Leveraging electronic health records for subtype-dependent directionality in depression and gastrointestinal disease: a retrospective cohort study

BACKGROUND: Depression and gastrointestinal (GI) disease frequently co-occur, yet the temporal directionality of this relationship, and whether it varies by GI subtype, remains poorly characterized in diverse populations. We aimed to determine whether depression or GI disease occurs first, and whether this directionality differs across irritable bowel syndrome (IBS), Crohn's disease, and ulcerative colitis (UC). METHODS: Using the University of California Health Data Warehouse and the NIH All of Us Research Program database, we compared temporal order of first diagnoses using a six month buffer. Cox models estimated bidirectional hazard ratios, stratified by GI subtype and replicated across six UC medical centers. RESULTS: Depression was diagnosed before IBS in 73.2% of cases (All of Us) and 65.2% (UCHDW), but GI disease was diagnosed first in most Crohn's disease cases (depression was diagnosed first in 46.8% of All of Us cases and 35.1% of UCHDW cases), with UC intermediate. IBS had the highest depression first percentage at five of six centers. Overall, 69.5% of comorbid patients were diagnosed with depression before GI disease (adjusted HR 1.66, 95% CI 1.62-1.71 vs 1.13, 1.09-1.17 for the reverse). CONCLUSIONS: Depression was more often diagnosed before GI disease than the reverse, with a subtype dependent gradient ranging from depression more often diagnosed first in IBS to GI disease more often diagnosed first in Crohn's disease. Antidepressant use was associated with a lower rate of subsequent GI disease. These findings, replicated across two databases, have implications for subtype specific screening and integrated care.