Background: Up to 40 per cent of people with active inflammatory bowel disease (IBD) also suffer from mood disorders such as anxiety and depression. Notwithstanding, the fundamental biological pathways driving depression in IBD remain unknown.Methods: We identified 33 core genes that drive depression in IBD patients and performed consensus molecular subtyping with the NMF algorithm in IBD. The CIBERSORT were employed to quantify the immune cells. Metabolic signature was characterized using the “IOBR” R package. The scoring system (D. score) based on PCA. Pre-clinical models are constructed using DSS.Results: Using transcriptome data from the GEO database of 630 IBD patients, we performed a thorough analysis of the correlation between IBD and depression in this research. Firstly, the samples were separated into two different molecular subtypes (D. cluster1 and D. cluster2) based on their biological signatures. Moreover, the immunological and metabolic differences between them were evaluated, and we discovered that D. cluster2 most closely resembled IBD patients concomitant with depression. We also developed a scoring system to assess the IBD-related depression and predict clinical response to anti-TNF- therapy, with a higher D. score suggesting more inflammation and worse reaction to biological therapies. Ultimately, we also identified through animal experiments an antidepressant, paroxetine, has the added benefit of lowering intestinal inflammation by controlling microorganisms in the digestive tract.Conclusions: This study highlights that IBD patients with or without depression show significant variations and antidepressant paroxetine may help reduce intestinal inflammation.

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Early diagnosis and prevention of glucocorticoid (GC)‐induced osteonecrosis of the femoral head (ONFH) continues to be a challenging problem for clinicians and researchers. However, the role of circulating biomarkers for GC‐induced ONFH, which may reveal individual susceptibility and facilitate earlier diagnosis, remains to be determined. The aim of this study was to identify potential biomarkers that may predict early GC‐induced ONFH. A total of 123 patients scheduled for initial systemic GC therapy were enrolled in this prospective nested case–control study. The serum concentrations of 13 potential biomarkers were measured in seven patients with GC‐induced ONFH, diagnosed instantly after short‐term use of GCs and in 20 controls who did not develop osteonecrosis despite similar GC therapy. Biomarkers were measured both before and after taking GCs to identify any differences in marker levels and the changes during GC therapy between two groups. Type I collagen cross‐linked C‐telopeptide (β‐CTX; p = 0.000) was significantly lower, high‐density lipoprotein cholesterol (p = 0.092) and apolipoprotein (apo)‐B/apo‐A1 (p = 0.085) tended to be lower and higher, respectively, before GC treatment in osteonecrosis group. After GC therapy, β‐CTX (p = 0.014) was significantly lower and amino terminal telopeptide of procollagen type I (PINP; p = 0.068) tended to be lower in the osteonecrosis group. As secondary outcomes, we observed remarkable changes in nine potential biomarkers following short‐term GC therapy in both groups. In conclusion, we found that β‐CTX, could potentially be used to predict GC‐induced ONFH before GC therapy. Lower β‐CTX and PINP are promising biomarkers for the early diagnosis of GC‐induced ONFH. These findings need to be confirmed in large‐scale prospective studies. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2348–2357, 2019