Molecular biomarkers predictive of sertraline treatment response in young children with fragile X syndrome

Reem Rafik AlOlaby, Stefan R. Sweha, Marisol Silva, Blythe Durbin-Johnson, Carolyn M. Yrigollen, Dalyir Pretto, Randi J Hagerman, Flora Tassone

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Objectives: 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 24-72. months. 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. Conclusion: 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.

Original languageEnglish (US)
JournalBrain and Development
DOIs
StateAccepted/In press - Nov 16 2016

Keywords

  • BDNF
  • Cytochrome P450
  • Fragile X syndrome
  • Molecular biomarkers
  • Neurotransmitters
  • Selective serotonin reuptake inhibitor
  • Serotonin
  • Sertraline

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Developmental Neuroscience
  • Clinical Neurology

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