Evaluating a Method to Estimate Mediation Effects With Discrete-Time Survival Outcomes

The utility of evaluating mediation effects spans across research domains. The model facilitates investigation of underlying mechanisms of event timing and, as such, has the potential to help strengthen etiological research and inform intervention work that incorporates the evaluation of mediating variables. In order for the analyses to be maximally useful however, it is critical to employ methodology appropriate for the data under investigation. The purpose of this paper is to evaluate a regression-based approach to estimating mediation effects with discrete-time survival outcomes. We empirically evaluate the performance of the discrete-time survival mediation model in a statistical simulation study, and demonstrate that results are functionally equivalent to estimates garnered from a potential-outcomes framework. Simulation results indicate that parameter estimates of mediation in the model were statistically accurate and precise across the range of examined conditions. Type 1 error rates were also tolerable in the conditions studied. Adequate power to detect effects in the model, with binary X and continuous M variables, required effect sizes of the mediation paths to be medium or large. Possible extensions of the model are also considered

Altered Sensitivity To Social Gaze In The Fmr1 Premutation And Pragmatic Language Competence

Background: The FMR1 premutation affects 1:291 women and is associated with a range of cognitive, affective, and physical health complications, including deficits in pragmatic language (i.e., social language). This study investigated attention to eye gaze as a fundamental social-cognitive skill that may be impaired in the FMR1 premutation and could underlie pragmatic deficits. Given the high prevalence of the FMR1 premutation, efforts to define its phenotype and mechanistic underpinnings have significant public health implications. Methods: Thirty-five women with the FMR1 premutation and 20 control women completed an eye-tracking paradigm that recorded time spent dwelling within the eye region in response to a face displaying either direct or averted gaze. Pragmatic language ability was coded from a conversational sample using the Pragmatic Rating Scale. Results: Women with the FMR1 premutation failed to show attentional preference to direct gaze and spent more time dwelling on the averted eyes relative to controls. While dwelling on the eyes was associated with better pragmatic language performance in controls, these variables were unrelated in the women with the FMR1 premutation. Conclusions: Altered sensitivity to social gaze, characterized by increased salience of averted gaze, was observed among women with the FMR1 premutation. Furthermore, women with the FMR1 premutation were unable to capitalize on information conveyed through the eyes to enhance social-communicative engagement, which differed from patterns seen in controls. These findings contribute to the growing characterization of social and communication phenotypes associated with the FMR1 premutation

Altered sensitivity to social gaze in the FMR1 premutation and pragmatic language competence

Abstract Background The FMR1 premutation affects 1:291 women and is associated with a range of cognitive, affective, and physical health complications, including deficits in pragmatic language (i.e., social language). This study investigated attention to eye gaze as a fundamental social-cognitive skill that may be impaired in the FMR1 premutation and could underlie pragmatic deficits. Given the high prevalence of the FMR1 premutation, efforts to define its phenotype and mechanistic underpinnings have significant public health implications. Methods Thirty-five women with the FMR1 premutation and 20 control women completed an eye-tracking paradigm that recorded time spent dwelling within the eye region in response to a face displaying either direct or averted gaze. Pragmatic language ability was coded from a conversational sample using the Pragmatic Rating Scale. Results Women with the FMR1 premutation failed to show attentional preference to direct gaze and spent more time dwelling on the averted eyes relative to controls. While dwelling on the eyes was associated with better pragmatic language performance in controls, these variables were unrelated in the women with the FMR1 premutation. Conclusions Altered sensitivity to social gaze, characterized by increased salience of averted gaze, was observed among women with the FMR1 premutation. Furthermore, women with the FMR1 premutation were unable to capitalize on information conveyed through the eyes to enhance social-communicative engagement, which differed from patterns seen in controls. These findings contribute to the growing characterization of social and communication phenotypes associated with the FMR1 premutation

Prevalence and Predictors of Anxiety Disorders in Adolescent and Adult Males with Autism Spectrum Disorder and Fragile X Syndrome

Anxiety disorders affect ~ 15-20% of youths without neurodevelopmental disorders, with persons having autism spectrum disorder (ASD) and fragile X syndrome (FXS) at elevated risk for anxiety disorders. Few studies have compared rates and predictors of anxiety disorders in adolescents with FXS or ASD. This study directly compares rates, predictors, and medication of anxiety disorders between age-matched, male adolescents with FXS (n = 31) or ASD (n = 20). Results indicate that 51.6% of FXS and 50.0% of ASD adolescents met criteria for an anxiety disorder. Cognitive scores and ASD severity did not predict anxiety. Of those with anxiety, ~ 40% of the FXS and 20% of the ASD participants were prescribed medications for anxiety

Social Avoidance Emerges in Infancy and Persists into Adulthood in Fragile X Syndrome

Fragile X syndrome (FXS) is characterized by both social approach and social avoidance. However, the age of emergence and developmental trajectory of social avoidance has not been examined. This study investigates the longitudinal developmental trajectory and dynamic nature of social avoidance in males with FXS from infancy through young adulthood (n = 191). Multiple facets of social avoidance were collected using the Social Avoidance Scale (Roberts et al. 2007, 2009). Overall, 81% of males with FXS displayed social avoidance, which emerged during infancy, increased in severity across childhood, and stabilized through adolescence and early adulthood. An exaggerated “warm up” effect was also observed in FXS. This study delineates the complex profile of social avoidance, a common and impairing behavioral feature of FXS

Biobehavioral composite of social aspects of anxiety in young adults with fragile X syndrome contrasted to autism spectrum disorder.

Social anxiety is a common disorder that has negative impacts across multiple domains of function. Several clinical groups are at elevated risk for social anxiety, including those with fragile X syndrome and those with autism spectrum disorder. Measuring social anxiety in these clinical subgroups is fraught with challenge, however, given the complexity of social anxiety and measurement limitations that are particularly acute in persons with neurodevelopmental disorders. The over-arching aim of this study was to contribute to our understanding of the nature of social anxiety in fragile X syndrome and its association with autism spectrum disorder. To address this aim, we created a multi-faceted composite representing behavioral and biological aspects of social anxiety and examined differences in two adolescent and young adult-aged groups: 59 males with fragile X syndrome and 18 males with autism spectrum disorder. Results indicated a lower score on the multivariate composite for the males with fragile X syndrome relative to autism spectrum disorder but with evidence that traits of autism and social anxiety overlap. We conclude that measuring anxiety and autism traits in fragile X syndrome and autism spectrum disorder is complex with features that overlap and interact in a dynamic manner