Interplay between stress response genes associated with attention-deficit hyperactivity disorder and brain volume

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• The glucocorticoid receptor (NR3C1) is crucial for stress response in the brain.
• NR3C1 gene polymorphisms are linked to attention-deficit hyperactivity disorder (ADHD).
• The serotonin transporter (5-HTT) gene polymorphism (5-HTTLPR) affects stress and ADHD severity, potentially via glucocorticoid levels.

Purpose of the Study:

• To investigate if NR3C1 moderates the relationship between stress exposure, ADHD severity, and brain structure.
• To explore the role of 5-HTTLPR in these interactions.

Main Methods:

• Utilized neuroimaging, genetic, and stress exposure data from 539 adolescents and young adults in the NeuroIMAGE ADHD cohort study.
• Assessed the effects of NR3C1 and 5-HTT genetic variations, stress exposure, and their interactions on ADHD symptom count and gray matter volume.

Main Results:

• Individuals with the NR3C1 ADHD risk haplotype showed a stronger positive association between stress and ADHD severity.
• This gene-environment interaction was more pronounced in 5-HTTLPR L-allele homozygotes compared to S-allele carriers.
• These interactions were reflected in the gray matter volume of specific brain regions, including the cerebellum and parahippocampal gyrus.

Conclusions:

• Genetic variations in the stress response pathway, specifically NR3C1 and 5-HTT, significantly influence how stress exposure impacts ADHD severity and brain structure.
• The interaction between NR3C1 and 5-HTT may help elucidate the variability observed in ADHD research concerning these genes and the hypothalamic-pituitary-adrenal axis.