Differentiating ADHD and oppositional defiant disorder through Synapsin III gene polymorphisms and neurocognitive...

This study investigated the genetic and neurocognitive distinctions between the cases with Attention-Deficit/Hyperactivity Disorder (ADHD)-only, ADHD+ Oppositional Defiant Disorder (ODD), and typically developing controls (TDCs) by analyzing Synapsin (SYN) III gene polymorphisms and neurocognitive profiles. A total of 59 children with ADHD only, 42 children with ADHD+ODD, and 100 TDCs were evaluated through comprehensive genotyping of SYN III gene polymorphisms, a neurocognitive assessment using CNS Vital Signs test battery, an IQ evaluation, and a semi-structured psychiatric interview. Parents completed the Turgay ADHD Rating Scale IV. The presence of rs133946 C/G in the second haplotype was significantly less prevalent in ADHD+ODD cases (p < 0.001). The absence of C/G haplotype in SYN III rs133946 polymorphism was significantly associated with a heightened risk of ADHD+ODD (β = 2.49, OR = 12.14, p = 0.001) compared to ADHD-only. Neurocognitive analyses revealed that individuals having more rs133946 polymorphism C/G haplotype units exhibited higher Stroop Test-Simple Reaction Time scores (β = 49.50, p = 0.044), despite shared executive function and memory impairments across ADHD groups. However, there were no statistically significant direct differences between ADHD-only and ADHD+ODD groups across all neurocognitive test scores, although both clinical groups differed from TDCs in distinct ways across several tests. The findings suggest that the absence of C/G haplotype in the SYN III rs133946 polymorphism may serve as a genetic marker for ODD comorbidity in ADHD. Although the counter-intuitive association between the absence of C/G haplotype, faster reaction times, and ODD comorbidity may seem beneficial on the surface, it may be one of the potential underlying mechanisms of increased impulsivity or reduced inhibitory control in children with ADHD+ODD.