Abstracts

Rationale: Many research studies describe comorbid neurological and psychiatric disorders in individuals with a brain disorder. Shared genetic risk factors can partially explain the observed phenotypic overlap, with a higher genetic correlation between psychiatric compared to neurological disorders. However, no studies comprehensively examined the comorbidity patterns of neurological and psychiatric disorders across the common types of brain disorders. Additionally, although many studies consider age, only a few studies have examined the sex-specific comorbidity of brain disorders. To fill this knowledge gap, we assessed the co-occurrence of brain disorders across age and sex in a large healthcare system.

Methods: Based on ICD-10 diagnosis codes, we identified over one million individuals diagnosed with at least one out of 20 common brain disorder types present in the aggregated health care data of eight million patients from the Cleveland Clinic healthcare system. The identified individuals were stratified into six distinct demographic groups based on age (children, adult, and elderly) and sex (male and female). For each of the 20 brain disorders and six demographic groups, we tested the enrichment of each comorbid neurological or psychiatric disorder compared to age- and sex-matched controls without brain disorders.

Results: Overall, we performed 2,280 tests and identified 327 significantly associated brain disorder pairs with an odds ratio >4. On average, each brain disorder had five significant comorbidities across all demographic groups. We replicated well-established disease-disease associations such as the co-occurrence of stroke and focal epilepsy. In line with previous evidence, we found that psychiatric disorders had, on average, a greater number of significant associations with other brain disorders compared to neurological disorders. Specifically, individuals with psychiatric disorders were enriched for other psychiatric disorders across all three age groups. We further identified distinct patterns of comorbid brain disorders for each age and sex group. For example, while generalized epilepsy was associated with autism spectrum disorder in children and adults, it was associated with Alzheimer’s disease and stroke in the elderly. Finally, we observed sex-specific differential patterns of enrichment across all tested brain disorders.

Conclusions: The goal of this research was to provide a unified resource for the age- and sex-specific clinical relationships between brain disorders. The results of our study will inform the clinical care of patients diagnosed with these conditions.

Funding: Please list any funding that was received in support of this abstract.: This work was supported by institutional funding from the Cleveland Clinic Foundation.