Enterogenic metabolomics signatures of depression: what are the possibilities for the future.

INTRODUCTION: An increasing number of studies indicate that the microbiota-gut-brain axis is an important pathway involved in the onset and progression of depression. The responses of the organism (or its microorganisms) to external cues cannot be separated from a key intermediate element: their metabolites. AREAS COVERED: In recent years, with the rapid development of metabolomics, an increasing amount of metabolites has been detected and studied, especially the gut metabolites. Nevertheless, the increasing amount of metabolites described has not been reflected in a better understanding of their functions and metabolic pathways. Moreover, our knowledge of the biological interactions among metabolites is also incomplete, which limits further studies on the connections between the microbial-entero-brain axis and depression. EXPERT OPINION: This paper summarizes the current knowledge on depression-related metabolites and their involvement in the onset and progression of this disease. More importantly, this paper summarized metabolites from the intestine, and defined them as enterogenic metabolites, to further clarify the function of intestinal metabolites and their biochemical cross-talk, providing theoretical support and new research directions for the prevention and treatment of depression.

The efficacy and acceptability of exposure therapy for the treatment of post-traumatic stress disorder in children and adolescents: a systematic review and meta-analysis.

BACKGROUND: Posttraumatic stress disorder (PTSD) is common among children and adolescents who have experienced traumatic events. Exposure therapy (ET) has been shown to be effective in treating PTSD in adults. However, its efficacy remains uncertain in children and adolescents. AIMS: To evaluate the efficacy and acceptability of ET in children and adolescents with PTSD. METHOD: We searched PubMed, EMBASE, Cochrane, Web of Science, PsycINFO, CINAHL, ProQuest, LILACS, and international trial registries for randomized controlled trials (RCTs) assessed ET in children and adolescents (aged ≤18 years) with PTSD up to August 31, 2020. The primary outcomes were efficacy (the endpoint score from PTSD symptom severity rating scales) and acceptability (all-cause discontinuation), secondary outcomes included efficacy at follow-up (score from PTSD scales at the longest point of follow-up), depressive symptoms (end-point score on depressive symptom severity rating scales) and quality of life/social functioning (end-point score on quality of life/social functioning rating scales). This study was registered with PROSPERO (CRD42020150859). RESULT: A total of 6 RCTs (278 patients) were included. The results showed that ET was statistically more efficacious than control groups (standardized mean differences [SMD]: - 0.47, 95% confidence interval [CI]: - 0.91 to - 0.03). In subgroup analysis, exposure therapy was more efficacious for patients with single type of trauma (SMD: - 1.04, 95%CI: - 1.43 to - 0.65). Patients with an average age of 14 years and older, ET was more effective than the control groups (SMD: - 1.04, 95%CI: - 1.43 to - 0.65), and the intervention using prolonged exposure therapy (PE) (SMD: - 1.04, 95%CI: - 1.43 to - 0.65) was superior than control groups. Results for secondary outcomes of efficacy at follow-up (SMD: - 0.64, 95%CI: - 1.17 to - 0.10) and depressive symptoms (SMD: - 0.58, 95%CI: - 0.93 to - 0.22) were similar to the previous findings for efficacy outcome. No statistically significant effects for acceptability and quality of life/social functioning were found. CONCLUSION: ET showed superiority in efficacy at post-treatment/follow-up and depressive symptoms improvement in children and adolescents with PTSD. Patients with single type of trauma may benefit more from ET. And ET is more effective in patients 14 years or older. Moreover, PE could be a better choice.

The efficacy and acceptability of group trauma-focused cognitive behavior therapy for the treatment of post-traumatic stress disorder in children and adolescents: A systematic review and meta-analysis.

BACKGROUND: Group trauma-focused cognitive behavior therapy (TF-CBT) is widely used to treat post-traumatic stress disorder (PTSD) in children and adolescents. However, the available evidence remains unclear. METHOD: PubMed, EMBASE, Cochrane, Web of Science, PsycINFO, CINAHL, ProQuest Dissertations, LILACS, and international trial registers were searched from database inception to April 30, 2022. We included randomized controlled trials (RCTs) that compared TF-CBT with any control condition for treating children and adolescents with PTSD. Analyses were performed using Review Manager version 5.3 and Stata 16.0. The risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool. This study was registered with PROSPERO (CRD42020206096). RESULTS: Eleven RCTs involving 1942 patients were included. Group TF-CBT was significantly more effective than other treatments at post-treatment (standardized mean difference [SMD]: -0.43, 95% confidence interval [CI]: -0.65 to -0.22), follow-up (SMD: -0.33, 95% CI: -0.52 to -0.13), and in relieving depressive symptoms (SMD: -0.29, 95% CI: -0.49 to -0.09), but not in terms of acceptability. Subgroup analyses showed that group TF-CBT was superior to other treatments in studies including children with post-traumatic stress symptoms (PTSS) (SMD: -0.54, 95% CI: -0.79 to -0.28) and psychiatric comorbidities (SMD: -0.48, 95% CI: -0.72 to -0.23). LIMITATIONS: The small sample sizes of identified studies limited some findings. CONCLUSION: When considering effectiveness at post-treatment and follow-up or the reduction of depressive symptoms, group TF-CBT could be a good choice for children and adolescents with PTSD. Among these patients, those with PTSS or psychiatric comorbidities may benefit the most.

A comprehensive analysis of the differential expression in the hippocampus of depression induced by gut microbiota compared to traditional stress.

Depression, which is a disease of heterogeneous etiology, is characterized by high disability and mortality rates. Gut microbiota are associated with the development of depression. To further explore any differences in the mechanisms of depression induced by gut microbiota and traditional stresses, as well as facilitate the development of microbiota-based interventions, a fecal microbiota transplantation (FMT) depression model was made. This was achieved by transplanting feces from major depressive disorder (MDD) patients into germ-free mice. Second, the mechanisms of the depression induced by gut microbiota were analyzed in comparison with those of the depression caused by different forms of stress. It turned out that mice exhibited depressive-like behavior after FMT. Then, PCR array analysis was performed on the hippocampus of the depressed mice to identify differentially expressed genes (DEGs). The KEGG analysis revealed that the pathways of depression induced by gut microbes are closely associated with immuno-inflammation. To determine the pathogenic pathways of physiological stress and psychological stress-induced depression, raw data was extracted from several databases and KEGG analysis was performed. The results from the analysis revealed that the mechanisms of depression induced by physiological and psychological stress are closely related to the regulation of neurotransmitters and energy metabolism. Interestingly, the immunoinflammatory response was distinct across different etiologies that induced depression. The findings showed that gut microbiota dysbiosis-induced depression was mainly associated with adaptive immunity, while physiological stress-induced depression was more linked to innate immunity. This study compared the pathogenesis of depression caused by gut microbiota dysbiosis, and physiological and psychological stress. We explored new intervention methods for depression and laid the foundation for precise treatment.

Maternal separation regulates sensitivity of stress-induced depression in mice by affecting hippocampal metabolism.

Depression is a serious mental illness. Previous studies found that early life stress (ELS) plays a vital role in the onset and progression of depression. However, relevant studies have not yet been able to explain the specific effects of early stress on stress-induced depression sensitivity and individual behavior during growth. Therefore, we constructed a maternal separation (MS) model and administered chronic social frustration stress at different stages of their growth while conducting metabolomics analysis on the hippocampus of mice. Our results showed that the immobility time of mice in the forced swimming test was significantly reduced at the end of MS. Meanwhile, mice with MS experience significantly decreased total movement distance in the open field test and sucrose preference ratio in the sucrose preference test when subjected to chronic social defeat stress (CSDS) during adolescence. In adulthood, the results were the opposite. In addition, we found that level changes in metabolites such as Beta-alanine, l-aspartic acid, 2-aminoadipic acid, and Glycine are closely related to behavioral changes. These metabolites are mainly enriched in Pantothenate, CoA biosynthesis, and Beta Alanine metabolism pathways. Our experiment revealed that the effects of ELS vary across different age groups. It will increase an individual's sensitivity to depression when facing CSDS in adolescence, but it will reduce their sensitivity to depression when facing CSDS in adulthood. This may be achieved by regulating the hippocampus's Pantothenate and CoA biosynthesis and Beta Alanine metabolism pathways represented by Beta-alanine, l-Aspartic acid, 2-aminoadipic acid, and Glycine metabolites.

[Advances in revision surgery after primary total hip arthroplasty for Crowe type â £ developmental dysplasia of the hip].

Objective: To review research advances of revision surgery after primary total hip arthroplasty (THA) for patients with Crowe type Ⅳ developmental dysplasia of the hip (DDH). Methods: The recent literature on revision surgery after primary THA in patients with Crowe type Ⅳ DDH was reviewed. The reasons for revision surgery were analyzed and the difficulties of revision surgery, the management methods, and the related prosthesis choices were summarized. Results: Patients with Crowe type Ⅳ DDH have small anteroposterior diameter of the acetabulum, large variation in acetabular and femoral anteversion angles, severe soft tissue contractures, which make both THA and revision surgery more difficult. There are many reasons for patients undergoing revision surgery after primary THA, mainly due to aseptic loosening of the prosthesis. Therefore, it is necessary to restore anatomical structures in primary THA, as much as possible and reduce the generation of wear particles to avoid postoperative loosening of the prosthesis. Due to the anatomical characteristics of Crowe type Ⅳ DDH, the patients have acetabular and femoral bone defects, and the repair and reconstruction of bone defects become the key to revision surgery. The acetabular side is usually reconstructed with the appropriate acetabular cup or combined metal block, Cage, or custom component depending on the extent of the bone defect, while the femoral side is preferred to the S-ROM prosthesis. In addition, the prosthetic interface should be ceramic-ceramic or ceramic-highly cross-linked polyethylene wherever possible. Conclusion: The reasons leading to revision surgery after primary THA in patients with Crowe type Ⅳ DDH and the surgical difficulties have been clarified, and a large number of clinical studies have proposed corresponding revision modalities based on which good early- and mid-term outcomes have been obtained, but further follow-up is needed to clarify the long-term outcomes. With technological advances and the development of new materials, personalized prostheses for these patients are expected to become a reality.

Altered Intestinal Microbiomes and Lipid Metabolism in Patients With Prolonged Disorders of Consciousness.

The intestinal microbiota regulate the brain function of the host through the production of a myriad of metabolites and are associated with various neurological diseases. Understanding the intestinal microbiome of patients with prolonged disorders of consciousness (DoC) is important for the evaluation and treatment of the disease. To investigate the differences in the intestinal microbiome and short-chain fatty acids (SCFAs) among patients in a vegetative state (VS), a minimally conscious state (MCS), and emerged from MCS (EMCS), as well as the influence of antibiotics on these patients, 16S ribosomal RNA (16S rRNA) sequencing and targeted lipidomics were performed on fecal samples from patients; in addition, analysis of the electroencephalogram (EEG) signals was performed to evaluate the brain function of these patients. The results showed that the intestinal microbiome of the three groups differed greatly, and some microbial communities showed a reduced production of SCFAs in VS patients compared to the other two groups. Moreover, reduced microbial communities and five major SCFAs, along with attenuated brain functional connectivity, were observed in MCS patients who were treated with antibiotics compared to those who did not receive antibiotic treatment, but not in the other pairwise comparisons. Finally, three genus-level microbiota-Faecailbacterium, Enterococcus, and Methanobrevibacter-were considered as potential biomarkers to distinguish MCS from VS patients, with high accuracy both in the discovery and validation cohorts. Together, our findings improved the understanding of patients with prolonged DoC from the intestinal microbiome perspective and provided a new reference for the exploration of therapeutic targets.