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GENETIC RISK FOR ALCOHOLISM:
THE P300 AND DECISION MAKING IN AT-RISK TWINS
by
Joshua Dallas Wyner
A Dissertation Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(NEUROSCIENCE)
August 2008
Copyright 2008 Joshua Dallas Wyner
Object Description
| Title | Genetic risk for alcoholism: the P300 and decision making in at-risk twins |
| Author | Wyner, Joshua Dallas |
| Author email | jwyner@usc.edu |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Neuroscience |
| School | College of Letters, Arts and Sciences |
| Date defended/completed | 2008-04-15 |
| Date submitted | 2008 |
| Restricted until | Unrestricted |
| Date published | 2008-06-21 |
| Advisor (committee chair) | Baker, Laura |
| Advisor (committee member) |
Raine, Adrian Bechara, Antoine Lu, Zhong-Lin Unger, Jennifer |
| Abstract | Despite decades of studies the etiology of alcoholism remains elusive. Recent work strongly supports genetic models, estimating the genetic contributions to risk at 32% - 73%. Further, studies have implicated inhibition as a key factor in alcoholism it is known to be comorbid with a number of disinhibitory disorders, including Attention-Deficit Hyperactivity Disorder, Obsessive-Compulsive Disorder, Conduct Disorder, Tourette s Syndrome, and Antisocial Personality Disorder. However, work by Cloninger and colleagues suggests that two distinct forms of alcoholism exist, and that these forms have correspondingly distinct biological components.; To examine this relationship in more detail, this study employed a behavioral control model first proposed by Jeffrey Gray, differentiating activation (the preparation of a response) from inhibition (the cessation of a potential response prior to overt action). Pre-adolescent twins were examined in the context of this model utilizing the P300 Event-Related Potential (ERP). P300 ERPs elicited during both NoGo and Oddball tasks were first examined for their relationship to behavioral control, as measured by impulsive response (NoGo errors). These P300s were thenexamined within twins at risk for both types of alcoholism, as defined by paternal alcohol abuse and paternal antisocial behavior. Finally, genetic analyses were performed on the P300 ERPs using the entire twin sample, in order to understand the etiology of inhibition and activation themselves.; Results showed different patterns of relationships between the NoGo and Oddball P300 ERPs with impulsive responses (NoGo errors), suggesting that NoGo P300 ERPs most likely index the inhibitory pathway of the behavioral control system, while Oddball P300 ERPs most likely index the activation pathway. Twins at risk for either type of alcoholism differed from controls in both NoGo and target Oddball P300 ERPs, but did not differ in novel P300 ERP amplitude. Conversely,Type I and Type II risk groups differed in novel Oddball P300 ERP amplitudes, but not NoGo or target Oddball P300 ERP amplitudes. This suggests that inhibitory differences underlie the risk for both types of alcoholism, but that activation differences underlie only Type II risk. Genetic analyses revealed that a two factor common pathway multivariate model best described the measured P300s, with one factor loading primarily onto novel Oddball P300s, and the other loading primarily onto NoGo P300s. It is concluded that these factors likely represent some form of activation and inhibition, further supporting the notion that inhibition differences are a common factor underlying all alcohol abuse risk, while genetically distinct activation differences underlie Type II but not Type I alcohol abuse risk. |
| Keyword | P300; event-related potential; alcoholism; twins; genetic; heritable; substance abuse |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Type | texts |
| Legacy record ID | usctheses-m1282 |
| Rights | Wyner, Joshua Dallas |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Wyner-20080621 |
| Archival file | uscthesesreloadpub_Volume32/etd-Wyner-20080621.pdf |
Description
| Title | Page 1 |
| Full text | GENETIC RISK FOR ALCOHOLISM: THE P300 AND DECISION MAKING IN AT-RISK TWINS by Joshua Dallas Wyner A Dissertation Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (NEUROSCIENCE) August 2008 Copyright 2008 Joshua Dallas Wyner |
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