Childhood Stress Rewires the Brain: Study Reveals Widespread White Matter Disruption

A study by Mass General Brigham involving over 9,000 participants found that early life adversity is linked to weaker white matter connections in the brain, which can raise the risk of cognitive challenges. However, supportive relationships may help buffer against these effects.

Researchers at Mass General Brigham have found that adverse experiences in early childhood are linked to reduced development of white matter, the brain’s communication pathways, during adolescence. This diminished connectivity is also associated with poorer performance on cognitive tasks. However, certain protective social factors, such as strong neighborhood cohesion and supportive parenting, may help buffer these effects. The findings are published in the Proceedings of the National Academy of Sciences.

White matter serves as the brain’s communication network, enabling different regions to work together to support thinking and behavior. These pathways continue to develop throughout childhood, and early life experiences can influence how they mature. Lead author Sofia Carozza, PhD, and senior author Amar Dhand, MD, PhD, from the Department of Neurology at Brigham and Women’s Hospital, a founding member of the Mass General Brigham system, sought to explore how white matter development affects cognitive functioning in adolescence.

Brain-Wide Effects of Adverse Experiences

“The aspects of white matter that show a relationship with our early life environment are much more pervasive throughout the brain than we’d thought. Instead of being just one or two tracts that are important for cognition, the whole brain is related to the adversities that someone might experience early in life,” said Carozza.

The team studied data from 9,082 children (about half of them girls, with an average age of 9.5) collected in the Adolescent Brain Cognitive Development (ABCD) study. This study, funded by the National Institutes of Health and conducted at 21 centers across the U.S., gathered information on brain activity and structure, cognitive abilities, environment, mood, and mental health. The researchers looked at several categories of early environmental factors, including prenatal risk factors, interpersonal adversity, household economic deprivation, neighborhood adversity, and social resiliency factors.

Carozza and Dhand used diffusion imaging scanning of the brain to measure fractional anisotropy (FA)—a way of estimating the integrity of the white matter connections—and streamline count, an estimate of their strength. They then used a computational model to compare how these features of white matter were related to both childhood environmental factors and current cognitive abilities such as language skills and mental arithmetic.

Widespread Impact of Childhood Environment

Their analysis revealed widespread differences in white matter connections throughout the brain depending on the children’s early-life environments. In particular, the researchers found lower-quality of white matter connections in parts of the brain tied to mental arithmetic and receptive language. These white matter differences accounted for some of the relationship between adverse life experiences in early childhood and lower cognitive performance in adolescence.

“We are all embedded in an environment, and features of that environment such as our relationships, home life, neighborhood, or material circumstances can shape how our brains and bodies grow, which in turn affects what we can do with them,” said Carozza. “We should work to make sure that more people can have those stable, healthy home lives that the brain expects, especially in childhood.”

The researchers note that their study is based on observational data, which means they cannot draw strong causal conclusions. Brain imaging was also only available at a single timepoint, offering a snapshot but not allowing researchers to track changes over time. Prospective studies—following children over time and collecting brain imaging information at multiple time points—would be needed to more definitively connect adversity and cognitive performance.

Reference: “Whole-brain white matter variation across childhood environments” by Sofia Carozza, Isaiah Kletenik, Duncan Astle, Lee Schwamm and Amar Dhand, 7 April 2025, Proceedings of the National Academy of Sciences.

Funding: Funding for the ABCD study was provided by the National Institutes of Health and federal partners under grant numbers U01DA041022, U01DA041025, U01DA041028, U01DA041048, U01DA041089, U01DA041093, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, and U24DA041147 (https://abcdstudy.org/federal-partners.html)