Scientific Understanding of Consciousness
Autism Diagnostic decline in Eye Fixation in Infants
Nature 504, 427–431 (19 December 2013)
Attention to eyes is present but in decline in 2–6-month-old infants later diagnosed with autism
Warren Jones & Ami Klin
Marcus Autism Center, Children’s Healthcare of Atlanta, Atlanta, Georgia 30329, USA
Division of Autism & Related Disabilities, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30022, USA
Center for Translational Social Neuroscience, Emory University, Atlanta, Georgia 30022, USA
Deficits in eye contact have been a hallmark of autism since the condition’s initial description. They are cited widely as a diagnostic feature and figure prominently in clinical instruments; however, the early onset of these deficits has not been known. Here we show in a prospective longitudinal study that infants later diagnosed with autism spectrum disorders (ASDs) exhibit mean decline in eye fixation from 2 to 6 months of age, a pattern not observed in infants who do not develop ASD. These observations mark the earliest known indicators of social disability in infancy, but also falsify a prior hypothesis: in the first months of life, this basic mechanism of social adaptive action—eye looking—is not immediately diminished in infants later diagnosed with ASD; instead, eye looking appears to begin at normative levels prior to decline. The timing of decline highlights a narrow developmental window and reveals the early derailment of processes that would otherwise have a key role in canalizing typical social development. Finally, the observation of this decline in eye fixation—rather than outright absence—offers a promising opportunity for early intervention that could build on the apparent preservation of mechanisms subserving reflexive initial orientation towards the eyes.
Autism Spectrum Disorders (ASDs) affect approximately 1 in every 88 individuals. These disorders are lifelong, believed to be congenital, and are among the most highly heritable of psychiatric conditions. However, the genetic heterogeneity of ASD—with estimates suggesting as many as three- to five-hundred distinct genes impacting aetiology—poses a stark challenge for understanding the biology of the condition: with so many different ‘causes’, a key question is how that genetic heterogeneity can be instantiated into common forms of disability.
One answer is that although the specific biological mechanisms may vary (in genes or pathways affected, in dosage or in timing), any such disruptions will contribute to an individual deviation from normative developmental processes; the mechanisms may initially be different, but a divergence from typical development is shared. In this way, widely varying initial liabilities can be converted into similar manifestations of impairment, giving rise to the spectrum of social disability we then call ‘autism’.
In typical development, the processes of normative social interaction are extremely early-emerging: from the first hours and weeks of life, preferential attention to familiar voices, faces, face-like stimuli and biological motion guide typical infants. These processes are highly conserved phylogenetically and lay the foundation for iterative specialization of mind and brain, entraining babies to the social signals of their caregivers.
In the current study, we tested the extent to which measures of these early-emerging normative processes may reveal disruptions in ASD at a point prior to the manifestation of overt symptoms. We measured preferential attention to the eyes of others, a skill present in typical infants but significantly impaired in 2-year-olds with ASD. We proposed that in infants later diagnosed with ASD, preferential attention to others’ eyes might be diminished from birth onwards.
Data were collected at 10 time points: at months 2, 3, 4, 5, 6, 9, 12, 15, 18 and 24. We studied 110 infants, enrolled as risk-based cohorts: n = 59 at high-risk for ASD (full siblings of a child with ASD) and n = 51 at low-risk (without first-, second- or third-degree relatives with ASD). Diagnostic status was ascertained at 36 months.
At each testing session, infants viewed scenes of naturalistic caregiver interaction while their visual scanning was measured with eye-tracking equipment. The 36 typically developing and ASD children viewed 2,384 trials of video scenes.
Typically developing children show strongly increasing eye fixation. Unaffected siblings also show increasing eye fixation. Siblings with subthreshold symptoms show neither increasing nor decreasing eye fixation, and infants later diagnosed with ASD show declining eye fixation.
The current results indicate that the development of infants later diagnosed with ASD differs already from that of their typical peers during the period from 2 to 6 months of age. These results, although still limited in sample size, document the derailment of skills that would otherwise guide typical socialization, and this early divergence from normative experience suggests a means by which diverse genetic liabilities are instantiated, developmentally, into a spectrum of affectedness. Given the interdependencs of individual experience with brain structure and function, and with gene expression and methylation, these results suggest how a single individual’s outcome will be shaped not only by initial genotypic vulnerabilities, but also by the atypical experiences that arise as a consequence of those vulnerabilities, instantiating a wide spectrum of affectedness.
In children later diagnosed with ASD, eye looking shows mean decline by at least 2 months. However, unexpectedly, those early levels of eye looking seem to begin at normative levels. This contradicts prior hypotheses of a congenital absence of social adaptive orientation and suggests instead that some social adaptive behaviours may initially be intact in newborns later diagnosed with ASD. If confirmed in larger samples, this would offer a remarkable opportunity for treatment: predispositions that are initially intact suggest a neural foundation that may be built upon, offering far more positive possibilities than if that foundation were absent from the outset. Equally exciting, these data fit well within the framework of long-studied animal models of the neural systems subserving filial orientation and attachment: they highlight a narrow period for future investigation, spanning the transition from experience-expectant to experience-dependent mechanisms. A critical next step will be to measure densely sampled developmental change in gene expression and brain growth, in tandem with detailed quantification of behaviour; in short, measuring gene–brain–behaviour growth charts of infant social engagement to understand the developmental pathogenesis of social disability.
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