Serotonin (5-HT) is an important factor for prenatal neurodevelopment whereby its neurotrophic actions can be regulated through maternal-fetal interactions. We explored if maternal 5-HTTLPR genotype is associated with clinical and cognitive measures of attention-deficit/hyperactivity disorder (ADHD) and comorbid autism spectrum disorder (ASD) in typically-developing and ADHD-diagnosed offspring, beyond classical inheritance and environmental- and comorbidity-mediators/confounders. Family-based variance decomposition analyses were performed incorporating 6–31 year-old offsprings' as well as parental genotypes of 462 ADHD and control families from the NeuroIMAGE cohort. Dependent measures were offsprings' ADHD symptom- and ASD trait-scores and cognitive measures including executive functioning (including response inhibition and cognitive flexibility), sustained attention, reward processing, motor control, and emotion recognition. Offsprings' stereotyped behavior was predicted by an interaction between maternal 5-HTTLPR genotype and offsprings' sex. Furthermore, offspring of mothers with low-expressing genotypes demonstrated larger reward-related reductions in reaction time. While specifically adult male offspring of these mothers reported a faster reversal learning with less errors, specifically young female offspring of these mothers were more accurate in identifying happy faces. Adult offspring from the mothers with low-expressing 5-HTTLPR genotypes were also slower in identifying happy faces. However, this association seemed to be mediated by offsprings' high anxiety levels. In sum, we found some support for a role of the maternal 5-HT system in modulating fetal brain development and behavior. Offsprings' cognitive measures might be more sensitive to small alterations within the maternal 5-HT system than their ADHD and ASD clinical phenotypes. Further studies are needed to specify the association between maternal genotype and risk for neurodevelopmental disorders.

血清素 (5-HT) 是产前神经发育的重要因素，其神经营养作用可以通过母胎相互作用进行调节。我们探讨了母体 5-HTTLPR 基因型是否与典型发育和被诊断为 ADHD 的后代的注意力缺陷/多动障碍 (ADHD) 和共病自闭症谱系障碍 (ASD) 的临床和认知测量相关，超越经典遗传和环境-和共病介质/混杂因素。结合来自 NeuroIMAGE 队列的 462 个 ADHD 和对照家庭的 6-31 岁后代以及父母基因型，进行了基于家庭的方差分解分析。依赖措施是后代 ADHD 症状和 ASD 特征评分和认知测量，包括执行功能（包括反应抑制和认知灵活性）、持续注意力、奖励处理、运动控制和情绪识别。后代的刻板行为是通过母体 5-HTTLPR 基因型和后代性别之间的相互作用来预测的。此外，具有低表达基因型的母亲的后代表现出更大的与奖励相关的反应时间减少。虽然这些母亲的成年男性后代报告了更快的逆向学习和更少的错误，但这些母亲的年轻女性后代在识别快乐面孔方面更准确。来自具有低表达 5-HTTLPR 基因型的母亲的成年后代在识别快乐面孔方面也较慢。然而，这种关联似乎是由后代的高焦虑水平介导的。总之，我们发现了一些支持母体 5-HT 系统在调节胎儿大脑发育和行为方面的作用。与他们的 ADHD 和 ASD 临床表型相比，后代的认知测量可能对母体 5-HT 系统内的微小变化更敏感。需要进一步的研究来明确母体基因型与神经发育障碍风险之间的关联。