Compositional and Functional Alterations in Intestinal Microbiota in Patients with Psychosis or Schizophrenia: A Systematic Review and Meta-analysis.

BACKGROUND AND HYPOTHESIS: Intestinal microbiota is intrinsically linked to human health. Evidence suggests that the composition and function of the microbiome differs in those with schizophrenia compared with controls. It is not clear how these alterations functionally impact people with schizophrenia. We performed a systematic review and meta-analysis to combine and evaluate data on compositional and functional alterations in microbiota in patients with psychosis or schizophrenia. STUDY DESIGN: Original studies involving humans and animals were included. The electronic databases PsycINFO, EMBASE, Web of Science, PubMed/MEDLINE, and Cochrane were systematically searched and quantitative analysis performed. STUDY RESULTS: Sixteen original studies met inclusion criteria (1376 participants: 748 cases and 628 controls). Ten were included in the meta-analysis. Although observed species and Chao 1 show a decrease in diversity in people with schizophrenia compared with controls (SMD = -0.14 and -0.66 respectively), that did not reach statistical significance. We did not find evidence for variations in richness or evenness of microbiota between patients and controls overall. Differences in beta diversity and consistent patterns in microbial taxa were noted across studies. We found increases in Bifidobacterium, Lactobacillus, and Megasphaera in schizophrenia groups. Variations in brain structure, metabolic pathways, and symptom severity may be associated with compositional alterations in the microbiome. The heterogeneous design of studies complicates a similar evaluation of functional readouts. CONCLUSIONS: The microbiome may play a role in the etiology and symptomatology of schizophrenia. Understanding how the implications of alterations in microbial genes for symptomatic expression and clinical outcomes may contribute to the development of microbiome targeted interventions for psychosis.

Compositional and functional alterations in the oral and gut microbiota in patients with psychosis or schizophrenia: A systematic review.

Background: Gut and oral microbiota are intrinsically linked to human health. Recent studies suggest a direct link with mental health through bidirectional gut-brain pathways. Emerging evidence suggests that the composition and/or function of intestinal microbiome differs in those with psychosis and schizophrenia as compared with controls. There is relatively little research on the predicted or actual functional alterations associated with the composition of oral and gut microbiota in patients with psychosis. We will perform a systematic review and meta-analysis to identify, evaluate and if possible, combine the published literature on compositional alterations in the oral and gut microbiota in patients with psychosis or schizophrenia compared with healthy controls. We also aim to explore the potential functional impact of any compositional changes. Methods: Original studies involving humans and animals using a case-control, cohort or cross-sectional design will be included. The electronic databases PsycINFO, EMBASE, Web of Science, PubMed/MEDLINE and Cochrane will be systematically searched. Quantitative analyses will be performed using random-effects meta-analyses to calculate mean difference with 95% confidence intervals. Discussion: Changes in microbiota composition in psychosis and schizophrenia have been correlated with alternations in brain structure and function, altered immunity, altered metabolic pathways and symptom severity. Changes have also been identified as potential biomarkers for psychosis that might aid in diagnosis. Understanding how predicted or actual functional alterations in microbial genes or metabolic pathways influence symptomatic expression and downstream clinical outcomes may contribute to the development of microbiome targeted interventions for psychosis. Registration: The study is prospectively registered in PROSPERO, the International Prospective Register of Systematic Reviews (CRD42021260208).

Stabilization of body balance with Light Touch following a mechanical perturbation: Adaption of sway and disruption of right posterior parietal cortex by cTBS.

Light touch with an earth-fixed reference point improves balance during quite standing. In our current study, we implemented a paradigm to assess the effects of disrupting the right posterior parietal cortex on dynamic stabilization of body sway with and without Light Touch after a graded, unpredictable mechanical perturbation. We hypothesized that the benefit of Light Touch would be amplified in the more dynamic context of an external perturbation, reducing body sway and muscle activations before, at and after a perturbation. Furthermore, we expected sway stabilization would be impaired following disruption of the right Posterior Parietal Cortex as a result of increased postural stiffness. Thirteen young adults stood blindfolded in Tandem-Romberg stance on a force plate and were required either to keep light fingertip contact to an earth-fixed reference point or to stand without fingertip contact. During every trial, a robotic arm pushed a participant's right shoulder in medio-lateral direction. The testing consisted of 4 blocks before TMS stimulation and 8 blocks after, which alternated between Light Touch and No Touch conditions. In summary, we found a strong effect of Light Touch, which resulted in improved stability following a perturbation. Light Touch decreased the immediate sway response, steady state sway following re-stabilization, as well as muscle activity of the Tibialis Anterior. Furthermore, we saw gradual decrease of muscle activity over time, which indicates an adaptive process following exposure to repetitive trials of perturbations. We were not able to confirm our hypothesis that disruption of the rPPC leads to increased postural stiffness. However, after disruption of the rPPC, muscle activity of the Tibialis Anterior is decreased more compared to sham. We conclude that rPPC disruption enhanced the intra-session adaptation to the disturbing effects of the perturbation.

Disruption of right posterior parietal cortex by continuous Theta Burst Stimulation alters the control of body balance in quiet stance.

Control of body balance relies on the integration of multiple sensory modalities. Lightly touching an earth-fixed reference augments the control of body sway. We aimed to advance the understanding of cortical integration of an afferent signal from light fingertip contact (LT) for the stabilisation of standing body balance. Assuming that right-hemisphere Posterior Parietal Cortex (rPPC) is involved in the integration and processing of touch for postural control, we expected that disrupting rPPC would attenuate any effects of light touch. Eleven healthy right-handed young adults received continuous Theta Burst Stimulation over the left- and right-hemisphere PPC with sham stimulation as an additional control. Before and after stimulation, sway of the blindfolded participants was assessed in Tandem-Romberg stance with and without haptic contact. We analysed sway in terms of the variability of Centre-of-Pressure (CoP) rate of change as well as Detrended Fluctuation Analysis of CoP position. Light touch decreased sway variability in both directions but showed direction-specific changes in its dynamic complexity: a positive increase in complexity in the mediolateral direction coincided with a reduction in the anteroposterior direction. rPPC disruption affected the control of body sway in two ways: first, it led to an overall decrease in sway variability irrespective of the presence of LT; second, it reduced the complexity of sway with LT at the contralateral, non-dominant hand. We speculate that rPPC is involved in the active exploration of the postural stability state, with utilisation of LT for this purpose if available, by normally inhibiting mechanisms of postural stiffness regulation.