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: 3.53). 03/2013; 8(3):e60435. DOI: 10.1371/journal.pone.0060435
Source: PubMed

ABSTRACT 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.

1 Follower
  • [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 abstract] [Hide abstract]
    ABSTRACT: Recent research suggests a relationship of inflammatory bowel disease (IBD) and depression. Our objective was to evaluate for improvement of depressive symptoms with treatment of IBD using immunosuppressive medications. A retrospective study of consecutive patients with IBD started on immunosuppressive agents [anti-tumor necrosis factor (anti-TNF) or immunomodulator therapy] was conducted. Patients were evaluated if disease activity indices using Harvey Bradshaw Index for Crohn's disease (CD) and Simple Clinical Colitis Disease Activity Index for ulcerative colitis (UC) and depressive indices using Patient Health Questionnaire-9 (PHQ-9) scores were obtained before and at least 30 days after initiation of therapy. Sixteen patients with UC and 53 patients with CD (all with active disease symptoms) were evaluated over a 60 day median follow-up evaluation (range 30, 140 days). Twenty-two patients started on immunomodulator therapy, and 47 patients started on anti-TNF therapy. Crohn's disease patients had significantly decreased PHQ-9 scores at follow-up [median 9 (range 3, 14) to 4 (1, 8)], with significant decreases only in those started on anti-TNF therapy. Changes in PHQ-9 and CRP were correlated (rho = 0.38, p < 0.05). In patients with UC, PHQ-9 scores [5 (3, 9) to 2 (0, 5)] were significantly decreased. Percentage at risk of moderate to severe depression (PHQ-9 scores a parts per thousand yen10) was lower after treatment [Crohn's disease 51-18 % (p < 0.05), ulcerative colitis 18-0 %]. Depressive scores decreased significantly in patients with IBD treated with immunosuppressive therapy and the number at risk for moderate to severe depression improved significantly.
    Digestive Diseases and Sciences 10/2014; 60(2). DOI:10.1007/s10620-014-3375-0 · 2.55 Impact Factor
  • [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 · 4.55 Impact Factor