0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Article |

Interstitial Cystitis and Panic Disorder:  A Potential Genetic Syndrome FREE

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
[+] Author Affiliations

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, MailmanSchool of Public Health, Columbia University (Drs Weissman, Gross, Heiman,Hodge, and Wickramaratne); and the New York State Psychiatric Institute, NewYork (Drs Weissman, Gross, Fyer, Gameroff, Hodge, and Wickramaratne).


Arch Gen Psychiatry. 2004;61(3):273-279. doi:10.1001/archpsyc.61.3.273.
Text Size: A A A
Published online

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.

We report results from a study designed to follow up genetic linkagefindings of a previously unidentified syndrome in some multiplex familieswith panic disorder (PD).1 This syndrome includedPD, various urinary problems (possibly interstitial cystitis [IC]), thyroiddisorders, mitral valve prolapse (MVP), and/or chronic headaches/migrainein some family members. The genetic linkage study had selected the familiesbased on initial evidence of at least 3 family members affected with PD.2,3 While the information on PD was obtainedfrom careful interviews, information on the bladder problems and other medicalconditions was obtained only through medical records and history checklists.By using these less-than-definitive methods for the medical conditions, logarithmof odds scores of 4.2 on chromosome 13 (marker D13S779)were obtained in the first 19 multiplex families with PD and these other medicalconditions.1 These findings were further supportedin a genome scan performed on an extended sample that included the initial19 families and an additional 41 families, for a total of 60 multiplex familieswith 587 individuals.4

We present findings from a new study aimed to follow up the bladder/kidneyproblems. The bladder/kidney problems yielded the highest logarithm of oddsscores in the genetic linkage study, but the diagnostic meaning was unclear.Our records were reviewed by a urologist (S.A.K.) who believed that they couldbe IC. We examined the rate of PD and the other syndrome disorders in a sampleof patients diagnosed as having IC by urologists using urodynamics and/orcystoscopy with bladder distention.

The specific hypothesis tested is that probands with IC and their first-degreerelatives (FDRs), compared with control subjects and their FDRs, will havean increased rate of the syndrome disorders, including PD, thyroid disorders,MVP, and/or severe headaches/migraine. These findings would partially validatethat the bladder problems seen in the linkage study could be IC and also addfurther support for the panic syndrome identified in the linkage study.

There are several hypotheses implicating various neurobiological mechanisms,such as autonomic dysregulation, in the cause of PD.5,6 Itis possible from a developmental perspective that a putative gene(s) wouldgive rise to additional dysfunctions in other areas, such as the bladder,in which regulation involves smooth muscle function or corticotropin-releasinghormone (CRH). Therefore, these seemingly unrelated conditions might be explainedby mutations in certain genes that exert effects on multiple aspects of physiologicaland anatomical features and lead to pleiotropic phenotypes in probands andtheir families. Pleiotropy is defined as the phenomenon by which a singlegene is responsible for several distinct and seemingly unrelated phenotypiceffects.7

Panic disorder is a highly familial complex genetic disorder8 with heritability, based primarily on twin studies,of about 49%.9 The lifetime prevalence of PDis about 1% to 3% cross-nationally, with a mean age of onset in early adulthood.Women have higher rates of PD than men, and the clinical manifestation ofPD is similar across diverse cultures.10 Symptomsinclude recurrent episodes of sudden unpredictable apprehension and associatedautonomic manifestations involving the cardiorespiratory system (shortnessof breath, chest pain, and palpitations), neurologic symptoms (dizziness,paresthesias, and trembling), gastrointestinal symptoms (nausea and abdominaldistress), other autonomic symptoms (hot flashes, chills, and sweating), andcognitive symptoms such as fear of dying. Treatment established through controlledclinical trials includes a range of pharmacological agents, most commonlyselective serotonin reuptake inhibitors, and behavioral approaches.11 None are fully effective, and PD is associated withincreased rates of medical use and suicide attempts.12

Interstitial cystitis is a chronic debilitating bladder syndrome ofunknown cause, and there is no generally accepted treatment.13 Therehave been several attempts to estimate the prevalence of IC in the UnitedStates.14 The largest most systematic set ofdata, based on self-report from the National Household Interview Study, showsa lifetime prevalence of 0.5% after weighting of the US population by age,race, and sex.15 It is more commonly foundin females, with a median age of onset at 40 years.16,17 Therole of genetic susceptibility has not been thoroughly investigated. One smalltwin study18 found considerably higher concordancein monozygotic vs dizygotic twins. Five of the 8 monozygotic and none of the26 dizygotic twins had confirmed IC.18 Preliminaryfindings from a family study18 suggest higherrates of IC in the FDRs of IC patients vs population controls.

Interstitial cystitis symptom presentation varies, but most commonlyincludes urinary frequency and urgency, nocturia, severe pain on bladder filling(typically relieved with voiding), and sterile urine.19,20 Interstitialcystitis encompasses a major portion of the chronic pelvic pain syndrome,21,22 which includes many urologic patientswith bladder and/or pelvic pain, irritative voiding symptoms, and negativeurine culture and cytologic test results.23 Interstitialcystitis in males is characterized by impairing clinical symptoms typicalof chronic prostatitis (pain on voiding and erectile dysfunction) withoutevidence of leukocytes or bacteria cultured in the prostatic secretions.2426 A syndrome remarkablyanalogous to IC, called feline IC, occurs in domestic cats. Studies2729 of cats and humanssuggest central nervous system involvement, including subtle abnormalitiesof the hypothalamic-pituitary-adrenal axis and a significant increase in tyrosinehydroxylase immunoreactivity in the locus coeruleus.

Available treatments for IC are based primarily on observational dataand a few clinical trials. Treatments included are cystoscopic hydrodistentionof the bladder, amitriptyline hydrochloride, antihistamine (oral hydroxyzinehydrochloride), pentosan polysulfate sodium, and intravesical dimethyl sulfoxidetherapy.30,31 These treatmentsmay improve symptoms, but there is insufficient information to know whethertreatment modifies the long-term course.32 Interstitialcystitis is considered a local manifestation of a systemic disease, possiblyan autoimmune disorder, but this is controversial. Systematic studies33,34 of large samples of patients withIC have found increased rates of autoimmune diseases, migraine headaches,and hypothyroid disease. Recently, the National Institute of Diabetes andDigestive and Kidney Diseases requested research applications in basic cellular,molecular, and genetic studies of IC.

PATIENTS

Eligible participants were English-speaking patients aged 18 to 70 yearsfrom 2 urology clinics in New York City, headed by Columbia University–affiliatedboard-certified urologists (D.K. and S.A.K.), based on their urologic diagnosis,independent of the other syndrome disorders.

Cases were women with IC and men with chronic prostatitis (with normalurine sediments and sterile urine and prostatic fluid), considered the maleequivalent of IC.22 Controls were patientswith bladder diseases that have well-established, diagnosable, underlyinganatomical causes. Controls included men and women with noninvasive bladdercancer or detrusor instability, a condition characterized by involuntary contractionsof the smooth muscular coat of the bladder. In women, the condition is usuallysecondary to cystocele (a condition in which the bladder base descends belowthe inferior ramus of the symphysis pubis either at rest or with straining,due to a defect in the anatomical support of the bladder), and in men, itis secondary to benign prostatic hypertrophy. Also included among controlswere women diagnosed as having cystocele and men with benign prostatic hypertrophyor prostate cancer.

ENROLLMENT OF STUDY PARTICIPANTS

To avoid selection bias, computer-generated lists of all patients diagnosedas having IC were provided to us by assistants (a medical student and a secretary)to the urologists who were unaware of our study hypothesis. For controls,we were given lists of cases that met the control inclusion criteria. No informationon psychiatric or other conditions was included, just the urologic diagnosis.As required by the institutional review board, all patients were first senta letter signed by their urologist inviting them to participate in the study.They were given an opportunity not to participate by calling in and declining.Those who did not call in within 2 weeks were followed up and invited to participate.The patients received no other information about the study from the urologistsor the investigators before receiving the letter. When subjects were calledback, they were told that we would ask health questions about themselves andtheir FDRs. All of the calls to the subjects for recruitment and interviewwere made by an assistant who was blind to the urologic diagnosis and didnot have access to the patients' medical records. Sixty-seven (72.8%) of the92 available cases and 79 (43.4%) of the 182 available controls agreed toparticipate in the study. All participants gave informed consent and agreedto provide family history information.

ASSESSMENTS

Urologic diagnoses were made by a board-certified experienced urologist(D.K. or S.A.K.), before this study, blinded to the study interview data.Urodynamic tests with cystometry and cystoscopy (with hydrodistention) reports35 were available for 126 (86.3%) of the patients (27.4%underwent both tests, 36.3% underwent urodynamic tests only, and 22.6% underwentcystoscopy only). Of the 9 patients who underwent neither test, 8 underwentultrasonography and other tests and 1 underwent ultrasonography only. Medicalrecords were missing for 9 of the 146 patients. Patients were assessed bya trained research assistant, under the supervision of a psychiatrist (R.G.).Both were blinded to the urologic diagnosis and were not affiliated academicallyor geographically with the urology clinic. Lifetime PD was determined by diagnosticassessment, similar to that used in the genetic linkage study.2 First,the anxiety section of the Schedule for Affective Disorders and Schizophrenia–LifetimeVersion,36 a structured psychiatric interview,was administered.37 The interviewer also wrotea narrative case history for patients who reported any psychiatric symptoms.The data were then used by the same 2 senior clinicians who diagnosed PD inthe linkage studies (M.M.W. and A.F.), blinded to the urologists' and theinterviewer diagnoses, to confirm the psychiatric diagnosis using the best-estimateprocedure.38 Psychiatric symptoms and informationon the medical conditions in the FDRs were obtained from the patients usingan extended version of the Family History Screen, a brief validated instrumentfor collecting lifetime psychiatric history on an informant and FDRs.39 There is a well-documented underreporting of diagnosisusing family history methods, because informants may not have sufficient informationabout all the relatives' symptoms to meet diagnostic criteria. Therefore,we used broader criteria for PD in the FDRs, including panic attacks. Medicalexaminations were not available on FDRs, but we used the same methods to obtainmedical conditions in the relatives as had been used in the linkage study.1

DATA ANALYSIS

t Tests and χ2 testswere used to test for group differences in demographic characteristics. Comparisonswere made between the 2 proband groups and between the FDRs of these 2 groups.

Probands

Separate logistic regression analyses were used to evaluate the associationof IC with each of the 4 disorders comprising the putative syndrome in probands(PD, MVP, thyroid disorder, and chronic headaches/migraine), with IC as anindependent variable (1 indicates present; and 0, absent) and each syndromedisorder as the outcome (1 indicates present; and 0, absent). We also createda binary outcome variable to capture the presence of any of the 4 syndromedisorders. Because probands with IC were younger and had more females thancontrols, age and sex were entered as covariates in all analyses. Each analysiswas performed twice, with age entered as a continuous variable and also asa 5-level categorical variable based on quintiles of the age distribution,because there was no a priori assumption about how age might be acting asa confounder. We tested the interaction between sex and proband IC statusin all analyses. Statistical significance was set at the 5% level (P<.05, 2-tailed).

First-Degree Relatives

Separate logistic regression analyses were used to evaluate the associationof proband IC with each of the 5 disorders comprising the syndrome in FDRs(PD, MVP, thyroid disorder, chronic headaches/migraine, and urologic [bladderor kidney] problems), with proband IC as the independent variable (1 indicatespresent; and 0, absent) and FDR's status on each syndrome disorder as theoutcome (1 indicates present; and 0, absent). We also created 2 binary outcomevariables to capture the presence in relatives of any of the 5 syndrome disordersand the presence of MVP, thyroid disorder, chronic headaches/migraine, and/orurologic problems. Panic disorder was omitted from this second definitionto rule out the possibility that the presence of PD explained the findings.All parameters were estimated using generalized estimating equations40 to adjust for the nonindependence of observationsamong relatives from the same family. We did not use survival or Cox proportionalhazards regression models because we did not have the age of onset in relatives.Statistical significance was set at the 5% level (P<.05,2-tailed).

To rule out the effects of PD, which is an independent familial disorder,we performed all of the previously described analyses on a restricted setof FDRs (those with probands who did not have PD). We also controlled forthe following variables: FDR age (because FDRs of IC probands were youngerthan FDRs of non-IC probands), FDR sex (to further reduce potential confounding),sex of the proband informant (because of differential reporting by sex), andthe relationship between FDR and proband (using a 3-level variable coded asparent, child, or sibling). Each analysis was performed twice, with age enteredas a continuous variable and also as a 5-level categorical variable basedon quintiles of the FDR age distribution, because there was no a priori assumptionabout how age might be acting as a confounder. We tested the interaction betweenFDR sex and proband IC status in all analyses. Statistical significance wasset at the 5% level (P<.05, 2-tailed).

Patients with IC were younger than controls (mean ± SD, 44.8± 13.3 vs 60.3 ± 9.6 years; P<.001),and most were women (83.6% vs 41.8%; P<.001).Cases and controls did not differ in race or ethnicity (88.1% vs 77.2% white),number of completed school years (mean ± SD, 15.2 ± 2.5 vs 14.8± 2.4), or percentage employed (74.6% vs 63.5%). All analyses wereadjusted for sex and age. We report the analyses adjusting for age as a continuousvariable, because the results were nearly identical when adjusting for ageas a categorical variable.

There was more than a 4-fold higher risk of PD and more than a 6-foldhigher risk of thyroid disorder among patients with IC compared with controls,and more than a 2-fold increased risk of having any of the disorders composingthe syndrome (Table 1). Ratesof headaches/migraine and MVP did not differ significantly between groups.There was no significant interaction between proband sex and IC status inany of the analyses (P range, .13-.83).

Table Graphic Jump LocationTable 1. Panic Disorder and Other Syndrome Conditions in Probands Withand Without IC

Eight hundred fifteen FDRs were identified (315 of IC probands and 500of controls). There were no sex differences in relatives by proband group.Relatives of probands with IC were younger (mean ± SD, 50 ±22 vs 54 ± 22 years; t784 = 2.47, P = .01) and had fewer children. All analyses were adjustedfor age. As with the proband analyses, we report the FDR analyses adjustingfor age as a continuous variable, because the results were nearly identicalwhen adjusting for FDR age as a categorical variable.

We first examined the prevalence of the syndrome disorders in all theFDRs of all probands, including probands with PD (data not shown). As expected,based on numerous family studies,41 PD wasfamilial. The odds of the outcome disorder in the FDRs of IC patients wereincreased more than 2-fold for PD, thyroid disorder, urologic problems (excludingbladder cancer), and the syndrome disorder whether PD was or was not includedin the definition. There was no significant interaction between FDR sex andproband IC status in any of the analyses (P range,.11-.62).

We next restricted our analysis to FDRs of probands without PD to determinewhether the syndrome was being transmitted independent of PD in the proband(Table 2). We also controlledfor sex of the informant to ensure that bias was not introduced by unequalrepresentation of female informants in the IC groups. The results did notchange substantially. The odds of the outcome disorder in the FDRs of IC patientswere increased more than 3-fold for PD, more than 2-fold for thyroid and urologicproblems, and nearly 2-fold for the syndrome whether PD was or was not includedas a syndrome disorder.

Table Graphic Jump LocationTable 2. Lifetime Disorders in FDRs of Probands With and Without IC,Excluding Probands With Panic Disorder

These results, in a sample of patients carefully diagnosed as havingIC, show an increased risk of PD and of the syndrome in IC patients and theirFDRs. These findings, together with findings from the genetic linkage study,1 while still tentative, suggest that in a subgroupof patients with PD, IC and other seemingly disparate disorders may be partof the same syndrome.

Previous studies found an increased comorbidity of PD with cardiovascularproblems,42 chronic headaches/migraine,43 MVP,44 and thyroiddisorders.45 It is usually assumed that theseassociations are spurious (ie, a misclassification due to an overlap of symptoms).None of the family studies of PD have determined whether medical disordersthat coaggregate with PD have an increased familial risk independent of PDin relatives of probands with IC. Our findings suggest that the associationsmay be a result of a shared cause, such as genetic susceptibility. Our findingsmay also explain some of the association observed between MVP and autoimmunethyroid disorders46,47 and migraine.48

A pleiotropic gene might give rise to any of several plausible biologicalmechanisms shared by IC, PD, and the other syndrome disorders. There are relateddata, although speculative, that may explain our findings or suggest morespecific hypotheses (the study of Weissman et al1 hasdetails). Autonomic dysregulation is implicated in the cause of PD.5,6 The bladder's function involves smoothmuscle function regulated through innervation from autonomic nuclei,49,50 so that changes in autonomic tonemight lead to voiding difficulties, as seen in patients with IC. Stress, whicharouses the noradrenergic system, was shown to be associated with symptomexacerbation in IC patients.51 Tricyclic antidepressants,mostly amitriptyline, which inhibit central norepinephrine, may be effectivein some patients with IC.52 Animal model datashow that cats with IC have increased plasma norepinephrine concentrations.53 Autonomic mechanisms have also been considered ascausative factors in other nonpsychiatric syndrome disorders. Mitral valveprolapse in patients with PD is usually the mild noncalcified type; its causehas been related to a more general dysautonomia.44 Migraineinvolves abnormal dilation of cerebral blood vessels, an action that is underautonomic control.54

Another way that autonomic reactivity might be involved in IC and PDis via neurogenic inflammation. Human and animal model data indicate a defectin the bladder's cytoprotective glycosaminoglycan lining that could allowpenetration of various substances that can activate bladder mast cells. Mastcell–derived proinflammatory and vasoactive molecules may, in turn,contribute to the pathogenesis of IC. Bladder mast cell activation is mediatedand augmented by neurotransmitters and neuropeptides, such as serotonin,55 and serotonergic imbalance is implicated in PD. Mastcells might also play a central role in the pathogenesis of migraine and immune-mediatedthyroid disorders.56

The common genetic susceptibility possibly shared by the disorders composingthe syndrome might be linked to the Barrington nucleus. This pontine nucleusimplicated in urination49 links parasympatheticpreganglionic neurons with prosencephalon-projecting nuclei, thus providingan anatomical substrate for coregulation of pelvic visceral symptoms and mentalactivity in the prosencephalon.57 The Barringtonnucleus contains numerous CRH neurons that project to the spinal parasympatheticnucleus innervating the bladder.58 Dysregulationof the hypothalamic-pituitary-adrenal axis plays a role in the cause of PD,59 and causes enhancement of central secretion of CRH.Increased CRH secretion from the Barrington nucleus might, in turn, inhibiturination and cause voiding problems typical of IC.

The strengths of our study include a sizable sample, state-of-the-arturologic diagnoses, reliable assessment of PD, and information on FDRs. Alimitation of the family history approach is that a patient with PD may bemore likely to report PD in relatives.60 Wetook care of this potential bias by also restricting our analysis to relativesof probands who did not have PD. Another limitation is the low response rateamong controls. However, this potential selection bias could not distort ourfindings in the FDRs, even if PD was not equally distributed between respondersand nonresponders in the control group, because the strategy we adopted ensuredthat results in relatives were independent of PD status in probands. Otherlimitations include the lack of medical assessment of MVP, thyroid disorder,or headaches/migraine. Moreover, we only assessed FDRs, and the genetic linkagestudy included multiplex families spanning several generations. Thus, disordersin the extended family may have been missed by including only FDRs. Pleiotropywould not require that all elements of the expression of the phenotype bepresent in an individual. Finally, while our results concerning the increasedrisk of the syndrome in the IC patients and their FDRs are consistent withthe findings of the genetic linkage study, a family history study alone cannotvalidate a genetic syndrome or confirm pleiotropy.

Potential clinical implications of this finding include identificationof new pharmacological interventions for IC, targeting specific neurotransmitterreceptors.61 Selective serotonin reuptake inhibitors,which are effective in PD patients, might inhibit serotonergic activationof mast cells and modulate exaggerated bladder activity through down-regulationof central postsynaptic serotonin receptors.62,63 Inaddition, trials of CRH antagonists as anxiolytic agents in PD patients arein process.64 These novel agents might be effectivealso in treating IC. Urologists should be aware of the increased prevalenceof PD, a treatable disorder, among their IC patients. Future research shouldinclude efforts to replicate the family aggregation and genetic findings andclinical trials with selective serotonin reuptake inhibitors for IC.

It is likely that the range of syndrome disorders is larger than wehave identified, including disorders shown to be associated with IC, suchas fibromyalgia, celiac disease, and irritable bowel syndrome, which in turnhave been associated with PD and/or migraine and other disorders of possibleautonomic or neuromuscular control, leading to the speculation that many orall of these conditions share underlying pathophysiologic features. Also,PD frequently co-occurs with mood and other anxiety disorders that have alsobeen associated with several other syndrome conditions. The phenotype of PDmay be broader than identified in this study. There is increasing recognitionthat phenotype hunting in family and genetic studies of psychiatric disordersmay profit from assessment of a wide range of medical and psychiatric disorders.65

Corresponding author and reprints: Myrna M. Weissman, PhD, Departmentof Psychiatry, College of Physicians and Surgeons, Columbia University, Divisionof Clinical and Genetic Epidemiology, New York State Psychiatric Institute,1051 Riverside Dr, Unit 24, New York, NY 10032 (e-mail: mmw3@columbia.edu)

Submitted for publication January 13, 2003; accepted September 22, 2003.

This study was supported by a National Alliance for Schizophrenia andDepression Senior Investigator Award (Dr Weissman); and grants MH2874 (DrWeissman) and MH35792 (Dr Fyer) and training grant 5T32-MH13043 (Dr Gross)from the National Institute of Mental Health, Rockville, Md.

Weissman  MMFyer  AJHaghighi  FHeiman  GDeng  ZHen  RHodge  SEKnowles  JA Potential panic disorder syndrome: clinical and genetic linkage evidence. Am J Med Genet. 2000;9624- 35
PubMed Link to Article
Fyer  AWeissman  M Genetic linkage study of panic: clinical methodology and descriptionof pedigrees. Am J Med Genet. 1999;88173- 181
PubMed Link to Article
Knowles  JAFyer  AJVieland  VJWeissman  MMHodge  SEHeiman  GAHaghighi  Fde Jesus  GMRassnick  HPreud'homme-Rivelli  XAustin  TCunjak  JMick  SFine  LDWoodley  KADas  KMaier  WAdams  PBFreimer  NBKlein  DFGilliam  TC Results of a genome-wide genetic screen for panic disorder. Am J Med Genet. 1998;81139- 147
PubMed Link to Article
Hamilton  SPFyer  AJDurner  MHerman  GAde Baisre  Leon AHodge  SEKnowles  JAWeissman  MM Further genetic evidence for a panic disorder syndrome mapping to chromosome13q. Proc Natl Acad Sci U S A. 2003;1002550- 2555
PubMed Link to Article
Sullivan  GMCoplan  JDKent  JMGorman  JM The noradrenergic system in pathological anxiety: a focus on panicwith relevance to generalized anxiety and phobias. Biol Psychiatry. 1999;461205- 1218
PubMed Link to Article
Gorman  JMKent  JMSullivan  GMCoplan  JD Neuroanatomical hypothesis of panic disorder, revised. Am J Psychiatry. 2000;157493- 505
PubMed Link to Article
King  RCStansfield  WD A Dictionary of Genetics.  New York, NY Oxford University Press Inc1990;
Weissman  MM Family genetic studies of panic disorder. J Psychiatr Res. 1993;27suppl 169- 78
PubMed Link to Article
Hettema  JMNeale  MCKendler  KS A review and meta-analysis of the genetic epidemiology of anxiety disorders. Am J Psychiatry. 2001;1581568- 1578
PubMed Link to Article
Weissman  MMBland  RCCanino  GJFaravelli  CGreenwald  SHwu  HGJoyce  PRKaram  EGLee  CKLellouch  JLepine  JPNewman  SCOakley-Browne  MARubio-Stipec  MWells  JEWickramaratne  PJWittchen  HUYeh  EK The cross-national epidemiology of panic disorder. Arch Gen Psychiatry. 1997;54305- 309
PubMed Link to Article
Gorman  JMKent  JMCoplan  JD Current and emerging therapeutics of anxiety and stress disorders. Davis  KLCharney  DCoyle  JTNemeroff  CedsNeuropsychopharmacology: The Fifth Generation of Progress. Baltimore,Md Lippincott Williams & Wilkins2002;967- 980
Weissman  MMKlerman  GLMarkowitz  JSOuellette  R Suicidal ideation and suicide attempts in panic disorder and attacks. N Engl J Med. 1989;3211209- 1214
PubMed Link to Article
Warren  JWKeay  SK Interstitial cystitis. Curr Opin Urol. 2002;1269- 74
PubMed Link to Article
Held  PJHanno  PMWein  AJPauly  MVCahn  MA Epidemiology of interstitial cystitis. Hanno  PMStaskin  DRKrane  RJWein  AJedsInterstitial Cystitis London England Springer-Verlag1990;29- 48
Jones  CANyberg  L Epidemiology of interstitial cystitis. Urology. 1997;49suppl2- 9
PubMed Link to Article
Simon  LJLandis  JRErickson  DRNyberg  LM The Interstitial Cystitis Data Base Study: concepts and preliminarybaseline descriptive statistics. Urology. 1997;49suppl64- 75
PubMed Link to Article
Curhan  GCSpeizer  FEHunter  DJCurhan  SGStampfer  MJ Epidemiology of interstitial cystitis: a population based study. J Urol 1999;161549- 552
PubMed Link to Article
Warren  JWKeay  SKMeyers  DXu  J Concordance of interstitial cystitis in monozygotic and dizygotic twinpairs. Urology 2001;57suppl 122- 25
PubMed Link to Article
Hanno  PM Diagnosis of interstitial cystitis. Urol Clin North Am. 1994;2163- 66
PubMed
Hanno  PMLandis  JRMatthews-Cook  YKusek  JNyberg  L  Jr The diagnosis of interstitial cystitis revisited: lessons learned fromthe National Institutes of Health Interstitial Cystitis Database study. J Urol 1999;161553- 557
PubMed Link to Article
Agarwal  MO'Reilly  PHDixon  RA Interstitial cystitis: a time for revision of name and diagnostic criteriain the new millennium? BJU Int. 2001;88348- 350
PubMed Link to Article
Kusek  JWNyberg  LM The epidemiology of interstitial cystitis: is it time to expand ourdefinition? Urology. 2001;57suppl 195- 99
PubMed Link to Article
Propert  KJSchaeffer  AJBrensinger  CMKusek  JWNyberg  LMLandis  JRthe Interstitial Cystitis Data Base Study Group, A prospective study of interstitial cystitis: results of longitudinalfollowup of the Interstitial Cystitis Data Base cohort. J Urol. 2000;1631434- 1439
PubMed Link to Article
Krieger  JNNyberg  L  JrNickel  JC NIH consensus definition and classification of prostatitis. JAMA. 1999;282236- 237
PubMed Link to Article
Ku  JHKim  MELee  NKPark  YH The prevalence of chronic prostatitis-like symptoms in young men: acommunity-based survey. Urol Res. 2001;29108- 112
PubMed Link to Article
Vastag  B Prostate disease begs understanding. JAMA. 2001;286406- 408
PubMed Link to Article
Buffington  CAChew  DJWoodworth  BE Feline interstitial cystitis. J Am Vet Med Assoc. 1999;215682- 687
PubMed
Peeker  RAldenborg  FDahlstrom  AJohansson  SLLi  JYFall  M Increased tyrosine hydroxylase immunoreactivity in bladder tissue frompatients with classic and nonulcer interstitial cystitis. J Urol. 2000;1631112- 1115
PubMed Link to Article
Lutgendorf  SKKreder  KJRothrock  NEHoffman  AKirschbaum  CSternberg  EMZimmerman  MBRatliff  TL Diurnal cortisol variations and symptoms in patients with interstitialcystitis. J Urol 2002;1671338- 1343
PubMed Link to Article
Parkin  JShea  CSant  GR Intravesical dimethyl sulfoxide (DMSO) for interstitial cystitis: apractical approach. Urology. 1997;49suppl105107
PubMed Link to Article
Theoharides  TCSant  GR Hydroxyzine therapy for interstitial cystitis. Urology. 1997;49suppl108- 110
PubMed Link to Article
Rovner  EPropert  KJBrensinger  CWein  AJFoy  MKirkemo  ALandis  JRKusek  JWNyberg  LMthe Interstitial Cystitis Data Base Study Group, Treatments used in women with interstitial cystitis: the InterstitialCystitis Data Base (ICDB) Study experience. Urology 2000;56940- 945
PubMed Link to Article
Alagiri  MChottiner  SRatner  VSlade  DHanno  PM Interstitital cystitis: unexplained associations with other chronicdisease and pain syndromes. Urology. 1997;49(suppl)52- 57
PubMed Link to Article
Koziol  JA Epidemiology of interstitial cystitis. Urol Clin North Am. 1994;217- 20
PubMed
Pontari  MAHanno  PMWein  AJ Logical and systematic approach to the evaluation and management ofpatients suspected of having interstitial cystitis. Urology. 1997;49suppl114- 120
PubMed Link to Article
Mannuzza  SFyer  AJKlein  DFEndicott  J Schedule for Affective Disorders and Schizophrenia–Lifetime Versionmodified for the study of anxiety disorders (SADS-LA): rationale and conceptualdevelopment. J Psychiatr Res. 1986;20317- 325
PubMed Link to Article
Fyer  AEndicott  JMannuzza  SKlein  D Schedule for Affective Disorders and Schizophrenia–LifetimeVersion, Modified for the Study of Anxiety Disorders.  New York New York State Psychiatric Institute1995;
Leckman  JFSholomskas  DThompson  WDBelanger  AWeissman  MM Best estimate of lifetime psychiatric diagnosis: a methodological study. Arch Gen Psychiatry. 1982;39879- 883
PubMed Link to Article
Weissman  MMWickramaratne  PAdams  PWolk  SVerdeli  HOlfson  M Brief screening for family psychiatric history: the Family HistoryScreen. Arch Gen Psychiatry. 2000;57675- 682
PubMed Link to Article
Zeger  SLLiang  KYAlbert  PS Models for longitudinal data: a generalized estimating equation approach. Biometrics. 1988;441049- 1060
PubMed Link to Article
Weissman  MMWickramaratne  PAdams  PBLish  JDHorwath  ECharney  DWoods  SWLeeman  EFrosch  E The relationship between panic disorder and major depression: a newfamily study. Arch Gen Psychiatry. 1993;50767- 780
PubMed Link to Article
Weissman  MMMarkowitz  JSOuellette  RGreenwald  SKahn  JP Panic disorder and cardiovascular/cerebrovascular problems: resultsfrom a community survey. Am J Psychiatry. 1947;471504- 1508
PubMed
Breslau  NSchultz  LRStewart  WFLipton  RWelch  KM Headache types and panic disorder: directionality and specificity. Neurology. 2001;56350- 354
PubMed Link to Article
Gorman  JMGoetz  RRFyer  MKing  DLFyer  AJLiebowitz  MRKlein  DF The mitral valve prolapse–panic disorder connection. Psychosom Med. 1988;50114- 122
PubMed Link to Article
Placidi  GPBoldrini  MPatronelli  AFiore  EChiovato  LPerugi  GMarazziti  D Prevalence of psychiatric disorders in thyroid diseased patients. Neuropsychobiology 1998;38222- 225
PubMed Link to Article
Brauman  ARosenberg  TGilboa  YAlgom  MFuchs  LSchlesinger  Z Prevalence of mitral valve prolapse in chronic lymphocytic thyroiditisand nongoitrous hypothyroidism. Cardiology. 1988;75269- 273
PubMed Link to Article
Channick  BJAdlin  EVMarks  ADDenenberg  BSMcDonough  MTChakko  CSSpann  JF Hyperthyroidism and mitral-valve prolapse. N Engl J Med 1981;305497- 500
PubMed Link to Article
Jackson  AC Neurologic disorders associated with mitral valve prolapse. Can J Neurol Sci. 1986;1315- 20
PubMed
Blok  BF Central pathways controlling micturition and urinary continence. Urology. 2002;59suppl 113- 17
PubMed Link to Article
Rocha  IBurnstock  GSpyer  KM Effect on urinary bladder function and arterial blood pressure of theactivation of putative purine receptors in brainstem areas. Auton Neurosci. 2001;886- 15
PubMed Link to Article
Rothrock  NELutgendorf  SKKreder  KJRatliff  TLZimmerman  B Daily stress and symptom exacerbation in interstitial cystitis patients[abstract]. Urology. 2001;57suppl 1122
PubMed Link to Article
Hanno  PM Amitriptyline in the treatment of interstitial cystitis. Urol Clin North Am. 1994;2189- 91
PubMed
Buffington  TPacak  K Increased plasma norepinephrine concentrations in cats with interstitialcystitis [abstract]. Urology. 2001;57suppl 1102
PubMed Link to Article
Appel  SKuritzky  AZahavi  IZigelman  MAkselrod  S Evidence for instability of the autonomic nervous system in patientswith migraine headache. Headache. 1992;3210- 17
PubMed Link to Article
Theoharides  TCKempuraj  DSant  GR Mast cell involvement in interstitial cystitis: a review of human andexperimental evidence. Urology. 2001;57suppl 147- 55
PubMed Link to Article
Theoharides  TC The mast cell: a neuroimmunoendocrine master player. Int J Tissue React. 1996;181- 21
PubMed
Valentino  RJMiselis  RRPavcovich  LA Pontine regulation of pelvic viscera: pharmacological target for pelvicvisceral dysfunctions. Trends Pharmacol Sci. 1999;20253- 260
PubMed Link to Article
Pavcovich  LAValentino  RJ Central regulation of micturition in the rat: the corticotropin-releasinghormone from Barrington's nucleus. Neurosci Lett. 1995;196185- 188
PubMed Link to Article
Abelson  JLCurtis  GC Hypothalamic-pituitary-adrenal axis activity in panic disorder: 24-hoursecretion of corticotropin and cortisol. Arch Gen Psychiatry. 1996;53323- 331
PubMed Link to Article
Chapman  TFMannuzza  SKlein  DFFyer  AJ Effects of informant mental disorder on psychiatric family historydata. Am J Psychiatry. 1994;151574- 579
PubMed
Steers  WD Interstitial cystitis: past and future. Urology. 2001;57suppl 1101- 102
PubMed Link to Article
Theoharides  TCSant  GR New agents for the medical treatment of interstitial cystitis. Expert Opin Investig Drugs. 2001;10521- 546
PubMed Link to Article
Steers  W Potential targets in the treatment of urinary incontinence. Rev Urol. 2001;3suppl 1S19- S26
Holsboer  F The rationale for corticotropin-releasing hormone receptor (CRH-R)antagonists to treat depression and anxiety. J Psychiatr Res. 1999;33181- 214
PubMed Link to Article
Hudson  JIMangweth  BPope  HG  JrDe  Col CHausmann  AGutweniger  SLaird  NMBiebl  WTsuang  MT Family study of affective spectrum disorder. Arch Gen Psychiatry. 2003;60170- 177
PubMed Link to Article

Figures

Tables

Table Graphic Jump LocationTable 1. Panic Disorder and Other Syndrome Conditions in Probands Withand Without IC
Table Graphic Jump LocationTable 2. Lifetime Disorders in FDRs of Probands With and Without IC,Excluding Probands With Panic Disorder

References

Weissman  MMFyer  AJHaghighi  FHeiman  GDeng  ZHen  RHodge  SEKnowles  JA Potential panic disorder syndrome: clinical and genetic linkage evidence. Am J Med Genet. 2000;9624- 35
PubMed Link to Article
Fyer  AWeissman  M Genetic linkage study of panic: clinical methodology and descriptionof pedigrees. Am J Med Genet. 1999;88173- 181
PubMed Link to Article
Knowles  JAFyer  AJVieland  VJWeissman  MMHodge  SEHeiman  GAHaghighi  Fde Jesus  GMRassnick  HPreud'homme-Rivelli  XAustin  TCunjak  JMick  SFine  LDWoodley  KADas  KMaier  WAdams  PBFreimer  NBKlein  DFGilliam  TC Results of a genome-wide genetic screen for panic disorder. Am J Med Genet. 1998;81139- 147
PubMed Link to Article
Hamilton  SPFyer  AJDurner  MHerman  GAde Baisre  Leon AHodge  SEKnowles  JAWeissman  MM Further genetic evidence for a panic disorder syndrome mapping to chromosome13q. Proc Natl Acad Sci U S A. 2003;1002550- 2555
PubMed Link to Article
Sullivan  GMCoplan  JDKent  JMGorman  JM The noradrenergic system in pathological anxiety: a focus on panicwith relevance to generalized anxiety and phobias. Biol Psychiatry. 1999;461205- 1218
PubMed Link to Article
Gorman  JMKent  JMSullivan  GMCoplan  JD Neuroanatomical hypothesis of panic disorder, revised. Am J Psychiatry. 2000;157493- 505
PubMed Link to Article
King  RCStansfield  WD A Dictionary of Genetics.  New York, NY Oxford University Press Inc1990;
Weissman  MM Family genetic studies of panic disorder. J Psychiatr Res. 1993;27suppl 169- 78
PubMed Link to Article
Hettema  JMNeale  MCKendler  KS A review and meta-analysis of the genetic epidemiology of anxiety disorders. Am J Psychiatry. 2001;1581568- 1578
PubMed Link to Article
Weissman  MMBland  RCCanino  GJFaravelli  CGreenwald  SHwu  HGJoyce  PRKaram  EGLee  CKLellouch  JLepine  JPNewman  SCOakley-Browne  MARubio-Stipec  MWells  JEWickramaratne  PJWittchen  HUYeh  EK The cross-national epidemiology of panic disorder. Arch Gen Psychiatry. 1997;54305- 309
PubMed Link to Article
Gorman  JMKent  JMCoplan  JD Current and emerging therapeutics of anxiety and stress disorders. Davis  KLCharney  DCoyle  JTNemeroff  CedsNeuropsychopharmacology: The Fifth Generation of Progress. Baltimore,Md Lippincott Williams & Wilkins2002;967- 980
Weissman  MMKlerman  GLMarkowitz  JSOuellette  R Suicidal ideation and suicide attempts in panic disorder and attacks. N Engl J Med. 1989;3211209- 1214
PubMed Link to Article
Warren  JWKeay  SK Interstitial cystitis. Curr Opin Urol. 2002;1269- 74
PubMed Link to Article
Held  PJHanno  PMWein  AJPauly  MVCahn  MA Epidemiology of interstitial cystitis. Hanno  PMStaskin  DRKrane  RJWein  AJedsInterstitial Cystitis London England Springer-Verlag1990;29- 48
Jones  CANyberg  L Epidemiology of interstitial cystitis. Urology. 1997;49suppl2- 9
PubMed Link to Article
Simon  LJLandis  JRErickson  DRNyberg  LM The Interstitial Cystitis Data Base Study: concepts and preliminarybaseline descriptive statistics. Urology. 1997;49suppl64- 75
PubMed Link to Article
Curhan  GCSpeizer  FEHunter  DJCurhan  SGStampfer  MJ Epidemiology of interstitial cystitis: a population based study. J Urol 1999;161549- 552
PubMed Link to Article
Warren  JWKeay  SKMeyers  DXu  J Concordance of interstitial cystitis in monozygotic and dizygotic twinpairs. Urology 2001;57suppl 122- 25
PubMed Link to Article
Hanno  PM Diagnosis of interstitial cystitis. Urol Clin North Am. 1994;2163- 66
PubMed
Hanno  PMLandis  JRMatthews-Cook  YKusek  JNyberg  L  Jr The diagnosis of interstitial cystitis revisited: lessons learned fromthe National Institutes of Health Interstitial Cystitis Database study. J Urol 1999;161553- 557
PubMed Link to Article
Agarwal  MO'Reilly  PHDixon  RA Interstitial cystitis: a time for revision of name and diagnostic criteriain the new millennium? BJU Int. 2001;88348- 350
PubMed Link to Article
Kusek  JWNyberg  LM The epidemiology of interstitial cystitis: is it time to expand ourdefinition? Urology. 2001;57suppl 195- 99
PubMed Link to Article
Propert  KJSchaeffer  AJBrensinger  CMKusek  JWNyberg  LMLandis  JRthe Interstitial Cystitis Data Base Study Group, A prospective study of interstitial cystitis: results of longitudinalfollowup of the Interstitial Cystitis Data Base cohort. J Urol. 2000;1631434- 1439
PubMed Link to Article
Krieger  JNNyberg  L  JrNickel  JC NIH consensus definition and classification of prostatitis. JAMA. 1999;282236- 237
PubMed Link to Article
Ku  JHKim  MELee  NKPark  YH The prevalence of chronic prostatitis-like symptoms in young men: acommunity-based survey. Urol Res. 2001;29108- 112
PubMed Link to Article
Vastag  B Prostate disease begs understanding. JAMA. 2001;286406- 408
PubMed Link to Article
Buffington  CAChew  DJWoodworth  BE Feline interstitial cystitis. J Am Vet Med Assoc. 1999;215682- 687
PubMed
Peeker  RAldenborg  FDahlstrom  AJohansson  SLLi  JYFall  M Increased tyrosine hydroxylase immunoreactivity in bladder tissue frompatients with classic and nonulcer interstitial cystitis. J Urol. 2000;1631112- 1115
PubMed Link to Article
Lutgendorf  SKKreder  KJRothrock  NEHoffman  AKirschbaum  CSternberg  EMZimmerman  MBRatliff  TL Diurnal cortisol variations and symptoms in patients with interstitialcystitis. J Urol 2002;1671338- 1343
PubMed Link to Article
Parkin  JShea  CSant  GR Intravesical dimethyl sulfoxide (DMSO) for interstitial cystitis: apractical approach. Urology. 1997;49suppl105107
PubMed Link to Article
Theoharides  TCSant  GR Hydroxyzine therapy for interstitial cystitis. Urology. 1997;49suppl108- 110
PubMed Link to Article
Rovner  EPropert  KJBrensinger  CWein  AJFoy  MKirkemo  ALandis  JRKusek  JWNyberg  LMthe Interstitial Cystitis Data Base Study Group, Treatments used in women with interstitial cystitis: the InterstitialCystitis Data Base (ICDB) Study experience. Urology 2000;56940- 945
PubMed Link to Article
Alagiri  MChottiner  SRatner  VSlade  DHanno  PM Interstitital cystitis: unexplained associations with other chronicdisease and pain syndromes. Urology. 1997;49(suppl)52- 57
PubMed Link to Article
Koziol  JA Epidemiology of interstitial cystitis. Urol Clin North Am. 1994;217- 20
PubMed
Pontari  MAHanno  PMWein  AJ Logical and systematic approach to the evaluation and management ofpatients suspected of having interstitial cystitis. Urology. 1997;49suppl114- 120
PubMed Link to Article
Mannuzza  SFyer  AJKlein  DFEndicott  J Schedule for Affective Disorders and Schizophrenia–Lifetime Versionmodified for the study of anxiety disorders (SADS-LA): rationale and conceptualdevelopment. J Psychiatr Res. 1986;20317- 325
PubMed Link to Article
Fyer  AEndicott  JMannuzza  SKlein  D Schedule for Affective Disorders and Schizophrenia–LifetimeVersion, Modified for the Study of Anxiety Disorders.  New York New York State Psychiatric Institute1995;
Leckman  JFSholomskas  DThompson  WDBelanger  AWeissman  MM Best estimate of lifetime psychiatric diagnosis: a methodological study. Arch Gen Psychiatry. 1982;39879- 883
PubMed Link to Article
Weissman  MMWickramaratne  PAdams  PWolk  SVerdeli  HOlfson  M Brief screening for family psychiatric history: the Family HistoryScreen. Arch Gen Psychiatry. 2000;57675- 682
PubMed Link to Article
Zeger  SLLiang  KYAlbert  PS Models for longitudinal data: a generalized estimating equation approach. Biometrics. 1988;441049- 1060
PubMed Link to Article
Weissman  MMWickramaratne  PAdams  PBLish  JDHorwath  ECharney  DWoods  SWLeeman  EFrosch  E The relationship between panic disorder and major depression: a newfamily study. Arch Gen Psychiatry. 1993;50767- 780
PubMed Link to Article
Weissman  MMMarkowitz  JSOuellette  RGreenwald  SKahn  JP Panic disorder and cardiovascular/cerebrovascular problems: resultsfrom a community survey. Am J Psychiatry. 1947;471504- 1508
PubMed
Breslau  NSchultz  LRStewart  WFLipton  RWelch  KM Headache types and panic disorder: directionality and specificity. Neurology. 2001;56350- 354
PubMed Link to Article
Gorman  JMGoetz  RRFyer  MKing  DLFyer  AJLiebowitz  MRKlein  DF The mitral valve prolapse–panic disorder connection. Psychosom Med. 1988;50114- 122
PubMed Link to Article
Placidi  GPBoldrini  MPatronelli  AFiore  EChiovato  LPerugi  GMarazziti  D Prevalence of psychiatric disorders in thyroid diseased patients. Neuropsychobiology 1998;38222- 225
PubMed Link to Article
Brauman  ARosenberg  TGilboa  YAlgom  MFuchs  LSchlesinger  Z Prevalence of mitral valve prolapse in chronic lymphocytic thyroiditisand nongoitrous hypothyroidism. Cardiology. 1988;75269- 273
PubMed Link to Article
Channick  BJAdlin  EVMarks  ADDenenberg  BSMcDonough  MTChakko  CSSpann  JF Hyperthyroidism and mitral-valve prolapse. N Engl J Med 1981;305497- 500
PubMed Link to Article
Jackson  AC Neurologic disorders associated with mitral valve prolapse. Can J Neurol Sci. 1986;1315- 20
PubMed
Blok  BF Central pathways controlling micturition and urinary continence. Urology. 2002;59suppl 113- 17
PubMed Link to Article
Rocha  IBurnstock  GSpyer  KM Effect on urinary bladder function and arterial blood pressure of theactivation of putative purine receptors in brainstem areas. Auton Neurosci. 2001;886- 15
PubMed Link to Article
Rothrock  NELutgendorf  SKKreder  KJRatliff  TLZimmerman  B Daily stress and symptom exacerbation in interstitial cystitis patients[abstract]. Urology. 2001;57suppl 1122
PubMed Link to Article
Hanno  PM Amitriptyline in the treatment of interstitial cystitis. Urol Clin North Am. 1994;2189- 91
PubMed
Buffington  TPacak  K Increased plasma norepinephrine concentrations in cats with interstitialcystitis [abstract]. Urology. 2001;57suppl 1102
PubMed Link to Article
Appel  SKuritzky  AZahavi  IZigelman  MAkselrod  S Evidence for instability of the autonomic nervous system in patientswith migraine headache. Headache. 1992;3210- 17
PubMed Link to Article
Theoharides  TCKempuraj  DSant  GR Mast cell involvement in interstitial cystitis: a review of human andexperimental evidence. Urology. 2001;57suppl 147- 55
PubMed Link to Article
Theoharides  TC The mast cell: a neuroimmunoendocrine master player. Int J Tissue React. 1996;181- 21
PubMed
Valentino  RJMiselis  RRPavcovich  LA Pontine regulation of pelvic viscera: pharmacological target for pelvicvisceral dysfunctions. Trends Pharmacol Sci. 1999;20253- 260
PubMed Link to Article
Pavcovich  LAValentino  RJ Central regulation of micturition in the rat: the corticotropin-releasinghormone from Barrington's nucleus. Neurosci Lett. 1995;196185- 188
PubMed Link to Article
Abelson  JLCurtis  GC Hypothalamic-pituitary-adrenal axis activity in panic disorder: 24-hoursecretion of corticotropin and cortisol. Arch Gen Psychiatry. 1996;53323- 331
PubMed Link to Article
Chapman  TFMannuzza  SKlein  DFFyer  AJ Effects of informant mental disorder on psychiatric family historydata. Am J Psychiatry. 1994;151574- 579
PubMed
Steers  WD Interstitial cystitis: past and future. Urology. 2001;57suppl 1101- 102
PubMed Link to Article
Theoharides  TCSant  GR New agents for the medical treatment of interstitial cystitis. Expert Opin Investig Drugs. 2001;10521- 546
PubMed Link to Article
Steers  W Potential targets in the treatment of urinary incontinence. Rev Urol. 2001;3suppl 1S19- S26
Holsboer  F The rationale for corticotropin-releasing hormone receptor (CRH-R)antagonists to treat depression and anxiety. J Psychiatr Res. 1999;33181- 214
PubMed Link to Article
Hudson  JIMangweth  BPope  HG  JrDe  Col CHausmann  AGutweniger  SLaird  NMBiebl  WTsuang  MT Family study of affective spectrum disorder. Arch Gen Psychiatry. 2003;60170- 177
PubMed Link to Article

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 60

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles