Role of SNAP‐25 MnlI variant in impaired working memory and brain functions in attention deficit/hyperactivity disorder

• Published in: Brain and behavior Vol. 12; no. 10; pp. e2758 - n/a
• Main Authors: Fang, Diangang, Yang, Binrang, Wang, Peng, Mo, Tong, Gan, Yungen, Liang, Guohua, Huang, Rong, Zeng, Hongwu
• Format: Journal Article
• Language: English
• Published: Los Angeles John Wiley & Sons, Inc 01-10-2022; John Wiley and Sons Inc; Wiley
• Subjects: ADHD; Attention deficit hyperactivity disorder; brain function; Children & youth; Dopamine; Gene expression; Hyperactivity; Magnetic resonance imaging; Memory; Mental disorders; Neurodevelopmental disorders; Original; Proteins; SNAP‐25; Time series; working memory; China
• ISSN: 2162-3279; 2162-3279
• DOI: 10.1002/brb3.2758

Introduction
Attention deficit/hyperactivity disorder (ADHD) is a hereditary neurodevelopmental disorder characterized by working memory (WM) deficits. The MnlI variant (rs3746544) of the synaptosomal‐associated protein 25 (SNAP‐25) gene is associated with ADHD. In this study, we investigated the role and underlying mechanism of SNAP‐25 MnlI variant in cognitive impairment and brain functions in boys with ADHD.
Method
We performed WM capacity tests using the fourth version of the Wechsler Intelligence Scale for Children (WISC‐IV) and regional homogeneity (ReHo) analysis for the resting‐state functional magnetic resonance imaging data of 56 boys with ADHD divided into two genotypic groups (TT homozygotes and G‐allele carriers). Next, Spearman's rank correlation analysis between the obtained ReHo values and the WM index (WMI) calculated for each participant.
Results
Compared with G‐allele carrier group, there were higher ReHo values for the left medial prefrontal cortex (mPFC) and higher WM capacity in TT homozygote group. Contrary to TT homozygote group, the WM capacity was negatively correlated with the peak ReHo value for the left mPFC in G‐allele carrier group.
Conclusion
These findings suggest that SNAP‐25 MnlI variant may underlie cognitive and brain function impairments in boys with ADHD, thus suggesting its potential as a new target for ADHD treatment.