Journal of affective disorders · 2026
Putamen function and MAOA genotype define genetic and neural subtypes of hyperactivity-impulsivity in ADHD.
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Feng Yuan, Gao Yuan, Liu Qianrong, Zhu Yu, Dang Chen, Wu Guisen, Zhong Shaogen, Shi Naizhen, Lin Xindi, Zhu Ziqing, Ju Changxi, Zhang Huiyi, Sui Jing, Liu Lu, Sun Li
Аннотация
BACKGROUND: Hyperactivity-impulsivity (HI) is a core ADHD symptom associated with the monoamine oxidase A (MAOA) gene. The neurobiological mechanisms underlying HI heterogeneity in children carrying the MAOA risk genotype remain unclear and may involve distinct subtypes.
METHODS: A total of 326 children with ADHD were genotyped for MAOA, including 108 non-risk and 218 risk carriers. Semi-supervised clustering of HI and executive function (EF) scores from the ADHD Rating Scale, Conners' Rating Scale, and BRIEF was used to classify MAOA risk carriers into subtypes, with non-risk patients as the reference. fALFF differences across subtypes, cognitive mediation between brain activity and behavior, and treatment response at follow-up were examined.
RESULTS: Two subtypes were identified among MAOA risk carriers. Compared with the non-risk group, Subtype 1 showed elevated HI and impaired EF, whereas Subtype 2 showed preserved EF and no HI elevation. Subtype 1 had increased fALFF in the inferior temporal gyrus and higher putamen fALFF than Subtype 2, while Subtype 2 showed increased fALFF in the angular gyrus relative to the non-risk group. Putamen fALFF was associated with inhibition, shifting, emotional control, and the Behavioral Regulation Index (BRI), and mediation analysis suggested an indirect effect on HI via the BRI. After 4 weeks of medication, Subtype 2 showed greater improvement in conduct problems and anxiety.
CONCLUSION: Putamen function may underlie HI heterogeneity among MAOA risk carriers and was associated with better EF, milder symptoms, and greater treatment response.
METHODS: A total of 326 children with ADHD were genotyped for MAOA, including 108 non-risk and 218 risk carriers. Semi-supervised clustering of HI and executive function (EF) scores from the ADHD Rating Scale, Conners' Rating Scale, and BRIEF was used to classify MAOA risk carriers into subtypes, with non-risk patients as the reference. fALFF differences across subtypes, cognitive mediation between brain activity and behavior, and treatment response at follow-up were examined.
RESULTS: Two subtypes were identified among MAOA risk carriers. Compared with the non-risk group, Subtype 1 showed elevated HI and impaired EF, whereas Subtype 2 showed preserved EF and no HI elevation. Subtype 1 had increased fALFF in the inferior temporal gyrus and higher putamen fALFF than Subtype 2, while Subtype 2 showed increased fALFF in the angular gyrus relative to the non-risk group. Putamen fALFF was associated with inhibition, shifting, emotional control, and the Behavioral Regulation Index (BRI), and mediation analysis suggested an indirect effect on HI via the BRI. After 4 weeks of medication, Subtype 2 showed greater improvement in conduct problems and anxiety.
CONCLUSION: Putamen function may underlie HI heterogeneity among MAOA risk carriers and was associated with better EF, milder symptoms, and greater treatment response.