title: Aberrant basal ganglia metabolism in fragile X syndrome: a magnetic resonance spectroscopy study.
abstract: BACKGROUND
  The profile of cognitive and behavioral variation observed in individuals with fragile X syndrome (FXS), the most common known cause of inherited intellectual impairment, suggests aberrant functioning of specific brain systems. Research investigating animal models of FXS, characterized by limited or lack of fragile X mental retardation protein, (FMRP), has linked brain dysfunction to deficits in the cholinergic and glutamatergic systems. Thus, we sought to examine in vivo levels of neurometabolites related to cholinergic and glutamatergic functioning in males and females with FXS.
  
  
  METHODS
  The study participants included 18 adolescents and young adults with FXS, and a comparison group of 18 individuals without FXS matched for age, sex and general intellectual functioning. Proton magnetic resonance spectroscopy (MRS) was used to assess neurometabolite levels in the caudate nucleus, a region known to be greatly enlarged and involved in abnormal brain circuitry in individuals with FXS. A general linear model framework was used to compare group differences in metabolite concentration.
  
  
  RESULTS
  We observed a decrease in choline (P = 0.027) and in glutamate + glutamine (P = 0.032) in the caudate nucleus of individuals with FXS, relative to individuals in the comparison group.
  
  
  CONCLUSIONS
  This study provides evidence of metabolite differences in the caudate nucleus, a brain region of potential importance to our understanding of the neural deficits underlying FXS. These metabolic differences may be related to aberrant receptor signaling seen in animal models. Furthermore, identification of the specific neurometabolites involved in FXS dysfunction could provide critical biomarkers for the design and efficacy tracking of disease-specific pharmacological treatments.
authors: Center for Interdisciplinary Brain Sciences Research, Stanford University, 401 Quarry Road, Stanford, CA 94305-5795, USA. areiss1@stanford.edu.
authors: Jennifer Lynn
authors: JL
authors: Bruno
authors: Elizabeth Walter
authors: EW
authors: Shelly
authors: Eve-Marie
authors: EM
authors: Quintin
authors: Maryam
authors: M
authors: Rostami
authors: Sweta
authors: S
authors: Patnaik
authors: Daniel
authors: D
authors: Spielman
authors: Dirk
authors: D
authors: Mayer
authors: Meng
authors: M
authors: Gu
authors: Amy A
authors: AA
authors: Lightbody
authors: Allan L
authors: AL
authors: Reiss
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