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A very high proportion of individuals with fragile X syndrome (FXS) (FMR1 full mutation, &gt; 200 CGG repeats) experience clinically significant anxiety. Recent evidence suggests that adult fragile X premutation carriers (55-200 CGG repeats) also are at risk for anxiety disorders, and they demonstrate limbic system alterations mediated by FMRP and/or elevated FMR1 mRNA that may explain this heightened risk. However, less is known about psychiatric symptoms including anxiety among children and adolescents with the premutation. We completed structured DSM-IV based diagnostic interviews focused on current anxiety in 35 children, adolescents or young adults with the premutation (ages 5-23 years, M = 11.3 ± 4.3; 27 male; 20 probands and 15 non-probands) and 31 controls (ages 5-18 years, M = 9.9 ± 3.6; 22 males). Among premutation carriers, 70.6% met criteria for at least one anxiety disorder (most frequently generalized anxiety disorder, specific phobia, social phobia, or obsessive compulsive disorder), compared to 22.6% of controls and 9.8% of the general population in this age range. Premutation carriers with intellectual disability, male gender, and proband status were associated with the highest rates of anxiety disorders. However, non-probands did have higher rates of having any anxiety disorder (40.0%) compared to general population norms. Although the results implicate anxiety as a target of screening and intervention among youth with the premutation, larger studies of unselected samples from the population of premutation carriers are needed to confirm and specify the degree and extent of psychiatric disorders in this condition.

Anxiety disorders in fragile X premutation carriers: Preliminary characterization of probands and non-probands