What Remains to Be Discovered in Schizophrenia Therapeutics: Contributions by Advancing the Molecular Mechanisms of Drugs for Psychosis and Schizophrenia DOI Creative Commons
Christoph U. Correll, Massimo Tusconi, Mauro Giovanni Carta

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(8), P. 906 - 906

Published: July 25, 2024

Schizophrenia is a frequently debilitating and complex mental disorder affecting approximately 1% of the global population, characterized by symptoms such as hallucinations, delusions, disorganized thoughts behaviors, cognitive dysfunction, negative symptoms. Traditional treatment has centered on postsynaptic dopamine antagonists, commonly known antipsychotic drugs, which aim to alleviate improve functioning quality life. Despite availability these medications, significant challenges remain in schizophrenia therapeutics, including incomplete symptom relief, resistance, medication side effects. This opinion article explores advancements treatment, emphasizing molecular mechanisms, novel drug targets, innovative delivery methods. One promising approach strategies that target neural networks circuits rather than single neurotransmitters, acknowledging complexity brain region interconnections involved schizophrenia. Another development biased agonists, selectively activate specific signaling pathways downstream receptors, offering potential for more precise pharmacological interventions with fewer The concept polypharmacy, where targets multiple pathways, exemplified KarXT, combining xanomeline trospium address both psychosis dysfunction. represents comprehensive strategy potentially improving outcomes patients. In conclusion, advancing understanding exploring therapeutic hold promise addressing unmet needs aiming effective tailored interventions. Future research should focus approaches achieve better clinical functional level life individuals

Language: Английский

The microbiota–gut–brain axis: pathways to better brain health. Perspectives on what we know, what we need to investigate and how to put knowledge into practice DOI Creative Commons
Anirikh Chakrabarti, Lucie Geurts, Lesley Hoyles

et al.

Cellular and Molecular Life Sciences, Journal Year: 2022, Volume and Issue: 79(2)

Published: Jan. 19, 2022

Abstract The gut and brain link via various metabolic signalling pathways, each with the potential to influence mental, cognitive health. Over past decade, involvement of microbiota in gut–brain communication has become focus increased scientific interest, establishing microbiota–gut–brain axis as a field research. There is growing number association studies exploring microbiota’s possible role memory, learning, anxiety, stress, neurodevelopmental neurodegenerative disorders. Consequently, attention now turning how can target nutritional therapeutic strategies for improved health well-being. However, while such that function are currently under development varying levels success, still very little yet known about triggers mechanisms underlying apparent on or most evidence comes from pre-clinical rather than well controlled clinical trials/investigations. Filling knowledge gaps requires standardised methodology human studies, including strong guidance specific areas axis, need more extensive biological sample analyses, identification relevant biomarkers. Other urgent requirements new advanced models vitro vivo mechanisms, greater omics technologies supporting bioinformatics resources (training, tools) efficiently translate study findings, targets populations. key building validated base rely increasing sharing multi-disciplinary collaborations, along continued public–private funding support. This will allow research move its next phase so we identify realistic opportunities modulate better

Language: Английский

Citations

134

Understanding the Role of the Gut Microbiome in Brain Development and Its Association With Neurodevelopmental Psychiatric Disorders DOI Creative Commons

Somarani Dash,

Yasir Ahmed Syed, Mojibur R. Khan

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: April 14, 2022

The gut microbiome has a tremendous influence on human physiology, including the nervous system. During fetal development, initial colonization of coincides with development system in timely, coordinated manner. Emerging studies suggest an active involvement and its metabolic by-products regulating early brain development. However, any disruption during this developmental process can negatively impact functionality, leading to range neurodevelopment neuropsychiatric disorders (NPD). In review, we summarize recent evidence as how association major neurodevelopmental psychiatric such autism spectrum disorders, attention-deficit hyperactivity disorder, schizophrenia. Further, discuss alterations also play role inducing drug resistance affected individuals. We propose model that establishes direct link dysbiosis exacerbated inflammatory state, functional deficits associated NPD. Based existing research, framework whereby diet intervention boost mental wellness subjects call for further research better understanding mechanisms govern gut-brain axis may lead novel approaches study pathophysiology treatment disorders.

Language: Английский

Citations

108

Gut Microbiome–Brain Alliance: A Landscape View into Mental and Gastrointestinal Health and Disorders DOI Creative Commons
Janet M. Sasso, Ramy M. Ammar,

Rumiana Tenchov

et al.

ACS Chemical Neuroscience, Journal Year: 2023, Volume and Issue: 14(10), P. 1717 - 1763

Published: May 8, 2023

Gut microbiota includes a vast collection of microorganisms residing within the gastrointestinal tract. It is broadly recognized that gut and brain are in constant bidirectional communication, which its metabolic production major component, form so-called microbiome–brain axis. Disturbances homeostasis caused by imbalance their functional composition activities, known as dysbiosis, cause dysregulation these pathways trigger changes blood–brain barrier permeability, thereby causing pathological malfunctions, including neurological disorders. In turn, can affect structure function through autonomic nervous system regulating motility, intestinal transit secretion, permeability. Here, we examine data from CAS Content Collection, largest published scientific information, analyze publication landscape recent research. We review advances knowledge related to human microbiome, complexity functionality, communication with central system, effect axis on mental health. discuss correlations between various diseases, specifically also explore metabolites regard impact associated diseases. Finally, assess clinical applications gut-microbiota-related substances development pipelines. hope this serve useful resource understanding current emerging field an effort further solving remaining challenges fulfilling potential.

Language: Английский

Citations

104

The Developing Microbiome From Birth to 3 Years: The Gut-Brain Axis and Neurodevelopmental Outcomes DOI Creative Commons
Hannah E. Laue, Modupe O. Coker, Juliette C. Madan

et al.

Frontiers in Pediatrics, Journal Year: 2022, Volume and Issue: 10

Published: March 7, 2022

The volume and breadth of research on the role microbiome in neurodevelopmental neuropsychiatric disorders has expanded greatly over last decade, opening doors to new models mechanisms gut-brain axis therapeutic interventions reduce burden these outcomes. Studies have highlighted window birth 3 years as an especially sensitive when may be most effective. Harnessing powerful during this critical developmental clarifies important investigations into microbe-human connection developing brain, affording opportunities prevent rather than treat illness. In review, we present overview intestinal age 3; its prospective relationship with neurodevelopment, particular emphasis immunological mechanisms. Next, neurobehavioral outcomes (such autism, anxiety, attention-deficit hyperactivity disorder) well cognitive development are described. sections, highlight importance pairing mechanistic studies murine large scale epidemiological that aim clarify typical health promoting early life across varied populations comparison dysbiosis. is focus human because it so readily alterable simple interventions, briefly outline what known about targeted More novel examinations environmental chemicals adversely impact potential a mediator or modifier discussed. Finally, look future emphasize need for additional identify alterations their gut how might correct optimize

Language: Английский

Citations

55

Gut-disc axis: A cause of intervertebral disc degeneration and low back pain? DOI Creative Commons
Wentian Li, Kaitao Lai, Neha Chopra

et al.

European Spine Journal, Journal Year: 2022, Volume and Issue: 31(4), P. 917 - 925

Published: March 14, 2022

Abstract Purpose Low back pain (LBP), a widely prevalent and costly disease around the world, is mainly caused by intervertebral disc (IVD) degeneration (IDD). Although numerous factors may trigger this degenerative process, microbiome dysbiosis has recently been implicated as one of likely causes. However, exact relationship between IDD not well understood. This review summarizes potential mechanisms discusses dysbiosis’s possible influence on LBP. Methods Prospective literature review. Results Alterations in composition host responses to microbiota causing pathological bone development involution, led concept gut-bone marrow axis axis. Moreover, gut-disc was also proposed explain microbiome’s role According existing evidence, could be an important factor for inducing aggravating through changing or regulating outside inside microenvironment IVD. Three which gut can induce IVD cause LBP are: (1) translocation bacteria across epithelial barrier into IVD, (2) regulation mucosal systemic immune system, (3) nutrient absorption metabolites formation at epithelium its diffusion Furthermore, investigate whether initiated pathogenic establish correlation presence certain microbial groups with question, diversity analysis based on16S rRNA data used characterise stool/blood from patients. Conclusion Future studies microbiome, fungi viruses necessary revolutionize our thinking about their diseases. we believe that inflammation inhibition interruption amplification cascade reaction targeting worthwhile treatment Level Evidence I Diagnostic: individual cross-sectional consistently applied reference standard blinding.

Language: Английский

Citations

51

An updated overview on the relationship between human gut microbiome dysbiosis and psychiatric and psychological disorders DOI Creative Commons
Alejandro Borrego-Ruiz, Juan J. Borrego

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2023, Volume and Issue: 128, P. 110861 - 110861

Published: Sept. 9, 2023

There is a lot of evidence establishing that nervous system development related to the composition and functions gut microbiome. In addition, central (CNS) controls imbalance intestinal microbiota, constituting bidirectional communication system. At present, various gut-brain crosstalk routes have been described, including immune, endocrine neural circuits via vagal pathway. Several empirical data associated microbiota alterations (dysbiosis) with neuropsychiatric diseases, such as Alzheimer's disease, autism Parkinson's other psychological disorders, like anxiety depression. Fecal transplantation (FMT) therapy has shown can transfer behavioral features recipient animals, which provides strong establish causal-effect relationship. Interventions, based on prebiotics, probiotics or synbiotics, demonstrated an important influence neurological disorders by synthesis neuroactive compounds interact regulation inflammatory processes. Further research needed demonstrate dysbiosis psychiatric how microbiota-based interventions may be used potential therapeutic tools.

Language: Английский

Citations

41

Repurposing Antidepressants and Phenothiazine Antipsychotics as Efflux Pump Inhibitors in Cancer and Infectious Diseases DOI Creative Commons
Bálint Rácz, Gabriella Spengler

Antibiotics, Journal Year: 2023, Volume and Issue: 12(1), P. 137 - 137

Published: Jan. 10, 2023

Multidrug resistance (MDR) is a major obstacle in the therapy of infectious diseases and cancer. One mechanisms MDR overexpression efflux pumps (EPs) that are responsible for extruding antimicrobial anticancer agents. EPs have additional roles detoxification may aid development bacterial infection progression Therefore, targeting be an attractive strategy to treat infections The discovery new drug require long timeline come with high costs. A potential alternative reduce time costs repurpose already existing drugs. Antidepressants antipsychotic agents widely used clinical practice treatment psychiatric disorders some somatic diseases. antipsychotics demonstrated various beneficial activities utilized This review aims provide brief overview antibacterial effects selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs) phenothiazine antipsychotics, while focusing on EPs. However, it should noted activity traditionally non-antibiotic implications regarding dysbiosis MDR.

Language: Английский

Citations

31

Probiotics, Live Biotherapeutic Products (LBPs), and Gut-Brain Axis Related Psychological Conditions: Implications for Research and Dietetics DOI
Duygu Ağagündüz, Elif Çelik, Özge Cemali

et al.

Probiotics and Antimicrobial Proteins, Journal Year: 2023, Volume and Issue: 15(4), P. 1014 - 1031

Published: May 24, 2023

Language: Английский

Citations

29

The current state of research for psychobiotics use in the management of psychiatric disorders–A systematic literature review DOI Creative Commons
Octavian Vasiliu

Frontiers in Psychiatry, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 23, 2023

The need to find new therapeutic interventions in patients diagnosed with psychiatric disorders is supported by the data suggesting high rates of relapse, chronic evolution, resistance, or lack adherence and disability. use pre-, pro-, synbiotics as add-ons management has been explored a way augment efficacy psychotropics improve chances for these reach response remission. This systematic literature review focused on tolerability psychobiotics main categories it conducted through most important electronic databases clinical trial registers, using PRISMA 2020 guidelines. quality primary secondary reports was assessed criteria identified Academy Nutrition Diabetics. Forty-three sources, mostly moderate quality, were reviewed detail, regarding assessed. Studies exploring effects mood disorders, anxiety schizophrenia spectrum substance eating attention deficit hyperactivity disorder (ADHD), neurocognitive autism (ASD) included. overall good, but evidence support their specific mixed. There have favor probiotics ADHD, ASD, also association selenium disorders. In several domains, research still an early phase development, e.g., (only three preclinical studies being found) (one identified). Although no well-defined recommendation could yet be formulated product there encouraging further research, especially if identification sub-populations that may benefit from this intervention. Several limitations field should addressed, i.e., majority finalized trials are short duration, inherent heterogeneity diversity Philae prevents generalizability results studies.

Language: Английский

Citations

24

The Effect of Probiotic Supplementation on the Gut–Brain Axis in Psychiatric Patients DOI Creative Commons
Hussein Sabit,

Areej Kassab,

Donia Alaa

et al.

Current Issues in Molecular Biology, Journal Year: 2023, Volume and Issue: 45(5), P. 4080 - 4099

Published: May 6, 2023

The pathophysiology of several psychiatric diseases may entail disturbances in the hypothalamic–pituitary–adrenal (HPA) axis and metabolic pathways. Variations how these effects present themselves be connected to individual variances clinical symptoms treatment responses, such as observation that a significant fraction participants do not respond current antipsychotic drugs. A bidirectional signaling pathway between central nervous system gastrointestinal tract is known microbiota–gut–brain axis. large small intestines contain more than 100 trillion microbial cells, contributing intestinal ecosystem’s incredible complexity. Interactions microbiota epithelium can alter brain physiology affect mood behavior. There has recently been focus on relationships impact mental health. According evidence, play role neurological illnesses. Intestinal metabolites origin, short-chain fatty acids, tryptophan metabolites, bacterial components might stimulate host’s immune system, are mentioned this review. We aim shed some growing gut inducing/manipulating disorders, which pave way for novel microbiota-based therapies.

Language: Английский

Citations

24