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Area of Science:

  • Neuroscience
  • Genetics
  • Developmental Disorders

Background:

  • Subcortical volumetric differences are linked to attention-deficit/hyperactivity disorder (ADHD).
  • Variability in effect sizes suggests selective neuronal vulnerability may contribute to these volumetric changes.
  • Previous research identified ADHD-associated structural brain anomalies.

Purpose of the Study:

  • To investigate gene expression variability in subcortical regions of typically developing brains.
  • To test the hypothesis that ADHD candidate gene expression and specific biological pathways correlate with ADHD-associated volumetric findings from the ENIGMA consortium.
  • To explore the role of apoptosis, oxidative stress, and autophagy in ADHD-related structural brain anomalies.

Main Methods:

  • Utilized data from the Allen Brain Atlas to analyze gene expression profiles in subcortical regions.
  • Correlated gene expression data with volumetric findings from the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) study on ADHD.
  • Focused on curated ADHD candidate genes and five a priori selected biological pathways.

Main Results:

  • Gene expression profiles for apoptosis, oxidative stress, and autophagy pathways were significantly correlated with ADHD-associated volumetric reductions across subcortical regions.
  • These correlations were notably strong and significant in children with ADHD.
  • The observed correlations were not significant in adults with ADHD.

Conclusions:

  • Variability in structural brain anomalies observed in ADHD may be partly explained by differential regional vulnerability.
  • Mechanisms including apoptosis, oxidative stress, and autophagy appear to play a role in these vulnerabilities.
  • Findings suggest distinct biological underpinnings for ADHD-related brain changes in children versus adults.