ebook_ADHD2019

28 Rohde, Buitelaar, Gerlach & Faraone group. Also in adults with ADHD, very similar cognitive subtypes have been iden- tified. 77 It is, however, unclear whether these cognitive subtypes of ADHD have external validity, and for example predict treatment response or course. It is also unclear whether cognitive deficits cause ADHD symptoms and drive the develop- ment of the clinical phenotype 38 or reflect the pleiotropic outcomes of risk factors. BRAIN IMAGING Brain imaging techniques allow researchers to visualize, measure and analyze the interior of the human brain, i.e. its structure and function, with unprecedented power (see Box 2.2). Alterations have been observed in virtually all neuroimaging modalities applied to the study of the ADHD brain, including structural and func- tional magnetic resonance imaging (MRI), electroencephalography (EEG), and magnetoencephalography (MEG). STRUCTURAL MRI Earlier studies had found that ADHD is associated with a 3-5% smaller total brain size compared to controls 78 due to a reduction of gray matter. 79 Consistent with genetic data suggesting ADHD is the extreme of a population trait, total brain volume correlates negatively with ADHD symptoms in the general population. 80 Meta-analyses further document smaller volumes in ADHD across several brain regions, most consistently in the right globus pallidus, right putamen, caudate and cerebellum. The most recent and largest meta-analysis included in total 1713 par- ticipants with ADHD and 1529 controls from 23 sites with a median age of 14 ye- ars (range 4-63 years). 81 The results of the mega-analysis (in which not just the ca- se-control differences per site were aggregated but all individual data points were taken in to account) indicated that the volumes of the accumbens, amygdala, cau- date, hippocampus, putamen, and intracranial volume were smaller in individuals with ADHD compared with controls. The effects sizes were small and between 0.10 and 0.19 in terms of Cohen’s d. There was no difference in volume size in the pallidum and thalamus between people with ADHD and controls. Effect sizes were highest in most subgroups of children (<15 years) versus adults (>21 years), and case-control differences in adults were non-significant. Psychostimulant me- dication use or symptom scores did not influence the results, nor did the presence of comorbid psychiatric disorders. The greater case-control differences at younger age and absence of such differences at older age support the brain maturation delay theory for ADHD. This theory states that ADHD is due to a delayed ma-