Depressive Symptoms in Crohn's Disease: Relationship with Immune Activation and Tryptophan Availability

Department of Psychiatry and Psychology, Maastricht University Medical Centre, EURON, Maastricht, The Netherlands.
PLoS ONE (Impact Factor: 3.23). 03/2013; 8(3):e60435. DOI: 10.1371/journal.pone.0060435
Source: PubMed


Crohn's disease (CD) is associated with immune activation and depressive symptoms. This study determines the impact of anti-tumor necrosis factor (TNF)-α treatment in CD patients on depressive symptoms and the degree to which tryptophan (TRP) availability and immune markers mediate this effect. Fifteen patients with CD, eligible for anti-TNF-α treatment were recruited. Disease activity (Harvey-Bradshaw Index (HBI), Crohn's Disease Activity Index (CDAI)), fatigue (Multidimensional Fatigue Inventory (MFI)), quality of life (Inflammatory Bowel Disease Questionnaire (IBDQ)), symptoms of depression and anxiety (Symptom Checklist (SCL-90), Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HDRS)), immune activation (acute phase proteins (APP)), zinc and TRP availability were assessed before treatment and after 2, 4 and 8 weeks. Anti-TNF-α increased IBDQ scores and reduced all depression scores; however only SCL-90 depression scores remained decreased after correction for HBI. Positive APPs decreased, while negative APPs increased after treatment. After correction for HBI, both level and percentage of γ fraction were associated with SCL-90 depression scores over time. After correction for HBI, patients with current/past depressive disorder displayed higher levels of positive APPs and lower levels of negative APPs and zinc. TRP availability remained invariant over time and there was no association between SCL-90 depression scores and TRP availability. Inflammatory reactions in CD are more evident in patients with comorbid depression, regardless of disease activity. Anti-TNF-α treatment in CD reduces depressive symptoms, in part independently of disease activity; there was no evidence that this effect was mediated by immune-induced changes in TRP availability.

Download full-text


Available from: Robert Verkerk,
1 Follower
59 Reads
  • Source
    • "It usually affects a younger age group with a worldwide distribution. It has a high impact on the psychological condition [8], as well as the social status and work abilities [9] in patients with this disease. Based on these negative effects on the general health and welfare of patients with CD and the drawbacks of the currently used medical treatments as well as the increased likelihood of surgical complications in these patients, a search for the causative factor(s) together with a proposal for the use of an alternative therapeutic strategy involving eradication of the causative factors could be of crucial importance in the management of this disease. "
    [Show abstract] [Hide abstract]
    ABSTRACT: There is a general consensus that Crohn's disease (CD) develops as the result of immune-mediated tissue damage triggered by infections with intestinal microbial agents. Based on the results of existing microbiological, molecular, and immunological studies, Klebsiella microbe seems to have a key role in the initiation and perpetuation of the pathological damage involving the gut and joint tissues in patients with CD. Six different gastroenterology centres in the UK have reported elevated levels of antibodies to Klebsiella in CD patients. There is a relationship between high intake of starch-containing diet, enhanced growth of gut microbes, and the production of pullulanases by Klebsiella. It is proposed that eradication of these microbes by the use of antibiotics and low starch diet, in addition to the currently used treatment, could help in alleviating or halting the disease process in CD.
    International Journal of Rheumatology 10/2013; 2013:610393. DOI:10.1155/2013/610393
  • [Show abstract] [Hide abstract]
    ABSTRACT: Studies have found that depression is more frequent in patients with inflammatory bowel disease (IBD) than the general population. Clinicians are now trying to pinpoint risk factors for psychological impairment in the IBD population. To examine the demographic and phenotypic variables associated with the development of depression among a diverse cohort of IBD patients. We also sought to describe psychotropic therapy prescribed to IBD patients. We conducted a retrospective cohort study including patients with Crohn's disease (CD) and ulcerative colitis (UC) without a prior psychiatric diagnosis and followed in the gastroenterology clinics of the private university hospital and public safety net hospital at a large academic centre in Miami (Florida). Predictive variables included demographic characteristics, IBD phenotype, exposure to IBD medications, history of a surgical stoma or seton placement, extra-intestinal manifestations, laboratory indices, aggressive disease and disease activity (based on imaging and endoscopic parameters). Proportional hazard regression models and stepwise Cox regression analysis were used for statistical analysis. Independent predictors of depression were female gender [HR: 1.3 (95% CI: 1.1-1.7), P = 0.01], aggressive disease [HR: 1.4 (95% CI: 1.02-1.9), P = 0.03] and active disease [HR: 1.5 (95% CI: 1.1-2.0), P = 0.04]. In the group that did develop a depressive disorder, 65% received pharmacologic therapy with one or more psychotropic agents. We found female gender, aggressive disease and increased endoscopic/radiological activity to be independently associated with the development of depression in inflammatory bowel disease.
    Alimentary Pharmacology & Therapeutics 03/2014; 39(8). DOI:10.1111/apt.12669 · 5.73 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Electroconvulsive therapy (ECT) remains the most effective and fast-acting treatment option for several psychiatric conditions, including treatment-resistant depression. Although ECT has been in use for 75 years, the mechanism of action is unknown. There is emerging evidence that modulation of the hypothalamic-pituitary-adrenal axis may mediate, in part, the therapeutic action of ECT. A growing body of evidence points to links between disturbances in the immune system and depression. However, the impact of ECT on immune functioning and the possible role of alterations in the immune system as a mechanism of action of ECT remain elusive. To provide a literature overview on the effects of ECT on the immune system. Relevant articles and abstracts in English were retrieved from PubMed/Medline using search terms related to ECT, inflammation, and immune system. The results of studies examining ECT-induced changes in immune functioning as well as the degree to which these represent possible mechanisms mediating the therapeutic action of ECT were summarized. Our search identified only a limited number of studies. The findings suggest that a single session of ECT induces an acute, transient immune activation, whereas repetitive ECT treatment results in long-term down-regulation of immune activation. However, inconsistency in findings and methodological issues, including sample size and lack of consideration of confounding factors affecting cytokine concentrations, precludes definitive conclusion. To elucidate the possible role of immunological changes mediating the effect of ECT, more prospective controlled studies with larger sample sizes are required.
    The journal of ECT 04/2014; 30(2). DOI:10.1097/YCT.0000000000000127 · 1.39 Impact Factor
Show more