Wide Variability in Autism's Course

Deborah Brauser

January 29, 2015

Developmental changes in symptom severity and adaptive functioning differ significantly among children with autism spectrum disorder (ASD), new research suggests.

Dr Peter Szatmari

A multisite, longitudinal study of more than 400 preschoolers newly diagnosed with ASD, plus follow-up to the age of 6 years, showed that 89% had more severe symptoms at baseline and a stable developmental trajectory and that 11% had less severe and improving symptoms.

In addition, 50% of all the participants had moderate and stable adaptive functioning, 29% had lower functioning and a worsening trajectory, and 21% had higher functioning and an improving trajectory.

Interestingly, sex, age at diagnosis, and baseline language and cognitive scores all acted as significant outcome predictors.

"One of the things that surprised us is that there's a lot more variability in these outcomes than we ever thought," lead author Peter Szatmari, MD, chief of the Child and Youth Mental Health Collaborative, Hospital for Sick Children, Center for Addiction and Mental Health, University of Toronto, in Canada, told Medscape Medical News.

"Plus, there were about 10% of the kids who lost a lot of their autistic symptoms, and about 20% who really improved in adaptive functioning. And they weren't necessarily the same kids. This was a very heterogeneous population, and that heterogeneity seems to increase as time goes on," said Dr Szatmari.

He said that the take-away for clinicians is that several domains within ASD should be monitored over time ― and that interventions should focus on both symptoms and functioning.

"Don't assume that just because there's improvement in one area that it automatically means there's improvement in another."

The study was published online January 28 in JAMA Psychiatry.

Need for New Data

Dr Szatmari noted that the diagnosis of ASD has changed dramatically during the past 10 to 15 years.

"The kids that we're identifying now are not the same kids that we identified then. So most of the outcome studies on kids with ASD are based on pretty old data," he said.

"We thought we needed a new outcome study that could capture the kids who are currently being diagnosed so that we can see what happens to them over time."

The investigators assessed 421 children recently diagnosed with ASD who were between the ages of 2 and 5 years at the time of enrollment in the Pathways in ASD Study (mean age, 39.9 months; 84.3% boys). This study was conducted at five sites in Canada.

All participants underwent baseline examinations as well as follow-ups 6 and 12 months later and when each child was 6 years of age.

Primary measurements included the Autism Diagnostic Observation Schedule (ADOS) calibrated severity score and the Vineland Adaptive Behavior Scales, 2nd Edition (VABS II). The latter evaluated daily living skills, socialization, communication, and motor skills.

In addition, the Autism Diagnostic Interview–Revised, the 99-item Child Behavior Checklist (CBCL), the Preschool Language Scale–Fourth Edition, and the Merrill-Palmer–Revised Scales of Development were used.

When examining the trajectory of symptom severity, the investigators found that the participants fell into two distinct subgroups. In group 1 (11.4%), the children had less severe symptoms at baseline and a significantly improving trajectory (P < .05). Their mean ADOS scores at baseline, 12 months later, and at age 6 were 48, 43, and 37, respectively.

However, children in group 2 (88.6%) had more severe symptoms at baseline (mean ADOS score, 358) and a stable trajectory.

"Sex was the only significant predictor of autistic symptom group trajectory membership (P = .03)," report the researchers. The girls were more likely than the boys to be in the group with less severe and improving symptoms.

Heterogeneous Disorder

When examining adaptive functioning, the investigators found three distinct groups. Group 1 included 29.2% of all participants and showed lower functioning VABS II scores at baseline and a worsening trajectory over the years.

On the other hand, group 2 (49.9%) showed moderate functioning at baseline and a stable trajectory, and group 3 (20.9%) showed higher functioning and improved trajectory.

Age at diagnosis (P = .02) and language competence and cognitive scores at baseline (P < .001 for both) predicted adaptive functioning trajectory group. For example, earlier age was associated with higher functioning and an improving trajectory.

All of the domain trajectory groups showed significant differences at the age of 6 on all outcome measures except for one variable. There were no significant between-group differences in CBCL total scores for externalizing problems.

The results "confirm the heterogeneous nature" of changes over time in ASD, write the investigators.

They add that it is important to note that there was "only a small amount" of overlap between the two types of developmental trajectories.

"As clinicians, we have a tendency for early intervention, to have one intervention and, because it's so intensive, to stick with it. We would argue that another model that should be tested is multiple interventions ― each of which is less intensive but target different domains simultaneously," said Dr Szatmari. "That might be more effective over the long run."

He noted that the idea of "personalized medicine" usually refers to customizing treatment on the basis of biomarkers.

"We're taking the same concept and saying, 'we need to personalize the treatment based on change over time.' And that's a novel idea," he said.

Convincing Evidence

"I think this is an excellent study that answers some important questions in terms of the developmental progress, or not, of children with [ASD]," Anthony L. Rostain, MD, professor of psychiatry and pediatrics at the Perelman School of Medicine at the University of Pennsylvania, in Philadelphia, told Medscape Medical News.

Dr Anthony Rostain

"It provides convincing evidence that the trajectory of development...doesn't proceed exactly the same for different children," he said.

Dr Rostain, whose clinical focus is on developmental neuropsychiatry, was not involved with this research. He noted that although the field has known about the heterogeneity of ASD, what is "really novel" in the current study is that the different developmental trajectories were separated and compared.

"What they found was that having a lot of symptomatology does not necessarily mean you don't gain adaptive functioning skill. And by the same token, in the children with less severe symptoms, not all of them got better. It really shows the importance of individualizing our assessment of each child," he said.

"There's an important lesson here. Adaptive functioning is what we all are really hoping will be the outcome of intervention. So just focusing on symptoms of autism may not be where we should be focusing our interventions."

Dr Rostain added that further longitudinal studies are now needed to see what happens to children later in life. For the current study, he noted that "we could certainly ask for a few more data points," and the investigators did not disclose whether certain interventions led to better outcomes.

"But I don't want to be critical. A study of this size is really impressive. The findings confirm what we've already known, but this makes it more convincing because of the methods employed and the sample size," he concluded.

The study authors and Dr Rostain have reported no relevant financial relationships.

JAMA Psychiatry. Published online January 28, 2015. Full text

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