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Maternal serotonin transporter genotype and offsprings' clinical and cognitive measures of ADHD and ASD
Sabrina I Hanswijk1, Daan van Rooij2, Jaap Oosterlaan3
1Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen Medical Center, Kapittelweg 29, 6525 EN Nijmegen, the Netherlands.
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.
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.
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