Differential sensitivity to life stress in FMR1 premutation carrier mothers of children with fragile X syndrome.

Objective: The premutation of the FMR1 gene (defined as between 55 and 200 COG repeats) is estimated to affect 1 in 149 females and 1 in 643 males, and some people who carry the FMR1 premutation display signs of impairment. Method: This study focuses on 82 premutation carrier mothers (M age = 51.4 years; SD = 7.7) of adolescent and adult children with fragile X syndrome (FXS). A Gene x Environment interaction approach examined the ways in which the experience of negative life events interacts with genetic vulnerability to predict depressive symptoms, anxiety, and daily cortisol levels. Results: The associations of life events with all 3 dependent measures were associated with COG repeat length but in a curvilinear manner. Mothers with midsize COG repeats who experienced above-average numbers of negative life events in the previous year had more depressive symptoms and anxiety and had a blunted cortisol awakening response, as compared with those with higher or lower repeat lengths. However, mothers with midsize COG repeats who experienced below-average numbers of negative life events in the previous year had the lowest levels of depressive symptoms and anxiety, and they exhibited the typical cortisol response to awakening, meeting the criteria for differential susceptibility. Conclusions: This research extends our understanding of the phenotypic effects of the expansion of the FMR1 gene, and it adds to the growing literature on the curvilinear relationship between COG repeat length and mental and physical health.