Archival ReportDecreased Fragile X Mental Retardation Protein Expression Underlies Amygdala Dysfunction in Carriers of the Fragile X Premutation
Section snippets
Participants
Participants included 23 men with the FMR1 premutation (mean age 32.9 years) and 25 matched control subjects (mean age 30.1 years). FMR1 DNA testing was used to confirm allele status for all participants. None of the participants with the premutation were mosaic for either repeat size or methylation—all had between 55 and 200 CGG repeats with no methylation. The control group was matched for age, IQ, level of education, handedness, psychoactive medication use, and ethnicity. Group demographic
Results
Participant FMR1 genetic, demographic, and clinical descriptive statistics are shown in Table 1. The FMRP distribution was positively skewed and therefore log-transformed to achieve normality. Fragile X mental retardation protein was reduced by 12% in the premutation group relative to control subjects, t(38) = 2.19, p < .034. Premutation carriers had significantly higher ADOS total scores than control subjects, with mean level (5.87) somewhat below the autism spectrum cutoff (7). Two control
Discussion
The results of this study demonstrate that relative to control subjects, men with an FMR1 premutation allele had smaller amygdala volumes and reduced amygdala activation during an emotion-matching task. In contrast to our prior study (18), in this investigation, we were able to determine that aberrant amygdala function was more strongly associated with reduced FMRP (the cause of FXS) than abnormal elevation of FMR1 mRNA (the hypothesized toxic mRNA gain-of-function model underlying FXTAS). To
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