Autonomic and Sensory Dysfunctions in FMR1 Conditions: Development, Mechanisms and Consequences

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PROJECT SUMMARY/ABSTRACT Despite the impairment in fragile X syndrome (FXS) and the fragile X premutation (FXpm), surprisingly little research has examined the underpinnings of these impairments. One potential factor that contributes to impairment is autonomic nervous system (ANS) dysfunction. Elevated physiological arousal, reflecting ANS dysfunction, has long been implicated as contributing to learning impairments and atypical behavior in FXS. While ANS dysfunction has been linked to impairment in both FXS and FXpm, research has not examined the presence, onset, developmental trajectory, or developmental consequences of ANS dysfunction or how molecular-genetic factors are associated. This project addresses these critical gaps with the following specific aims: (1) Identify the onset and developmental trajectory of baseline ANS dysfunction through prospective longitudinal assessment at 6, 9, 12, and 24 months in FXS (n=30 males) and FXpm (n=30; 15 males and 15 females) contrasted to typical controls (n=45; 30 males and 15 females); (2) Determine how molecular-genetic variation relates to the onset and/or developmental trajectory of ANS dysfunction in FXS and FXpm; (3) Characterize behavioral and ANS reactivity to sensory stimuli through prospective longitudinal assessment at 6, 9, 12, and 24 months in FXS and FXpm; and (4) Document the consequences of ANS dysfunction across infancy on sensory processing impairments, adaptive skills, ASD symptoms, and social communication, concurrently and at 24 months in FXS and FXpm. This work will have tremendous impact by greatly expanding information on the mechanistic underpinnings, biological pathways, and timing of symptom progression, which is essential to identify targets and timing of treatment to reduce symptom severity in FXS and FXpm. Our focus on infancy is critical, as evidence has documented that intervention provided early in life has the potential to accelerate development and improve developmental trajectories over time in a multi-dimensional manner.