Document Detail


Polymorphisms in the maternal sex steroid pathway are associated with behavior problems in male offspring.
MedLine Citation:
PMID:  22336992     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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).
CONCLUSION: 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:
Amir Miodovnik; Andreas I Diplas; Jia Chen; Chenbo Zhu; Stephanie M Engel; Mary S Wolff
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Psychiatric genetics     Volume:  22     ISSN:  1473-5873     ISO Abbreviation:  Psychiatr. Genet.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-04-24     Completed Date:  2012-08-15     Revised Date:  2014-04-03    
Medline Journal Info:
Nlm Unique ID:  9106748     Medline TA:  Psychiatr Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  115-22     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Cohort Studies
Cytochromes / genetics*
Female
Gonadal Steroid Hormones / metabolism*
Humans
Male
Mental Disorders / genetics*
Polymorphism, Genetic*
Steroids / metabolism*
Grant Support
ID/Acronym/Agency:
5T32HD049311/HD/NICHD NIH HHS; ES09584/ES/NIEHS NIH HHS; P01 ES009584/ES/NIEHS NIH HHS; P01 ES009584-10/ES/NIEHS NIH HHS; T32 HD049311-05/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Cytochromes; 0/Gonadal Steroid Hormones; 0/Steroids
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