Mood and anxiety disorders in females with the FMR1 premutation

Abstract

Fragile X syndrome (FXS) is a model for studying the relative contributions of genetic and environmental factors to psychiatric disorders in mothers of children with disabilities. Here, we examine the frequency and predictors of mood and anxiety disorders in mothers with the FMR1 premutation. Ninety-three females with the FMR1 premutation were in the study and were compared to 2,159 women from the National Comorbidity Survey Replication (NCS-R) dataset. Mood and anxiety disorders were assessed using the SCID-I. Our data reflect elevated lifetime major depressive disorder (MDD), lifetime panic disorder without agoraphobia and current agoraphobia without panic disorder in the FMR1 premutation sample. Also, we found a low frequency of lifetime social phobia, specific phobia, and post-traumatic stress disorders and current specific phobia in the FMR1 premutation sample. The profile of MDD in the FMR1 premutation sample was not episodic or comorbid with an anxiety disorder, as in the NCS-R dataset. Never having been married and smaller CGG repeat length were associated with increased likelihood of MDD while increased children with FXS in the family and greater child problem behaviors were associated with increased likelihood of an anxiety disorder in the FMR 1 premutation group. Major depression in females with the FMR1 premutation may not be characterized as an episodically chronic recurrent disorder as it is in community samples and may have a genetic basis given the relationship with CGG repeat length and lack of association with all child and most demographic factors.

Fragile X premutation in women: recognizing the health challenges beyond primary ovarian insufficiency

“…Regarding anxiety disorders, Roberts et al (2009) [49] found that overall, these women displayed a lower frequency of anxiety disorders, although as mentioned before, specific entities such as lifetime panic disorder without agoraphobia and agoraphobia without panic at the time of the study were more likely among carriers. This lower frequency of anxiety disorders goes against previous findings by other groups who have found that women carriers tend to have an increased risk of anxiety disorders; in fact, Franke et al (1998) [47] reported a 41% lifetime diagnosis rate of anxiety disorder among carriers with FXS children.…”

“…Unlike the findings of Roberts et al (2009) [49], Obadia et al (2013) [50], when evaluating the characteristics of postpartum depression (PPD) during a pilot study done in carriers, found that mothers of children with FXS are at higher risk for PPD than female carriers without affected children and that for each additional child with FXS, the risk more than doubled. PPD episodes in this study were linked to having children with FXS since all PPD episodes occurred after carriers had a child who was eventually diagnosed with FXS, even though the syndrome's diagnosis was usually done years later.…”

“…Nevertheless, the key to this difference may be related to the presence of affected children. Roberts et al (2009) [49] found that anxiety disorders in this population were strongly related to child variables, including the number of children with FXS and/or child problem behavior.…”

“…Specifically, about social phobia, Roberts et al (2009) [49] did not find an increase among carriers of the premutation even though authors such as Franke et al (1998) [47] reported an increased risk independent of having children with FXS. The weakness of the data provided by Franke et al (1998) [47] to draw such conclusion lies on the small number of carriers without FXS children recruited.…”

“…Johnston et al (2001) [48] reported schizotypal traits and emotional difficulties including social anxiety and depressed mood. Roberts et al (2009) [49] found a high frequency of lifetime major depressive disorder, lifetime panic disorder without agoraphobia, and current agoraphobia without panic at the time of the study. The author stated that a large proportion of women carriers are affected by a major depressive disorder at some point in their lives, but few of them reported recurrent episodes.…”