Many neurobiological factors determine changes of adaptive behavior in autism

Variation in clinical outcome is linked with both group- and individual-level variation in anatomy of cortical regions enriched for genes relevant to autism spectrum disorder, according to a study published in the American Journal of Psychiatry.

“Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition,” Charlotte M. Pretzsch, PhD, of the department of forensic and neurodevelopmental sciences at the Institute of Psychiatry, Psychology and Neuroscience at King’s College, and colleagues wrote. “However, across the lifespan, some individuals with ASD improve in terms of adaptive behavior, while others may not change significantly or regress.”

Researchers sought to gain an understanding of the biological processes that drive differences in clinical outcomes, at the individual and subgroup levels, for those with ASD across their respective lifespans.

The longitudinal study included 483 participants aged 6 to 30 years from the Longitudinal European Autism Project (204 with ASD and 279 neurotypical individuals) who were assessed at baseline and then intervals separated by 12 and 24 months. Patients’ adaptive behaviors were gauged by the Vineland Adaptive Behavior Scale–II; neuroanatomical data was gained through structural MRI; neuroimaging data measuring cortical volume, thickness and surface area was taken via brain imaging software; and genetic data was also assessed. Those with ASD were divided into clinically meaningful “increasers,” “no-changers” and “decreasers” regarding adaptive behavior.

Researchers compared neuroanatomy between outcome groups, examined whether deviations from the neurotypical neuroanatomical profile were associated with outcome at the individual level and explored the observed neuroanatomical differences’ potential genetic underpinnings.

Results showed neurotypical and individuals with autism did not differ significantly in age, IQ, total cortical volume and total surface area at baseline, but differed in sex distribution, and mean cortical thickness was larger in the ASD group than in the neurotypical group.

In neuroanatomy, overlapping differences were found in frontal, occipital (increasers less than decreasers, and parietal (increasers more than decreasers) cortical volume; parieto-occipital and temporal (increasers more than decreasers) surface area; and temporal cortical thickness (increasers more than decreasers) in children. Similarities were found in fronto-parietal surface area (increasers more than decreasers) and temporal cortical thickness (increasers more than decreasers). These findings suggest that in ASD, variation in neuroanatomy and adaptive outcome are associated across the lifespan.

For neuroanatomy, an individual’s deviation from the neurotypical developmental trajectory predicted their adaptive outcome. For increasers vs. decreasers, a greater cortical volume atypicality index predicted a decline in adaptive behavior. Conversely, a more positive surface area atypicality index (increasers vs. decreasers), cortical volume atypicality index (increasers vs. no-changers) and surface area atypicality index (decreasers vs. no-changers) predicted an improvement in adaptive behavior.

Decreasers displayed greater absolute deviations from the neurotypical group than did the increasers, meaning greater neuroanatomical deviation predicted a worsening in adaptive behavior.

Regions differing between increasers and decreasers in surface area were enriched for genes downregulated in ASD (OR = 3.07), co-expression modules downregulated in ASD (OR=2.26), and many genes differentially expressed in bipolar disorder (OR=1.62) and schizophrenia (OR=1.57). In contrast, regions differing between increasers and no-changers in cortical volume were enriched for co-expression modules upregulated in ASD.

“Taken together, our study findings are among the first to characterize neuroanatomical (and associated genetic) anomalies associated with adaptive outcome in ASD,” Pretzsch and colleagues wrote.