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

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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.

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Acknowledgements

We would like to thank the research participants and their families; Marilyn Juarez for data analysis help, Lisa Cordeiro and Jennifer Cogswell for assistance in scheduling and testing; Louise Gane for assistance with recruitment; Kylee Cook for help with data entry and management and Charles DeCarli for the use of his hippocampal tracing protocol. Funding from the National Institutes of health Grants HD02274 and HD36071 (R.J.H.) and MH77554 (D.H.) and MH078041 (D.H. and S.M.R.) supported this work.

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Authors and Affiliations

  1. Medical Investigation of Neurodevelopmental Disorders (M.I.N.D.) Institute, University of California-Davis, Medical Center, Sacramento, USA

    Kami Koldewyn, David Hessl, John Adams, Flora Tassone, Paul J. Hagerman, Randi J. Hagerman & Susan M. Rivera

  2. Center for Mind and Brain, University of California-Davis, 202 Cousteau Place, Davis, CA, 95618, USA

    Kami Koldewyn & Susan M. Rivera

  3. Department of Psychology, University of California-Davis, Davis, CA, USA

    Susan M. Rivera

  4. Department of Psychiatry and Behavioral Sciences, University of California-Davis, Medical Center, Sacramento, USA

    David Hessl

  5. Department of Biochemistry and Molecular Medicine, University of California-Davis, School of Medicine, Sacramento, USA

    Flora Tassone & Paul J. Hagerman

  6. Department of Pediatrics, University of California-Davis, Medical Center, Sacramento, USA

    Randi J. Hagerman

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  1. Kami Koldewyn
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  2. David Hessl
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Correspondence to Susan M. Rivera.

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Koldewyn, K., Hessl, D., Adams, J. et al. Reduced Hippocampal Activation During Recall is Associated with Elevated FMR1 mRNA and Psychiatric Symptoms in Men with the Fragile X Premutation. Brain Imaging and Behavior 2, 105–116 (2008). https://doi.org/10.1007/s11682-008-9020-9

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  • DOI: https://doi.org/10.1007/s11682-008-9020-9

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