age. Furthermore, autistic trait stability could largely be accounted for by genetic factors, with the environment unique to each twin playing a minor role. The environment shared by twins had virtually no effect on the longitudinal stability in autistic traits. Conclusions Autistic traits are highly stable across middle childhood. and this stability is caused primarily by genetic factors.

Gene Expression to Neurobiology and Behavior

Characteristic features of autism include atypical social perception and social-communication skills, and atypical visual attention, alongside rigid and repetitive thinking and behavior. Debate has focused on whether the later emergence of atypical social skills is a consequence of attention problems early in life, or, conversely, whether early social deficits have knock-on consequences for the later development of attention skills. We investigated this question based on evidence from infants at familial risk for a later diagnosis of autism by virtue of being younger siblings of children with a diagnosis. Around 9months, at-risk siblings differed as a group from controls, both in measures of social perception and inhibitory control. We present preliminary data from an ongoing longitudinal research program, suggesting clear associations between some of these infant measures and autism-related characteristics at 3years. We discuss the findings in terms of the emergent nature of autism as a result of complex developmental interactions among brain networks.