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Aberrant basal ganglia metabolism in fragile X syndrome: a magnetic resonance spectroscopy study

Jennifer Lynn Bruno1, Elizabeth Walter Shelly1, Eve-Marie Quintin1, Maryam Rostami1, Sweta Patnaik1, Daniel Spielman2, Dirk Mayer23, Meng Gu2, Amy A Lightbody1 and Allan L Reiss124*

Author Affiliations

1 Center for Interdisciplinary Brain Sciences Research, Stanford University, 401 Quarry Road, Stanford, CA 94305-5795, USA

2 Department of Radiology, Stanford University, 300 Pasteur Drive, Stanford, CA 94305-5105, USA

3 Neuroscience Program, SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025-3493, USA

4 Department of Pediatrics, Stanford University, 300 Pasteur Drive, Stanford, CA 94305-5208, USA

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Journal of Neurodevelopmental Disorders 2013, 5:20  doi:10.1186/1866-1955-5-20

Published: 28 August 2013



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.


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.


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.


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.

Fragile X syndrome; Magnetic resonance spectroscopy; Choline; Glutamate; Caudate nucleus