This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Fragile X syndrome (fraX) is the most common known cause of inherited mental impairment with well over 100,000 individuals affected in the U.S. Mutations in the FMR1 gene give rise to a clinical phenotype that includes increased risk for aberrant cognitive, behavioral and emotional function. The major emphasis of the 5-year study proposed in this application is a prospective, longitudinal extension of the work completed during the current grant period, during which key cognitive, behavioral, neuroendocrinological, genetic and environmental data were collected from 120 families across the U.S. and Canada, each having a child proband affected with fraX and a typically developing sibling. To the best of our knowledge, this study would be the first longitudinal investigation of a large, school-age fraX cohort in which both biological and environmental factors contributing to clinical outcome were assessed on a prospective basis. We also propose to extend our investigation into the neurobiology of this disorder using advanced brain imaging techniques. Specifically, longitudinal imaging studies will be used to explicate the developmental trajectory of brain structure and function in children with fraX as compared to key control groups.
Specific Aims : 1) To use a longitudinal, prospective experimental design (with """"""""Time 1"""""""" and """"""""Time 2"""""""" assessments) to elucidate the developmental trajectory of cognitive, behavioral and emotional development in probands with fraX compared to their like-gender siblings;2)to specify the longitudinal trajectory of hypothalamic-pituitary-adrenal (HPA) function and measures of FMR1 gene expression in probands with fraX;and 3)to utilize neuromaging techniques to specify the trajectory of brain structure and function in children with fraX compared to specific age-, gender-, handedness-, SES- and IQ-matched control groups. Although knowledge of cognition, behavior and the brain in children and adults with fraX has grown considerably over the past 20 years, longitudinal data from school-age children with this condition are limited. Cross-sectional findings and limited longitudinal data to date support the hypothesis that an age-related decline in standardized cognitive and adaptive behavioral scores occurs among school-age children with fraX. However, many questions remain unanswered regarding this phenomenon, in particular as related to extent, timing and neural basis. These unanswered questions offer a compelling rationale for conducting a longitudinal study of a large group of school-age boys and girls with fraX as proposed in this application.
|Green, Shulamite A; Hernandez, Leanna; Bookheimer, Susan Y et al. (2016) Salience Network Connectivity in Autism Is Related to Brain and Behavioral Markers of Sensory Overresponsivity. J Am Acad Child Adolesc Psychiatry 55:618-626.e1|
|Kodumuri, Nishanth; Sebastian, Rajani; Davis, Cameron et al. (2016) The association of insular stroke with lesion volume. Neuroimage Clin 11:41-5|
|Levine, Andrew J; Soontornniyomkij, Virawudh; Achim, Cristian L et al. (2016) Multilevel analysis of neuropathogenesis of neurocognitive impairment in HIV. J Neurovirol 22:431-41|
|OrdÃ³Ã±ez, Anna E; Loeb, Frances F; Zhou, Xueping et al. (2016) Lack of Gender-Related Differences in Childhood-Onset Schizophrenia. J Am Acad Child Adolesc Psychiatry 55:792-9|
|Agis, Daniel; Goggins, Maria B; Oishi, Kumiko et al. (2016) Picturing the Size and Site of Stroke With an Expanded National Institutes of Health Stroke Scale. Stroke 47:1459-65|
|Joshi, Shantanu H; Vizueta, Nathalie; Foland-Ross, Lara et al. (2016) Relationships Between Altered Functional Magnetic Resonance Imaging Activation and Cortical Thickness in Patients With Euthymic Bipolar I Disorder. Biol Psychiatry Cogn Neurosci Neuroimaging 1:507-517|
|Becker, James T; Kingsley, Lawrence A; Molsberry, Samantha et al. (2015) Cohort Profile: Recruitment cohorts in the neuropsychological substudy of the Multicenter AIDS Cohort Study. Int J Epidemiol 44:1506-16|
|Ajilore, Olusola; Vizueta, Nathalie; Walshaw, Patricia et al. (2015) Connectome signatures of neurocognitive abnormalities in euthymic bipolar I disorder. J Psychiatr Res 68:37-44|
|Chung, Yoonho; Jacobson, Aron; He, George et al. (2015) Prodromal Symptom Severity Predicts Accelerated Gray Matter Reduction and Third Ventricle Expansion Among Clinically High Risk Youth Developing Psychotic Disorders. Mol Neuropsychiatry 1:13-22|
|Masters, Michael; Bruner, Emiliano; Queer, Sarah et al. (2015) Analysis of the volumetric relationship among human ocular, orbital and fronto-occipital cortical morphology. J Anat 227:460-73|
Showing the most recent 10 out of 536 publications