Longstanding links between attention-related problems and changes in the brain’s cortex during childhood and adolescence could simply be due to developmental differences between the sexes, a study suggests.
The findings, in PNAS, showed that links between attention problems and slowed rates of cortical thinning were no longer evident after taking sex into account.
The results call into question proposals to use brain maturation patterns as biomarkers for attention deficit/hyperactivity disorder (ADHD) and related conditions.
More generally, they reveal the importance of accounting for sex differences during scientific investigations.
“For nearly two decades, delayed age-related cortical thinning has been widely viewed as a neurodevelopmental marker of attention-related psychopathology and ADHD,” reported Shannon O’Connor, PhD, from the University of Vermont, and co-workers.
“However, our findings suggest that this association may be largely confounded by sex differences in cortical development.”
Delayed thinning of the brain’s cortex—its outermost layer of grey matter—has long been proposed as a biomarker for ADHD-related conditions.
To investigate its value further, O’Connor and team studied 26,496 MRI scans from 11,025 adolescents.
The team initially found there was a link between attention problems and reduced rates of age-related cortical thinning across predominantly frontoparietal regions. Reduced rates of age-related thinning were associated with higher scores relating to attention problems.
However, this link dramatically reduced after accounting for sex differences in cortical thickness trajectories.
There were no significant age and attention problem interactions on cortical thickness when the sexes were studied separately. Furthermore, the genetic risk of ADHD was also not associated with slowed thinning in this region of the brain.
“Taken together, these findings suggest that previously reported associations between attention problems and delayed cortical thinning are largely attributable to unaccounted-for sex differences in neurodevelopment,” the authors concluded.
“Our results call into question an influential framework in developmental neuroscience and psychiatry that has shaped clinical understanding of ADHD for nearly 20 years, underscoring that cortical maturation patterns should not be interpreted as biomarkers for attention-related psychopathology without rigorous accounting for sex-related variation in brain development.”
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