Reduced Hippocampal Activation During Recall is Associated with Elevated FMR1 mRNA and Psychiatric Symptoms in Men with the Fragile X Premutation

Abstract

Recent studies reveal that young carriers of the fragile X premutation are at increased risk for psychiatric conditions, memory problems and executive deficits. Post mortem and structural MRI studies suggest the hippocampus is preferentially affected by the premutation. The current study utilized magnetic resonance imaging (MRI) to explore the relationship between hippocampal structure and function as well as molecular/genetic and psychiatric measures in men with the fragile X premutation. Although the groups did not differ in hippocampal volume, the premutation group showed reduced left hippocampal activation and increased right parietal activation during a recall task relative to controls. These results suggest that brain function underlying memory recall is affected by premutation status. Left hippocampal activation was negatively correlated with both FMR1 mRNA level and psychiatric symptomology in the premutation group. These associations support the theory that increased levels of FMR1 mRNA affect brain function and contribute to psychiatric symptoms.