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.
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
Case-control and family history study.
Two metropolitan urology clinics.
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.
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.
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