IQ-Based Developmental Phenotypes of ASD Between Ages 2 and 7 Years and Their Correlates

Background: Longitudinal Investigation of the developmental phenotypes of ASD offers a promising strategy for of identifying homogeneous pathophysiology-based subgroups. Here, we investigate cognitive phenotypes defined by IQ trajectory change between ages 2 and 7 in the Autism Phenome Project (APP) longitudinal cohort.

Objectives:  To: (1) examine cognitive development between ages 2 and 7; (2) define ASD phenotypes derived from IQ-based developmental trajectories during this period; and (3) investigate associations between trajectory membership, and adaptive functioning, problem behaviors, and autism severity.

Methods: Latent class modeling using adjusted DQ scores derived from the Mullen Scales of Early Learning and the Differential Abilities Scale-II at ages 2 and 7 was implemented in 97 individuals with ASD. After classifying the ASD participants into trajectory groups, we examined changes in IQ, adaptive functioning, problem behaviors, and autism severity using a repeated measures approach with multiple comparison correction. All models included fixed effects for time, trajectory group, and their interaction. Problem behaviors, autism severity, and adaptive functioning were assessed using the CBCL, ADOS-2, and VABS-2, respectively.

Results: Three distinct IQ trajectory groups were identified. The first had IQs ≤ 77 at both times (Greater challenges: n=36; 37%). The second had IQs ≥ 75 at both times (Lesser challenges: n=23; 24%). A third group exhibited IQs < 82 at age 2, and had scores of ≥ 70 at age 7 with increases of ≥ 1 standard deviation (Changers: n=38; 39%). Repeated measures analyses revealed that the Lesser challenges group had significantly higher IQ scores than the Changers (31 points) and the Greater challenges groups (39 points) at age 2 (both p < .001). The 60% of the sample that was in either the Changers or Lesser challenges groups had significant improvements in IQ from age 2 to 7 (30 and 10 points, respectively, both p<.001). On the VABS-2, at age 2, there were significant differences across trajectory groups, driven mainly by differences between the Greater challenges and the Lesser challenges groups (t=4.23, p<.001). On the VABS-2, between ages 2 and 7, the Lesser challenges group showed no change, while the Changers improved by 6 points (t=2.43, p=.02), and the Greater challenges group declined by 9.4 points (t=-4.5, p<.001). On the Externalizing scales of the CBCL, there was no group difference at age 2, however the Changers experienced a significant 8-point decline in Externalizing (t=4.32, p <.001), while the other groups did not. Autism severity changed significantly only in the Lesser Challenges group (t=4.88, p<.001).

Conclusions:  A significant proportion of children with low early cognitive abilities will undergo significant intellectual development by age 7. This Changers group also exhibited significant reductions in externalizing symptoms by age 7, suggesting that reducing these symptoms by middle childhood is related to positive changes in cognitive development and adaptive functioning. Only the Lesser Challenges group showed a significant reduction in autism symptom severity during this period. A follow-up study of the APP at ages 8-12 is ongoing.