Dissecting the Mediating Role of Cortical Structures in the Pathogenesis of Socioeconomic Status to ADHD: A Mendelian Randomization Study and Mediation Analysis

Abstract

Background:

Research has consistently demonstrated a negative correlation between socioeconomic status (SES) and the prevalence of ADHD, with SES exerting a significant influence on brain development. ADHD, closely intertwined with neurological development, often manifests as impairments within brain regions associated with memory, executive function, and emotion regulation. Nevertheless, the specific brain structural mediators linking SES to ADHD remain unclear.

Method:

We explored whether the brain surface area (SA) and thickness (TH) mediated the relationship between SES indicators (Townsend deprivation index at recruitment, average total household income before tax, and job involves heavy manual or physical work) and ADHD utilizing two-step Mendelian Randomization (MR) and multivariate MR method.

Results:

The MR analysis indicated that higher SES corresponds to a lower prevalence of ADHD. Genetically predicted household income was positively correlated with the SA of insula (β = .31, p = 1.02 × 10⁻⁴), and physical work was positively correlated with the TH of entorhinal cortex (β = .74, p = 3.73 × 10⁻⁵). Mediation analysis showed that the SA of insula was identified as a partial mediator in the protective effect of household income against ADHD prevalence, with a mediation ratio of 5.6%. Concerning potential causal relationships between IDPs and ADHD, reduced total brain SA increased ADHD risk (OR = 0.77, p = 5.60 × 10⁻⁹), while reduced the TH of lateral occipital was protective (OR = 1.54, p = 2.02 × 10⁻⁴).

Conclusions:

SES influences ADHD through brain structural changes, offering insights for prevention and intervention strategies.