4.7 Article

Constant-severe pain in chronic pancreatitis is associated with genetic loci for major depression in the NAPS2 cohort

期刊

JOURNAL OF GASTROENTEROLOGY
卷 55, 期 10, 页码 1000-1009

出版社

SPRINGER JAPAN KK
DOI: 10.1007/s00535-020-01703-w

关键词

Pain chronic; Chronic pancreatitis; Depression; Antidepressants; Human genetics

资金

  1. NIDDK [T32 DK063922-17]
  2. NIH [DK061451, R21 DK098560, U01 DK108306]
  3. National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [UL1 RR024153, UL1TR000005]
  4. NIH Roadmap for Medical Research (University of Pittsburgh) [UL1 RR024153, UL1TR000005]

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Background Pain is the most debilitating symptom of recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) and often requires chronic opioids or total pancreatectomy with islet autotransplantation to manage. Pain is a complex experience that can be exacerbated by depression and vice versa. Our aim was to test the hypothesis that depression-associated genes are associated with a constant-severe pain experience in RAP/CP patients. Study A retrospective study was done using North American Pancreatitis Study II (NAPS2) genotyped RAP and CP patients with completed case report forms (n = 1,357). Subjects were divided based on pattern of pain and pain severity asconstant-severe pain(n = 787) versusnot constant-severe pain(n = 570) to conduct a nested genome-wide association study. The association between reported antidepressant medication use and depression gene loci was tested. Results Constant-severe pain was reported in 58% (n = 787) of pancreatitis patients. No differences in sex or alcohol consumption were found based on pain severity. Antidepressant use was reported in 28% (n = 223), and they had lower SF-12 mental quality of life (MCS,p < 2.2 x 10(- 16)). Fifteen loci associated with constant-severe pain (p < 0.00001) were found to be in or near depression-associated genes including ROBO2, CTNND2, SGCZ, CNTN5 and BAIAP2. Three of these genes respond to antidepressant use (SGCZ, ROBO2, and CTNND2). Conclusion Depression is a major co-factor in the pain experience. This genetic predisposition to depression may have utility in counseling patients and in instituting early antidepressant therapy for pain management of pancreatitis patients. Prospective randomized trials are warranted.

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