Infants Strong Pupillary Light Reflex Linked To Later Autism Diagnosis

Infants who are later diagnosed with autism spectrum disorders react more strongly to sudden changes in light, a new study indicates. The finding lends support to the view that sensory processing plays an important role in the development of the disorder.

Despite being defined by symptoms in social communication, researchers are increasingly embracing the view that the earliest signs of autism may reside in more basic processes of brain development. Also, in the latest edition of the diagnostic manual used to diagnose the condition in many countries, sensory symptoms have been included as defining features.

Researchers looked at the pupillary light reflex in 9-to-10 month old infants – this reflex is a basic regulatory mechanism controlling the amount of light that reaches the retina. The infants who fulfilled criteria for autism at three years of age constricted their pupils more than infants who did not fulfill autism criteria at follow up.

Additionally, the amount of pupil restriction in infancy was associated with the strength of autism symptoms at follow up.

Sharp Contrasts

Terje Falck-Ytter, Associate Professor at the Department of Psychology at Uppsala University and Principal Investigator for the study, said:

“Earlier studies on older children with autism has suggested a weak pupillary light reflex in this group. These findings motivated us to assess the reflex in infant siblings of children with autism. Most of these infants develop typically, yet the probability of later being diagnosed with autism is considerably higher in this group than in the general population.

Surprisingly, we found that in infancy, the group differences were in the opposite direction than in older children: We found stronger reflexes in the infants later diagnosed with autism than in controls. We believe the findings are important because they point to a very basic function that has not been studied before in infants with later autism diagnosis.”

The study is a part of the larger project Early Autism Sweden (EASE), which is a collaboration between Uppsala University and the Center of Neurodevelopmental Disorders at Karolinska Institutet (KIND) in Sweden. In this particular experiment, data from Sweden were combined with data from a similar longitudinal study of siblings with an older sibling with autism conducted at Birkbeck, University of London (UK).

The participants in the current experiment were 9-10-months old when their pupillary light reflexes were examined and were followed until three years, when the diagnostic evaluation was conducted.

Stronger PLR in infancy is associated with ASD diagnosis

Stronger PLR in infancy is associated with ASD diagnosis at three years of age.
a) Average pupil traces for all infants expressed as the site-normalized relative constriction of the pupil following the stimuli onset at 0 ms.
b) Mean relative constriction normalized within site by dividing with the TD group average, together with individual data points.
Credit: Pär Nyström, et al.

In total, 147 infants with an older sibling with autism took part in the study, of whom 29 met criteria for autism at follow-up. The study also included a control group consisting of 40 infants from the general population.

Pupillary Light Reflex

The pupillary light reflex (PLR) is a reflex that controls the diameter of the pupil, in response to the intensity (luminance) of light that falls on the retinal ganglion cells of the retina in the back of the eye, thereby assisting in adaptation to various levels of lightness/darkness. A greater intensity of light causes the pupil to constrict (miosis/myosis; thereby allowing less light in), whereas a lower intensity of light causes the pupil to dilate (mydriasis, expansion; thereby allowing more light in).

The pupillary response to light is not purely reflexive, but is modulated by cognitive factors, such as attention, awareness, and the way visual input is interpreted. For example, if a bright stimulus is presented to one eye, and a dark stimulus to the other eye, perception alternates between the two eyes (i.e., binocular rivalry):

Sometimes the dark stimulus is perceived, sometimes the bright stimulus, but never both at the same time. Using this technique, it has been shown the pupil is smaller when a bright stimulus dominates awareness, relative to when a dark stimulus dominates awareness.

Several studies indicate an attenuated PLR in children and adults with an ASD diagnosis relative to controls. In children with ASD, the relative constriction (but not the latency) of the reflex is correlated to the amount of their sensory atypicalities.

“Currently, autism cannot be reliably diagnosed before 2-3 years of age, but we hope that with more knowledge about the early development of the condition, reliable diagnosis will be possible earlier, which should facilitate early access to intervention and support for the families. New knowledge about early development in autism may also provide new leads on strategies for early intervention” Falck-Ytter says. “Yet, the results in this study demonstrated significant group differences only, and it is too early to say whether the method can facilitate early detection in a clinical context.”

The study was supported in part by the Swedish Research Council in partnership with FAS, FORMAS, and VINNOVA (Crossdisciplinary Research Programme Concerning Children’s and Young People’s Mental Health).

Pär Nyström, Teodora Gliga, Elisabeth Nilsson Jobs, Gustaf Gredebäck, Tony Charman, Mark H. Johnson, Sven Bölte & Terje Falck-Ytter
Enhanced pupillary light reflex in infancy is associated with autism diagnosis in toddlerhood
Nature Communications volume 9, Article number: 1678 (2018) doi:10.1038/s41467-018-03985-4