Neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD) emerge during early childhood and are more prevalent in males. In contrast, anxiety and mood disorders commonly emerge during adolescence and are more frequent in females. However, our understanding of the mechanisms that underlie sex differences in the occurrence of various forms of psychopathology is limited. The Research Domain Criteria (RDoC) project provides a dimensional and transdiagnostic framework as an alternative to our traditional categorical conceptualization of psychiatric disorders in order to better characterize the full range of typical to atypical functioning and to better understand sex differences and comorbidity. It is critical to consider RDoC constructs within the context of development, particularly when examining disorders that emerge in childhood and often progress to increasingly severe forms or new comorbidities later in development. Further, given evidence of sex differences in the developmental course of psychopathology and trajectories of brain development, longitudinal research is necessary to understand whether biobehavioral markers of internalizing and externalizing psychopathology differ across development for girls and boys. The proposed study will leverage neuroimaging and behavioral data from existing longitudinal studies to examine the effect of sexual dimorphism on the development of motor, emotional, and cognitive control from early childhood through adolescence (ages 4-17 years) among a large sample of children with ADHD (n=329) and typically developing controls (n=273). There is considerable evidence that ADHD lies at the extreme of a continuous dimension rather than a discrete syndrome with clear boundaries between disorder and health. Motor, cognitive, and emotional control systems, thought to develop in parallel, are implicated in the pathophysiology of ADHD and other neuropsychiatric disorders. Furthermore, ADHD is often comorbid with other disorders in childhood and girls and boys with ADHD experience differential risk for deleterious outcomes in adolescence and adulthood. Therefore, studying developmental changes in dimensional RDoC constructs among a sample of children with and without ADHD will inform our understanding of sex differences in psychopathology more broadly defined. We propose to compare the developmental trajectories of cognitive, emotional, and motor control both in terms of behavior and neuroanatomy, and to relate these trajectories to externalizing and internalizing symptoms using dimensional analyses. This study will draw from and integrate data across two ongoing longitudinal studies: one of preschool children (age 4-5 years at time 1; n=145) followed into middle childhood and a second large sample of (confirmed) pre-pubertal 8-12 year-old children (n=437), a subset of whom have completed longitudinal follow-up visits in adolescence (ages 12-17; n=106). Combining these datasets permits for generalized mixed effects modeling of biobehavioral measures of dimensional constructs within a sample of children spanning typical and atypical development which is critical for advancing the RDoC initiative.
Evidence of sexually dimorphic trajectories of brain development and neuropsychological function may be related to the differential prevalence of various neuropsychiatric disorders among men and women. The proposed research will contribute to the fundamental knowledge about the nature of sex differences in psychopathology. This will be accomplished through examination of developmental trajectories from childhood into adolescence of motor, cognitive, and emotional control and brain structure in relation to internalizing and externalizing symptoms among girls and boys with and without a childhood diagnosis of ADHD.
