Family Study of Affective and Anxiety Spectrum Disorders

本研究的主要目的是利用遗传流行病学、发展心理病理学和临床精神病学/心理学的方法，确定心境障碍谱系的内表型。主要的研究问题集中在情绪障碍谱(即症状、症状簇、亚型)的家族传递的特殊性，以及与焦虑障碍和偏头痛综合征的共病在确定情绪障碍亚型中的作用。 本研究采用家庭研究设计，对有情绪、焦虑和偏头痛障碍的先证者进行嵌套病例对照研究，主要研究问题如下。我们建议招募500名患有双相I、双相II、严重抑郁、恐慌症/广泛性痴呆、恐惧症、偏头痛和未受影响的对照的先证者，通过精神病学和非精神病学的临床环境和系统的社区样本来确定，以增强对人群的普适性。约2500名成年一级亲属和配偶以及750名子女(8-17岁)将组成家庭学习部分。先证者和亲属将使用结构化诊断面谈和标准化诊断标准进行评估，然后进行临床验证面谈和诊断共识程序。评估工具将收集有关DSM-IV标准以及情绪障碍和共病情况的信息。这将提供用于验证当前诊断系统的诊断阈值和边界的信息。参加这一阶段研究的家庭将被邀请参加下一阶段的研究，该阶段的研究旨在确定可能包括潜在遗传因素的中间表现形式的情感障碍的家族性内表型。将对这些家庭进行纵向跟踪，以评估一生中情绪障碍谱、亚型和综合征的发展情况。将同时编写单独的方案，以发展对特定内表型的研究和随着家系鉴定和特征的进展而进行的纵向评估。 这项研究的主要贡献将包括：(1)识别在家庭中真实存在的特定情绪障碍亚型的临床表型；(2)改进诊断命名法的表型；(3)解决共病障碍，特别是焦虑和偏头痛，作为情绪障碍亚型或相反指标的作用；以及(4)阐明特定年龄和发育的情绪障碍显著成分在整个生命周期中的表达模式。 在过去的一年里，我们在开展家庭研究方面取得了重大进展。我们现在已经开始招募研究对象，并计划在明年采访一半的先证者和亲属。过去一年的成就包括：(1)根据情感障碍和精神分裂症(SADS)时间表开发了一个半结构诊断性访谈，收集了主要精神障碍的亚阈值频谱；(2)与这些领域的专家协商，生成了关于睡眠综合征、头痛综合征和病史的诊断性访谈；(3)制定了系统的家族史访谈，通过告密者报告收集精神障碍的谱系和病史；(4)选择和试点了一套自我报告的综合功能领域评估；(5)发展一、二、三级亲属的有系统的家谱统计表格；。(6)建立网页界面和以SQL SERVER为基础的电脑资料库，以监察招募、筛选受试者、输入家谱资料、追踪研究进展和拟备研究登记的摘要统计数字；。(7)列举访问管理和临床监测研究受试者的程序；。(8)聘用和培训10名临床访谈员；。(9)发展与本地转介来源的联系；。(10)初步拟备嵌套的病例对照研究，以确定具有家族特异性的内在表型；。以及(11)制定从研究参与者及其亲属那里收集生物样本的程序。

The chief goal of this study is to identify the endophenotypes of the spectrum of mood disorders using the methods of genetic epidemiology, developmental psychopathology and clinical psychiatry/psychology. The major research questions focus on the specificity of familial transmission of the mood disorder spectrum (i.e., symptoms, symptom clusters, subtypes) and the role of comorbidity with anxiety disorders and migraine syndromes in defining subtypes of mood disorders. This study employs a family study design of probands with mood, anxiety and migraine disorders with nested case control studies of the key study questions described below. We propose to recruit 500 probands with bipolar I, bipolar II, major depression, panic/GAD, phobias, migraine, and unaffected controls, ascertained through both psychiatric and non-psychiatric clinical settings and systematic community samples, in order to enhance generalizability to the population. Approximately 2500 first-degree adult relatives and spouses and 750 child offspring (ages 8-17) will comprise the family study component. Probands and relatives will be evaluated using structured diagnostic interviews and standardized diagnostic criteria followed by clinical validation interviews and diagnostic consensus procedures. Assessment instruments will collect information on the DSM-IV criteria as well as the spectrum of mood disorders and comorbid conditions. This will provide information that will be used to validate the diagnostic thresholds and boundaries of the current diagnostic systems. Families enrolled in this phase of research will be invited to participate in the next phase of research which is designed to identify familial endophenotypes of affective disorders that may comprise intermediate forms of expression of underlying genetic factors. These families will be followed longitudinally to evaluate the development of the mood disorder spectrum, subtypes, and syndromes across the lifespan. Separate protocols will be written concurrently to develop the research on specific endophenotypes and longitudinal evaluation as the identification and characterization of families proceeds. The major contributions of this research will include: (1) Identification of clinical phenotypes that breed true in families and are specific to particular subtypes of mood disorders; (2) Refinement of phenotypes for the diagnostic nomenclature; (3) Resolution of the role of comorbid disorders, particularly anxiety and migraine, as indicators of subtypes of mood disorders or the converse; and (4) Elucidation of age and development-specific patterns of expression of salient components of the mood disorder spectrum across the lifespan. During the past year, we have made substantial progress in launching the family study. We have now begun to recruit study subjects and plan to interview half of the probands and relatives during the next year. The accomplishments of the past year include: (1) development of a semi-structured diagnostic interview based on the Schedule for Affective Disorders and Schizophrenia (SADS)that collects subthreshold spectra of the major mental disorders; (2) generation of diagnostic interviews for sleep syndromes, headache syndromes, and medical history in consultation with experts in these domains ;(3) development of a systematic family history interview to collect the spectra of mental disorders and medical history through informant reports; (4) selection and piloting of a package of self-reported assessments of comprehensive domains of function; (5) development of a systematic pedigree enumeration form for identification of first, second and third degree relatives; (6) establishment of a web interface and SQL server-based computerized data base to monitor recruitment, screen subjects, enter family pedigree information, track study progress, and prepare summary statistics on study enrollment;(7) enumeration of procedddures for interview administration and clinical monitoring of study subjects;(8) hiring and training of 10 clinical interviewers; (9) development of liaisons with local referral sources; (10) initial preparation of nested case-control studies to identify endophenotypes with familial specificity; and (11) development of procedures for collection of biologic samples from the study participants and their relatives.