Neural and genetic mechanisms of cognition in externalizing behavior.

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DESCRIPTION (provided by applicant): One of the major risks for drug abuse is a general predisposition to externalizing behavior (EB), which is a broad category that includes impulsivity, antisocial behavior, and aggression, as well as drug abuse. Understanding the psychological and biological mechanisms involved in externalizing behavior is therefore important for understanding drug abuse and for the development of successful prevention and treatment of drug abuse. Externalizing behavior is strongly genetically influenced, and genetic research is therefore well placed to illuminate its biological basis. The proposed research will use both genetic and neuroimaging methods, in order to investigate the neurobiological mechanisms involved in patterns of cognition associated with externalizing behavior. Externalizing behavior is known to be associated with cognitive deficits, including low intelligence and poor working memory (which is the ability to hold and manipulate information in mind, despite distraction). Little is known about the specific genes that influence these cognitive deficits, but genes related to the neurotransmitter dopamine are likely to be important because dopamine influences both externalizing behavior and cognitive functions like working memory. The proposed study will collect DNA from 60 people in order to identify variations in dopaminergic genes. Participants will be assessed for level of externalizing behavior and will have their brains scanned using functional magnetic resonance imaging (fMRI) while they are engaged in a working memory task. The fMRI data will provide maps of brain activity when people engage in these tasks, which can then be analyzed to determine how brain activity is associated with externalizing behavior and how these associations are influenced by specific genes. This study will be a pilot study allowing estimation of the number of participants, both male and female, that will be needed in a larger study that can rigorously test hypotheses regarding genetic effects on cognition in externalizing behavior. PUBLIC HEALTH RELEVANCE: The proposed research is relevant to public health in that externalizing behavior represents the shared risk for a number of common disorders, including drug dependence, alcohol dependence, antisocial personality disorder, conduct disorder, and ADHD. Any findings regarding the neural and genetic mechanisms that underlie externalizing behavior will have immediate impact for basic and applied research that could lead to improvements in the prevention and treatment of these disorders and their subclinical manifestations (such as antisocial behavior and drug abuse).