A Family-Genetic Study of Pathological Gambling

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DESCRIPTION (provided by applicant): Pathological gambling (PG) has become a major health concern, particularly as gambling opportunities have proliferated. Despite its importance, there are no direct family interview studies of PG. The goal of this project is to explore the familial nature of PG through a blind and controlled family study. We plan to assess 124 subjects with DSM-IV PG and 124 matched controls (identified through random digit dialing), providing a comprehensive phenotypic assessment, and then blindly interviewing their first-degree relatives 18 years and older. Probands and relatives will be assessed using the NORC DSM Screen for Gambling Problems (NODS); the Structured Clinical Interview for DSM-IV (SCID); the Family History Research Diagnostic Criteria (FH-RDC), an interview designed to collect family history; the Structured Interview for DSM-IV Personality Disorder (SIDP-IV); and the Minnesota Impulsive Disorders Interview (MIDI), to collect information on other impulse control disorders that may be related to PG. Children under 18 years will be assessed through the proband with the Child Behavior Checklist (CBCL). Interviewers will be fully trained in the administration of these instruments and will undergo careful training to achieve reliability, and will meet monthly with the PI for ongoing training to ensure diagnostic reliability. Because PG has frequently been considered related to mood disorders, attention deficit hyperactivity disorder, addictive disorders, and impulse control disorders, as well as being part of an obsessive-compulsive spectrum, we will be particularly interested in assessing relatives for these conditions. Best-estimate diagnoses will be made for each subject based on raw interview data, case narratives, and medical records. This should lead to best-estimate diagnostic evaluations for 248 probands (124 PG, 124 control) and nearly 1,500 relatives (750 per proband group). A complete analysis of the data will be performed to test the study hypotheses using survival curves, proportional hazards regression, and both logistic and linear regression. The primary goal of the study is to determine whether PG is familial, to examine the pattern of familial aggregation of comorbid disorders, and to investigate the clinical characteristics associated with PG in probands and relatives. Secondary goals will be to examine the validity of Blaszczynski's "pathways" model (hypothesizing three distinct subtypes of PG), and to verify whether the aggregation of PG, substance misuse, and antisocial personality disorder comprise an "externalizing factor" as hypothesized by Krueger. The findings should add to our understanding of the etiology, pathophysiology, classification, subtyping, and treatment of PG. Future studies will include collecting blood samples for DNA from genetically informative families for linkage and association studies; follow-up studies of probands to assess the course of PG; and follow-up studies of offspring of probands with PG to examine early traits which may predispose to PG.