Developing Brain, Impulsivity and Compulsivity

Summary

Participation Requirements

Description

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 trajector...

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) 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) an extended multigenerational family design to assess genomic hypotheses. Objectives: Primary Objectives: 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. 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. Study Population: We aim to recruit 1100 participants over the next 7 years. Individuals between 6 and 80 years of age with a wide range of impulsivity/compulsivity behaviors - ranging from normal to mildly/extremely impaired - will be recruited. No specific demographic groups will be targeted. Recruitment will be mainly done in the District of Columbia/Maryland/Virginia area, however some participants needed for primary aim B (heritability) might travel from elsewhere. Description of Sites/Facilities Enrolling Participants: The National Institute of Health is the sole site for enrollment of participant. Study Duration: The estimated study duration from the beginning of the study (study opens to enrollment) to the end (completion of data analyses) is 10 years. Participant Duration: Primary Objective A: Participants may complete follow-up visits for as long as the study is open; thus, they might complete visits over a 7 to 10-year period. Primary Objective B: Participants will complete the study after one visit and may complete forms at home; thus, the estimated time for participation is less than a month.

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