A first glimpse of the developmental profile of sibling resilience: 2-24 months eye tracking-based developmental trajectories of eye fixation

Background:   We recently created eye tracking-based “growth charts” of social visual engagement via Functional Data Analysis of data collected at 2-24 months (10 data points) for N=32 infants ascertained diagnostically at age 36 months as either having ASD (N=13) or typical development (TD; N=29). From the 2^nd month onwards (to 24 months), infants later diagnosed with ASD exhibit mean decline in eye fixation relative to TD infants; this decline is highly correlated with severity of clinical outcome at 24 months (r= -0.75, p = 0.007); and decline in the first year alone predicts severity of future outcome (r= -0.71, p= 0.015).

Objectives:   We hypothesized that A. this decline mirrors failure in transition from experience-expectant, reflexive, sub-cortically guided eye fixation to experience-dependent, interactive, cortically guided eye fixation; and B. early divergence from normative development suggests a means by which diverse genetic liabilities are instantiated into a spectrum of affectedness.

Methods:   To explore the latter, we used this dimensional assay (decline in eye fixation) to guide the analyses of developmental trajectories of siblings who were ascertained at 36 months as either unaffected (HR-ASD_No-Dx; N=18) or infants with transient/subthreshold ASD symptoms, or BAP (HR-ASD_BAP; N=10). We divided this group on the basis of early decline in eye fixation. 

Results:   16 infants exhibited no sign of early decline – 15 were clinically unaffected at outcome (HR-ASD_No-Dx), while 1 was identified as BAP (HR-ASD_BAP). These infants exhibit remarkably similar developmental change in eye fixation, across all growth measures quantifying this process. In contrast, 12 showed signs of early decline in eye fixation – 9 were identified at outcome as BAP and 3 as unaffected. In these infants, although their eye fixation is initially in decline, it changes course and begins to increase at approximately 18 months of age. More remarkably, we see in the 2^ndderivative that the developmental changes leading to the 18-month course correction actually have their origins at approximately 9 months of age, when the developmental decline reaches a point of inflection.

Conclusions:   This contrast, between the developmental trajectory for infants who later met criteria for ASD versus the trajectory for those who showed early eye fixation decline but did not ultimately receive a diagnosis, may offer a first glimpse of the developmental profile of sibling resilience. We hypothesize that “rate of change” (the 2^nd derivative) most closely reflects activity (onset/change/completion) of underlying biological processes, and may constitute a quantitative behavioral phenotype delimiting a window of opportunity (around 9 months) for intervention that could capitalize on potential for resilience, which is expressed naturally in some siblings but not in others.

Sponsors: National Institute of Mental Health (P50 MH100029), Simons Foundation, Marcus Foundation, Whitehead Foundation.