MedicalResearch.com Interview with: Alex Leow, MD PhD Psychiatric Institute Chicago, IL 60612 and   Tony J. Simon, PhD University of California, Davis MIND Institute Sacramento, CA 95817 MedicalResearch.com: What are the main findings of the study? Answer: Fragile X syndrome (FXS) is the most common inherited cause of intellectual disabilities and the most prevalent known single-gene cause of autism in males. The fragile X mental retardation 1 gene (FMR1) can be mutated with expanded numbers of CGG trinucleotide repeats in the 5’ untranslated region on the Xq27.3 site of the X chromosome. Normally, unaffected individuals have fewer than 45 CGG repeats in FMR1. When the size of the CGG repeat exceeds 200 FMR1 is silenced and the mutation is categorized as full, generating the FXS phenotype. If the expansion is between 55–200 repeats, then the individual is generally classified as a fragile X premutation carrier (fXPC). An estimated 40% of male and 8-16% of female premutation carriers later develop Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS), which is a late-onset (usually 50-70 years old) neurodegenerative disorder. We recruited 46 neurologically symptomless young to middle aged carriers of the FMR1 gene mutation. They were age and gender matched with 42 unaffected control individuals without the gene mutation. Both groups were evaluated by cognitive testing as well as novel neuroimaging techniques termed “brain connectomics,” based on diffusion tensor imaging (DTI) whole-brain tractography.  A connectome is a comprehensive map, like a wiring diagram, of neural connections in the brain. Our study is the first-ever connectome study to compare fXPCs and controls. In short, brain connectomics enable scientists for the first time to study the global organizational properties of the human brain by applying cutting edge computational techniques, based on graph theory, to these comprehensive maps of neural connections (i.e., the brain graphs). Our main finding was that, in neurologically symptomless male carriers  we detected a correlation between brain graphs’ efficiency in processing information and the number of CGG repeats in the mutated region of FMR1 (we estimated that each additional CGG repeat that in these males represents an effective increase of ~1.5 years  of “brain aging”). The correlation may prove to be an effective marker of early brain aging in otherwise neurologically symptomless premutation carriers. The study also further confirmed previous findings of smaller brain stem volumes in male fXPCS than in male controls. (more…)