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Microbiota-Orientated Treatments for Major Depression and Schizophrenia.

ABSTRACT: BACKGROUND AND SIGNIFICANCE:There is a need to develop new hypothesis-driven treatment for both both major depression (MD) and schizophrenia in which the risk of depression is 5 times higher than the general population. Major depression has been also associated with poor illness outcomes including pain, metabolic disturbances, and less adherence. Conventional antidepressants are partly effective, and 44% of the subjects remain unremitted under treatment. Improving MD treatment efficacy is thus needed to improve the SZ prognosis. Microbiota-orientated treatments are currently one of the most promising tracks. METHOD:This work is a systematic review synthetizing data of arguments to develop microbiota-orientated treatments (including fecal microbiota transplantation (FMT)) in major depression and schizophrenia. RESULTS:The effectiveness of probiotic administration in MD constitutes a strong evidence for developing microbiota-orientated treatments. Probiotics have yielded medium-to-large significant effects on depressive symptoms, but it is still unclear if the effect is maintained following probiotic discontinuation. Several factors may limit MD improvement when using probiotics, including the small number of bacterial strains administered in probiotic complementary agents, as well as the presence of a disturbed gut microbiota that probably limits the probiotics' impact. FMT is a safe technique enabling to improve microbiota in several gut disorders. The benefit/risk ratio of FMT has been discussed and has been recently improved by capsule administration. CONCLUSION:Cleaning up the gut microbiota by transplanting a totally new human gut microbiota in one shot, which is referred to as FMT, is likely to strongly improve the efficacy of microbiota-orientated treatments in MD and schizophrenia and maintain the effect over time. This hypothesis should be tested in future clinical trials.

SUBMITTER: Fond GB

PROVIDER: S-EPMC7230529 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Microbiota-Orientated Treatments for Major Depression and Schizophrenia.

Fond Guillaume B GB Lagier Jean-Christophe JC Honore Stéphane S Lancon Christophe C Korchia Théo T Sunhary De Verville Pierre-Louis PL Llorca Pierre-Michel PM Auquier Pascal P Guedj Eric E Boyer Laurent L

Nutrients 20200408 4

<h4>Background and significance</h4>There is a need to develop new hypothesis-driven treatment for both both major depression (MD) and schizophrenia in which the risk of depression is 5 times higher than the general population. Major depression has been also associated with poor illness outcomes including pain, metabolic disturbances, and less adherence. Conventional antidepressants are partly effective, and 44% of the subjects remain unremitted under treatment. Improving MD treatment efficacy i ...[more]

PMID: 32276499

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Project description:ObjectivesRecently, the presence of a complete five subunit Kinase, Endopeptidase and Other Proteins of small Size (KEOPS) complex was confirmed in humans. The highly conserved KEOPS protein complex has established roles in tRNA modification, protein translation and telomere homeostasis in yeast, but little is known about KEOPS mRNA expression and function in human brain and disease. Here, we characterise KEOPS expression in post-mortem tissue from subjects diagnosed with major depression (MDD) and schizophrenia and assess whether KEOPS is associated with telomere length dysregulation in neuropsychiatric disorders.MethodsWe assessed mRNA expression of KEOPS complex subunits TP53RK, TPRKB, GON7, LAGE3, OSGEP, and OSGEP mitochondrial ortholog OSGEPL1 in the dorsolateral prefrontal cortex (DLPFC) of subjects with MDD, schizophrenia and matched non-psychiatrically ill controls (n = 20 per group) using qPCR. We conducted bioinformatic analysis using Kaleidoscope, data mining post-mortem transcriptomic datasets to characterise KEOPS expression in human brain. Finally, we assayed relative telomere length in the DLPFC using a qPCR-based assay and carried out correlation analysis with KEOPS subunit mRNA expression to determine if the KEOPS complex is associated with telomere length dysregulation in neuropsychiatric disorders.ResultsThere were no significant changes in KEOPS mRNA expression in the DLPFC in MDD or schizophrenia compared to non-psychiatrically ill controls. Relative telomere length was not significantly altered in MDD or schizophrenia, nor was there an association between relative telomere length and KEOPS subunit gene expression in these subjects.ConclusionsThis study is the first to describe KEOPS complex expression in post-mortem brain and neuropsychiatric disorders. KEOPS subunit mRNA expression is not significantly altered in the DLPFC in MDD or schizophrenia. Unlike in yeast, the KEOPS complex does not appear to play a role in telomere length regulation in humans or in neuropsychiatric disorders.

Project description:Schizophrenia is a psychiatric disorder that causes great suffering and debilitation worldwide. We have a multitude of medications that are effective for psychosis. However, these have not been successful in treating the negative and cognitive symptom domains of schizophrenia. These symptoms are responsible for the larger part of functional impairments that result from schizophrenia. In addition, there are many patients for whom no significant improvement is achieved even in the positive symptom domain. Hence, other treatment modalities have been explored to help these patients. Electroconvulsive therapy and transcranial magnetic stimulation are two of the most promising adjunct treatment methods for medication resistant schizophrenia. Electroconvulsive therapy is the gold standard treatment for catatonias whether associated with schizophrenia, mood disorders or other non-psychiatric disorders. Although not effective for negative symptoms, electroconvulsive therapy provides substantial augmentation to antipsychotic medications in improving positive symptoms and overall severity. Electroconvulsive therapy should be considered more often in patients with inadequate response to antipsychotic medications even when they do not have prominent affective symptoms. Transcranial magnetic stimulation has emerged as a promising useful therapeutic tool in targeting medication resistant auditory hallucinations and negative symptoms. Transcranial magnetic stimulation has proven to be very safe and well-tolerated by the patients in spite of its labor intensiveness. The incorporation of transcranial magnetic stimulation to routine clinical use awaits further studies to substantiate its efficacy and to optimize and customize treatment parameters to individual patients and their symptom patterns. Moreover, combining transcranial magnetic stimulation with electroconvulsive therapy to synergize their likely different mechanisms of action is another exciting possibility.

Dataset Information

Microbiota-Orientated Treatments for Major Depression and Schizophrenia.

Publications

Microbiota-Orientated Treatments for Major Depression and Schizophrenia.

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