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Investigation of Phenotypes Associated with Mood and Anxiety Among Male and Female Fragile X Premutation Carriers

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Abstract

The fragile X disorder spectrum, due to a CGG expansion in FMR1, includes fragile X syndrome (>200 repeats) and the premutation-associated disorders of ovarian insufficiency and tremor/ataxia syndrome (~55–199 repeats). Altered neurobehavioral profiles including variation of phenotypes associated with mood and anxiety may be expected among younger premutation carriers given this spectrum of disorders. However, previous studies have produced conflicting findings, providing the motivation to examine these phenotypes further. We investigated measures of mood and anxiety in 119 males and 446 females age 18–50 ascertained from families with a history of fragile X syndrome and from the general population. Scores were analyzed using a linear model with repeat length as the main predictor, adjusting for potential confounders. Repeat length was not associated with anxiety, but was marginally associated with depression and negative affect in males and negative affect only in females. These results suggest that premutation carriers may be at risk for emotional morbidity; however, phenotypic differences were subtle and of small effect size.

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Acknowledgements

We would like to thank Dr. David Kleinbaum for his assistance in the statistical analysis as well as Weiya He and Maneesha Yadav-Shah for their laboratory assistance. Importantly, we want to dedicate this work to Dr. Rick Letz who helped develop the testing battery and analyze the initial data set. This project could not have been accomplished without his significant input. Finally we would like to thank the study participants who made this work possible. This work was supported by the National Institutes of Health grant R01 HD29909.

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Correspondence to Stephanie L. Sherman.

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Edited by Pierre Roubertoux.

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Hunter, J.E., Allen, E.G., Abramowitz, A. et al. Investigation of Phenotypes Associated with Mood and Anxiety Among Male and Female Fragile X Premutation Carriers. Behav Genet 38, 493–502 (2008). https://doi.org/10.1007/s10519-008-9214-3

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