Clinical trial: the effects of a trans-galactooligosaccharide prebiotic on faecal microbiota and symptoms in irritable bowel syndrome

Gut microflora-mucosal interactions may be involved in the pathogenesis of irritable bowel syndrome (IBS). To investigate the efficacy of a novel prebiotic trans-galactooligosaccharide in changing the colonic microflora and improve the symptoms in IBS sufferers. In all, 44 patients with Rome II positive IBS completed a 12-week single centre parallel crossover controlled clinical trial. Patients were randomized to receive either 3.5 g/d prebiotic, 7 g/d prebiotic or 7 g/d placebo. IBS symptoms were monitored weekly and scored according to a 7-point Likert scale. Changes in faecal microflora, stool frequency and form (Bristol stool scale) subjective global assessment (SGA), anxiety and depression and QOL scores were also monitored. The prebiotic significantly enhanced faecal bifidobacteria (3.5 g/d P < 0.005; 7 g/d P < 0.001). Placebo was without effect on the clinical parameters monitored, while the prebiotic at 3.5 g/d significantly changed stool consistency (P < 0.05), improved flatulence (P < 0.05) bloating (P < 0.05), composite score of symptoms (P < 0.05) and SGA (P < 0.05). The prebiotic at 7 g/d significantly improved SGA (P < 0.05) and anxiety scores (P < 0.05). The galactooligosaccharide acted as a prebiotic in specifically stimulating gut bifidobacteria in IBS patients and is effective in alleviating symptoms. These findings suggest that the prebiotic has potential as a therapeutic agent in IBS.

Effect of micronutrient supplementation on mood in nursing home residents

One third of older people in nursing and/or residential homes have significant symptoms of depression. In younger people, deficiencies in selenium, vitamin C and folate are associated with depression. This study examines the association between micronutrient status and mood before and after supplementation. The objective was to determine whether the administration of selenium, vitamin C and folate improved mood in frail elderly nursing home residents. Mood was assessed using the Hospital Anxiety and Depression rating scale (HAD), and Montgomery-Asberg Depression Rating Scale (MADRS). Micronutrient supplementation was provided for 8 weeks in a double-blinded randomised controlled trial. Significant symptoms of depression (29%) and anxiety (24%) were found at baseline. 67% of patients had low serum concentrations of vitamin C, but no-one was below the reference range for selenium. Depression was significantly associated with selenium levels, but not with folate or vitamin C levels. No individual with a HAD depression score of >= 8, had selenium levels >1.2 mu M. In those patients with higher HAD depression scores, there was a significant reduction in the score and a significant increase in serum selenium levels after 8 weeks of micronutrient supplementation. Placebo group scores were unchanged. This small study concluded that depression was associated with low levels of selenium in frail older individuals. Following 8 weeks of micronutrient supplementation, there was a significant increase in selenium levels and improved symptoms of depression occurred in a subgroup. Copyright (C) 2008 S. Karger AG, Basel

Artichoke leaf extract reduces symptoms of irritable bowel syndrome and improves quality of life in otherwise healthy volunteers suffering from concomitant dyspepsia: a subset analysis

Objectives: Does artichoke leaf extract (ALE) ameliorate symptoms of Irritable bowel syndrome (IBS) in otherwise healthy volunteers suffering concomitant dyspepsia? Methods: A subset analysis of a previous dose-ranging, open, postal study, in adults suffering dyspepsia. Two hundred and eight (208) adults were identified post hoc as suffering with IBS. IBS incidence, self-reported usual bowel pattern, and the Nepean Dyspepsia Index (NDI) were compared before and after a 2-month intervention period. Results: There was a significant fall in IBS incidence of 26.4% (p<0.001) after treatment. A significant shift in self-reported usual bowel pattern away from "alternating constipation/diarrhea" toward "normal" (p<0.001) was observed. NDI total symptom score significantly decreased by 41% (p<0.001) after treatment. Similarly, there was a significant 20% improvement in the NDI total quality-of-life (QOL) score in the subset after treatment. Conclusion: This report supports previous findings that ALE ameliorates symptoms of IBS, plus improves health-related QOL.

Turmeric extract may improve irritable bowel syndrome symptomology in otherwise healthy adults: a pilot study

Objectives: To assess the effects of turmeric (Curcuma longa) extract on irritable bowel syndrome (IBS) symptomology in otherwise healthy adults. Design: Partially blinded, randomized, two-dose, pilot study. Subjects: Five hundred (500) volunteers were screened for IBS using the Rome II criteria. Two hundred and seven (207) suitable volunteers were randomized. Interventions: One or two tablets of a standardized turmeric extract taken daily for 8 weeks. Outcomes measures: IBS prevalence, symptom-related quality of life (IBSQOL) and self-reported effectiveness. Results: IBS prevalence decreased significantly in both groups between screening and baseline (41% and 57%), with a further significant drop of 53% and 60% between baseline and after treatment, in the one- and two-tablet groups respectively (p < 0.001). A post-study analysis revealed abdominal pain/discomfort score reduced significantly by 22% and 25% in the one- and two-tablet group respectively, the difference tending toward significance (p = 0.071). There were significant improvements in all bar one of the IBSQOL scales of between 5% and 36% in both groups, approximately two thirds of all subjects reported an improvement in symptoms after treatment, and there was a favorable shift in self-reported bowel pattern. There were no significant differences between groups. Conclusions: Turmeric may help reduce IBS symptomology. Placebo controlled trials are now warranted to confirm these findings.

The psychological, neurochemical and functional neuroanatomical mediators of the effects of positive and negative mood on executive functions

In this review we evaluate the cognitive and neural effects of positive and negative mood on executive function. Mild manipulations of negative mood appear to have little effect on cognitive control processes, whereas positive mood impairs aspects of updating, planning and switching. These cognitive effects may be linked to neurochemistry: with positive mood effects mediated by dopamine while negative mood effects may be mediated by serotonin levels. Current evidence on the effects of mood on regional brain activity during executive functions, indicates that the prefrontal cortex is a recurrent site of integration between mood and cognition. We conclude that there is a disparity between the importance of this topic and awareness of how mood affects, executive functions in the brain. Most behavioural and neuroimaging studies of executive function in normal samples do not explore the potential role of variations in mood, yet the evidence we outline indicates that even mild fluctuations in mood can have a significant influence on neural activation and cognition. (c) 2006 Elsevier Ltd. All rights reserved.

Controlled trial of the short- and long-term effect of psychological treatment of post-partum depression - 1. Impact on maternal mood!

Background: Psychological interventions for postnatal depression can be beneficial in the short term but their longer-term impact is unknown, Aims To evaluate the long-term effect on maternal mood of three psychological treatments in relation to routine primary care. Method: Women with post-partum depression (n=193)were assigned randomly to one of four conditions: routine primary care, non-directive counselling, cognitive-behavioural therapy or psychodynamic therapy. They were assessed immediately after the treatment phase (at 4.5 months) and at 18 and 60 months post-partum. Results: Compared with the control, ail three treatments had a significant impact at 4.5 months on maternal mood (Edinburgh Postnatal Depression Scale, EPDS). Only psychodynamic therapy produced a rate of reduction in depression (Structured Clinical interview for DSM III-R) significantly superior to that of the control. The benefit of treatment was no longer apparent by 9 months postpartum, treatment did not reduce subsequent episodes of post-partum depression. Conclusions: Psychological intervention for post-partum depression improves maternal mood (EPDS) in the short term. However, this benefit is not superior to spontaneous remission in the long term.

An item response analysis of the motor and behavioral subscales of the unified Huntington's disease rating scale in huntington disease gene expansion carriers

Although the Unified Huntington's Disease Rating Scale (UHDRS) is widely used in the assessment of Huntington disease (HD), the ability of individual items to discriminate individual differences in motor or behavioral manifestations has not been extensively studied in HD gene expansion carriers without a motor-defined clinical diagnosis (ie, prodromal-HD or prHD). To elucidate the relationship between scores on individual motor and behavioral UHDRS items and total score for each subscale, a nonparametric item response analysis was performed on retrospective data from 2 multicenter longitudinal studies. Motor and behavioral assessments were supplied for 737 prHD individuals with data from 2114 visits (PREDICT-HD) and 686 HD individuals with data from 1482 visits (REGISTRY). Option characteristic curves were generated for UHDRS subscale items in relation to their subscale score. In prHD, overall severity of motor signs was low, and participants had scores of 2 or above on very few items. In HD, motor items that assessed ocular pursuit, saccade initiation, finger tapping, tandem walking, and to a lesser extent, saccade velocity, dysarthria, tongue protrusion, pronation/supination, Luria, bradykinesia, choreas, gait, and balance on the retropulsion test were found to discriminate individual differences across a broad range of motor severity. In prHD, depressed mood, anxiety, and irritable behavior demonstrated good discriminative properties. In HD, depressed mood demonstrated a good relationship with the overall behavioral score. These data suggest that at least some UHDRS items appear to have utility across a broad range of severity, although many items demonstrate problematic features.

Role for protease activity in visceral pain in irritable bowel syndrome

Mediators involved in the generation of symptoms in patients with irritable bowel syndrome (IBS) are poorly understood. Here we show that colonic biopsy samples from IBS patients release increased levels of proteolytic activity (arginine cleavage) compared to asymptomatic controls. This was dependent on the activation of NF-kappaB. In addition, increased proteolytic activity was measured in vivo, in colonic washes from IBS compared with control patients. Trypsin and tryptase expression and release were increased in colonic biopsies from IBS patients compared with control subjects. Biopsies from IBS patients (but not controls) released mediators that sensitized murine sensory neurons in culture. Sensitization was prevented by a serine protease inhibitor and was absent in neurons lacking functional protease-activated receptor-2 (PAR2). Supernatants from colonic biopsies of IBS patients, but not controls, also caused somatic and visceral hyperalgesia and allodynia in mice, when administered into the colon. These pronociceptive effects were inhibited by serine protease inhibitors and a PAR2 antagonist and were absent in PAR2-deficient mice. Our study establishes that proteases are released in IBS and that they can directly stimulate sensory neurons and generate hypersensitivity symptoms through the activation of PAR2.

Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome

BACKGROUND & AIMS: The mechanisms underlying abdominal pain perception in irritable bowel syndrome (IBS) are poorly understood. Intestinal mast cell infiltration may perturb nerve function leading to symptom perception. We assessed colonic mast cell infiltration, mediator release, and spatial interactions with mucosal innervation and their correlation with abdominal pain in IBS patients. METHODS: IBS patients were diagnosed according to Rome II criteria and abdominal pain quantified according to a validated questionnaire. Colonic mucosal mast cells were identified immunohistochemically and quantified with a computer-assisted counting method. Mast cell tryptase and histamine release were analyzed immunoenzymatically. Intestinal nerve to mast cell distance was assessed with electron microscopy. RESULTS: Thirty-four out of 44 IBS patients (77%) showed an increased area of mucosa occupied by mast cells as compared with controls (9.2% +/- 2.5% vs. 3.3 +/- 0.8%, respectively; P < 0.001). There was a 150% increase in the number of degranulating mast cells (4.76 +/- 3.18/field vs. 2.42 +/- 2.26/field, respectively; P = 0.026). Mucosal content of tryptase was increased in IBS and mast cells spontaneously released more tryptase (3.22 +/- 3.48 pmol/min/mg vs. 0.87 +/- 0.65 pmol/min/mg, respectively; P = 0.015) and histamine (339.7 +/- 59.0 ng/g vs. 169.3 +/- 130.6 ng/g, respectively; P = 0.015). Mast cells located within 5 microm of nerve fibers were 7.14 +/- 3.87/field vs. 2.27 +/- 1.63/field in IBS vs. controls (P < 0.001). Only mast cells in close proximity to nerves were significantly correlated with severity and frequency of abdominal pain/discomfort (P < 0.001 and P = 0.003, respectively). CONCLUSIONS: Colonic mast cell infiltration and mediator release in proximity to mucosal innervation may contribute to abdominal pain perception in IBS patients.

Magnetic resonance imaging of a randomized controlled trial investigating predictors of recovery following psychological treatment in adolescents with moderate to severe unipolar depression: study protocol for Magnetic Resonance - Improving Mood with Psychoanalytic and Cognitive Therapies (MR-IMPACT)

Background Major depressive disorders (MDD) are a debilitating and pervasive group of mental illnesses afflicting many millions of people resulting in the loss of 110 million working days and more than 2,500 suicides per annum. Adolescent MDD patients attending NHS clinics show high rates of recurrence into adult life. A meta-analysis of recent research shows that psychological treatments are not as efficacious as previously thought. Modest treatment outcomes of approximately 65% of cases responding suggest that aetiological and clinical heterogeneity may hamper the better use of existing therapies and discovery of more effective treatments. Information with respect to optimal treatment choice for individuals is lacking, with no validated biomarkers to aid therapeutic decision-making. Methods/Design Magnetic resonance-Improving Mood with Psychoanalytic and Cognitive Therapies, the MR-IMPACT study, plans to identify brain regions implicated in the pathophysiology of depressions and examine whether there are specific behavioural or neural markers predicting remission and/or subsequent relapse in a subsample of depressed adolescents recruited to the IMPACT randomised controlled trial (Registration # ISRCTN83033550). Discussion MR-IMPACT is an investigative biomarker component of the IMPACT pragmatic effectiveness trial. The aim of this investigation is to identify neural markers and regional indicators of the pathophysiology of and treatment response for MDD in adolescents. We anticipate that these data may enable more targeted treatment delivery by identifying those patients who may be optimal candidates for therapeutic response.

Effects of hydration status on cognitive performance and mood

Although it is well known that water is essential for human homeostasis and survival, only recently have we begun to understand its role in the maintenance of brain function. Herein, we integrate emerging evidence regarding the effects of both dehydration and additional acute water consumption on cognition and mood. Current findings in the field suggest that particular cognitive abilities and mood states are positively influenced by water consumption. The impact of dehydration on cognition and mood is particularly relevant for those with poor fluid regulation, such as the elderly and children. We critically review the most recent advances in both behavioural and neuroimaging studies of dehydration and link the findings to the known effects of water on hormonal, neurochemical and vascular functions in an attempt to suggest plausible mechanisms of action. We identify some methodological weaknesses, including inconsistent measurements in cognitive assessment and the lack of objective hydration state measurements as well as gaps in knowledge concerning mediating factors that may influence water intervention effects. Finally, we discuss how future research can best elucidate the role of water in the optimal maintenance of brain health and function.

Mood and recall of autobiographical memory: the effect of focus of self-knowledge

Mood state facilitates recall of affectively congruent memories (i.e., mood-congruent recall). Mood state may also promote motivation to alleviate a negative affective state, leading to retrieval of affectively incongruent memories (i.e., mood incongruent recall). The present study demonstrates that the focus of self-knowledge influences the occurrence of both mood-congruent recall and mood-incongruent recall. Three experiments found that mood-congruent recall occurred when participants recalled their experiences from a self-aspect that was related to the elicitor of moods, whereas mood-incongruent recall occurred when they recalled their experiences from a self-aspect that was unrelated to the elicitor of moods. These results suggest that the nature of the self-aspect from which persons recall their experiences determines whether mood-congruent or mood-incongruent recall occurs.

Effects of structure of self-knowledge on mood-incongruent effect

Some people recall more positive memories in negative moods than in neutral moods, which is called mood-incongruent effect. Although previous research suggested that structure of self-knowledge influences mood-incongruent effect (Sakaki, 2004), it is possible that motivation for mood-regulation mediates relation between structure of self-knowledge and mood-incongruent effect. The present study aimed at exploring this possibility by using self-complexity. In Study 1, participants with higher self-complexity, whose self-knowledge has more self-aspects with a higher level of differentiation, recalled more positive memories in negative moods (compared to neutral moods) than participants with lower self-complexity, whose self-knowledge has a fewer self-aspects with larger overlap. Study 1 also revealed that these effects hold even when the motivation for mood-regulation was partialed out. Study 2 examined mood-incongruent effect under positive moods, in which participants are unlikely motivated to alter their moods, and it was found that participants with higher self-complexity recalled more negative memories in positive moods (compared to neutral moods) than participants with lower self-complexity.