title: Polymorphisms in the maternal sex steroid pathway are associated with behavior problems in male offspring.
abstract: OBJECTIVE
  Slight perturbations in maternal sex steroid production and metabolism may interfere with normal fetal neurodevelopment. The balance of maternal estrogens and androgens may have direct fetal effects, may influence the fetal hypothalamic-pituitary-gonadal axis, or may alter local hormonal activity within the fetal brain. We investigated maternal functional polymorphisms of CYP17, CYP19, and CYP1B1, which control three major enzymatic steps in sex steroid biosynthesis and metabolism, in relation to childhood behaviors.
  
  
  METHODS
  The Mount Sinai Children's Environmental Health Study enrolled a multiethnic urban pregnancy cohort from 1998 to 2002 (n=404). DNA was obtained from maternal blood (n=149) and from neonatal cord blood (n=53). At each visit, mothers completed the Behavior Assessment System for Children, a parent-reported questionnaire used to evaluate children for behavior problems. We focused on problem behaviors more commonly associated with attention deficit-hyperactivity disorder (Hyperactivity, Attention Problems, Externalizing Behaviors, Conduct Disorder, Poor Adaptability) to determine whether maternal genetic variants in sex steroid production and metabolism influence sexually dimorphic behaviors in offspring.
  
  
  RESULTS
  The more active gene variants were significantly associated with Attention Problems and poorer Adaptive Skills in male compared with female offspring. The CYP19 variant allele was also significantly associated with worse scores for boys on the Hyperactivity, Externalizing Problems Composite, and Adaptive Skills Composite scales (P<0.05).
  
  
  CONCLUSIONS
  We observed maladaptive behaviors in the male offspring of mothers who carried functional polymorphisms in the sex steroid pathway. The strongest associations were in domains commonly affected in attention deficit-hyperactivity disorder.
authors.affiliation: Department of Preventive Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, PO Box 1057, New York, NY 10029, USA. amir.miodovnik@mssm.edu
authors.forename: Amir
authors.initials: A
authors.lastname: Miodovnik
authors.forename: Andreas I
authors.initials: AI
authors.lastname: Diplas
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.forename: Chenbo
authors.initials: C
authors.lastname: Zhu
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Engel
authors.forename: Mary S
authors.initials: MS
authors.lastname: Wolff
mesh_terms: D015331:Cohort Studies; D003580:Cytochromes / Q000235:genetics*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000235:genetics*; D011110:Polymorphism, Genetic; D013256:Steroids / Q000378:metabolism*
chemical_list: D003580:Cytochromes; D012739:Gonadal Steroid Hormones; D013256:Steroids