The multi-generational familial aggregation of interstitial cystitis, other chronic nociplastic pain disorders, depression, and panic disorder

Abstract

Background 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. Methods 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. Results 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. Conclusions Our results support a common, heritable component to IC and other nociplastic and psychiatric conditions.

Interstitial cystitis—an imbalance of risk and protective factors?

“…Predisposing risk factors that can increase susceptibility to IC include genetic vulnerability ( 12 ), family ( 104 , 119 ) medical ( 120 ) and mental health history ( 121 ), personality traits ( 122 ), ELA and RLA ( 14 ), age ( 119 ). and gender ( 123 ).…”

“…Although trauma-informed care is not specifically mentioned in all pelvic pain guidelines, clinicians are encouraged to listen attentively, convey interest and compassion, and validate patients’ symptom experiences ( 200 ). Screening for a family history of COPC beyond first-degree relatives may be useful during the initial evaluation of patients presenting with pain, anxiety, or depression because it could lead to earlier diagnosis of other relatives who could benefit from treatment ( 12 ).…”

“…Predisposing risk factors are those that can increase susceptibility to IC. These include genetic vulnerability and family medical and mental health history ( 12 ), personality traits ( 101 ), early (ELA) ( 102 , 103 ) and recent (RLA) life adversities ( 14 ), age, ( 104 ), race ( 105 ), and gender ( 106 ). In cats and rodents, predisposing factors include genetic vulnerability, ELA, personality traits, breed, sex, housing, and RLA (e.g., social conflict) ( 1 , 107 ).…”