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Two decades ago, a landmark study indicated that the brains of children with attention-deficit/hyperactivity disorder (ADHD) take longer to reach maturity. However, recent research suggests that this finding, derived from brain scans of a few hundred youngsters, was an illusion.
The new investigation indicates that what was once considered a defining characteristic of the ADHD brain actually reflects typical sex-based differences in how male and female brains develop throughout childhood. The earlier data, based on a less extensive sample size, may have been skewed to more closely represent the average brain development trajectory of boys, according to the new research.
In 2007, a research project pioneered new avenues in the study of ADHD. A team affiliated with the National Institute of Mental Health demonstrated that children diagnosed with ADHD, who exhibited external struggles with attention and impulsivity, possessed distinct brain structures underlying these behavioral traits when contrasted with children not diagnosed with ADHD.
The researchers utilized MRI scans to examine the brains of 223 children with ADHD and a comparable control group of children without the condition. The study concluded that the brains of children with ADHD followed a different developmental path compared to those without ADHD. Throughout childhood, the cortex—the brain’s outermost layer—thickens and then thins. The research indicated that this progression was notably delayed in children with ADHD.
At the time, this discovery seemed highly logical, as it aligned well with the observed behaviors associated with ADHD, stated Matthew Albaugh, a clinical neuroscientist at the University of Vermont. “You observe children who may be acting somewhat younger than their chronological age,” he remarked to Live Science.
The 2008 publication was considered “foundational” to the field, according to Albaugh. The research even suggested that children with ADHD experienced earlier maturation in brain regions associated with movement, which was theorized to account for their hyperactivity. At the time, researchers believed this work presented a coherent and understandable narrative.
Sex differences undermine brain data
However, scientific findings are seldom so straightforward. In their recent study, published on May 18 in the journal PNAS, Albaugh and his associates have cast doubt upon those earlier conclusions.
Results from a 2007 study show the differences in brain development between children with ADHD (in blue) and a child without the disorder (in purple) through ages 7 to 13. This data showed delayed cortical thinning in children with ADHD, but a new study casts doubt on that finding.
(Image credit: P. Shaw et al. (2007))
The recent work utilized a robust data source to demonstrate that the previously reported delayed maturation is likely an artifact of the data, stemming from differences in how boys’ and girls’ brains develop. Once these varying patterns are accounted for, the study authors indicated, there is no discernible difference in brain maturation between individuals with and without ADHD.
The team aimed to replicate the 2008 paper, employing data from the Adolescent Brain Cognitive Development (ABCD) study. This project, funded by the National Institutes of Health, is observing over 11,000 9- and 10-year-olds for approximately a decade, according to study lead author Shannon O’Connor, a research project assistant at the University of Vermont. The study gathers data on various behavioral traits and brain metrics and stands as the largest imaging study of its kind in the United States to follow participants over time, O’Connor informed Live Science.
The ABCD study requested parents to report any attention-related issues their child experienced. When the researchers initially examined the connection between attention problems and cortical thickness, they found associations similar to those uncovered by the original study nearly 20 years prior.
However, the team sought to leverage the extensive dataset provided by the ABCD to test the impact of accounting for other factors in the children’s lives. O’Connor had observed in other analyses of the ABCD data that boys tended to exhibit a slower rate of cortical thinning compared to girls. When the team factored in these differential rates, the correlations between attention issues and brain structure vanished.
“That’s what caused the entire structure to collapse,” Albaugh commented. Previous studies had considered gender differences at single points in time, but not their progression over time, he noted. As participants left these smaller studies, their meticulously balanced analyses might have shifted to disproportionately reflect the slower rate of cortical thinning observed in boys.
Upon further examination of the data, the team divided the cohort into separate groups of only boys and only girls. Within each sex considered individually, no relationship was found between cortical thickness and attention.
The replication crisis rolls on
Dr. Max Wiznitzer, a pediatric neurologist at Case Western Reserve University who was not involved in the new research, described it as “well designed” and stated that it “asked the pertinent questions.” The recent findings were based on attention problems reported by parents rather than formal ADHD diagnoses, prompting Albaugh’s team to conduct subsequent studies on subsets of clinically diagnosed patients, which yielded comparable outcomes.
The new discoveries contribute to the broader replication crisis affecting neuroscience. Emerging, powerful datasets and more sophisticated imaging technologies have, in some instances, undermined rather than corroborated significant neuroscience studies that previously guided the field. Albaugh suggested that these newer datasets imply that many of these initial findings “might have been coincidences.”
It is noteworthy that the influence of sex differences has been largely overlooked in neuroscience, and this research underscores how acknowledging sex as a variable can refine a study’s conclusions.
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Albaugh was quick to assert that the findings do not alter the fundamental understanding that ADHD is a biological condition with a significant genetic basis. However, it does leave the field without reliable biological markers for the condition, according to Wiznitzer.
This study ought to motivate researchers in the field to pursue biological signatures that can aid in the diagnosis and treatment of individual patients, rather than focusing on group averages, he added. Cortical thickness was never employed in such a manner.
“If I administer medication and a person’s behavior improves, in a sense, their cortical thickness becomes irrelevant,” Wiznitzer stated. “From a clinical standpoint, the improvement is what you are aiming for.”
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