Summary: Two new longitudinal studies from the UC Davis MIND Institute reveal links between early brain development and later autism traits. One study associates early larger brain volume with a distinct autism subtype, while the other connects patterns of white matter growth to changes in symptom severity over early childhood.
Source: UC Davis
Two major longitudinal studies from the UC Davis MIND Institute offer new evidence tying brain structure—both overall size and white matter growth—to differences in autism spectrum disorder (ASD).
Both investigations draw on extensive MRI data collected through the Autism Phenome Project (APP) and the Girls with Autism, Imaging of Neurodevelopment (GAIN) studies. By following the same children from diagnosis into later childhood, these studies provide insight that cross-sectional research cannot.
“There is no other single-site data set like ours,” said Christine Wu Nordahl, associate professor in the Department of Psychiatry and Behavioral Sciences, a MIND Institute faculty member and co-senior author on both papers. “In one of the studies we have over 1,000 MRI scans from 400 children, which is unprecedented. It has taken 15 years of sustained effort to build this resource.”
Big brains: a distinct autism subtype?
In the first paper, published in Biological Psychiatry, researchers measured cerebral volume with MRI in 294 children diagnosed with autism and 135 typically developing peers, tracking development from ages 3 to 12. They identified a subgroup of children with autism who showed disproportionately large brain volume relative to their height—a pattern referred to as disproportionate megalencephaly. This subtype has been associated with higher rates of intellectual disability and less favorable outcomes.
Earlier cross-sectional studies suggested that enlarged brains in young children with autism “normalized” by later childhood. However, because those studies compared different children at different ages, they could be subject to sampling bias. The MIND Institute’s longitudinal approach reveals a different picture: children who had larger brains at age 3 often continued to have larger brains at age 12.
A key reason for the discrepancy, the authors explain, is inclusion. Many prior studies excluded children with significant intellectual disability—children who are more likely to present the large-brain subtype and who become harder to scan as they age. David Amaral, co-senior author and distinguished professor of psychiatry and behavioral sciences, suggested that earlier conclusions about brain size “normalizing” may reflect who was available and able to be scanned at older ages, rather than true biological change.
Nordahl and colleagues emphasize that scanning older children with intellectual disability requires different methods than scanning toddlers. The team developed protocols to obtain quality imaging from older, awake children who have intellectual and behavioral challenges, ensuring those most affected by ASD are included in the research.
“It is essential to include dimensions of autism that most affect everyday life, such as intellectual disability, anxiety and language ability,” said Joshua Lee, a postdoctoral scholar at the MIND Institute and lead author. “To understand autism fully, we must include everyone diagnosed with the condition, not only those who are easiest to image.”
White matter: connecting clinical change to brain development
The second study, also published in Biological Psychiatry, examined white matter development using diffusion-weighted imaging in 125 children with autism and 69 typical controls aged roughly 2.5 to 7 years. White matter consists of the brain’s communication pathways and supports information transfer between regions.
Researchers found that patterns of white matter growth were associated with changes in autism symptom severity. Children whose symptoms increased over time tended to show slower white matter development, while children whose symptoms decreased exhibited faster white matter maturation. These findings point to white matter growth as a biological process linked to the course of autism symptoms in early childhood.
“Biologically, this highlights the importance of white matter trajectories in ASD,” said Derek Sayre Andrews, postdoctoral scholar and lead author on the paper. “In the future, measures of white matter development may help identify children likely to benefit from targeted interventions and serve as biomarkers for tracking treatment response.”
Variability in autism severity over time
This white matter analysis builds on prior MIND Institute findings that, while many children maintain relatively stable levels of autism-related behaviors across childhood, a substantial group experiences meaningful increases or decreases in symptom severity. Linking those behavioral shifts to underlying white matter growth provides a tangible biological clue about mechanisms that may drive change.
Examining sex differences
Both studies are notable for their inclusion of larger numbers of girls than is typical in autism imaging research. That broader representation allowed the team to examine brain development in girls separately from boys.
“For the first time, our sample of girls is large enough to evaluate their brain growth trajectories independently,” Nordahl said. “We find that the large-brain subtype appears less frequently in girls, although there are subtle differences in how autistic girls’ brains develop over time.” Nordahl has also investigated the amygdala’s role in psychiatric outcomes for young girls, and she notes these longitudinal data will support many future studies on sex-specific patterns in ASD.
Collectively, the authors say these studies move the field closer to using biological measures of brain development to improve clinical care and quality of life for people with autism. “Our goal is to translate an understanding of underlying biology into interventions and supports that make a meaningful difference,” Andrews said.
Co-authors on “Longitudinal Evaluation of Cerebral Growth Across Childhood in Boys and Girls with Autism Spectrum Disorder” include Sally Ozonoff, Marjorie Solomon, Sally J. Rogers and Derek Sayre Andrews. Funding for this work came from the National Institute of Mental Health and support from the UC Davis MIND Institute Intellectual and Developmental Disabilities Research Center and the Autism Center of Excellence.
Co-authors on “A Longitudinal Study of White Matter Development in Relation to Changes in Autism Severity Across Early Childhood” include Joshua K. Lee, Danielle Jenine Harvey, Einat Waizbard-Bartov, Marjorie Solomon and Sally J. Rogers. This study also received support from the National Institute of Mental Health and the UC Davis MIND Institute research programs.
Source: UC Davis
Contact: Marianne Sharp – UC Davis
Image: The image is in the public domain