Subtle differences in intercranial volumes (ICV) were found among age groups and individuals with attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD). These findings, from a comprehensive cohort study, were published in the American Journal of Psychiatry.

Researchers relied on imaging data from the Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) consortium for this study. Structural T1-weighted whole-brain magnetic resonance images from 5827 healthy controls were compared to those of patients with OCD (n=2323), ADHD (n=2271), and ASD (n=1777). Analyses were performed by age group: children (<12 years of age), adolescents (between 12 and 17 years of age), and adults (aged 18 years or older). The investigators examined subcortical volume, cortical thickness, and cortical surface area differences.

Among children, when compared with OCD, those with ADHD had smaller ICV (effect size, 20.28) and hippocampal volumes (effect size, 20.22). When compared with ASD, those with ADHD had smaller ICV (effect size, 20.23). These differences were likely driven by medication because ICV did not differ significantly for children who were medicated. Among medicated children, those with OCD had larger amygdala volumes when compared with children with ADHD (effect size, 0.43) and children with ASD had thicker cuneus cortex than children with OCD (effect size, 0.60), but had thinner middle temporal gyrus than children with ADHD (effect size, 20.44).

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For adolescents, a similar pattern of smaller ICV for those with ADHD when compared with individuals with ASD (effect size, 20.22) was observed. Among patients with OCD, a significantly lower surface area of the medial orbitofrontal cortex was detected when compared with adolescents with ADHD (effect size, 20.22).

Among adults, significantly thicker cortical gray matter in frontal regions were observed among patients with ASD when compared with those with OCD or ADHD (effect size range, 0.17-0.30). Among unmedicated adults, those with ASD had significantly larger surface area of the parahippocampal gyrus than adults with ADHD (effect size, 0.33). After adjusting for IQ, adults with ASD had significantly thicker cortices of the frontal pole (effect size, 0.23), the superior frontal gyrus (effect size, 0.22), and the pars orbitalis (effect size, 0.20).

Limitations of the study included the reliance on data collected from 151 cohorts worldwide and a lack of information on all acquisition parameters (eg, radiofrequency coil and imaging sequence) from all collection sites. These factors could not be accounted or corrected for and may have introduced bias to the data.

The study authors noted that the study “constitutes the largest neuroimaging investigation to date of structural brain alterations across ADHD, ASD, and OCD.” There were no shared differences across the 3 disorders, and shared differences across any 2 disorders did not remain after correcting for multiple comparisons. Despite being common and often comorbid neurodevelopmental disorders, the study found robust yet subtle differences across age groups and the disorders in terms of cortical and subcortical brain structures.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Boedhoe P S W, van Rooij D, Hoogman M, et al. Subcortical brain volume, reginal cortical thickness, and cortical surface area across disorders: findings from the ENIGMA ADHD, ASD, and OCD working groups. Am J Psychiatry. 2020;appiajp202019030331. doi:10.1176/appi.ajp.2020.19030331.