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间质性膀胱炎与惊恐障碍:一种潜在的遗传综合征。

Interstitial cystitis and panic disorder: a potential genetic syndrome.

作者信息

Weissman Myrna M, Gross Raz, Fyer Abby, Heiman Gary A, Gameroff Marc J, Hodge Susan E, Kaufman David, Kaplan Steven A, Wickramaratne Priya J

机构信息

Departments of Psychiatry and Urology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

出版信息

Arch Gen Psychiatry. 2004 Mar;61(3):273-9. doi: 10.1001/archpsyc.61.3.273.

DOI:10.1001/archpsyc.61.3.273
PMID:14993115
Abstract

BACKGROUND

Evidence from a genetic linkage study had suggested a possible syndrome in some families with panic disorder (PD). This syndrome includes bladder problems (possibly urinary interstitial cystitis [IC]), thyroid disorders, chronic headaches/migraine, and/or mitral valve prolapse. In 19 multiplex families with PD, one marker (D13S779) on chromosome 13 gave a logarithm of odds score of more than 4 when individuals with any of the syndrome conditions were analyzed as affected. Families with the bladder problems yielded the highest logarithm of odds scores. These findings were replicated in an extended sample of 60 families. Whereas PD had been well characterized by direct interview, the urologic problems had been found only via medical history checklists and records. A case review by a board-certified urologist suggested they could be IC.

OBJECTIVE

To determine whether patients diagnosed as having IC by urodynamics and/or cystoscopy and their first-degree relatives (FDRs) have increased rates of the syndrome conditions, thus validating that the bladder problems observed in the linkage study could be IC and providing further support for the panic syndrome.

DESIGN

Case-control and family history study.

SETTING

Two metropolitan urology clinics.

PARTICIPANTS

One hundred forty-six probands (67 with IC and 79 with other urologic disorders) and 815 FDRs.

MAIN OUTCOME MEASURES

Lifetime rates of syndrome conditions in probands and FDRs who were blind to urologic or psychiatric diagnoses in the proband.

RESULTS

Compared with patients without IC, patients with IC had a significantly higher lifetime prevalence of PD (controlling for age and sex) (odds ratio, 4.05; 95% confidence interval, 1.22-13.40; P =.02) and a higher lifetime prevalence of any of the syndrome disorders (controlling for age and sex) (odds ratio, 2.22; 95% confidence interval, 0.89-5.54; P =.09). First-degree relatives of probands with (vs without) IC were significantly more likely to have PD, thyroid disorder, urologic problems, and any of the syndrome disorders (controlling for age and sex of the relative and sex of the proband) (adjusted odds ratio, 1.95; 95% confidence interval, 1.13-3.38; P =.02). These results in relatives were not influenced by PD in probands, and did not change substantially when controlling for the proband-relative relationship, modeling age as a categorical (vs continuous) variable, or excluding FDRs with PD. There were no interactions between proband IC status and sex of the relative.

CONCLUSIONS

The increased frequency of seemingly disparate disorders in patients with IC and their FDRs is consistent with the genetic linkage findings in families with PD. These findings suggest that the bladder problems observed in the linkage study may be IC. The hypothesis that there is a familial, possibly pleiotropic, syndrome that may include IC, PD, thyroid disorders, and other disorders of possible autonomic or neuromuscular control deserves further investigation.

摘要

背景

一项基因连锁研究的证据表明,一些患有惊恐障碍(PD)的家庭可能存在一种综合征。该综合征包括膀胱问题(可能是间质性膀胱炎[IC])、甲状腺疾病、慢性头痛/偏头痛和/或二尖瓣脱垂。在19个患有PD的复合家庭中,当对患有任何一种综合征病症的个体进行患病分析时,13号染色体上的一个标记(D13S779)的优势对数得分超过4。患有膀胱问题的家庭产生的优势对数得分最高。这些发现已在60个家庭的扩大样本中得到重复验证。虽然通过直接访谈已对PD进行了充分的特征描述,但泌尿系统问题仅通过病史清单和记录发现。一位获得委员会认证的泌尿科医生进行的病例审查表明,这些问题可能是IC。

目的

确定经尿动力学和/或膀胱镜检查诊断为患有IC的患者及其一级亲属(FDRs)是否有更高的综合征病症发生率,从而验证在连锁研究中观察到的膀胱问题可能是IC,并为惊恐综合征提供进一步支持。

设计

病例对照和家族史研究。

地点

两家大都市的泌尿科诊所。

参与者

146名先证者(67名患有IC,79名患有其他泌尿系统疾病)和815名FDRs。

主要观察指标

先证者和FDRs中对先证者的泌尿系统或精神疾病诊断不知情的综合征病症的终生发生率。

结果

与没有IC的患者相比,患有IC的患者的PD终生患病率显著更高(控制年龄和性别)(优势比,4.05;95%置信区间,1.22 - 13.40;P = 0.02),并且任何一种综合征病症的终生患病率更高(控制年龄和性别)(优势比,2.22;95%置信区间,0.89 - 5.54;P = 0.09)。患有(与未患有)IC的先证者的一级亲属更有可能患有PD、甲状腺疾病、泌尿系统问题和任何一种综合征病症(控制亲属的年龄和性别以及先证者的性别)(调整后的优势比,1.95;95%置信区间,1.13 - 3.38;P = 0.02)。亲属中的这些结果不受先证者中PD的影响,并且在控制先证者与亲属的关系、将年龄建模为分类(而非连续)变量或排除患有PD的FDRs时,变化不大。先证者的IC状态与亲属的性别之间没有相互作用。

结论

IC患者及其FDRs中看似不同的疾病频率增加与PD家庭中的基因连锁研究结果一致。这些发现表明,在连锁研究中观察到的膀胱问题可能是IC。存在一种家族性的、可能具有多效性的综合征的假设,该综合征可能包括IC、PD、甲状腺疾病以及其他可能涉及自主神经或神经肌肉控制的疾病,值得进一步研究。

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