Developing Brain, Impulsivity and Compulsivity

Study Description: Many neuropsychiatric disorders have extreme impairing impulsivity and compulsivity behaviors at their core. We hypothesized that the development of symptoms of impulsivity and compulsivity during childhood/adolescence and early adulthood will be associated with atypical trajectories of brain features including cortical glutamate (the main excitatory neurotransmitter) and functional/structural brain connectivity. Additionally, we hypothesize that cortical glutamate will be under genetic control (i.e., heritable) and that common genetic variant risk for disorders characterized by extreme impulsivity (e.g., attention deficit hyperactivity disorder) and by extreme compulsivity (e.g., obsessive compulsive disorder, autism spectrum disorder) will also be associated with atypical cortical glutamate trajectories. To elucidate the relationships between the developing brain, compulsivity/impulsivity and genomics, we will collect clinical assessments including clinician-led interviews, neurobehavioral assessments, neuroimaging data, and genomic samples using 1) a prospective longitudinal design to answer developmental hypotheses; 2) a twin design to assess heritability hypotheses. Objectives: Primary Objective: A) To assess the effects of impulsivity and compulsivity on the developmental trajectories of cortical glutamate. B) To determine the heritability of cortical glutamate. Secondary Objectives: A) To establish the reliability of glutamate measurements. B) To examine the impact of atypical glutamate levels on developing structural and functional connections within the fronto-striatal circuits. C) To assess within twin pair differences in neurodevelopmental markers (cortical glutamate, structural/functional MRI) in relation to differences in symptom domains. Endpoints: Primary Endpoint: A) Age-related change in cortical glutamate levels and its moderation by individual differences in levels of impulsivity and compulsivity. B) Heritability of cortical glutamate (proportion of variance explained by additive genetic factors). Secondary Endpoints: A) 1) Glutamate levels estimated at 3 Tesla at short intervals to establish test-retest reliability. 2\) Glutamate levels estimated at both 3 Tesla and 7 Tesla (cross scanner validation). B) Measures of the brain's structural and functional connectivity. C) Within twin-pair differences in neurodevelopmental markers symptom domains (impulsivity/compulsivity).