Frequency and severity of the symptoms of irritable bowel syndrome across the anxiety disorders and depression

High rates of irritable bowel syndrome (IBS) symptoms have been reported in individuals diagnosed with anxiety and depressive disorders. However, most studies have investigated these relations in a single disorder, rather than a heterogeneous group of patients, thereby not allowing for comparisons across anxiety disorders and depression, or for considering the effects of comorbidity. Thus, the present study investigated the symptoms of IBS in a diverse group of patients (N=357) by administering questionnaires and a diagnostic interview. A high frequency of IBS symptoms was found in patients with panic disorder, generalized anxiety disorder, and major depressive disorder. However, the frequency of IBS symptoms in patients with social anxiety disorder, specific phobia, and obsessive-compulsive disorder was comparable to rates found in community samples. In addition, anxiety sensitivity and illness attitudes and intrusiveness were predictive of elevated IBS symptomatology. Together, these findings emphasize the role physiological symptoms of anxiety and worry in the co-occurrence of the anxiety disorders and IBS.     

Prevalence and impact of irritable bowel syndrome in people with epilepsy

PurposeEpilepsy is known to be associated with affective disorders and sleep alterations, as well as with gastrointestinal conditions such as peptic ulcers and inflammatory bowel disease. There is comparatively little evidence linking epilepsy and gastrointestinal functional disorders. The objective of this study was to determine the prevalence and impact of irritable bowel syndrome (IBS) in patients with epilepsy.MethodsWe carried out a cross-sectional observational study on 65 consecutive people with epilepsy (PWE) and age- and sex-matched controls. Irritable bowel syndrome and functional dyspepsia (FD) diagnosis were based on Rome III criteria. Clinical and demographic characteristics were recorded, and instruments evaluating sleep quality, depressive/anxiety symptoms, insomnia, and health-related quality of life were also completed.ResultsIrritable bowel syndrome prevalence was significantly different between groups (3% in controls and 16% in patients with epilepsy; p = 0.04), while no difference was found in FD (2% vs. 6%, respectively). People with epilepsy with IBS had significantly more insomnia and depressive and anxiety symptoms. No demographic or clinical characteristics were significantly different between groups. The presence of IBS did not affect health-related quality of life in PWE. On multivariate analysis, insomnia and depressive and anxiety symptoms did not independently predict IBS diagnosis.ConclusionIrritable bowel syndrome was more frequent in PWE compared with that in healthy controls. Irritable bowel syndrome does not appear to affect health-related quality of life but is associated with a greater burden of affective symptoms and insomnia.     

Stress, coping, and depression in non-ulcer dyspepsia patients

Thirty adults with upper gastrointestinal symptoms in the absence of structural organic disease diagnosed with non-ulcer dyspepsia (NUD) were compared to 30 healthy adults who had visited the hepatobiliary clinic for medical evaluation of non-organic complaints without NUD. Medical investigation in both groups were negative. Before independent gastrointestinal physicians conducted diagnostic evaluations, all subjects were evaluated for anxiety and depressive symptoms, stressful life events, coping style, and social support. The measures included Symptom Checklist 90-Revised (SCL-90-R), Beck Depression Inventory (BDI), Spielberger State-Trait Anxiety Inventory (STAI), Ways of Coping Checklist, and Interpersonal Support Evaluation List, and a self-report questionnaire, which measured the quantity of perceived stressful life events. The NUD patients reported significantly more symptoms of depression, more perceived stressful life events, less problem-focused coping, and less social support than the control subjects. Depressive symptoms were negatively correlated with interpersonal support, whereas, problem-focused coping was positively correlated with interpersonal support in the NUD patients. The two groups did not differ significantly in terms of anxiety and emotion-focused coping. The implications of these findings for the diagnosis and treatment of NUD are discussed.     

Impact of functional bowel symptoms on quality of life and fatigue in quiescent Crohn disease and irritable bowel syndrome

Background Patients with irritable bowel syndrome (IBS) and Crohn disease (CD) have impaired quality of life (Qol) associated with fatigue. Whether IBS‐like symptoms have a similar impact on Qol and fatigue in quiescent CD than in IBS is currently unknown. Our aims were (i) to evaluate the prevalence of IBS‐like symptoms in quiescent CD and (ii) to compare the impact of IBS‐like symptoms on Qol and fatigue in both diseases. Methods A total of 92 quiescent CD, 40 IBS and 20 healthy subjects similar in age were included prospectively in five French academic centers. IBS symptoms were evaluated through the Rome III criteria. The severity of IBS symptoms, Qol, fatigue, depression and anxiety was measured using questionnaires (Francis Score, Likert scales, Fatigue Impact Scale, short‐form Beck and Hospital Anxiety and Depression Scale). Key Results Irritable bowel syndrome‐like symptoms were found in 42/92 (45.6%) patients with quiescent CD. The presence of IBS‐like symptoms was associated with significant more profound alterations of Qol, high scores of fatigue, depression, but similar levels of anxiety. Compared to CD patients with IBS‐like symptoms, IBS patients had more severe gastrointestinal symptoms and alterations of Qol, but similar scores of fatigue, depression and anxiety. In quiescent CD patients, fatigue was independently associated with the presence of IBS‐like symptoms (OR = 1.018, 95% CI: 1.002–1.034, P = 0.02). Conclusions & Inferences The prevalence of IBS‐like symptoms is elevated in quiescent CD. The presence of IBS‐like symptoms in quiescent CD is probably associated with the range of fatigue/depression disorders. The mechanism underlying the occurrence of IBS‐like symptoms in quiescent CD needs to be further explored.     

Patients with irritable bowel syndrome and dysmotility express antibodies against gonadotropin‐releasing hormone in serum

Background The etiology of irritable bowel syndrome (IBS) and dysmotility is in most cases unknown. Organic, pathognomonic changes have not been described. We have previously demonstrated sporadic expressions of antibodies against gonadotropin‐releasing hormone (GnRH) in serum from these patients. The aim of this study was to screen for the presence of GnRH antibodies in healthy subjects and patients with gastrointestinal (GI) diseases. Methods Consecutive patients suffering from either IBS, idiopathic dysmotility, GI complaints secondary to diabetes mellitus, celiac disease or inflammatory bowel disease (IBD) were included. Healthy blood donors served as controls. Blood samples were taken for analyzing IgM and IgG antibodies against GnRH using an ELISA method. Medical records were scrutinized with respect to duration of symptoms, co‐existing diseases, drug treatments, hereditary factors, and laboratory analyses. Key Results Healthy controls expressed low levels of GnRH IgM antibodies in a prevalence of 23%. The prevalence of GnRH IgM antibodies in IBS and dysmotility patients was 42% (P = 0.008), and the levels were higher (P = 0.000). Patients with diabetes mellitus expressed GnRH IgM antibodies in the same prevalence as controls (25%), but in higher levels (P = 0.02). Patients with celiac disease or IBD had the same or lower levels of antibodies. There were no associations between antibodies, other co‐existing diseases or laboratory analyses. Conclusions & Inferences Higher levels of GnRH IgM antibodies were detected in patients with IBS and dysmotility, but not organic GI diseases, compared with healthy controls. These findings suggest that IBS and dysmotility to some extent may be of an autoimmune origin.     

Gastrointestinal‐specific anxiety: an important factor for severity of GI symptoms and quality of life in IBS

Background Gastrointestinal (GI)‐specific anxiety (GSA) has been proposed to influence symptom severity and quality of life (QOL) in patients with irritable bowel syndrome (IBS). The Visceral Sensitivity Index (VSI) is a recently developed, reliable and valid measure of GSA. Our aim was to evaluate the association between GSA, GI symptom severity, and QOL in IBS patients. Methods Sixty healthy subjects and 306 patients fulfilling the Rome II criteria for IBS were studied. Demographic and disease‐related factors were assessed. Patients completed VSI and GI Symptom Rating Scale (GSRS) and questionnaires to determine psychological symptom severity (Hospital Anxiety and Depression Scale), QOL (Short form 36), and presence of functional GI disorders (Rome II Modular Questionnaire). Key Results Compared with healthy subjects, patients with IBS had more severe GSA (34.7 ± 16.9 vs. 2.2 ± 4.4 [mean ± standard deviation]; P < 0.0001). In the IBS group, more severe GSA was seen in patients with more severe GI symptoms (P < 0.0001), general anxiety (P < 0.0001) and depression (P < 0.0001), and with lower socioeconomic status (P < 0.05). In a regression analysis, GSA was the strongest predictor for GI symptom severity (GSRS total score), followed by number of Rome II diagnoses, presence of meal‐related IBS symptoms, and gender (R² = 0.34). Gastrointestinal‐specific anxiety was also, together with general anxiety, depression, socioeconomic status, and gender, found to be independently associated with mental QOL (R² = 0.62). Conclusions & Inferences Gastrointestinal‐specific anxiety seems to be an important factor for GI symptom severity and QOL in patients with IBS.     

Hypervigilance in irritable bowel syndrome compared with organic gastrointestinal disease

Objective

Irritable bowel syndrome (IBS) patients are suggested to selectively attend to gastrointestinal (GI) sensations compared with healthy controls. However, it remains unclear whether there are differences between IBS and other chronic GI disorders. We aimed to evaluate the presence of hypervigilance towards the GI tract in IBS compared with patients with organic GI diseases.

Methods

We included 36 IBS patients and 40 age- and gender-matched patients with organic GI disease. They completed the Hospital Anxiety and Depression Scale (HADS) and underwent three tests: (1) word association—write down as many words as possible representing signs of disease; (2) word recognition (tachistoscope)—four categories of words (positive affects, non-GI symptoms, GI symptoms, negative affects) displayed for increasing time until identified; (3) word recollection—memorize words (10 GI symptoms, 10 positive affects, 10 negative affects).

Results

The word-association task did not show group differences. IBS patients were significantly faster than organic GI patients at recognizing words representing GI symptoms (21 vs. 26 ms; P=.04) and negative affects (27 vs. 34 ms; P=.03), but also tended to be faster at recognizing positive affects (24 vs. 29 ms; P=.08) and non-GI symptoms (22 vs. 27 ms; P=.2). Both groups remembered a similar number of words, but IBS patients tended to recall more incorrect GI words than organic patients (1.3 vs. 1.0; P=.06). There were no group differences in HADS scores.

Conclusion

Compared to patients with organic GI disease, IBS patients seem to be hypervigilant for information regarding GI sensations and maybe also negative information.     

Anxiety and depression comorbidities in irritable bowel syndrome (IBS): a systematic review and meta-analysis

Irritable bowel syndrome (IBS) has been associated with high prevalence of psychological disorders. However, it remains unclear whether IBS and each of its subtypes (predominant diarrhea IBS-D, constipation IBS-C, mixed IBS-M) are associated with higher anxiety and depressive symptoms levels. This study aimed to determine the associations of IBS and each of its subtypes with anxiety and/or depression. We conducted a systematic review and meta-analysis using five electronic databases (PubMed, PsychINFO, BIOSIS, Science Direct, and Cochrane CENTRAL). We selected case–control studies comparing anxiety and depression levels of patients with IBS to healthy controls, using standardized rating scales. Outcomes were measured as random pooled standardized mean differences (SMD). Ten studies were included in our analysis (885 patients and 1,384 healthy controls). Patients with IBS had significant higher anxiety and depression levels than controls (respectively, SMD = 0.76, 95 % CI 0.47; 0.69, p < 0.01, I2 = 81.7 % and SMD = 0.80, 95 % CI 0.42; 1.19, p < 0.01, I2 = 90.7 %). This significant difference was confirmed for patients with IBS-C and -D subtypes for anxiety, and only in IBS-D patients for depression. However, other IBS subtypes had a statistical trend to be associated with both anxiety and depressive symptomatology, which suggests a lack of power due to the small number of studies included. Patients with IBS had significantly higher levels of anxiety and depression than healthy controls. Anxiety and depression symptomatology should be systematically checked and treated in IBS patients, as psychological factors are important moderators of symptom severity, symptom persistence, decisions to seek treatment, and response to treatment.     

Patient satisfaction after gut‐directed hypnotherapy in irritable bowel syndrome

Background Gut‐directed hypnotherapy is an effective treatment option for irritable bowel syndrome (IBS). However, clinical observations suggest that patient satisfaction with hypnotherapy is not always associated with improvement in IBS symptoms. Methods We evaluated 83 patients with IBS treated with gut‐directed hypnotherapy (1 h week^?1, 12 weeks). After the treatment period, patients reported their satisfaction with the treatment (ranging from 1 = not at all satisfied, to 5 = very satisfied) and completed questionnaires to assess IBS symptom severity, quality of life, cognitive function, sense of coherence, depression, and anxiety before and after treatment. Key Results After hypnotherapy improved IBS symptom severity, quality of life, cognitive function, and anxiety were seen. Thirty patients (36%) were very satisfied with the treatment and 57 (69%) patients scored 4 or 5 on the patient satisfaction scale. Patient satisfaction was associated with less severe IBS symptoms and better quality of life after the treatment. In a multiple linear regression analysis, only the quality of life domain sexual relations was independently associated with patient satisfaction after hypnotherapy, explaining 22% of the variance. Using 25% reduction of IBS symptom severity to define an IBS symptom responder, 52% of the responders were very satisfied with hypnotherapy, but this was also true for 31% in the non‐responder group. Conclusions & Inferences Patient satisfaction with gut‐directed hypnotherapy in IBS is associated with improvement of quality of life and gastrointestinal (GI) symptoms. However, other factors unrelated to GI symptoms also seems to be of importance for patient satisfaction, as a substantial proportion of patients without GI symptom improvement were also very satisfied with this treatment option.     

Determination of subjective burden from chronic inflammatory bowel disease and its psychosocial consequences. Results from a study of 200 patients

Somatic symptoms of chronic organic diseases do not sufficiently explain the degree to which the individual's daily life is impaired. Quality of life questionnaires are increasingly used to measure long term effects of therapy and rehabilitation. The present study is concerned with determining factors associated with the quality of life of patients suffering from inflammatory bowel disease (IBS). We investigated 200 consecutive inpatients with IBS (Crohn's disease 119, ulcerative colitis 81; 142 males, females; mean age 36.8 years) of the Niederrhein Clinic, a centre for gastroenterologic diseases and metabolic disorders. We assessed sociodemographic data of the last three years, the results of all recent clinical examinations (pattern and extension of inflammatory lesions) CDAI and CAI to determine the activity of the disease, expert ratings of disease severity as well as impact on family, partnership, social environment and leisure activities, psychometric data concerning anxiety (STAI), depression (Paranoid-Depressivit?tsskala), and coping (FKV). The subjective impairment was measured by structured interviews. The inflammatory activity of IBS and the intensity of symptoms correlated only insignificantly with the subjective impairment. Depression (as measured by the Paranoid-Depressivit?tsskala) and a depressive style of coping (FKV) revealed to be the best predictors for subjective impairment. For patients with a mild to moderate degree of IBS quality of life does not significantly depend on the degree and severity of disease. A depressive coping style seems to be a crucial target of rehabilitation and psychotherapy in IBS.     

Associations of tryptophan hydroxylase gene polymorphisms with irritable bowel syndrome

Background Alterations in serotonin (5‐HT) are suspected in the pathophysiology of irritable bowel syndrome (IBS). Tryptophan hydroxylase (TPH) is the rate‐limiting enzyme in the biosynthesis of serotonin and has two isoforms: TPH1 and TPH2. Genetic variants in both genes have been studied in various disorders related to serotonin dysregulation. The aim of this study was to examine whether TPH gene variants were associated with IBS and IBS‐related gastrointestinal (GI) symptoms. Methods Five single nucleotide polymorphisms (SNPs) from the TPH1 and one SNP from the TPH2 were genotyped in 199 IBS patients and 79 healthy controls. All subjects were Caucasian women of European origin. Irritable bowel syndrome patients filled in a daily diary with five GI symptoms and stool characteristics for 28 days. Key Results The TPH1 SNPs showed no association with the diagnosis of IBS. However, among IBS patients, all five TPH1 SNPs showed some association with diarrhea and loose type of stool consistency, with P‐values rating from 0.01 to 0.20. The TPH2 SNP showed a trend towards a reduced risk of IBS and possible associations with stool characteristics, both hard and loose stools. However, no P‐values were less than the conservative multiple‐comparison‐adjusted threshold of 0.001 and hence these results must be interpreted cautiously. Conclusions & Inferences This study is the first to assess associations of TPH gene variants with IBS‐related GI symptoms and stool characteristics. The possible association of TPH gene variants with diarrhea needs to be verified in an independent sample.     

Adaptive cognitive emotion regulation moderates the relationship between dysfunctional attitudes and depressive symptoms during a stressful life period: A prospective study

Background and objectivesDysfunctional cognitions are known to emerge in stressful situations and are critical for the onset of depressive symptoms. The goal of this study is to investigate whether adaptive and/or maladaptive emotion regulation strategies moderate the relationship between dysfunctional attitudes and depressive symptoms under stress.MethodsIn a longitudinal study, 92 healthy but unselected undergraduates were followed for three months including a stress period (four weeks of examinations).ResultsOur findings demonstrate that the more adaptive emotion regulation strategies are used in daily life (measured at baseline), the weaker the relationship between dysfunctional attitudes and depressive symptoms during stress. Interestingly, no single strategy demonstrates a unique predictive value, but only the combination of several adaptive strategies moderates the relationship between dysfunctional attitudes and depressive symptoms. Although participants with elevated depressive symptoms use more maladaptive emotion regulation strategies, these latter strategies do not moderate the association between dysfunctional attitudes and depressive symptoms.LimitationsThe use of a sample of undergraduates limits the generalizability and the clinical significance of our results.ConclusionsAltogether, although dysfunctional attitudes are activated and accessible in response to certain life stressors, the strategies that healthy individuals use to adaptively regulate these cognitions seem important in determining the likelihood of depressive symptoms.     

Disturbed in vitro adrenergic modulation of cytokine production in inflammatory bowel diseases in remission

OBJECTIVE: Psychological stress has been implicated in the pathophysiology of both inflammatory and functional gastrointestinal (GI) diseases. The goal of this study was to address neuroendocrine modulation of cytokine production by peripheral blood cells in GI diseases. METHODS: We analyzed the in vitro effects of the beta-adrenergic agonist terbutaline and the glucocorticoid agonist dexamethasone on TNF-alpha and IL-10 production by LPS-stimulated monocytes in whole cell blood cultures in patients with inflammatory bowel diseases in remission (N=10), diarrhoea-predominant irritable bowel syndrome (IBS, N=12), patients with a recent gastroenteritis (post-infectious group, N=10), and healthy controls (N=15). RESULTS: In response to terbutaline, there was a significant increase in IL-10 production (concentration effect: p<0.05), which was diminished in IBD (group effect: p<0.01), comparable in IBS and controls, but enhanced in the post-infectious group (group x concentration effect: p<0.05). In contrast, terbutaline resulted in a concentration-dependent suppression of TNF-alpha production, which was comparable in all groups. Dexamethasone suppressed TNF-alpha production in a dose-dependent manner in all groups, but this effect was significantly more pronounced in post-infectious subjects (group effect: p<0.05). CONCLUSIONS: In IBD, disturbed adrenergic regulation of IL-10 could be part of the mechanism(s) underlying the modulation of disease activity by psychological stress. Diarrhoea-predominant IBS was not associated with altered adrenergic or glucocorticoid regulation of cytokine production by peripheral blood cells, whereas a recent history of gastroenteritis was associated with disturbed neuroendocrine modulation of cytokine production, which may play role in the pathophysiology of post-infectious IBS.     

The role of childhood abuse in Axis I and Axis II psychiatric disorders and medical disorders of unknown origin among irritable bowel syndrome patients

OBJECTIVE: High rates of early abuse and psychopathology are commonly reported among treatment-seeking patients with irritable bowel syndrome (IBS). The purpose of this study is to further explore the relations among IBS, early abuse, Axes I and II psychopathology, and other medically unexplained disorders. METHODS: One hundred and ninety-six IBS patients seeking nondrug treatment for their symptoms were characterized in terms of their gastrointestinal (GI) status, psychiatric status (Axis I and Axis II), early abuse status, and the presence of other functional disorders. Patients were divided into two groups based on early abuse status. RESULTS AND CONCLUSION: No significant differences emerged between abused and nonabused groups on either the presence of Axis II disorders or other functional health conditions, although there were high levels of both in the IBS population. Patients with a history of abuse were significantly more likely to meet criteria for an Axis I disorder, especially substance abuse disorders, dysthymia, and generalized anxiety disorder.     

Evaluation of the integrated cognitive model of depression and its specificity in a migrant population

This study empirically tested the specificity of the integrated cognitive model (ICM) of depression, which postulates that negative life events interact with dysfunctional attitudes to increase the frequency and severity of automatic thoughts, subsequently affecting depressive symptoms. We also examined the three competing models: the linear mediation model, the alternative etiologies model, and the symptom model. We anticipated that we might examine these models more appropriately using data from a population at an increased risk of developing depressive symptoms. As such, two-wave panel data were obtained from a group of 107 Korean migrants who had been in Australia less than 1 year. Structural equation modeling revealed that the ICM provided an adequate and much better fit than the three competing models. The ICM was also found to support the cognitive specificity theory of depression and anxiety. These findings suggest that dysfunctional attitudes can be a common cognitive moderator of depression and anxiety, whereas automatic thoughts and anxious self-statements can be specific cognitive mediators of anxiety and depression, respectively.     

No difference in symptoms of irritable bowel syndrome between healthy subjects and patients with recurrent depression in remission

There is bidirectional comorbidity between anxiety/depression and irritable bowel syndrome (IBS). To investigate the prevalence of IBS symptoms, and factors associated with gastrointestinal symptoms in patients with recurrent depressive disorder. Patients (n = 95) with recurrent type of major depression according to DSM-IV criteria and sex- and age-matched controls (n = 190) were sent questionnaires investigating symptoms of IBS [Gastrointestinal Symptom Rating Scale (GSRS)-IBS] and symptoms of anxiety and depression [Hospital Anxiety and Depression Scale (HADS)]. Medical records were checked over a 10-year period for chronic somatic symptoms or diseases. Seventy-three patients with unipolar disorder (mean age 63.6 years SD 13.8; range 23-86 years) and 156 controls (mean age 59.2 years SD 11.6, range 21-85 years) responded. Patients with recurrent depression had higher GSRS-IBS scores and showed a strong correlation between symptoms of IBS and anxiety-depression (r(s) = 0.54; P < 0.001). IBS symptoms were also associated with multiple pain symptoms, higher health-seeking behaviour and selective-serotonin-reuptake inhibitor intake. However, patients with recurrent depression (n = 46) in remission (HADS-Depression score <8) did not have more symptoms of IBS than controls (GSRS-IBS median score 6.0 vs 6.5; P = 0.46). There is a strong association between symptoms of IBS and symptoms of anxiety and depression, whereas depressive patients in remission do not have more IBS symptoms than controls.     

Electrogastrography as a diagnostic tool for delayed gastric emptying in functional dyspepsia and irritable bowel syndrome

Several pathophysiological mechanisms have been proposed in functional gastrointestinal (GI) disorders, e.g. altered GI motility and sensitivity. The aim of this study was to investigate gastric electrical activity (GEA) in patients with functional dyspepsia (FD) or irritable bowel syndrome (IBS) compared with healthy controls (HC), and to assess if abdominal symptoms and delayed gastric emptying are associated with alterations in GEA, as determined by electrogastrography (EGG). Forty patients with FD, IBS or both were compared with 22 HC. EGG was performed before and after a standard meal. Frequencies and amplitudes pre- and post-prandially were analysed. Furthermore, gastric emptying and symptom scores were assessed. Eight of 40 patients (20%; three FD, three IBS, two FD and IBS) had delayed gastric emptying. Disturbed gastric emptying and lack of a postprandial increase in the EGG amplitude were significantly correlated (r = 0.8; P < 0.005). No differences between controls and patients were observed in the distribution of EGG frequencies. Treatment with the prokinetically active macrolide erythromycin improved gastric emptying, GEA and symptoms (n = 4). The data suggest that EGG could be useful as a diagnostic tool in patients with FD and IBS to identify a subgroup of patients with delayed gastric emptying.     

Effects of serotonin transporter inhibition on gastrointestinal motility and colonic sensitivity in the mouse

Serotonin-selective reuptake transporter (SERT) expression is decreased in animal models of intestinal inflammation and in individuals with inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS), and it is possible that resultant changes in intestinal serotonin signalling contribute to the manifestation of clinical features associated with these disorders. The objective of this investigation was to determine whether inhibition of SERT function leads to changes in gut motility and sensitivity. Mice underwent a 14-day treatment with the SERT inhibitor, paroxetine (20 mg kg(-1)), or vehicle (saline/propylene glycol). Gastrointestinal (GI) transit following charcoal gavage, colonic motility, stool frequency and visceromotor responses to colorectal distension were evaluated. In mice treated with paroxetine, stool output was decreased, upper GI transit was delayed, and colonic sensitivity to a nociceptive stimulus was attenuated. These results demonstrate that reduced SERT function (via pharmacological blockade) significantly alters GI motility and sensitivity in mice, and support the concept that altered SERT expression and function could contribute to symptoms associated with IBS and IBD.     

Altered profiles of intestinal microbiota and organic acids may be the origin of symptoms in irritable bowel syndrome

Background The profile of intestinal organic acids in irritable bowel syndrome (IBS) and its correlation with gastrointestinal (GI) symptoms are not clear. We hypothesized in this study that altered GI microbiota contribute to IBS symptoms through increased levels of organic acids. Methods Subjects were 26 IBS patients and 26 age‐ and sex‐matched controls. Fecal samples were collected for microbiota analysis using quantitative real‐time polymerase chain reaction and culture methods, and the determination of organic acid levels using high‐performance liquid chromatography. Abdominal gas was quantified by image analyses of abdominal X‐ray films. Subjects completed a questionnaire for GI symptoms, quality of life (QOL) and negative emotion. Key Results Irritable bowel syndrome patients showed significantly higher counts of Veillonella (P = 0.046) and Lactobacillus (P = 0.031) than controls. They also expressed significantly higher levels of acetic acid (P = 0.049), propionic acid (P = 0.025) and total organic acids (P = 0.014) than controls. The quantity of bowel gas was not significantly different between controls and IBS patients. Finally, IBS patients with high acetic acid or propionic acid levels presented with significantly worse GI symptoms, QOL and negative emotions than those with low acetic acid or propionic acid levels or controls. Conclusions & Inferences These results support the hypothesis that both fecal microbiota and organic acids are altered in IBS patients. A combination of Veillonella and Lactobacillus is known to produce acetic and propionic acid. High levels of acetic and propionic acid may associate with abdominal symptoms, impaired QOL and negative emotions in IBS.     

Dysfunctional attitudes and 5-HT2 receptors during depression and self-harm

OBJECTIVE: Dysfunctional attitudes are negatively biased assumptions and beliefs regarding oneself, the world, and the future. In healthy subjects, increasing serotonin (5-HT) agonism with a single dose of d-fenfluramine lowered dysfunctional attitudes. To investigate whether the converse, a low level of 5-HT agonism, could account for the higher levels of dysfunctional attitudes observed in patients with major depression or with self-injurious behavior, cortex 5-HT(2) receptor binding potential and dysfunctional attitudes were measured in patients with major depressive disorder, patients with a history of self-injurious behavior, and healthy comparison subjects (5-HT(2) receptor density increases during 5-HT depletion). METHOD: Twenty-nine healthy subjects were recruited to evaluate the effect of d-fenfluramine or of clonidine (control condition) on dysfunctional attitudes. Dysfunctional attitudes were assessed with the Dysfunctional Attitude Scale 1 hour before and 1 hour after drug administration. In a second experiment, dysfunctional attitudes and 5-HT(2) binding potential were measured in 22 patients with a major depressive episode secondary to major depressive disorder, 18 patients with a history of self-injurious behavior occurring outside of a depressive episode, and another 29 age-matched healthy subjects. Cortex 5-HT(2) binding potential was measured with [(18)F]setoperone positron emission tomography. RESULTS: In the first experiment, dysfunctional attitudes decreased after administration of d-fenfluramine. In the second experiment, in the depressed group, dysfunctional attitudes were positively associated with cortex 5-HT(2) binding potential, especially in Brodmann's area 9 (after adjustment for age). Depressed subjects with extremely dysfunctional attitudes had higher 5-HT(2) binding potential, compared to healthy subjects, particularly in Brodmann's area 9. CONCLUSIONS: Low levels of 5-HT agonism in the brain cortex may explain the severely pessimistic, dysfunctional attitudes associated with major depression.