Spatial organization of cells and variable expression of autophagy, apoptosis, and neurodevelopmental genes might underlie selective brain region vulnerability in Attention-Deficit/Hyperactivity Disorder

Genetically influenced changes in brain organization occur over the course of development. Large-scale brain imaging studies by the ENIGMA Consortium identified structural changes associated with attention-deficit/hyperactivity disorder (ADHD). It is not clear why some brain regions are impaired and others spared by the etiological risks for ADHD. We hypothesized that spatial variation in brain cell organization and/or pathway expression levels contribute to selective brain region vulnerability (SBRV) in ADHD. In this study, we used the largest available collection of imaging results from the ADHD ENIGMA Consortium along with high-resolution postmortem brain microarray data from Allen Brain Atlas from 22 sub-cortical and cortical brain regions to investigate our selective brain region vulnerability (SBRV) hypothesis. We performed deconvolution of the bulk transcriptomic data to determine abundances of neuronal and non-neuronal cells in the brain. We then assessed the relationships between gene set expression levels, cell abundance, and standardized effect sizes representing regional changes in brain sizes in cases of ADHD. Our analysis yielded significant correlations between apoptosis, autophagy, and neurodevelopment genes with reductions in regional brain sizes in ADHD, along with associations to regional abundances of dopaminergic neurons, astrocytes, oligodendrocytes, and neural progenitor cells. This works provides novel mechanistic insights into SBRV in ADHD.

• Publication year

  2019

• Venue

  bioRxiv

• Publication date

  2019-05-29

• Fields of study

  Biology, Medicine, Psychology

• Identifiers
  DOI 10.1101/652792
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

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