Microbiota-Orientated Treatments for Major Depression and Schizophrenia.

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.

A Systematic Review of the Effect of Probiotic Supplementation on Schizophrenia Symptoms.

BACKGROUND: Derangements of the gut microbiome have been linked to increased systemic inflammation and central nervous system disorders, including schizophrenia. This systematic review thus aimed to investigate the hypothesis that probiotic supplementation improves schizophrenia symptoms. METHODS: By using the keywords (probiotic OR gut OR microbiota OR microbiome OR yogurt OR yoghurt OR lactobacillus OR bifidobacterium) AND (schizophrenia OR psychosis), a preliminary search of the PubMed, Medline, Embase, Google Scholar, ClinicalTrials.gov, Clinical Trials Register of the Cochrane Collaboration Depression, Anxiety and Neurosis Group (CCDANTR), and Cochrane Field for Complementary Medicine databases yielded 329 papers published in English between January 1, 1960 and May 1, 2018. Attempts were made to search grey literature as well. RESULTS: Three clinical studies were reviewed, comparing the use of probiotics to placebo controls. Applying per-protocol analysis and a fixed-effects model, there was no significant difference in schizophrenia symptoms between the group that received probiotic supplementation and the placebo group post-intervention as the standardized mean difference was -0.0884 (95% CI -0.380 to 0.204, p = 0.551). Separate analyses were performed to investigate the effect of probiotic supplementation on positive or negative symptoms of schizophrenia alone. In both instances, no significant difference was observed as well. CONCLUSION: Based on current evidence, limited inferences can be made regarding the efficacy of probiotics in schizophrenia. Although probiotics may have other benefits, for example to regulate bowel movement and ameliorate the metabolic effects of antipsychotic medications, the clinical utility of probiotics in the treatment of schizophrenia patients remains to be validated by future clinical studies.

Latent toxoplasmosis reduces gray matter density in schizophrenia but not in controls: voxel-based-morphometry (VBM) study.

OBJECTIVES: To address the role of latent T. gondii infection in schizophrenia we studied the influence of latent toxoplasmosis on brain morphology. METHODS: An optimized voxel-based morphometry of magnetic resonance imaging was analyzed by analysis of variance with diagnosis and seropositivity as factors in 44 schizophrenic patients (12 T. gondii positive) and 56 controls (13 T. gondii positive). RESULTS: Grey matter (GM) volume was reduced in schizophrenia patients compared with controls in the cortical regions, hippocampus and in the caudate. In the schizophrenia sample we found a significant reduction of GM volume in T. gondii positive comparing with T. gondii-negative patients bilaterally in the caudate, median cingulate, thalamus and occipital cortex and in the left cerebellar hemispheres. T. gondii-positive and -negative controls did not differ in any cluster. Among participants seropositive to T. gondii the reduction of GM in the schizophrenia subjects was located in the same regions when comparing the entire sample (11,660 over-threshold voxels (P ≤ 0.05, FWR corrected). The differences between T. gondii-negative patients and controls consisted only of 289 voxels in temporal regions. CONCLUSIONS: Our study is the first to document that latent toxoplasmosis reduces GM in schizophrenia but not in controls.