PROVIT-CLOCK: A Potential Influence of Probiotics and Vitamin B7 Add-On Treatment and Metabolites on Clock Gene Expression in Major Depression.

INTRODUCTION: An increasing body of evidence suggests a strong relationship between gut health and mental state. Lately, a connection between butyrate-producing bacteria and sleep quality has been discussed. The PROVIT study, as a randomized, double-blind, 4-week, multispecies probiotic intervention study, aims at elucidating the potential interconnection between the gut's metabolome and the molecular clock in individuals with major depressive disorder (MDD). METHODS: The aim of the PROVIT-CLOCK study was to analyze changes in core clock gene expression during treatment with probiotic intervention versus placebo in fasting blood and the connection with the serum- and stool-metabolome in patients with MDD (n = 53). In addition to clinical assessments in the PROVIT study, metabolomics analyses with 1H nuclear magnetic resonance spectroscopy (stool and serum) and gene expression (RT-qPCR) analysis of the core clock genes ARNTL, PER3, CLOCK, TIMELESS, NR1D1 in peripheral blood mononuclear cells of fasting blood were performed. RESULTS: The gene expression levels of the clock gene CLOCK were significantly altered only in individuals receiving probiotic add-on treatment. TIMELESS and ARNTL gene expression changed significantly over the 4-week intervention period in both groups. Various positive and negative correlations between metabolites in serum/stool and core clock gene expression levels were observed. CONCLUSION: Changing the gut microbiome by probiotic treatment potentially influences CLOCK gene expression. The preliminary results of the PROVIT-CLOCK study indicate a possible interconnection between the gut microbiome and circadian rhythm potentially orchestrated by metabolites.

The PROVIT Study-Effects of Multispecies Probiotic Add-on Treatment on Metabolomics in Major Depressive Disorder-A Randomized, Placebo-Controlled Trial.

The gut-brain axis plays a role in major depressive disorder (MDD). Gut-bacterial metabolites are suspected to reduce low-grade inflammation and influence brain function. Nevertheless, randomized, placebo-controlled probiotic intervention studies investigating metabolomic changes in patients with MDD are scarce. The PROVIT study (registered at clinicaltrials.com NCT03300440) aims to close this scientific gap. PROVIT was conducted as a randomized, single-center, double-blind, placebo-controlled multispecies probiotic intervention study in individuals with MDD (n = 57). In addition to clinical assessments, metabolomics analyses (1H Nuclear Magnetic Resonance Spectroscopy) of stool and serum, and microbiome analyses (16S rRNA sequencing) were performed. After 4 weeks of probiotic add-on therapy, no significant changes in serum samples were observed, whereas the probiotic groups' (n = 28) stool metabolome shifted towards significantly higher concentrations of butyrate, alanine, valine, isoleucine, sarcosine, methylamine, and lysine. Gallic acid was significantly decreased in the probiotic group. In contrast, and as expected, no significant changes resulted in the stool metabolome of the placebo group. Strong correlations between bacterial species and significantly altered stool metabolites were obtained. In summary, the treatment with multispecies probiotics affects the stool metabolomic profile in patients with MDD, which sets the foundation for further elucidation of the mechanistic impact of probiotics on depression.

PROVIT: Supplementary Probiotic Treatment and Vitamin B7 in Depression-A Randomized Controlled Trial.

Gut microbiota are suspected to affect brain functions and behavior as well as lowering inflammation status. Therefore, an effect on depression has already been suggested by recent research. The aim of this randomized double-blind controlled trial was to evaluate the effect of probiotic treatment in depressed individuals. Within inpatient care, 82 currently depressed individuals were randomly assigned to either receive a multistrain probiotic plus biotin treatment or biotin plus placebo for 28 days. Clinical symptoms as well as gut microbiome were analyzed at the begin of the study, after one and after four weeks. After 16S rRNA analysis, microbiome samples were bioinformatically explored using QIIME, SPSS, R and Piphillin. Both groups improved significantly regarding psychiatric symptoms. Ruminococcus gauvreauii and Coprococcus 3 were more abundant and ß-diversity was higher in the probiotics group after 28 days. KEGG-analysis showed elevated inflammation-regulatory and metabolic pathways in the intervention group. The elevated abundance of potentially beneficial bacteria after probiotic treatment allows speculations on the functionality of probiotic treatment in depressed individuals. Furthermore, the finding of upregulated vitamin B6 and B7 synthesis underlines the connection between the quality of diet, gut microbiota and mental health through the regulation of metabolic functions, anti-inflammatory and anti-apoptotic properties. Concluding, four-week probiotic plus biotin supplementation, in inpatient individuals with a major depressive disorder diagnosis, showed an overall beneficial effect of clinical treatment. However, probiotic intervention compared to placebo only differed in microbial diversity profile, not in clinical outcome measures.

Interleukin-6 Gene Expression Changes after a 4-Week Intake of a Multispecies Probiotic in Major Depressive Disorder-Preliminary Results of the PROVIT Study.

Major depressive disorder (MDD) is a prevalent disease, in which one third of sufferers do not respond to antidepressants. Probiotics have the potential to be well-tolerated and cost-efficient treatment options. However, the molecular pathways of their effects are not fully elucidated yet. Based on previous literature, we assume that probiotics can positively influence inflammatory mechanisms. We aimed at analyzing the effects of probiotics on gene expression of inflammation genes as part of the randomized, placebo-controlled, multispecies probiotics PROVIT study in Graz, Austria. Fasting blood of 61 inpatients with MDD was collected before and after four weeks of probiotic intake or placebo. We analyzed the effects on gene expression of tumor necrosis factor (TNF), nuclear factor kappa B subunit 1 (NFKB1) and interleukin-6 (IL-6). In IL-6 we found no significant main effects for group (F(1,44) = 1.33, p = ns) nor time (F(1,44) = 0.00, p = ns), but interaction was significant (F(1,44) = 5.67, p < 0.05). The intervention group showed decreasing IL-6 gene expression levels while the placebo group showed increasing gene expression levels of IL-6. Probiotics could be a useful additional treatment in MDD, due to their anti-inflammatory effects. Results of the current study are promising, but further studies are required to investigate the beneficial effects of probiotic interventions in depressed individuals.

Creativity and borderline personality disorder: evidence from a voxel-based morphometry study.

INTRODUCTION: Throughout the history, various examples of eminent creative people suffering from mental disorders along with some empirical research reports strengthened the idea of a potential link between creativity and psychopathology. METHODS: This study investigated different facets of psychometrically determined creativity in 20 females diagnosed with borderline personality disorder (BPD) relative to 19 healthy female controls. In addition, group differences in grey matter (GM) were examined. RESULTS: Behavioural findings revealed no significant differences between the BPD group and healthy controls with respect to verbal and figural-graphic creative task performance and creativity-related personality characteristics. Whole-brain voxel-based morphometry analyses revealed a distinct pattern of GM reductions in the BPD group (relative to controls) in a network of brain regions closely associated with various cognitive and emotional functions (including the bilateral orbital inferior frontal gyri and the left superior temporal gyrus), partly overlapping with creativity-related brain regions. Correlation analyses moreover revealed that in the BPD group GM reductions in the orbital parts of the inferior and middle frontal gyri were associated with lower levels of creativity. CONCLUSIONS: This study provides no indications in favour of the putative link between creativity and psychopathology, as sometimes reported in the literature.

Self-disgust in mental disorders -- symptom-related or disorder-specific?

BACKGROUND: Dysfunctional disgust experiences occur in a variety of mental disorders. Previous research focused on disgust proneness directed towards stimuli in the external environment. However, self-disgust, the devaluation of one' own physical appearance and personality (personal disgust) as well as one' own behavior (behavioral disgust) has hardly been investigated thus far, although it may play a crucial role in specific psychopathologies. METHODS: We investigated 112 patients diagnosed with different mental disorders (major depression, schizophrenia, borderline personality disorder (BPD), eating disorders, and spider phobia) and 112 matched mentally healthy individuals. Participants answered the Questionnaire for the Assessment of Self-Disgust (QASD) with two subscales 'personal disgust' and 'behavioral disgust', and the Brief Symptom Inventory (BSI) that provides an overview of patients' psychological problems and their intensity. RESULTS: Compared to healthy controls self-disgust was elevated in mental disorders. Personal disgust was more pronounced than behavioral disgust in patients, whereas there was no difference in controls. Patients with BPD and eating disorders reported the highest scores on both subscales. Findings also suggest that self-disgust is related to specific psychological problems. In mental disorders psychoticism and hostility were the best predictors for personal disgust, while anxiety and interpersonal sensitivity predicted behavioral disgust. Additionally, we found disorder-specific predictors for personal disgust (e.g., hostility in schizophrenia). Finally, traumatic events during childhood constitute a risk factor for self-disgust. CONCLUSIONS: The current study provides first evidence for the differential meaning of self-disgust for specific mental disorders and symptoms.

[Religious/spiritual well-being in mentally ill persons: a comparison of anxious/depressives, addicts and healthy controls]. / Religiös/Spirituelles Befinden bei psychisch Kranken: Ängstlich/Depressive und Suchtkranke im Vergleich zu gesunden Kontrollpersonen.

OBJECTIVE: The aim of this study is to investigate different dimensions of religiosity and spirituality among psychiatric in-patients. The study examines differences between addictive (ICD 10: F1x) and anxious/depressive (ICD 10: F3x/F4x) patients and considers the main implications for treatment. METHOD: Differences in dimensions of religious/spiritual well-being (RSWB) between addictive (n = 389) and anxious/depressive patients (n = 200) are investigated, also by comparison to a control group (n = 1,500). Furthermore dimensions of RSWB are related to personality factors and different psychiatric parameters within the psychiatric groups. RESULTS: The psychiatric groups show a lower amount of overall RSWB (p < 0.001) than the healthy controls. Furthermore, dimensions of RSWB turned out to be negatively correlated with several psychiatric symptoms. CONCLUSIONS: Based on these results we emphasize religious/spiritual issues within psychiatric treatment. Moreover, there may be a strong potential of the RSWB dimensions such as "Hope" or "Forgiveness" as positive therapeutic factors in psychiatric treatment.

Altered state and trait disgust in borderline personality disorder.

Clinical experience suggests that the emotion disgust plays an important role in borderline personality disorder (BPD). We investigated 30 female patients with BPD and 30 healthy women who answered different measures of trait disgust, specifically disgust proneness, disgust sensitivity, and self-disgust. Moreover, all participants rated affective facial expressions as well as affective scenes according to perceived or elicited basic emotions. The patients with BPD reported elevated trait disgust, especially for the area of self-disgust. They also rated facial expressions of disgust as more intense than did the healthy women but only when the person who displayed this emotion was male. This sex-specific disgust bias was independent of depression and experienced sexual/physical abuse in the clinical group. Altogether, the patients with BPD showed a broad spectrum of altered disgust processes, which was positively correlated with disorder severity. Consequently, the assessment of disgust reactivity should be introduced as a diagnostic tool for this disorder.