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21 Feb 2017

Hoogman M et al. Lancet Psychiatry 2017; Epub ahead of print

Analysis of brain structure in ADHD has been largely limited, and in an effort to combat previous study weaknesses* the ENIGMA ADHD working group was founded. Through a collaborative approach, the current study aimed to determine whether there were structural differences within the brains of children and adults with ADHD compared with those without ADHD.

A cross-sectional mega-analysis was performed using data obtained through the ENIGMA working group collaboration. Harmonised data were obtained through acquisition of T1-weighted brain magnetic resonance imaging (MRI) data using implemented standardised protocols. Pooling of these results allowed investigation of subcortical and intracranial volume (primary objective). Association of brain volume and age, psychostimulant medication use and comorbidity with other psychiatric disorders was analysed by running and re-running selected models (secondary objective).

The largest dataset to date was accrued from 3242 participants (1713 participants with and 1529 without ADHD, respectively), with a median age of 14 years (age range 4–63 years) across 23 sites. MRI scans indicated smaller volumes in the subcortical brain regions studied of individuals with ADHD compared with those without; specifically in the accumbens (Cohen’s d = -0.15), amygdala (d = ‑0.19), caudate (d = -0.11), hippocampus (d = -0.11), putamen (d = -0.14) and intracranial volume (d = -0.10). However, no difference in the pallidum and thalamus was measured between the two groups. Exploratory lifespan modelling suggested a delay of maturation and a delay of degeneration, as effect sizes were highest in most subgroups of children (<15 years) versus adults (>21 years): in the accumbens (d = -0.19 vs -0.10), amygdala (d = -0.18 vs -0.14), caudate (d = -0.13 vs -0.07), hippocampus (d = -0.12 vs -0.06), putamen (d = -0.18 vs -0.08) and intracranial volume (d = -0.14 vs 0.01). No difference for the pallidum (p=0.79) or thalamus (p=0.89) was observed between adults and children. Furthermore, no significant differences between adults with ADHD and healthy volunteers were observed (all p>0.03).

The use of psychostimulant medication did not appear to affect the results (p>0.15). Furthermore, a comparison of this analysis set with that obtained for psychostimulant lifetime usage indicated no difference in volumes between the two groups. Meta-analysis indicated no significant effect (p>0.02) in correlation of ADHD symptom scores and brain volumes. Similarly, no significant effect was observed when the model was run for children only. A comparison of differences in brain volume in participants with and without a diagnosis of ADHD did not present an association with additional comorbid psychiatric conditions (p>0.5).

Despite implemented harmonisation protocols, differences in diagnostic routines and data acquisition across sites contributed to sample heterogeneity. As such, findings from this study should be utilised in generating hypotheses for future studies looking to further our understanding of neural substrates of ADHD.

This global collaboration has extended the brain maturation delay theory of ADHD, highlighting a reduction in striatal volume in participants with ADHD compared with those without. Brain volume differences were also more prominent in children with ADHD compared with those without.

Read more about the brain maturation delay theory for ADHD here


*Previous analyses of brain structures in ADHD have yielded limited evidence as a result of small sample size, small statistical power and inclusion of only published data as source material

Hoogman M, Bralten J, Hibar DP, et al. Subcortical brain volume differences in participants with attention deficit hyperactivity disorder in children and adults: a cross-sectional mega-analysis. Lancet Psychiatry 2017; Epub ahead of print.

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