Impact of chemotherapy on the association between fear of cancer recurrence and the gut microbiota in breast cancer survivors

BackgroundDysfunctional processing of fear memory may be involved in the pathophysiology of fear of cancer recurrence (FCR), which is cited as the major unmet psychological need of cancer survivors. Emerging evidence has shown that the microbiota-gut-brain (MGB) axis affects depressive and anxiety disorders, and chemotherapy-associated psychological distress. We therefore hypothesized that the gut microbiota is associated with FCR in cancer survivors.MethodsThis cross-sectional study enrolled women diagnosed with invasive breast cancer who were not currently undergoing chemotherapy. Fecal samples were obtained to assess the gut microbiota. FCR grade was assessed using the Concerns About Recurrence Scale (CARS).ResultsMean age of the participants (n = 126) was 58 years; 47% had stage I disease. Multiple regression analysis with adjustment for possible confounders showed that the relative abundance of the Bacteroides genus (beta = 0.180, p = 0.03) was significantly and directly associated with FCR. In the 57 participants with a history of chemotherapy, higher FCR was associated with lower microbial diversity (p = 0.04), lower relative abundance of Firmicutes (p = 0.03) and higher relative abundance of Bacteroidetes (p = 0.04) at the phylum level, and higher relative abundance of Bacteroides (p < 0.01) and lower relative abundance of Lachnospiraceae.g (p = 0.03) and Ruminococcus (p = 0.02) at the genus level.ConclusionOur findings provide the first evidence of an association between the gut microbiota and FCR and suggest that chemotherapy-induced changes in gut microbiota can influence FCR. Further studies should examine the effects of the gut microbiota on FCR using a prospective design.     

Gene expression in blood of children and adolescents: Mediation between childhood maltreatment and major depressive disorder

Investigating major depressive disorder (MDD) in childhood and adolescence can help reveal the relative contributions of genetic and environmental factors to MDD, since early stages of disease have less influence of illness exposure. Thus, we investigated the mRNA expression of 12 genes related to the hypothalamic–pituitary–adrenal (HPA) axis, inflammation, neurodevelopment and neurotransmission in the blood of children and adolescents with MDD and tested whether a history of childhood maltreatment (CM) affects MDD through gene expression. Whole-blood mRNA levels of 12 genes were compared among 20 children and adolescents with MDD diagnosis (MDD group), 49 participants without MDD diagnosis but with high levels of depressive symptoms (DS group), and 61 healthy controls (HC group). The differentially expressed genes were inserted in a mediation model in which CM, MDD, and gene expression were, respectively, the independent variable, outcome, and intermediary variable. NR3C1, TNF, TNFR1 and IL1B were expressed at significantly lower levels in the MDD group than in the other groups. CM history did not exert a significant direct effect on MDD. However, an indirect effect of the aggregate expression of the 4 genes mediated the relationship between CM and MDD. In the largest study investigating gene expression in children with MDD, we demonstrated that NR3C1, TNF, TNFR1 and IL1B expression levels are related to MDD and conjunctly mediate the effect of CM history on the risk of developing MDD. This supports a role of glucocorticoids and inflammation as potential effectors of environmental stress in MDD.     

Reduced platelet BDNF level in patients with major depression

Serum and plasma brain-derived neurotrophic factor (BDNF) levels as well as brain BDNF have previously been shown to be decreased in patients with major depressive disorder (MDD). We explored whether platelet BDNF levels, circulating stored BDNF, would be lower in MDD patients than in normal controls. BDNF levels were examined in platelet-rich plasma (PRP) and platelet-poor plasma (PPP) in 20 hospitalized non-suicidal MDD patients, 20 recent-suicidal MDD patients, and 20 normal controls. Platelet BDNF content was calculated by subtracting PPP BDNF level from PRP BDNF level, and dividing the result by the total platelet count, and it was expressed as pg/10⁶ platelets. Individuals were evaluated using a Structured Clinical Interview for DSM-IV and a Hamilton Depression Rating Scale. Platelet BDNF contents were significantly lower in non-suicidal patients (3.09 ± 2.53 pg/10⁶ platelets) and recent-suicidal MDD patients (3.16 ± 1.99 pg/10⁶ platelets) than in healthy controls (6.17 ± 2.64 pg/10⁶ platelets) (p < 0.01). However, platelet BDNF contents had no significant differences between non-suicidal and recent-suicidal patients. PRP BDNF levels were also significantly lower in non-suicidal and suicidal MDD patients than in healthy controls (p = 0.029), while PPP BDNF had no significant difference between 3 groups (p = 0.971). Our findings suggest that there is a decrease in the platelet BDNF of patients with major depression. Reduced platelet BDNF contents as circulating stored BDNF could be associated with lower serum BDNF level in patients with major depression.     

Elevated triglyceride levels are associated with cognitive impairments among patients with major depressive disorder

BackgroundCognitive deficits have been identified as one of core clinical symptoms of major depressive disorder (MDD). Accumulating evidence indicated that triglycerides (TG) might be associated with MDD and cognitive decline.ObjectiveThis study examined whether patients with MDD had poorer cognitive functions than healthy controls, and further investigate whether TG levels were involved in MDD, and its cognitive impairments in a Han Chinese population.Method115 patients with MDD and 119 healthy controls were enrolled. Cognitive functions were assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and serum TG levels were examined using enzymatic colorimetry.ResultsTG levels were higher in patients with MDD than healthy controls after controlling for the variables. Cognitive test scores were lower in patients with MDD than healthy controls except for visuospatial/constructional index after controlling for the variables. TG levels were negatively correlated with visuospatial/constructional score, delayed memory score and RBANS total score of MDD. Further multivariate regression analysis showed that TG levels were negatively associated with visuospatial/constructional score, attention score, delayed memory score and RBANS total score of MDD.ConclusionsOur findings supported that serum TG levels might be involved in MDD, and play an important role in cognitive impairments of MDD, especially in delayed memory. Moreover, patients with MDD experienced greater cognitive impairments than healthy controls except for visuospatial/constructional index.     

Serum brain-derived neurotrophic factor in bipolar and unipolar depression: A potential adjunctive tool for differential diagnosis

The differential diagnosis of Bipolar Disorder (BD) and Major Depressive Disorder (MDD) is a diagnostic challenge during depressive episodes. Noteworthy, the proper differentiation between BD depressive state and MDD has important treatment implications. BDNF levels may be valuable adjunctive tool for this differential diagnosis. Ten subjects with MDD, forty with BD type I and thirty healthy comparison subjects were recruited. All subjects had BDNF serum levels measured and, in patients, BDNF serum levels were assessed during acute depressive episode. Optimal sensitivity and specificity of serum BDNF for the differential diagnosis of unipolar and bipolar depression were determined by the receiver operating characteristic (ROC) curve analysis, using a nonparametric approach. Serum BDNF levels in depressive BD patients were lower compared to MDD patients and controls (0.15 ± 0.08, 0.35 ± 0.08, and 0.38 ± 0.12, respectively, p < 0.001). The area under the curve (AUC) of the ROC analysis in BD depression vs. MDD was 0.95 (ranged from 0.89 to 1.00). Overall, the AUC of the ROC analysis (BD depression vs. MDD and controls) was 0.94 (95% CI 0.89 to 0.99, p < 0.001). A proposed “best” cutoff of 0.26 resulted in 88% sensitivity and 90% specificity. Serum BDNF levels appear as a promising tool to discriminate bipolar from unipolar depression. Our results suggest the role of BDNF as an adjunctive tool to promote prompt and accurate diagnosis of BD. However, further investigation and replication of these results are warranted.     

Weak reward source memory in depression reflects blunted activation of VTA/SN and parahippocampus

Reward responses in the medial temporal lobes and dopaminergic midbrain boost episodic memory formation in healthy adults, and weak memory for emotionally positive material in depression suggests this mechanism may be dysfunctional in major depressive disorder (MDD). To test this hypothesis, we performed a study in which unmedicated adults with MDD and healthy controls encoded drawings paired with reward or zero tokens during functional magnetic resonance imaging. In a recognition test, participants judged whether drawings were previously associated with the reward token (‘reward source’) or the zero token (‘zero source’). Unlike controls, depressed participants failed to show better memory for drawings from the reward source vs the zero source. Consistent with predictions, controls also showed a stronger encoding response to reward tokens vs zero tokens in the right parahippocampus and dopaminergic midbrain, whereas the MDD group showed the opposite pattern—stronger responses to zero vs reward tokens—in these regions. Differential activation of the dopaminergic midbrain by reward vs zero tokens was positively correlated with the reward source memory advantage in controls, but not depressed participants. These data suggest that weaker memory for positive material in depression reflects blunted encoding responses in the dopaminergic midbrain and medial temporal lobes.     

Structural MRI correlates for vulnerability and resilience to major depressive disorder

Background

In major depressive disorder (MDD), it is unclear to what extent structural brain changes are associated with depressive episodes or represent part of the mechanism by which the risk for illness is mediated. The aim of this study was to investigate whether structural abnormalities are related to risk for the development of MDD.

Methods

We compared healthy controls with a positive family history for MDD (HC-FHP), healthy controls with no family history of any psychiatric disease (HC-FHN) and patients with MDD. Groups were age- and sex-matched. We analyzed data from high-resolution magnetic resonance imaging using voxel-based morphometry. We performed small volume corrections for our regions of interest (hippocampus, dorsolateral [DLPFC] and dorsomedial prefrontal cortex [DMPFC], anterior cingulate cortex [ACC] and basal ganglia) using a family-wise error correction (p < 0.05) to control for multiple comparisons.

Results

There were 30 participants in the HC-FHP group, 64 in the HC-FHN group and 33 patients with MDD. The HC-FHP group had smaller right hippocampal and DLPFC grey matter volumes compared with the HC-FHN group, and even smaller right hippocampal volumes compared with patients with MDD. In addition, the HC-FHP group exhibited smaller white matter volumes in the DLPFC and left putamen but also greater volumes in 2 areas of the DMPFC compared with the HC-FHN group. Patients with MDD exhibited smaller volumes in the ACC, DMPFC, DLPFC and the basal ganglia compared with healthy controls.

Limitations

The retrospective identification of family history might result in a bias toward unidentified participants in the control group at risk for MDD, diminishing the effect size.

Conclusion

Volume reductions in the hippocampus and DLPFC might be associated with a greater risk for MDD. The HC-FHP group had smaller hippocampal volumes compared with patients with MDD, which is suggestive for neuroplastic effects of treatment. The HC-FHP group had not yet experienced a depressive episode and therefore might have been resilient and might have had some protective strategies. Whether resilience is associated with the larger white matter volumes in the DMPFC (e.g., owing to compensatory, neuroplastic remodelling mechanisms) needs to be confirmed in future studies.     

Disorder-specific volumetric brain difference in adolescent major depressive disorder and bipolar depression

Structural abnormalities in frontal, limbic and subcortical regions have been noted in adults with both major depressive disorder (MDD) and bipolar disorder (BD). In the current study, we examined regional brain morphology in youth with MDD and BD as compared to controls. Regional brain volumes were measured in 32 MDD subjects (15.7?±?2.1 years), 14 BD subjects (16.0?±?2.4 years) and 22 healthy controls (16.0?±?2.8 years) using magnetic resonance imaging (MRI). Regions of interest included the hippocampus, dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), caudate, putamen and thalamus. Volumetric differences between groups were significant (F_26,80?=?1.80, p?=?0.02). Post-hoc analyses indicated that individuals with MDD showed reduced left hippocampus volumes (p?=?0.048) as well as right ACC white and gray matter volumes (p?=?0.003; p?=?0.01) compared to controls. BD participants also displayed reduced left hippocampal and right/left putamen volumes compared to controls (p?<?0.001; p?=?0.015; p?=?0.046 respectively). Interestingly, right and left ACC white matter volumes were smaller in MDD than in BD participants (p?=?0.019; p?=?0.045 respectively). No volumetric group differences were observed for the DLPFC and thalamus. Discriminant analysis was able to correctly classify 81.0 % of subjects as having BD or as MDD based on imaging data. Confirmation and extension of our findings requires larger sample sizes. Our findings provide new evidence of distinct, specific regional brain volumetric differences between MDD and BD that may be used to distinguish the two disorders.     

Microbiote et dépression : une piste thérapeutique prometteuse

There is increasing evidence towards an interaction between the intestinal microbiota, gut, and central nervous system. Based on this compelling body of evidence, there is growing enthusiasm for research focused on translating this emerging association into novel therapies for psychiatric illnesses. The links between gut microbiota disturbances and brain dysfunction have clearly been demonstrated in rodents. Researchers have proven that gut microbiota plays a major role in the central nervous system development, and that germ-free mice (mice born by c-section and without microbiota) do develop severe behavioral disorders mimicking MD with social withdrawal, self-neglect, eating and sleep disorders, anxiety, as well as hopelessness. A recent study has demonstrated that this major depression phenotype could be transferable from one mouse to another through microbiota transplantation. Moreover, microbiota dysfunctions have been associated with peripheral immune inflammation as well as neuro-inflammation (also called microglia activation). Subjects with irritable bowel syndrome (IBS) display higher rates of comorbid MD. The gut microbiota of patients with Major Depression (MD) to be similar to that of patients with IBS-diarrhea subtype (IBS-D) in that sense that their gut microbiota was less diverse than that from healthy control samples, with similar abundances of alterations (high proportions of Bacteroides and Prevotella). IBS is currently considered to be the paradigmatic microbiota-related disorder. Another study found the MD groups exhibited increased levels of Enterobacteriaceae and Alistipes (nocive bacteria), though reduced levels of Faecalibacterium (healthy bacteria). In this study, a negative correlation was likewise observed between Faecalibacterium and severity of depressive symptoms. Alpha gut microbiota diversity within samples was associated with depressive severity in two studies. Another study found altered microbiota signatures in the gut microbiota of MD patients, including Bacteroidetes, Proteobacteria, Firmicutes, and Actinobacteria phyla and, more specifically, 16 bacterial families. Probiotics are microorganisms that, when consumed, contribute to the host gut microbial flora, thereby producing beneficial effects on health. Among several possibilities for MD treatment that have garnered substantial interest in recent times, probiotics hold particular appeal. The effectiveness of probiotic administration in MD constitutes a strong evidence for developing microbiota-orientated treatments in this indication. Probiotics have yielded medium-to-large significant effects in the setting of depression (d = −.73 [95% CI = −1.02; −.44]). Whereas the first study evaluating the therapeutic efficacy of prebiotics or probiotics on depression or anxiety was conducted over a decade ago, approximately half of all existing studies were published over the past two years, reflecting the rapidly growing interest in this area. Duration of probiotic administration across trials ranged from 8 days to 45 weeks, whereas it is still unclear if the effect is maintained following probiotic discontinuation.     

Effects of cigarette smoking on cortical thickness in major depressive disorder

Findings of surface-based morphometry studies in major depressive disorder (MDD) are still inconsistent. Given that cigarette smoking is highly prevalent in MDD and has documented negative effects on the brain, it is possible that some of the inconsistencies may be partly explained by cigarette use. The aim of the current study was to examine the influence of cigarette smoking on brain structure in MDD. 50 MDD patients (25 smokers and 25 non-smokers) and 22 age, education, gender and BMI matched non-smoker healthy controls underwent structural magnetic resonance imaging. Thickness and area of the cortex were measured using surface-based morphometry implemented with Freesurfer (v5.3.0). The non-smoker MDD patients had significantly increased cortical thickness, including in the left temporal cortex (p < 0.001), right insular cortex (p = 0.033) and left pre- and postcentral gyrus (p = 0.045), compared to healthy controls. We also found decreased cortical thickness in MDD patients who smoked compared to non-smoking patients in regions that overlapped with the regions found to be increased in non-smoking patients in comparison to controls. Non-smoker MDD patients had increased surface area in the right lateral occipital cortex (p = 0.009). We did not find any region where cortical thickness or surface area significantly differed between controls and either smoker MDD patients or all MDD patients. The findings of the current study suggest that cigarette smoking is associated with cortical thinning in regions found to be increased in patients with MDD. However, these results should be considered preliminary due to methodological limitations.     

Elevated levels of cerebrospinal fluid neuron-specific enolase (NSE), but not S100B in major depressive disorder

Objectives. Alterations in neuronal and glial integrity are considered to be of pathogenic impact on major depressive disorder (MDD). For MDD, data on cerebrospinal fluid (CSF) levels of neuron-specific enolase (NSE) are lacking and scarce for glial protein S100B. Methods. We measured CSF levels of NSE and S100B in 31 patients with MDD and 32 mentally healthy controls using electrochemiluminescence immunoassays (ECLIA). Results. Adjusted means of NSE were significantly elevated in the MDD patients (11.73 ng/ml (9.95–13.52 95% CI) compared to the controls (6.17 ng/ml (4.55–7.78), F = 9.037, P = 0.004. Effect size for adjusted mean group difference of 5.57 ng/ml was found invariably high (Cohen’s d = 1.23). Differentiating MDD from controls, a NSE cut-off of 7.94 ng/ml showed sensitivity of 81% (95% CI 63.7–90.8) and specificity of 75% (95% CI 57.9–86.7). Adjusted levels of S100B did not differ significantly between the two groups (1.12 ng/ml (0.77–1.48) in MDD, 0.97 ng/ml (0.64–1.30) in controls). Conclusions. Our results of elevated CSF-NSE levels support neuronal pathology in MDD and the potential use of CSF-NSE as marker in clinical diagnostics. Missing group differences in S100B do not promote a specific glial pathology in depressive disorders.     

Salivary alpha-amylase and cortisol responsiveness following electrical stimulation stress in major depressive disorder patients

Major depressive disorder (MDD) is often associated with dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis by chronic stress. In comparison, psychosocial stress-induced activation of salivary α-amylase (sAA) functions as a marker of sympathoadrenal medullary system (SAM) activity. However, in contrast to salivary cortisol, sAA has been less extensively studied in MDD patients. The present study measured sAA and salivary cortisol levels in patients with MDD. The authors determined Profile of Mood State (POMS) and State-Trait anxiety Inventory (STAI) scores, Heart Rate Variability (HRV), and sAA and salivary cortisol levels in 88 patients with MDD and 41 healthy volunteers following the application of electrical stimulation stress. Patients with major depressive disorder were 8 points or more on Hamilton Depression Scale (HAM-D) scores. Tension-Anxiety, Depression-Dejection, Anger-Hostility, Fatigue, and Confusion scores in patients with major depressive disorder were significantly increased compared to healthy controls. In contrast, Vigor scores in patients with MDD were significantly decreased compared with healthy controls. There was no difference in heart rate variability measures between MDD patients and healthy controls. The threshold of electrical stimulation applied in MDD patients was lower than that in healthy controls. SAA levels in female MDD patients were significantly elevated relative to controls both before and after electrical stimulation. Finally, there were no differences in salivary cortisol levels between major depressive patients and controls. In the present study only three time points were explored. Furthermore, the increased secretion of sAA before and after stimulation could allude to an increased responsiveness of novel and uncontrollable situations in patients with MDD. These preliminary results suggest that sAA might be a useful biological marker of MDD.     

Altered inhibition of negative emotions in subjects at family risk of major depressive disorder

Unaffected 1st degree relatives of patients with major depressive disorder (MDD) are more likely to develop MDD than healthy controls. The aim of our study was to establish neuronal correlates of familial susceptibility in the process of inhibition of emotional information. Unaffected 1st degree relatives of patients with MDD (N = 21) and matched healthy controls (N = 25) underwent a functional magnetic resonance imaging procedure with an inhibition task. Blood oxygenated level dependent signal was evaluated for the two groups during inhibition of positive, negative and neutral information. In a 2 × 3 ANOVA unaffected relatives of patients with MDD were compared to healthy controls, jointly and separately for all three levels of emotional valence of the information. The interaction between group and emotional valence of the inhibited information was significant, indicating “a negative neural drift” in unaffected relatives of patients with MDD. The unaffected relatives of patients with MDD displayed an increased activation during inhibiting of negative material in the right middle cingulate cortex and the left caudate nucleus (p < 0.05, family wise error corrected). There was no difference between the two groups in terms of inhibiting positive or neutral stimuli. Our findings provide the first evidence that unaffected relatives of patients with MDD differ from the standard population in terms of neural correlates of inhibition of negative emotional information. Overactivation of cingulate cortex and caudate nucleus may indicate a learnt strategy aimed at coping with increased susceptibility to negative information schemata and may have future consequences for therapy.     

Peripheral blood nerve growth factor levels in major psychiatric disorders

Nerve growth factor (NGF) plays crucial roles in promoting neural growth and survival, and mediating synaptic and morphological plasticity. Several studies investigated the correlation between peripheral NGF levels and major psychiatric disorders, including schizophrenia (SCZ), major depressive disorder (MDD) and bipolar disorder (BPD); however, the findings were inconsistent. This meta-analysis sought to investigate blood NGF levels in patients with psychiatric disorders compared with healthy subjects and examined potential effects of blood fraction, medication and disease status. A total of 21 eligible studies, encompassing 1342 patients suffering from psychiatric disorders and 1225 healthy subjects, were enrolled in the present meta-analysis. No obvious publication bias was observed either for SCZ, MDD or BPD by the Begg's test (P > 0.05). Random-effects meta-analysis showed that SCZ (Z = 2.14, P = 0.033, SMD = −1.08, 95% CI = −2.07 to −0.09) and MDD (Z = 2.57, P = 0.010, SMD = −0.61, 95% CI = −1.08 to −0.14) patients had significantly reduced NGF levels, compared with healthy controls. Notably, this decrease was enhanced in un-medicated patients of SCZ (P = 0.004) and medicated or chronic patients of MDD (P < 0.001). No significant difference of NGF levels was observed between BPD patients and controls (P > 0.05). These results supported an association between the reduction of NGF levels and psychiatric disorders. It remains unclear whether the change of NGF levels is a prerequisite for its function in psychiatric disorders development or merely an epiphenomenon unrelated to the pathophysiologic mechanisms.     

Characterization of major depressive disorder using a multiparametric classification approach based on high resolution structural images

Background

Major depressive disorder (MDD) is one of the most disabling mental illnesses. Previous neuroanatomical studies of MDD have revealed regional alterations in grey matter volume and density. However, owing to the heterogeneous symptomatology and complex etiology, MDD is likely to be associated with multiple morphometric alterations in brain structure. We sought to distinguish first-episode, medication-naive, adult patients with MDD from healthy controls and characterize neuroanatomical differences between the groups using a multiparameter classification approach.

Methods

We recruited medication-naive patients with first-episode depression and healthy controls matched for age, sex, handedness and years of education. High-resolution T₁-weighted images were used to extract 7 morphometric parameters, including both volumetric and geometric features, based on the surface data of the entire cerebral cortex. These parameters were used to compare patients and controls using multivariate support vector machine, and the regions that informed the discrimination between the 2 groups were identified based on maximal classification weights.

Results

Thirty-two patients and 32 controls participated in the study. Both volumetric and geometric parameters could discriminate patients with MDD from healthy controls, with cortical thickness in the right hemisphere providing the greatest accuracy (78%, p ≤ 0.001). This discrimination was informed by a bilateral network comprising mainly frontal, temporal and parietal regions.

Limitations

The sample size was relatively small and our results were based on first-episode, medication-naive patients.

Conclusion

Our investigation demonstrates that multiple cortical features are affected in medication-naive patients with first-episode MDD. These findings extend the current understanding of the neuropathological underpinnings of MDD and provide preliminary support for the use of neuroanatomical scans in the early detection of MDD.     

Mood-congruent memory in depression – The influence of personal relevance and emotional context

The investigation of veridical mood-congruent memory (MCM) in major depressive disorder (MDD) has been subject of many studies, whereas mood-congruent false memory has received comparatively little attention. The present study examined the influence of valence, personal relevance and the valence of the context of the learning material on true and false MCM in 20 inpatients with MDD and 20 healthy controls. Sixty positive, negative, neutral or personally relevant nouns were either combined with a positive, negative or neutral adjective. Word pairs were presented to participants in a learning trial. In a recognition task, participants had to identify the previously studied word pairs. A MCM effect could not be found for hits. However, in exploratory analyses, word pairs containing personally relevant nouns were more rated towards old by the patient relative to the control group. Furthermore, depressed patients tended to rate items more towards old than controls when the words were presented in a negative new context. Results are in line with previous findings in depression research emphasizing the role of mood-congruent false memories for mood disorders.     

Altered intestinal microbiota in irritable bowel syndrome

Abstract Recent studies have suggested that alterations in the composition of the intestinal microbiota may play an important role in irritable bowel syndrome (IBS) symptoms. However, an association between the composition of the intestinal microbiota and IBS symptoms has not been clearly demonstrated. In the current issue of the Journal, Tana et al. suggest that altered intestinal microbiota contributes to the symptoms of IBS through increased levels of organic acids. In fecal samples, IBS patients had significantly higher numbers of Veillonella and Lactobacillus than healthy controls. They also showed significantly higher levels of acetic acid and propionic acid. Furthermore, IBS patients with high acetic acid or propionic acid levels presented more severe symptoms, impaired quality of life and negative emotions. These results are in accordance with the concept that the gut microbiota influences the sensory, motor and immune system of the gut and interacts with higher brain centers. Small intestinal bacterial overgrowth observed in a subset of IBS patients describes quantitative changes in the small intestinal microbiota. Data on qualitative changes in the gut microbiota in IBS patients are lacking. Different members of gut bacteria may have different influence on gut function. The concepts identified here may lead to the development of novel therapeutic strategies for IBS using manipulation of the intestinal microbiota.     

Increased cerebrospinal fluid interleukin-6 levels in patients with schizophrenia and those with major depressive disorder

Elevated peripheral levels of interleukin-6 (IL-6) are common findings in schizophrenia and depression. However, previous studies that measured cerebrospinal fluid (CSF) IL-6 levels in these disorders reported controversial results. The present study examined whether CSF IL-6 levels are altered in patients with schizophrenia and those with depression. Lumbar punctures were performed in 32 patients with schizophrenia, 30 with major depressive disorder (MDD), and 35 healthy controls. Serum samples were simultaneously collected from all subjects in the patient groups and from 32 of the control group. CSF and serum IL-6 levels were determined by enzyme-linked immunosorbent assay. Both the patients with schizophrenia and MDD had significantly higher CSF IL-6 levels compared to the controls (schizophrenia: P = 0.0027; MDD: P = 0.012). IL-6 levels were significantly higher in the CSF than in the serum. No significant correlation was observed between CSF and serum IL-6 levels. The present findings suggest that IL-6 of central origin is associated with the pathophysiology of schizophrenia and MDD, although confounding effect of smoking status can not be entirely excluded.