Item – Theses Canada

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OCLC number
81188676
Author
LeMarquand, David Gordon,1966-
Title
Serotonin and disorders of human disinhibition : alcohol abuse and dependence, aggression and impulsivity.
Degree
Ph. D. -- McGill University, 1998
Publisher
Ottawa : National Library of Canada = Bibliothèque nationale du Canada, [2000]
Description
4 microfiches
Notes
Includes bibliographical references.
Abstract
A wealth of data supports the hypothesis that the neurotransmitter serotonin regulates the intake of ethanol, and is involved in the development of alcoholism in humans. Reduced functioning of the serotonergic system hypothetically increases alcohol intake in both animals and humans. In this thesis, it was proposed that the effect of lowered serotonergic function on alcohol intake is mediated by an increase in disinhibition. The hypothesis that lowered serotonin increases disinhibition was tested in separate groups of individuals at high risk for the development of psychopathology: nonalcoholic young men with a strong family history of paternal alcoholism, and adolescent men with previous histories of physically aggressive behavior. Lowered serotonergic synthesis (and thus presumably function) was experimentally induced through a transient dietary reduction in the availability of the amino add precursor of serotonin, tryptophan. Disinhibition was quantified using a go/no-go task previously shown to characterize psychopaths and children with attention deficit hyperactivity disorder as disinhibited. In the first study, acute tryptophan depletion had no effect on aggressive responding on a modified competitive reaction time aggression task, but increased disinhibition in young men at risk for alcoholism. This effect was independent of the tryptophan depletion-induced mood alterations. The effect tryptophan depletion on disinhibition was not replicated in the second study with previously aggressive adolescent men. A number of explanations for this were posited, including the presence of a ceiling effect. An association between disinhibition and executive functioning (cognitive abilities associated with proper functioning of the prefrontal cortex, such as working memory, planning abilities) was demonstrated in the second study. In a third preliminary study, no association between disinhibition on the go/no-go task and allelic polymorphisms of the dopamine D4 receptor gene was noted. This runs contrary to recent population studies suggesting that a specific polymorphism of the dopamine D4 receptor gene is associated with novelty seeking (of which impulsivity is putatively a component). Overall, the results suggest that lowering serotonergic function increases disinhibition in young men at risk for alcoholism, a subgroup of individuals that may possess a susceptibility to the effects of acute tryptophan depletion. These individuals may demonstrate alterations in central serotonergic function that may be related to the increased risk for the future development of alcoholism noted in this group. The results also confirm the predicted association between poor executive functioning and disinhibition.
ISBN
0612444902
9780612444904