Should We Consider Microbiota-Based Interventions as a Novel Therapeutic Strategy for Schizophrenia? A Systematic Review and Meta-Analysis DOI Creative Commons
Lucas Hassib,

Alexandre Kanashiro,

João Francisco Cordeiro Pedrazzi

et al.

Brain Behavior & Immunity - Health, Journal Year: 2024, Volume and Issue: 43, P. 100923 - 100923

Published: Dec. 11, 2024

Schizophrenia is a chronic psychiatric disorder characterized by variety of symptoms broadly categorized into positive, negative, and cognitive domains. Its etiology multifactorial, involving complex interplay genetic, neurobiological, environmental factors, its neurobiology associated with abnormalities in different neurotransmitter systems. Due to this multifactorial neurobiology, leading wide heterogeneity clinical presentations, current antipsychotic treatments face challenges, underscoring the need for novel therapeutic approaches. Recent studies have revealed differences gut microbiome individuals schizophrenia compared healthy controls, establishing an intricate link between gastrointestinal health, suggesting that microbiota-targeted interventions could help alleviate symptoms. Therefore, meta-analysis investigates whether microbiota manipulation can ameliorate psychotic outcomes patients receiving pharmacological treatment. Nine (n = 417 participants) were selected from 81 records, comprising seven randomized controlled trials two open-label studies, all low risk bias, included systematic review meta-analysis. The overall combined effect size indicated significant symptom improvement following treatment (Hedges' g 0.48, 95% CI 0.09 0.88, p 0.004, I2 62.35%). However, according Hedges' criteria, was small (approaching moderate), study moderate based on criteria. This also discusses preclinical elucidate neural, immune, metabolic pathways which manipulation, particularly Lactobacillus Bifidobacterium genera, may exert beneficial effects via gut-brain axis. Finally, we address main confounding factors identified our review, highlight key limitations, offer recommendations guide future high-quality larger participant cohorts explore microbiome-based therapies as primary or adjunctive schizophrenia.

Language: Английский

Schizophrenia: from neurochemistry to circuits, symptoms and treatments DOI
Oliver Howes, Bernard R Bukala, Katherine Beck

et al.

Nature Reviews Neurology, Journal Year: 2023, Volume and Issue: 20(1), P. 22 - 35

Published: Dec. 18, 2023

Language: Английский

Citations

54
Knowing is Half the Battle: The Factors Leading to Efficient Recruitment of Representative Samples in Schizophrenia Research DOI
Joohyun Yoon, Megan Mayer, Tala Berro

et al.

Pharmaceutical Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 11, 2025

Language: Английский

Citations

2
The effects of ketogenic metabolic therapy on mental health and metabolic outcomes in schizophrenia and bipolar disorder: a randomized controlled clinical trial protocol DOI Creative Commons
Calogero Longhitano,

Sabine Finlay,

Isabella Peachey

et al.

Frontiers in Nutrition, Journal Year: 2024, Volume and Issue: 11

Published: Aug. 21, 2024

Background Schizophrenia, schizoaffective disorder, and bipolar affective disorder are debilitating psychiatric conditions characterized by a chronic pattern of emotional, behavioral, cognitive disturbances. Shared psychopathology includes the pre-eminence altered states, disorders thoughts, behavioral control. Additionally, those share epidemiological traits, including significant cardiovascular, metabolic, infectious, respiratory co-morbidities, resulting in reduced life expectancy up to 25 years. Nutritional ketosis has been successfully used treat range neurological preclinical data have convincingly shown potential for its use animal models psychotic disorders. More recent from open clinical trials pointed toward dramatic reduction psychotic, affective, metabolic symptoms both schizophrenia disorder. Objectives investigate effects nutritional via modified ketogenic diet (MKD) over 14 weeks stable community patients with or schizophrenia. Design A randomized placebo-controlled trial 100 non-hospitalized adult participants diagnosis who capable consenting willing change their diets. Intervention Dietitian-led medically supervised compared following Australian Guide Healthy Eating weeks. Outcomes The primary outcomes include measures, reported as symptom improvement functional changes Positive Negative Symptoms Scale (PANSS), Young Mania Rating (YMS), Beck Depression Inventory (BDI), WHO Disability Schedule, Affect Lability Cambridge Cognitive Battery. secondary body weight, blood pressure, liver kidney function tests, lipid profiles, markers insulin resistance. Ketone glucose levels will be study correlation between outcomes. Optional hair cortisol analysis assess long-term stress variations fecal microbiome composition. Autonomic nervous system activity measured wearable devices (OURA ring EMBRACE wristband) form skin conductance, oximetry, continuous pulse monitoring, rate, movement tracking, sleep quality. Based on encouraging results established research, other neurodevelopment disorders, schizophrenia, we predict that therapy well tolerated result improved global measures social functioning. We additionally may exist level achieved cognitive, intervention group.

Language: Английский

Citations

10
Negative Symptoms in Schizophrenia: An Update on Research Assessment and the Current and Upcoming Treatment Landscape DOI

Preetika Govil,

Joshua T. Kantrowitz

CNS Drugs, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 12, 2025

Language: Английский

Citations

0
Schizophrenia Management: Systematic Review of Current Medications and Phase-3 Agents (2008–2024) DOI Creative Commons

Salma Abdelmoteleb,

Jayant Totlani,

Salma Ramadan

et al.

Neuroscience Applied, Journal Year: 2025, Volume and Issue: 4, P. 105507 - 105507

Published: Jan. 1, 2025

Language: Английский

Citations

0
Is muscarinic receptor agonist effective and tolerant for schizophrenia? DOI Creative Commons
Xiaonan Guo,

Rongshan Deng,

Jianbo Lai

et al.

BMC Psychiatry, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 2, 2025

Several randomized clinical trials (RCTs) have recently examined the efficacy and tolerability of muscarinic receptor agonists in schizophrenia. However, whether therapeutics targeting receptors improve symptom management reduce side effects remains systemically unexplored. Embase, PubMed, Web Science were searched from inception until Jan 9, 2025. Altogether, safety outcomes four RCTs (397 individuals group, 374 placebo control group) meta-analyzed. To compare scores positive negative syndrome scale (PANSS), response rate, discontinuation adverse events with vs. patients schizophrenia, changes pooled as mean difference (MD) for continuous risk ratio (RR) categorical outcomes. It revealed that superior to terms decrease total PANSS score (MD, - 9.92; 95% CI, -12.46 -7.37; I2 = 0%), subscore 3.21; -4.02 -2.40; -1.79; -2.47 -1.11; 48%). According study-defined RR was 2.08 (95% 1.59 2.72; 0%). No significance found rate. Muscarinic associated a higher nausea (RR 4.61, 2.65 8.02; 3%), particular, xanomeline-trospium risks dyspepsia, vomiting, constipation. The findings highlighted an advantage tolerated event profiles

Language: Английский

Citations

0
Inhibition of reactive oxygen species production accompanying alternatively activated microglia by risperidone in a mouse ketamine model of schizophrenia DOI
Risako Fujikawa, Jun Yamada,

Shoichiro Maeda

et al.

Journal of Neurochemistry, Journal Year: 2024, Volume and Issue: unknown

Published: May 21, 2024

Recent studies have highlighted the potential involvement of reactive oxygen species (ROS) and microglia, a major source ROS, in pathophysiology schizophrenia. In our study, we explored how second-generation antipsychotic risperidone (RIS) affects ROS regulation microglial activation hippocampus using mouse ketamine (KET) model KET administration resulted schizophrenia-like behaviors male C57BL/6J mice, such as impaired prepulse inhibition (PPI) acoustic startle response hyper-locomotion. These were mitigated by RIS. We found that gene expression level an enzyme responsible for production (Nox2), which is primarily associated with activated was lower KET/RIS-treated mice than KET-treated mice. Conversely, levels antioxidant enzymes (Ho-1 Gclc) higher The density increased counteracted Hierarchical cluster analysis revealed three morphological subtypes microglia. control most microglia resting-ramified (type I, 89.7%). shifted composition to moderately ramified II, 44.4%) hyper-ramified III, 25.0%). type II decreased 32.0%, while III 34.0%. An vitro assay showed dissociated hippocampal this effect Furthermore, discovered NOX2 inhibitor could counteract KET-induced behavioral deficits. findings suggest pharmacological RIS may play crucial role ameliorating schizophrenia-related symptoms. Moreover, modulating regulate has emerged novel avenue developing innovative treatments

Language: Английский

Citations

2
Rethinking the First Episode of Schizophrenia: Identifying Convergent Mechanisms During Development and Moving Toward Prediction DOI
Jennifer K. Forsyth, Carrie E. Bearden

American Journal of Psychiatry, Journal Year: 2023, Volume and Issue: 180(11), P. 792 - 804

Published: Nov. 1, 2023

Language: Английский

Citations

6
Assessing NH300094, a novel dopamine and serotonin receptor modulator with cognitive enhancement property for treating schizophrenia DOI Creative Commons

Zijin Feng,

Zhijing Hu,

Lei Li

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 24, 2024

Background: Schizophrenia is a serious psychiatric disorder that significantly affects the quality of life patients. The objective this study to discover novel antipsychotic candidate with highly antagonistic activity against both serotonin and dopamine receptors, demonstrating robust efficacy in animal models positive, negative, cognitive symptoms schizophrenia. Methods: In present study, we examined drug (NH300094) on 5-HT 2A , 2C 1A 1B 7 H 1 M Alpha D 2L 2S 3 receptor functional assay vitro . addition, multiple models, including dizocilpine (MK-801) induced hyper-locomotion; APO climbing; Conditioned Avoidance Response (CAR); DOI-Induced Head Twitch; Forced swimming test; Scopolamine impairment model, were used verify NH300094 preclinical. Results: assays have indicated potent antagonist receptors higher relative (5-HT IC 50 = 0.47 nM) than (D 1.04 nM; 11.71 31.55 nM). Preclinical vivo pharmacological results showed was effective which more extensive clinic Risperidone. Furthermore, safety window for extrapyramidal side effects wider Risperidone (For NH300094, mice catalepsy model ED / Mice MK-801 104.6-fold; Risperidone, 12.9-fold), suggests potentially better clinical profile NH300094. Conclusion: modulator, has good therapeutic potential treatment schizophrenia cognition disorders.

Language: Английский

Citations

1
Is muscarinic receptor agonist effective and tolerant for schizophrenia? A systematic review and meta-analysis DOI Creative Commons
Xiaonan Guo,

Rongshan Deng,

Jianbo Lai

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

Abstract Background: Several randomized clinical trials (RCTs) have recently examined the efficacy and tolerability of muscarinic receptor agonists in schizophrenia. However, whether therapeutics targeting receptors improve symptom management reduce side effects remains systemically unexplored. Methods: Embase, PubMed, Web Science were searched from inception until May 16, 2024. Altogether, safety outcomes four RCTs (397 individuals group, 374 placebo control group) meta-analyzed. To compare scores positive negative syndrome scale (PANSS), response rate, discontinuation adverse events with vs patients schizophrenia, changes pooled as mean difference (MD) for continuous risk ratio (RR) categorical outcomes. Results: It revealed that superior to terms decrease total PANSS score (MD, − 9.92; 95% CI, -12.46 -7.37; I2 = 0%), subscore 3.21; -4.02 -2.40; -1.79; -2.47 -1.11; 48%). According study-defined RR was 2.08 (95% 1.59 2.72; 0%). No significance found rate. Muscarinic associated a higher nausea (RR 4.61, 2.65 8.02; 3%), particular, xanomeline-trospium risks dyspepsia, vomiting, constipation. Conclusions: The findings highlighted an advantage tolerated event profiles

Language: Английский

Citations

1