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A Potential Genetic Syndrome

Myrna M. Weissman, PhD; Raz Gross, MD, MPH; Abby Fyer, MD; Gary A. Heiman, PhD; Marc J. Gameroff, PhD; Susan E. Hodge, DSc; David Kaufman, MD; Steven A. Kaplan, MD; Priya J. Wickramaratne, PhD

Arch Gen Psychiatry. 2004;61:273-279.

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 syn-drome 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.

From the Division of Clinical and Genetic Epidemiology (Dr Weissman), Departments of Psychiatry (Drs Weissman, Fyer, Gameroff, Hodge, and Wickramaratne) and Urology (Drs Kaufman and Kaplan), College of Physicians and Surgeons, Columbia University, New York, NY; the Department of Epidemiology, Mailman School of Public Health, Columbia University (Drs Weissman, Gross, Heiman, Hodge, and Wickramaratne); and the New York State Psychiatric Institute, New York (Drs Weissman, Gross, Fyer, Gameroff, Hodge, and Wickramaratne).

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