ADHD Associated with Delays in Subcortical Brain Volume Maturation

A study published in The Lancet helps confirm that attention-deficit/hyperactivity disorder (ADHD) is a neurologic disease marked by structural differences in several subcortical regions of the brain, compared with the non-ADHD population.¹ An international collaborative effort involving geneticists, neurologists, and psychiatrists from the ENIGMA ADHD Working Group found significantly smaller brain volume in the accumbens, amygdala, caudate, hippocampus, and putamen of children with ADHD vs controls. Three of these regions — the accumbens, amygdala, and hippocampus — were newly identified as involved in the expression of ADHD.

The ENIGMA ADHD Working Group was formed in 2013 to perform large-scale collaborative studies pooling ADHD imaging data (structural T1-weighted brain magnetic resonance images [MRIs]) across multiple decades of life. Previous neurodevelopmental research pointed strongly to structural variations in subcortical regions of the brain in ADHD,² which underwent cross-sectional analysis in the current study.

The investigators analyzed data collected from a total of 1713 children and adults with ADHD and 1529 non-ADHD controls, ranging in age from 4 to 63 years (median age = 14 years), from 23 separate cohorts. Significant differences in volume of multiple subcortical regions were apparent (measured by Cohen’s d effect = -.15) in the amygdala, caudate, hippocampus, and putamen (d =-.19, -.11, -.11, and -.14, respectively) while intracranial volume was reduced by .10. No differences in volume were seen in the palladium (P =.95) or thalamus (P =.39) in either group.

Age appeared to play a significant role, as differences in regional brain volume were significantly more pronounced in childhood and largely “non-existent” in adults, the investigators reported. Effect sizes in case-control analyses for differences in accumbens, amygdala, caudate, hippocampus, and intracranial volume were greater in children younger than age 15 with ADHD compared with other age groups and also greater in the hippocampus in adolescents (age 15 to 21) with ADHD compared with age-matched controls.

Additionally, smaller volumes were observed in female subjects, consistent with sex differences reported in earlier research.³ Lesser volumes were noted across all structures examined, with the exception of the accumbens and the caudate; however, significant volume differences between participants with ADHD and controls were not reported.

The collective hypothesis of the ENGIMA ADHD Working Group enhances previous models of delayed maturation in the cerebral cortex,⁴ further identifying specific regions where peak volume is delayed at the subcortical level in children. The large-scale aggregate sampling of MRI data in the study allowed for analysis across a 60-year lifespan in ADHD, suggesting the potential for “later onset of decreases in subcortical volumes beyond the fourth decade of life in ADHD,” the group concluded.

References

1. 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 [published online February 15, 2017]. Lancet Psychiatry. doi:10.1016/S2215-0366(17)30049-4
2. Sonuga-Barke E, Bitsakou P, Thompson M. Beyond the dual pathway model: evidence for the dissociation of timing, inhibitory, and delay-related impairments in attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2010;49:345-355.
3. Ruigrok AN, Salimi-Khorshidi G, Lai MC, et al. A meta-analysis of sex differences in human brain structure. Neurosci Biobehav Rev. 2014;39:34-50.
4. Shaw P, Eckstrand K, Sharp W, et al. Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation. Proc Natl Acad Sci USA. 2007;104:19649-19654.