The researchers say that the findings - from brain images of more than 3,200 people - provide strong evidence that ADHD is a disorder of the brain.
The differences observed in their study were most prominent in children, but also present in adults with the condition.
For the study, the team measured differences in the brain structure of 1,713 people with a diagnosis of ADHD and 1,529 people without, all aged between four and 63 years old.
The affected regions include the amygdala, which is involved in the regulation of emotion.
With funding from the National Institutes of Health, researchers from the global ENIGMA ADHD Working Group embarked on what they said is the largest study performed on brain differences in people with and without ADHD. "This is another big confirmation that it is a disorder of the brain and it will help with the stigma that ADHD is something created socially".
The findings were calculated from a survey of of 1,713 people with ADHD and 1,529 people without, and has now been published in the journal The Lancet Psychiatry. The research team noted that similar differences are common in psychiatric conditions like depression.
ADHD causes inattention, hyperactivity and impulsivity, although a given person may not show all those traits.
The finding that children with ADHD had smaller brain structures fits with a "delayed peak volume" theory that ADHD is associated with an "altered velocity of cortical development", the authors said.
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Of seven subcortical brain regions targeted in the study, five, including the amygdala, were found to be smaller in those with ADHD compared with a control group.
The regions which had a reduced volume were the amygdala, the hippocampus, the nucleus accumbens, the putamen and the caudate nucleus. The other regions with decreased volume were the caudate nucleus (which plays a role in goal-directed action), the putamen (linked to learning and responding to stimuli), the nucleus acumbens (rewards and motivation), and the hippocampus (which helps form memories).
The differences in brain sizes are not the result of psychostimulants, which some of those who have ADHD take as medication.
Typically, people with ADHD have poor attention skills and could be hyperactive.
Lead researcher Martine Hoogman told Trouw that the study suggests children with ADHD have brains that mature later: 'I hope that above all the study removes stigmatisation, ' she told the paper.
Prescriptions for drugs such as Ritalin for children diagnosed with ADHD are thought to have doubled in the last decade, despite concerns they can cause adverse reactions like weight loss, liver toxicity and suicidal thoughts.
The research was praised by Columbia University's Jonathan Posner as "an important contribution" to the study of the condition. He also calls for further studies to track brain differences in the development of ADHD, and suggests that there should also be an investigation of any medication effects.