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Children with ADHD show reduced brain volumes

Children as young as four years old with symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD) showed reduced brain volumes in regions essential for behavioural control. This is according to a study funded by the National Institutes of Health (NIH), which represents the first comprehensive examination of cortical brain volume in preschool children with ADHD and provides an indication that anomalous brain structure is evident in the early stages of development.

Using high-resolution anatomical MRI scans along with cognitive and behavioural measures, researchers from Kennedy Krieger Institute studied the brain development of 90 medication- naïve pre-schoolers between the ages of 4 and 5 years. The study, funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, found that pre-schoolers with ADHD showed significantly reduced brain volume across multiple regions of the cerebral cortex, including the frontal, temporal, and parietal lobes. The brain regions showing greatest ADHD-related reductions included those known to be critical for cognitive and behavioural control and predictability of behavioural symptoms.

"These findings confirm what parents have known for a while – even in very young children, ADHD is a real biological condition with pronounced physical and cognitive manifestations," said Dr E Mark Mahone, lead study author and research scientist at the Kennedy Krieger Institute.

ADHD is the most commonly diagnosed form of psychopathology during the pre-school years, and during early childhood, it is associated with significant long-term health and economic costs. To date, studies assessing structural brain development in children with ADHD have examined school-aged samples, despite most children with the disorder showing symptoms early in the preschool years. This study carefully identified children with symptoms of ADHD closer to their onset, allowing for better understanding of the brain mechanisms associated with the onset of the condition.

"MRI research in children can be challenging – particularly so for young children with ADHD – as it requires them to lie still for periods up to 30-40 minutes," said Mahone. "To address this challenge, we employed an individualised behavioural desensitisation procedure using a mock scanner to help prepare the children for the scans, leading to a nearly 90% success rate."

These findings represent the first phase of a study that will follow a preschool age cohort into adolescence, in hopes of identifying early biological signs in preschool years that can help predict which children are most at risk for developing ADHD.

"Our hope is that by following these children from early on in life, we will be able to determine which early brain and behavioural signs are most associated with later difficulties, or even better, which aspects of early development can predict better outcome and recovery from the condition," said Mahone. "By understanding the brains of children who grow into the disorder as well as those who grow out of it, we can begin to implement targeted, preventative interventions in young children with the goal of reducing adverse outcomes or even reversing the course of this condition."

Objectives: Attention-deficit/hyperactivity disorder (ADHD) is a common neurological disorder with symptom onset early in childhood. Growing evidence suggests anomalous brain development across multiple brain regions is evident in school-aged children; however, few studies have examined whether such differences are notable in the preschool years when symptom onset typically occurs.
Methods: High resolution anatomical (MPRAGE) images and cognitive and behavioral measures were analyzed in a total of 90 medication-naïve preschoolers, ages 4–5 years (52 with ADHD, 38 controls; 64.4% boys).
Results: Results revealed reductions in bilateral frontal, parietal, and temporal lobe gray matter volumes in children with ADHD relative to typically developing children, with largest effect sizes noted for right frontal and left temporal lobe volumes. Examining frontal lobe sub-regions, the largest between group effect sizes were evident for left orbitofrontal cortex, left primary motor cortex (M1), and left supplementary motor complex (SMC). ADHD-related reductions in specific sub-regions (left prefrontal, left premotor, left frontal eye field, left M1, and right SMC) were significantly correlated with symptom severity, such that higher ratings of hyperactive/impulsive symptoms were associated with reduced cortical volumes.
Conclusions: These findings represent the first comprehensive examination of cortical volume in preschool children with ADHD, providing evidence that anomalous brain structure in ADHD is evident very early in development. Furthermore, findings set the stage for developing our understanding of the way in which developmental trajectories of anomalous brain development are associated with the unfolding of symptoms in childhood ADHD.

Lisa A Jacobson, Deana Crocetti, Benjamin Dirlikov, Keith Slifer, Martha Bridge Denckla, Stewart H Mostofsky, E Mark Mahone

[link url=""]Kennedy Krieger Institute material[/link]
[link url=""]Journal of the International Neuropsychological Society abstract[/link]

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