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Drug Alcohol Depend. 2004 Feb 7;73(2):121-32.

Neurobehavior disinhibition in childhood predisposes boys to substance use disorder by young adulthood: direct and mediated etiologic pathways.

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Department of Pharmaceutical Sciences, Center for Education and Drug Abuse Research, School of Pharmacy, University of Pittsburgh, 711 Salk Hall, Pittsburgh, PA 15261, USA.



The development of substance use disorder (SUD) was prospectively investigated in 66 boys having fathers with SUD and 104 boys having fathers with no adult Axis I or II psychiatric disorder. Evaluations were conducted to determine the context in which neurobehavior disinhibition in relation to parental SUD, parental neglect of the child and child's social maladjustment culminated in a DSM-III-R diagnosis of SUD.


A neurobehavior disinhibition latent trait was derived using indicators of behavior undercontrol, affect dysregulation and executive cognitive functioning in the boys when they were 10-12 and again at 16 years of age. These latter characteristics have been frequently observed in individuals who have a prefrontal cortex disturbance. The data were analyzed to determine whether the score on the neurobehavior disinhibition construct mediates the association between father's and mother's SUD and son's SUD.


SUD in the mother and father predicted neurobehavior disinhibition in the son. The neurobehavior disinhibition score in the sons predicted SUD between ages 10-12 and 19. Neurobehavior disinhibition, in conjunction with social maladjustment and drug use frequency, mediated the association between paternal and maternal SUD and son's SUD. Neurobehavior disinhibition was unrelated to neglect of the child by either the father or mother; however, paternal but not maternal neglect at age 10-12 predicted SUD at age 19.


The association of neurobehavior disinhibition in childhood and SUD by young adulthood suggests that a prefrontal cortex dysfunction contributes to SUD liability. The results extend previous findings demonstrating that neurobehavior disinhibition is an important component of the liability to SUD.

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