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In the largest study of its kind and well powered to detect small effect sizes, Martine Hoogman and colleagues in the ENIGMA collaboration assessed differences in the subcortical structures and intracranial volume of 1713 individuals with attention deficit hyperactivity disorder (ADHD) and 1529 unaffected controls across 23 sites.
This study is the first meta-analysis to document accumbens, hippocampal, and amygdala differences in ADHD individuals.
Their results show reduced volumes in the accumbens, amygdala, caudate, hippocampus, putamen, and intracranial volume in individuals with ADHD compared with healthy controls in the mega-analysis. Reduced volumes were detected in childhood, but were not present by adulthood.
The amygdala, which showed the largest effect size of the subcortical structures tested. This is not surprising given emotion dysregulation is a core characteristic of the ADHD phenotype. However there remains the possibility that emotional dysregulation is a separate event, or represent a distinct type of ADHD
Further studies will need to identify whether shared environmental or genetic risk factors is responsible for the emotional dysregulation see in ADHD. This would be important in understanding ADHD as a purely cognitive disorder or a combined cognitive and mood disorder.
Although epidemiological studies have provided evidence for the existence of adult-onset ADHD and that it may have a biological cause and a developmental trajectory distinct from that of child-onset ADHD, it’s interesting to note that the subcortical volumetric reductions seen in ADHD children are not present in adults with ADHD. It is possible that Adult samples in the present study might have included both child-onset and adult-onset ADHD, and thus, within-group heterogeneity might be responsible for the failure to detect volumetric differences from controls. This question can be answered by longitudinal imaging studies.
In contrast to previous meta-analyses which have suggested that basal ganglia volumes normalise in ADHD following medication, this study did not find any relationship between previous medication and subcortical volumetric reductions in ADHD. Further randomised placebo controlled studies would be required to address this.
In the ENIGMA study sites the clinical protocols used varied and this might explain the absence of an association between brain volumes and clinical symptoms. Future studies should aim to standardize the clinical assessments including that for emotional dysregulation.
The ENIGMA study is important because of the large sample size used to study this heterogenous condition and have provided more evidence to support the theory that ADHD is associated with substantial effects on the subcortical nuclei volumes.