title: Beyond classical inheritance: the influence of maternal genotype upon child's brain morphology and behavior.
abstract: Genetic variance has been associated with variations in brain morphology, cognition, behavior, and disease risk. One well studied example of how common genetic variance is associated with brain morphology is the serotonin transporter gene polymorphism within the promoter region (5-HTTLPR). Because serotonin is a key neurotrophic factor during brain development, genetically determined variations in serotonin activity during maturation, in particular during early prenatal development, may underlie the observed association. However, the intrauterine microenvironment is not only determined by the child's, but also the mother's genotype. Therefore, we hypothesized that maternal 5-HTTLPR genotype influences the child's brain development beyond direct inheritance. To test this hypothesis, we investigated 76 children who were all heterozygous for the 5-HTTLPR (sl) and who had mothers who were either homozygous for the long (ll) or the short allele (ss). Using MRI, we assessed brain morphology as a function of maternal genotype. Gray matter density of the somatosensory cortex was found to be greater in children of ss mothers compared with children of ll mothers. Behavioral assessment showed that fine motor task performance was altered in children of ll mothers and the degree of this behavioral effect correlated with somatosensory cortex density across individuals. Our findings provide initial evidence that maternal genotype can affect the child's phenotype beyond effects of classical inheritance. Our observation appears to be explained by intrauterine environmental differences or by differences in maternal behavior.
authors.affiliation: Donders Institute for Brain, Cognition, and Behaviour, Department of Cognitive Neuroscience, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands, and N.vanderknaap@donders.ru.nl.
authors.forename: Noortje J F
authors.initials: NJ
authors.lastname: van der Knaap
authors.affiliation: Department of Child and Adolescent Psychiatry, Generation R Study Group.
authors.forename: Hanan
authors.initials: H
authors.lastname: El Marroun
authors.affiliation: Donders Institute for Brain, Cognition, and Behaviour, Department of Cognitive Neuroscience, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands, and.
authors.forename: Floris
authors.initials: F
authors.lastname: Klumpers
authors.affiliation: Department of Child and Adolescent Psychiatry, Generation R Study Group.
authors.forename: Sabine E
authors.initials: SE
authors.lastname: Mous
authors.affiliation: Generation R Study Group, Department of Epidemiology, Department of Pediatrics, Erasmus Medical Centre, 3000 CB Rotterdam, The Netherlands.
authors.forename: Vincent W V
authors.initials: VW
authors.lastname: Jaddoe
authors.affiliation: Generation R Study Group, Department of Epidemiology.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: Donders Institute for Brain, Cognition, and Behaviour, Department of Cognitive Neuroscience, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands, and.
authors.forename: Judith R
authors.initials: JR
authors.lastname: Homberg
authors.affiliation: Department of Child and Adolescent Psychiatry, Department of Radiology, and.
authors.forename: Tonya
authors.initials: T
authors.lastname: White
authors.affiliation: Department of Child and Adolescent Psychiatry, Generation R Study Group, Department of Epidemiology.
authors.forename: Henning
authors.initials: H
authors.lastname: Tiemeier
authors.affiliation: Donders Institute for Brain, Cognition, and Behaviour, Department of Cognitive Neuroscience, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands, and.
authors.forename: Guillén
authors.initials: G
authors.lastname: Fernández
mesh_terms: D001921:Brain / Q000033:anatomy & histology / Q000254:growth & development*; D002648:Child; D002652:Child Behavior / Q000502:physiology*; D018672:Community Health Planning; D005260:Female; D007839:Functional Laterality; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009034:Mother-Child Relations; D009035:Mothers; D009426:Netherlands; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic / Q000235:genetics*; D011597:Psychomotor Performance / Q000502:physiology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D018709:Statistics, Nonparametric
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins
keywords: child; development; gray matter density; maternal genotype; serotonin transporter polymorphism; somatosensory cortex