Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Oct 15;86(8):621-630.
doi: 10.1016/j.biopsych.2019.03.983. Epub 2019 Apr 3.

Prefrontal Cortex Dopamine Transporter Gene Network Moderates the Effect of Perinatal Hypoxic-Ischemic Conditions on Cognitive Flexibility and Brain Gray Matter Density in Children

Patrícia Maidana Miguel  1 , Lenir Orlandi Pereira  1 , Barbara Barth  2 , Euclides José de Mendonça Filho  3 , Irina Pokhvisneva  4 , Thao T T Nguyen  4 , Elika Garg  4 , Bruna Regis Razzolini  2 , Dawn Xin Ping Koh  5 , Heather Gallant  6 , Roberto Britto Sassi  7 , Geoffrey B C Hall  6 , Kieran John O'Donnell  8 , Michael J Meaney  9 , Patrícia Pelufo Silveira  10
Affiliations

Prefrontal Cortex Dopamine Transporter Gene Network Moderates the Effect of Perinatal Hypoxic-Ischemic Conditions on Cognitive Flexibility and Brain Gray Matter Density in Children

Patrícia Maidana Miguel et al. Biol Psychiatry. .

Abstract

Background: Genetic polymorphisms of the dopamine transporter gene (DAT1) and perinatal complications associated with poor oxygenation are risk factors for attentional problems in childhood and may show interactive effects.

Methods: We created a novel expression-based polygenic risk score (ePRS) reflecting variations in the function of the DAT1 gene network (ePRS-DAT1) in the prefrontal cortex and explored the effects of its interaction with perinatal hypoxic-ischemic-associated conditions on cognitive flexibility and brain gray matter density in healthy children from two birth cohorts-MAVAN from Canada (n = 139 boys and girls) and GUSTO from Singapore (n = 312 boys and girls).

Results: A history of exposure to several perinatal hypoxic-ischemic-associated conditions was associated with impaired cognitive flexibility only in the high-ePRS group, suggesting that variation in the prefrontal cortex expression of genes involved in dopamine reuptake is associated with differences in this behavior. Interestingly, this result was observed in both ethnically distinct birth cohorts. Additionally, parallel independent component analysis (MAVAN cohort, n = 40 children) demonstrated relationships between single nucleotide polymorphism-based ePRS and gray matter density in areas involved in executive (cortical regions) and integrative (bilateral thalamus and putamen) functions, and these relationships differ in children from high and low exposure to hypoxic-ischemic-associated conditions.

Conclusions: These findings reveal that the impact of conditions associated with hypoxia-ischemia on brain development and executive functions is moderated by genotypes associated with dopamine signaling in the prefrontal cortex. We discuss the potential impact of innovative genomic and environmental measures for the identification of children at high risk for impaired executive functions.

Keywords: ADHD; Cognitive flexibility; DAT1; Dopamine transporter gene; Hypoxic-ischemic conditions; Parallel independent component analysis.

PubMed Disclaimer

Comment in

  • Assessing the Candidates.
    Malhotra AK. Malhotra AK. Biol Psychiatry. 2019 Oct 15;86(8):573-574. doi: 10.1016/j.biopsych.2019.07.013. Biol Psychiatry. 2019. PMID: 31558219 No abstract available.

Publication types

Substances

LinkOut - more resources