title: Depression and anxiety symptoms among women who carry the FMR1 premutation: impact of raising a child with fragile X syndrome is moderated by CRHR1 polymorphisms.
abstract: The fragile X mental retardation gene, FMR1, contains a polymorphic CGG repeat in the 5'-untranslated region of exon 1. Once unstable, this repeat is capable of expansion across generations. Women who carry a premutation allele (55-199 repeats) are at risk of passing on a full mutation allele (>200 repeats) to their offspring. A full mutation leads to the most common form of inherited intellectual disability, fragile X syndrome (FXS). Mounting evidence suggests that premutation carriers may be vulnerable to symptoms of anxiety and depression. The goal of this study was to test the hypothesis that among women who carry a premutation, the stress of raising a child with FXS would be moderated by genetic factors influencing endogenous cortisol responses, which could in turn modulate anxiety and depression symptoms. To this end, we genotyped single nucleotide polymorphisms (SNPs) at the corticotrophin releasing hormone receptor 1 locus (CRHR1) in 460 women. Participants completed self-report questionnaires assessing symptoms of depression [Centers for Epidemiological Studies Depression Scale (CESD)], anxiety [State-Trait Anxiety Inventory (STAI) and Social Phobia and Anxiety Inventory (SPAI)], and mood [Positive and Negative Affect Schedule (PANAS)]. Results indicate a statistically significant interaction between CRHR1 genotype and the status of raising a child with FXS to predict social anxiety symptoms reported on the SPAI (rs7209436, P = 0.0001). Our data suggest that genetic variants in CRHR1 that associate with differential cortisol activation may also modulate levels of anxiety related to the stress of raising a child with FXS among women who carry an FMR1 premutation.
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: Jessica Ezzell
authors.initials: JE
authors.lastname: Hunter
authors.forename: Mary
authors.initials: M
authors.lastname: Leslie
authors.forename: Gloria
authors.initials: G
authors.lastname: Novak
authors.forename: Debra
authors.initials: D
authors.lastname: Hamilton
authors.forename: Lisa
authors.initials: L
authors.lastname: Shubeck
authors.forename: Krista
authors.initials: K
authors.lastname: Charen
authors.forename: Ann
authors.initials: A
authors.lastname: Abramowitz
authors.forename: Michael P
authors.initials: MP
authors.lastname: Epstein
authors.forename: Adriana
authors.initials: A
authors.lastname: Lori
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Binder
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Cubells
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Sherman
mesh_terms: D000293:Adolescent; D000328:Adult; D001007:Anxiety / Q000150:complications / Q000235:genetics*; D002648:Child; D002668:Child Rearing; D003710:Demography; D003863:Depression / Q000150:complications / Q000235:genetics*; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010555:Personality Inventory; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics*; D000099052:CRF Receptor, Type 1
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; C497683:FMR1 protein, human