Ocular and neural genes jointly regulate the visuospatial working memory in ADHD children

Area of Science:

• Neurogenetics
• Psychiatric Genetics
• Cognitive Neuroscience

Background:

• Working memory (WM) deficits are common in attention deficit hyperactivity disorder (ADHD).
• The genetic underpinnings of WM, particularly in ADHD, remain largely uncharacterized.
• Previous research suggests a significant heritability for WM

Purpose of the Study:

• To comprehensively investigate the genetic basis of visual-spatial working memory (VSWM) in individuals with ADHD.
• To utilize a wide range of genetic analyses to identify specific genetic factors influencing VSWM in ADHD.

Main Methods:

• Recruited 802 individuals meeting DSM-IV ADHD diagnostic criteria.
• Assessed VSWM using the Rey-Osterrieth Complex Figure Test (RCFT), measuring detail delayed (DD), structure delayed (SD), structure immediate (SI), and detail immediate (DI) memory indexes.
• Conducted multi-level genetic analyses including SNP, gene, pathway, polygenic risk score (PRS), and protein network analyses, using PRS derived from ADHD and other psychiatric disorders.

Main Results:

• Single-marker analyses did not yield significant results.
• Gene-based analysis identified RAB11FIP1 associated with DD scores (P=1.96E-06).
• Pathway analyses revealed enrichment in forebrain neuron fate commitment for DD (P=4.78E-04) and dopamine transport for SD (P=5.90E-04).
• A significant negative correlation was observed between DD scores and ADHD PRS (P=0.0025).

Conclusions:

• Emphasized the combined role of ocular and neural genes in VSWM regulation.
• Revealed a shared genetic basis between ADHD and VSWM, with ADHD-related genes implicated.
• Demonstrated a significant relationship between ADHD PRS and VSWM performance, suggesting implications for clinical practice and future research.