TY - JOUR
T1 - Maternal serotonin transporter genotype and offsprings' clinical and cognitive measures of ADHD and ASD
AU - Hanswijk, Sabrina I.
AU - van Rooij, Daan
AU - Oosterlaan, Jaap
AU - Luman, Marjolein
AU - Hoekstra, Pieter J.
AU - Hartman, Catharina A.
AU - Franke, Barbara
AU - Sprooten, Emma
AU - Homberg, Judith R.
AU - Buitelaar, Jan K.
N1 - Publisher Copyright:
© 2021
PY - 2021/8/30
Y1 - 2021/8/30
N2 - 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.
AB - 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.
KW - 5-HTTLPR
KW - Attention-deficit/hyperactivity disorder
KW - Autism spectrum disorder
KW - Maternal effects
KW - rs25531
UR - https://www.scopus.com/pages/publications/85106960454
U2 - 10.1016/j.pnpbp.2021.110354
DO - 10.1016/j.pnpbp.2021.110354
M3 - Article
C2 - 34000292
AN - SCOPUS:85106960454
SN - 0278-5846
VL - 110
JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry
JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry
M1 - 110354
ER -