title: Molecular biomarkers predictive of sertraline treatment response in young children with fragile X syndrome.
abstract: OBJECTIVE
  Several neurotransmitters involved in brain development are altered in fragile X syndrome (FXS), the most common monogenic cause of autism spectrum disorder (ASD). Serotonin plays a vital role in synaptogenesis and postnatal brain development. Deficits in serotonin synthesis and abnormal neurogenesis were shown in young children with autism, suggesting that treating within the first years of life with a selective serotonin reuptake inhibitor might be the most effective time. In this study we aimed to identify molecular biomarkers involved in the serotonergic pathway that could predict the response to sertraline treatment in young children with FXS.
  
  
  METHODS
  Genotypes were determined for several genes involved in serotonergic pathway in 51 children with FXS, ages 24-72months. Correlations between genotypes and deviations from baseline in primary and secondary outcome measures were modeled using linear regression models.
  
  
  RESULTS
  A significant association was observed between a BDNF polymorphism and improvements for several clinical measures, including the Clinical Global Impression scale (P=0.008) and the cognitive T score (P=0.017) in those treated with sertraline compared to those in the placebo group. Additionally, polymorphisms in the MAOA, Cytochrome P450 2C19 and 2D6, and in the 5-HTTLPR gene showed a significant correlation with some of the secondary measures included in this study.
  
  
  CONCLUSIONS
  This study shows that polymorphisms of genes involved in the serotonergic pathway could play a potential role in predicting response to sertraline treatment in young children with FXS. Larger studies are warranted to confirm these initial findings.
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California, Davis, School of Medicine, Davis, CA, USA.
authors.forename: Reem Rafik
authors.initials: RR
authors.lastname: AlOlaby
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California, Davis, School of Medicine, Davis, CA, USA.
authors.forename: Stefan R
authors.initials: SR
authors.lastname: Sweha
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California, Davis, School of Medicine, Davis, CA, USA.
authors.forename: Marisol
authors.initials: M
authors.lastname: Silva
authors.affiliation: Department of Biostatistics, University of California, Davis, School of Medicine, Davis, CA, USA.
authors.forename: Blythe
authors.initials: B
authors.lastname: Durbin-Johnson
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California, Davis, School of Medicine, Davis, CA, USA.
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Yrigollen
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California, Davis, School of Medicine, Davis, CA, USA.
authors.forename: Dalyir
authors.initials: D
authors.lastname: Pretto
authors.affiliation: MIND Institute, University of California Davis Medical Center, Davis, CA, USA; Department of Pediatrics, University of California, Davis, School of Medicine, Davis, CA, USA.
authors.forename: Randi J
authors.initials: RJ
authors.lastname: Hagerman
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California, Davis, School of Medicine, Davis, CA, USA; MIND Institute, University of California Davis Medical Center, Davis, CA, USA. Electronic address: ftassone@ucdavis.edu.
authors.forename: Flora
authors.initials: F
authors.lastname: Tassone
mesh_terms: D000067877:Autism Spectrum Disorder / Q000188:drug therapy* / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D005600:Fragile X Syndrome / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008995:Monoamine Oxidase / Q000235:genetics / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D020280:Sertraline / Q000627:therapeutic use*; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D003577:Cytochrome P-450 Enzyme System; D020780:Matrix Metalloproteinase 9; D008995:Monoamine Oxidase; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; C493230:SLC6A4 protein, human; C579458:monoamine oxidase A, human
keywords: BDNF; Cytochrome P450; Fragile X syndrome; Molecular biomarkers; Neurotransmitters; Selective serotonin reuptake inhibitor; Serotonin; Sertraline