title: High rates of comorbid depressive and anxiety disorders among women with premutation of the FMR1 gene.
abstract: Phenotypic variations are emerging from investigations of carriers of the fragile X mental retardation 1 (FMR1) premutation gene (55 to 200 CGG repeats). Initial studies suggest elevated psychiatric and reproductive system dysfunction, but have largely used self-reports for assessment of psychiatric history. The present study used diagnostic psychiatric interviews and assessed reproductive and menstrual history in women with FMR1 premutation. History of psychiatric diagnoses and data on reproductive functioning were collected in 46 women with FMR1 premutation who were mothers of at least one child with the fragile X full mutation. Results showed a significantly earlier age of menopause (mean age = 45.6 years) relative to the national average age of menopause (mean age = 51 years) and a high rate (76%) of lifetime depressive or anxiety history, with 43% of the overall sample reporting a comorbid history of both diagnoses. Compared to those free of psychiatric history, significantly longer premutation length was observed among women with psychiatric history after adjusting for age, with comorbid women having the highest number of CGG repeats (mean = 95.8) compared to women free of psychiatric history (mean = 79.9). Psychiatric history did not appear significantly related to reproductive system dysfunction, though results may have been obscured by the high rates of psychiatric dysfunction in the sample. These data add to the growing evidence base that women with the FMR1 premutation have an increased risk of psychiatric illness and risk for early menopause. Future investigations may benefit from inclusion of biochemical reproductive markers and longitudinal assessment of psychiatric and reproductive functioning.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Kenna
authors.forename: Molly
authors.initials: M
authors.lastname: Tartter
authors.forename: Scott S
authors.initials: SS
authors.lastname: Hall
authors.forename: Amy A
authors.initials: AA
authors.lastname: Lightbody
authors.forename: Quynh
authors.initials: Q
authors.lastname: Nguyen
authors.forename: C Paula
authors.initials: CP
authors.lastname: de los Angeles
authors.forename: Allan L
authors.initials: AL
authors.lastname: Reiss
authors.forename: Natalie L
authors.initials: NL
authors.lastname: Rasgon
mesh_terms: D000328:Adult; D001008:Anxiety Disorders / Q000150:complications / Q000453:epidemiology* / Q000235:genetics*; D015897:Comorbidity; D003863:Depression / Q000150:complications / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D014481:United States / Q000453:epidemiology
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human
keywords: FMR1 premutation; anxiety; depressive disorders; menopause; women