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Interstitial cystitis/painful bladder syndrome (IC) is a chronic pelvic pain condition which has high comorbidity with other nociplastic, or unexplained, pain disorders [e.g. fibromyalgia (FM), irritable bowel syndrome (IBS), and myalgic encephalomyelitis/chronic fatigue (ME/CFS)] and some psychiatric conditions [major depressive disorder (MDD) and panic disorder (PD)]. Here we investigated the shared familiality of IC and these other nociplastic and psychiatric conditions.
Subjects were identified in the Utah Population Database, which links genealogy data back to the 1800s to medical record diagnosis billing code data back to 1995. We computed the relative risk of each of these disorders among first (FDR), second (SDR), and third-degree relatives (TDR) of six proband groups: IC, FM, IBS, ME/CFS, PD, and MDD. Given the known familial aggregation of each of these disorders, we conducted our analyses to test for heritable interrelationships using proband subgroups whose members did not have the diagnosis assessed in their relatives.
We observed strong evidence for heritable interrelationships among all six disorders. Most analyses indicated significantly increased risk for each of the six disorders in FDR, SDR, and TDR of all or most proband groups. Out of 30 possible bidirectional disorder interrelationships, 26 were significant among FDR, 23 were significant among SDR, and 7 were significant among TDR. Clustering was observed in both close and distant relatives.
Our results support a common, heritable component to IC and other nociplastic and psychiatric conditions.
Background. This and the companion paper present two sequential family studies of obsessive–compulsive disorder (OCD) conducted by the same research group, but with different sampling and best-estimate procedures. In addition to providing further data on familial transmission of OCD, we used comparison of disparate findings (moderate, specific familial aggregation in this first study versus a stronger effect for other anxiety disorders than for OCD alone in the second) to examine possible effects of proband characteristics and informant data on outcome.
Method. In this initial study we interviewed 179 first-degree relatives of 72 OCD probands and 112 relatives of 32 never mentally ill (NMI) controls. Informant data were obtained on an additional 126 relatives (total ‘combined’ samples of 263 and 154 respectively). Analyses used best-estimate diagnoses made by consensus of two ‘blinded’ senior clinicians who reviewed all diagnostic materials including proband informant data about relatives.
Results. Significantly higher risk for OCD but not other anxiety disorders was found in relatives of OCD probands compared to relatives of controls in both the directly interviewed and combined samples. There was no relationship between proband age at onset of OCD and strength of familial aggregation.
Conclusions. These data indicate moderate familial aggregation of OCD, but do not support increased transmission by early onset probands, or a familial relationship between OCD and other anxiety disorders with the possible exception of generalized anxiety disorder.
Background. Overall findings of our first direct interview family study of obsessive–compulsive disorder (OCD) indicated that OCD is familial. In this replication study, we carefully examined the role of informant data in ascertaining OCD in relatives.
Method. We interviewed 112 relatives of 57 OCD patients and 115 relatives of 41 not ill controls predominantly by telephone. Additional analyses included a combined sample of relatives about whom any diagnostic information was available (228 OCD and 239 controls). To examine the contribution of proband information about relatives, we considered two sets of best-estimate diagnoses. First, we ascertained best-estimate diagnoses for relatives using information from direct interviews and from all informants except the proband. Then, we re-diagnosed relatives based on all available information, including reports from the proband about their relatives.
Results. When relative diagnoses were derived without the benefit of proband informant reports, no evidence of familial OCD transmission was found. When diagnoses were made including information from the proband about the relative, evidence of familial OCD was found, but only when the diagnostic threshold was lowered to include cases with probable OCD or OCD symptoms. Other diagnoses (generalized anxiety disorder, social phobia, drug use disorder) were also higher among OCD relatives.
Conclusions. This second study provides less robust support for familial transmission of OCD. Evidence for familial transmission of OCD was found only when diagnoses were made using information from the affected proband about their relatives. Taken in context of past findings, our own inconsistent results suggest that OCD may be heterogeneous with regard to familial transmission. Also, more careful attention should be paid to the contribution of informant reports, especially from relatives affected by the same disorder.
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