A Family-Genetic Study of Pathological Gambling

描述（由申请人提供）：病理性赌博（PG）已成为一个主要的健康问题，特别是随着赌博机会的激增。尽管它的重要性，有没有直接的家庭采访研究PG。本项目的目标是探索PG的家庭性质，通过一个盲目的和控制的家庭研究。我们计划评估124名DSM-IV PG受试者和124名匹配的对照（通过随机数字拨号确定），提供全面的表型评估，然后盲访他们18岁及以上的一级亲属。先证者和亲属将使用NORC DSM赌博问题筛查（NODS）进行评估; DSM-IV的结构化临床访谈（SCID）;家族史研究诊断标准（FH-RDC），旨在收集家族史的访谈; DSM-IV人格障碍的结构化访谈（SIDP-IV）;和明尼苏达州冲动性障碍访谈（Minnesota Impulsive Disorders Interview，简称IMDS），收集可能与PG相关的其他冲动控制障碍的信息。18岁以下的儿童将通过先证者进行评估，儿童行为检查表（CBCL）访视员将接受这些仪器管理方面的全面培训，并将接受仔细培训以实现可靠性，并将每月与PI会面进行持续培训，以确保诊断可靠性。因为PG经常被认为与情绪障碍、注意缺陷多动障碍、成瘾性障碍和冲动控制障碍有关，也是强迫症谱的一部分，所以我们对评估这些疾病的亲属特别感兴趣。将根据原始访谈数据、病例叙述和病历对每例受试者进行最佳估计诊断。这将导致对248名先证者（124名PG，124名对照）和近1,500名亲属（每个先证者组750名）进行最佳估计的诊断评估。将使用生存曲线、比例风险回归以及逻辑和线性回归对数据进行完整分析，以检验研究假设。本研究的主要目的是确定PG是否是家族性的，检查共病疾病的家族聚集模式，并调查先证者和亲属中与PG相关的临床特征。次要目标是检查Blaszczynski的“途径”模型的有效性（假设PG的三种不同亚型），并验证PG、药物滥用和反社会人格障碍的聚集是否构成克鲁格假设的“外部化因素”。研究结果应增加我们的病因，病理生理学，分类，亚型和治疗PG的理解。未来的研究将包括收集血液样本的DNA从遗传信息的家庭连锁和关联研究;后续研究的先证者，以评估PG的过程中;和后续研究的先证者与PG的后代，以检查早期的特征，可能易患PG。

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.