Developing Brain, Impulsivity and Compulsivity

Overview

Background: Impulsivity is acting 'without thinking.' Compulsivity is being overly inflexible. People vary in how impulsive or compulsive they are. Extreme versions of these behaviors play a role in mental disorders. Researchers want to study changes in the brain to learn more about these behaviors. Differences in genes may also play a role. Objective: To learn about genetic \& brain features that explain why levels of impulsivity and compulsivity vary across people. Eligibility: People ages 6 - 80 Design: Participants will be screened with a medical history and medical record review. Participants will talk about their mental and behavioral development. They may discuss topics like drug use and sexual activity. They will complete surveys about their compulsivity and impulsivity. Parents of child participants may also complete these surveys. Participants may take memory, attention, and thinking tests. They may give blood or saliva samples for gene studies and they may give blood to make induced pluripotent stem cells. Participants may have their face and irises photographs taken. Participants may have a magnetic resonance imaging scan. It will take pictures of their brain. The scanner is shaped like a cylinder. Participants will lie on a table that slides in and out of the scanner. A coil will be placed over their head. They will lie still, watch a movie, and play a game. Participants may ask family members to join the study. Researchers are particularly interested in recruiting twin pairs to the study. Participants under age 25 may repeat these tests every 1-2 years until they turn 25 or until the study ends. For those over age 25, participation will last less than 1 month.

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).