SUBSTANCE ABUSE VULNERABILITY AND PREFRONTAL METABOLISM

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The liability for a psychoactive substance abuse disorder (PSUD) is multifactorial and comprises biological, psychological and social domains. However, very little is known about neurobiological characteristics that may contribute to the risk for PSUD. Increased vulnerability for PSUD has been linked to behavioral disorders, such as Conduct Disorder (CD) in childhood and adolescence, and Antisocial Personality Disorder in adults. There is converging evidence from neuropsychological, neuroimaging, and neurophysiological studies that these behavior disorders are associated with a disfunction of the prefrontal cortex of the brain. Consequently, we postulate that a behavioral and neurobiological component of the liability to PSUD is associated with a variation in prefrontal cortex energy and membrane phospholipid metabolism that is detectable by in vivo 31P magnetic resonance spectroscopy. The specific aims of this exploratory (R21) study are: 1) Examine the association between early-onset Conduct Disorder, familial risk for PSUD with variations in prefrontal cortical cerebral energy and phospholipid metabolism measured by in vivo 31P magnetic resonance spectroscopy. 2) Determine the associations between prefrontal cortical cerebral energy metabolism and membrane phospholipid metabolic activity with trait and state measures of aggression, inattention, impulsivity and hyperactivity; these behaviors are implicated to be important components of PSUD vulnerability and have also been observed to be manifestations of a prefrontal brain dysfunction. In keeping with the guidelines of the exploratory grants program, the investigation proposed is in an undeveloped avenue of biomedical research, utilizing a novel technology to be carried out within an existing prospective family study aimed at delineating the parameters of drug abuse etiology. This project is directed toward demonstrating the feasibility and potential value of 31P magnetic resonance spectroscopy, as a specific biomedical method for the characterization of a neurobiological basis of PSUD vulnerability.