Fyer A J, Weissman M M
Department of Psychiatry, College of Physicians and Surgeons at Columbia University, New York, New York, USA.
Am J Med Genet. 1999 Apr 16;88(2):173-81.
This paper describes the clinical methodology and currently collected pedigrees from an ongoing genetic study of panic disorder. The main objectives are to (1) document the clinical aspects of the study for current [Knowles et al., 1998: Am. J. Med. Genet. (Neuropsychiatr. Genet.) 81:138-147] and future reports of genetic analysis; (2) assist other investigators working on the genetic aspects of panic disorder who wish to compare results; and (3) illustrate the numerous judgment calls required in such studies that may lead to methodological variability and could account for differences in findings between studies. We also describe initial strategies to identify more genetically homogeneous panic disorder subtypes. Families were recruited through letters to magazines, word of mouth referral, and screening in anxiety disorder clinics and were asked to participate if at initial diagnostic screening they appeared to have at least three members (in two generations) affected with panic disorder. Diagnostic evaluations included a lifetime clinician-administered semistructured psychiatric interview, family history assessment, and pertinent medical records. Diagnoses for linkage analysis are derived from a best-estimate procedure that includes independent review of all materials by two senior investigators. All clinical evaluations were done blind to genotypes. Fifty-five pedigrees including 679 individuals have been collected to date. DNA is available from 500 family members of whom almost half (48%) are definitely or probably affected with panic disorder. Most (93%) of these subjects were directly interviewed, and the clinical data include not only lifetime psychiatric and medical diagnoses and but also detailed narrative histories describing sequence and context of symptoms. Family sizes range from 4-36 individuals (mean = 12.3) and the number of affected individuals per family from 2-12.
本文描述了惊恐障碍正在进行的基因研究中的临床方法及目前收集的家系。主要目的是：（1）记录该研究的临床情况，以供当前[诺尔斯等人，1998年：《美国医学遗传学杂志》（神经精神遗传学）81:138 - 147]及未来的基因分析报告使用；（2）协助其他从事惊恐障碍基因方面研究且希望比较结果的研究者；（3）说明此类研究中需要做出的众多判断，这些判断可能导致方法上的差异，并可解释不同研究结果之间的差异。我们还描述了识别更多基因同质的惊恐障碍亚型的初步策略。通过向杂志致信、口口相传推荐以及在焦虑症诊所进行筛查来招募家庭，若在初始诊断筛查中一个家庭似乎至少有三名成员（两代人）患有惊恐障碍，便邀请其参与研究。诊断评估包括由临床医生进行的终生半结构式精神科访谈、家族史评估以及相关医疗记录。连锁分析的诊断源自一种最佳估计程序，该程序包括由两名资深研究者对所有资料进行独立审查。所有临床评估均在对基因型不知情的情况下进行。迄今为止，已收集了55个家系，共679人。可从500名家庭成员处获取DNA，其中近一半（48%）肯定或可能患有惊恐障碍。这些受试者中的大多数（93%）接受了直接访谈，临床数据不仅包括终生精神科和医学诊断，还包括描述症状发生顺序和背景的详细叙述性病史。家庭规模从4人至36人不等（平均 = 12.3），每个家庭中受影响个体的数量从2人至12人不等。
