G-protein beta3 subunit 825CC genotype is associated with unexplained (functional) dyspepsia

Background & Aims: In patients with functional dyspepsia, altered α-adrenoreceptor function and depression are prevalent, features that are linked to a G-protein β3 (GNB3) subunit gene polymorphism (C825T). We aimed to assess the association of specific G-protein β3 subunit genotypes with functional dyspepsia. Methods: In study A, abdominal symptoms were assessed in 67 patients with unexplained, upper abdominal symptoms and 259 consecutive blood donors with and without abdominal symptoms. In study B, a further 56 patients with functional dyspepsia and 112 age- and sex-matched healthy controls from a blood donor population study were evaluated. Genomic DNA was isolated from buccal swabs and genotyping of the C825T polymorphisms was performed by polymerase chain reaction and restriction analysis. Results: In the blood donors with no abdominal symptoms in study A (controls, n = 161), genotype distribution was 17 TT, 77 TC, and 67 CC. In blood donors and patients with unexplained abdominal symptoms, genotype distribution was 22 TT, 54 TC, and 89 CC (P = 0.007 vs. controls). In study B, the genotype distribution in functional dyspepsia patients was 4 TT, 18 CT, and 34 CC compared with 4 TT, 62 CT, and 46 CC in the controls (P < 0.02). Combining studies A and B, the odds ratio (OR) adjusted for age and sex for upper abdominal symptoms associated with the CC genotype was 2.2 (95% confidence interval [CI]: 1.4–3.3), compared with subjects with TC and TT genotype carrying an allele. Conclusions: Homozygous GNB3 825C carrier status is associated with unexplained predominantly upper abdominal symptoms.Gerald Holtmann, Winfried Siffert, Sebastian Haag, Norbert Mueller, Mathias Langkafel, Wolfgang Senf, Rainer Zotz and Nicholas J. Talle

Is there a benefit from intensified medical and psychological interventions in patients with functional dyspepsia not responding to conventional therapy?

The definitive version is available at www.blackwell-synergy.com Article first published online: 12 FEB 2007Aim: In a prospective randomized, controlled trial, to compare the long-term outcome of intensive medical therapy (with or without cognitive-behavioural or muscle relaxation therapy) vs. standard medical therapy in patients with refractory functional dyspepsia (FD), referred to a tertiary referral medical center. Methods: A total of 100 consecutive FD patients were allocated to a standardized symptom-oriented 4 month therapy (SMT, n = 24), intensive medical therapy (IMT, medical therapy with testing-for and targeting-of abnormalities of motor-and-sensory function, n = 28) or IMT plus psychological interventions (either progressive-muscle relaxation (IMT-MR, n = 20) or cognitive-behavioural therapy (IMT-CBT, n = 28). The symptom intensity (SI) and health-related quality-of-life (HRQoL) after 12 months were prespecified primary outcome parameters. Results: After 12 months, significantly greater improvement of SI occurred in patients with IMT-all (with or without psychological interventions) compared with SMT (P &lt; 0.025 vs. IMT-all). IMT, IMT-MR and IMT-CBT alone also resulted in significantly better improvement of the primary outcome parameters (P all &lt; 0.025 vs. SMT). HRQoL significantly improved in all groups with intensive medical therapy but not standard medical therapy. Differences between intensive medical therapy-all and standard medical therapy were not significant. Concomitant anxiety and depression was improved significantly by IMT-CBT (vs. SMT) but not other treatments. Conclusions: In FD patients with refractory symptoms, intensified medical management involving function testing and psychological intervention yields superior long-term-outcomes. Additional CBT may be effective for the control of concomitant anxiety and depression.S. Haag, W. Senf, S. Tagay, M. Langkafel, U. Braun-Lang, A. Pietsch, G. Heuft, N. J. Talley and G. Holtman

Clinical presentation and personality factors are predictors of the response to treatment in patients with functional dyspepsia - a randomdized, double-blind placebo-controlled crossover study

The role of psychological factors or symptom pattern for the response to treatment in patients with unexplained (functional) dyspepsia is unknown. We hypothesized that patients with reflux- and ulcer-like symptoms would be more likely to respond to acid-lowering therapy, while psychological disturbances would be associated with a less favorable response to treatment. Seventy-eight patients with a diagnosis of functional dyspepsia were recruited and 75 completed the trial. Patients were treated for 4 weeks in a double-blind, placebo-controlled crossover trial starting in random order with either active drug (ranitidine, 150 mg b.d.) or placebo. Every 7 days, medication was switched from active drug to placebo, or vice versa. At entry, patient characteristics were assessed utilizing a semistructured standardized interview and standardized questionnaires, and weekly intensity of symptoms was assessed utilizing a visual analogue scale. Patients with a greater reduction of the symptom score during active treatment and an overall reduction of the global symptom score by more than 50% at the end of the study period were categorized as responders. Logistic regression analysis was utilized to assess the influence of symptom type and presence of psychological disturbances on the treatment response. During treatment the symptom score decreased significantly, from 32.1 ± 1.44 (SD) to 21.3 ± 1.9 at the end of the trial (P Gerald Holtmann, Sven-Uwe Kutscher, Sebastian Haag, Mathias Langkafel, Gereon Heuft, Jutta Neufang-Hueber, Harald Goebell, Wolfgang Senf and Nicholas J. Talle