Pharmacological Interventions for Negative Symptoms in Schizophrenia: A Systematic Review of Randomised Control Trials DOI Creative Commons
Lorenzo Moccia, Francesca Bardi, Maria Benedetta Anesini

et al.

Biomedicines, Journal Year: 2025, Volume and Issue: 13(3), P. 540 - 540

Published: Feb. 21, 2025

Background/Objectives: While positive symptoms of schizophrenia are often satisfactorily controlled, negative difficult to treat, persisting despite treatment. Different strategies have been devised deal with this problem. We aimed review drug treatment for in controlled trials marketed drugs. Methods: searched the PubMed database and resulting records’ reference lists identify eligible using schizophrenia[ti] AND “negative symptom*”[ti] as a search strategy. determined eligibility through Delphi rounds among all authors. Results: On 11 February 2025, we identified 1485 records on 3 more from lists. Eligible were 95 records. Most studies double-blind, randomized trials, carried-out add-on patients stabilized antipsychotics. Other antipsychotics most frequent comparators, followed by antidepressants, recently, antioxidants gaining importance trials. Many especially those conducted Western world, found no significant effects compared placebo, while Iranian positive, although not strong effect size. Conclusions: Current research has contributed little progress schizophrenia. The reason might reside absence knowledge mechanisms whereby these generated, which prevents us designing possibly effective strategies, and/or chronicity symptoms, they first be established even when do become fully apparent.

Language: Английский

Epigenetic Modifications in Schizophrenia and Related Disorders: Molecular Scars of Environmental Exposures and Source of Phenotypic Variability DOI Creative Commons
Juliet Richetto, Urs Meyer

Biological Psychiatry, Journal Year: 2020, Volume and Issue: 89(3), P. 215 - 226

Published: March 28, 2020

Epigenetic modifications are increasingly recognized to play a role in the etiology and pathophysiology of schizophrenia other psychiatric disorders with developmental origins. Here, we summarize clinical preclinical findings epigenetic alterations relevant disease models discuss their putative origin. Recent suggest that certain risk loci can influence stochastic variation gene expression through processes, highlighting intricate interaction between genetic control neurodevelopmental trajectories. In addition, substantial portion related may be acquired environmental factors manifested as molecular "scars." Some these scars brain functions throughout entire lifespan even transmitted across generations via germline inheritance. modifications, whether caused by or factors, plausible sources phenotypic heterogeneity offer target for therapeutic interventions. The further elucidation thus increase our knowledge regarding schizophrenia's heterogeneous and, long term, advance personalized treatments use biomarker-guided

Language: Английский

Citations

143
Neurobiological Highlights of Cognitive Impairment in Psychiatric Disorders DOI Open Access
Аnna Morozova, Yana Zorkina, Olga Abramova

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(3), P. 1217 - 1217

Published: Jan. 22, 2022

This review is focused on several psychiatric disorders in which cognitive impairment a major component of the disease, influencing life quality. There are plenty data proving that accompanies and even underlies some disorders. In addition, sources provide information biological background problems associated with mental illness. scientific aims to summarize current knowledge about neurobiological mechanisms people schizophrenia, depression, mild dementia (including Alzheimer’s disease).The provides prevalence illness markers.

Language: Английский

Citations

72
Role of histone deacetylases and their inhibitors in neurological diseases DOI Creative Commons
Liying Zhang,

Sen-Yu Zhang,

Ri Wen

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: unknown, P. 107410 - 107410

Published: Sept. 1, 2024

Histone deacetylases (HDACs) are zinc-dependent that remove acetyl groups from lysine residues of histones or form protein complexes with other proteins for transcriptional repression, changing chromatin structure tightness, and inhibiting gene expression. Recent in vivo vitro studies have amply demonstrated the critical role HDACs cell biology nervous system during both physiological pathological processes provided new insights into conduct research on neurological disease targets. In addition, HDAC inhibitors show promise treatment various diseases. This review summarizes regulatory mechanisms important its downstream targets diseases, therapeutic efficacy Additionally, current pharmacological situation, problems, developmental prospects described. A better understanding pathogenic may reveal interventions diseases help to relieve healthcare pressure through preventive measures.

Language: Английский

Citations

17
Advances in CNS PET: the state-of-the-art for new imaging targets for pathophysiology and drug development DOI Creative Commons

Stuart P. McCluskey,

Christophe Plisson, Eugenii A. Rabiner

et al.

European Journal of Nuclear Medicine and Molecular Imaging, Journal Year: 2019, Volume and Issue: 47(2), P. 451 - 489

Published: Sept. 21, 2019

Abstract Purpose A limit on developing new treatments for a number of central nervous system (CNS) disorders has been the inadequate understanding in vivo pathophysiology underlying neurological and psychiatric lack tools to determine brain penetrance, target engagement, relevant molecular activity novel drugs. Molecular neuroimaging provides address this. This article aims provide state-of-the-art review PET tracers CNS targets, focusing developments last 5 years targets recently available in-human imaging. Methods We an overview criteria used evaluate tracers. then National Institute Mental Health Research Priorities list identify key targets. conducted PubMed search (search period 1st January 2013 31st December 2018), which yielded 40 across 16 met our selectivity criteria. For each tracer, we summarised evidence its properties potential use studies drug evaluation, including affinity, inter intra-subject variability, pharmacokinetic parameters. also consider limitations missing characterisation data, but not specific applications development. Where multiple were present target, comparison their properties. Results conclusions Our shows that have developed proteinopathy particularly tau, as well purinoceptor P2X7, phosphodiesterase enzyme PDE10A, synaptic vesicle glycoprotein 2A (SV2A), amongst others. Some most promising these include 18 F-MK-6240 tau imaging, 11 C-UCB-J imaging SV2A, C-CURB C-MK-3168 fatty acid amide hydrolase, F-FIMX metabotropic glutamate receptor 1, F-MNI-444 adenosine 2A. identifies recurrent issues within field. Many discussed blocking reducing confidence selectivity. Additionally, late-stage identification substantial off-target sites highlights incomplete pre-clinical prior translation, human disease state carried out without confirmation test-retest reproducibility.

Language: Английский

Citations

105
NMDA receptor hypofunction for schizophrenia revisited: Perspectives from epigenetic mechanisms DOI

Melissa A. Snyder,

Wen‐Jun Gao

Schizophrenia Research, Journal Year: 2019, Volume and Issue: 217, P. 60 - 70

Published: April 9, 2019

Language: Английский

Citations

80
Hidden Role of Gut Microbiome Dysbiosis in Schizophrenia: Antipsychotics or Psychobiotics as Therapeutics? DOI Open Access
Nayla Munawar, Khansa Ahsan, Khalid Muhammad

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(14), P. 7671 - 7671

Published: July 18, 2021

Schizophrenia is a chronic, heterogeneous neurodevelopmental disorder that has complex symptoms and uncertain etiology. Mounting evidence indicates the involvement of genetics epigenetic disturbances, alteration in gut microbiome, immune system abnormalities, environmental influence disease, but single root cause mechanism involved yet to be conclusively determined. Consequently, identification diagnostic markers development psychotic drugs for treatment schizophrenia faces high failure rate. This article surveys etiology with particular focus on microbiota regulation microbial signaling correlates brain through vagus nerve, enteric nervous system, production postbiotics. Gut microbially produced molecules may lay groundwork further investigations into role dysbiosis pathophysiology schizophrenia. Current limited psychotherapy antipsychotic have significant side effects. Therefore, alternative therapeutic options merit exploration. The use psychobiotics alone or combination antipsychotics promote novel strategies. In view individual microbiome structure personalized response drugs, tailored targeted manipulation diversity naturally by prebiotics (non-digestible fiber) successful patients.

Language: Английский

Citations

72
Chromatin domain alterations linked to 3D genome organization in a large cohort of schizophrenia and bipolar disorder brains DOI
Kiran Girdhar, Gabriel E. Hoffman, Jaroslav Bendl

et al.

Nature Neuroscience, Journal Year: 2022, Volume and Issue: 25(4), P. 474 - 483

Published: March 24, 2022

Language: Английский

Citations

54
HDAC Inhibitors: Innovative Strategies for Their Design and Applications DOI Creative Commons
Mateusz Daśko, Beatriz de Pascual‐Teresa,

Irene Ortín

et al.

Molecules, Journal Year: 2022, Volume and Issue: 27(3), P. 715 - 715

Published: Jan. 21, 2022

Histone deacetylases (HDACs) are a large family of epigenetic metalloenzymes that involved in gene transcription and regulation, cell proliferation, differentiation, migration, death, as well angiogenesis. Particularly, disorders the HDACs expression linked to development many types cancer neurodegenerative diseases, making them interesting molecular targets for design new efficient drugs imaging agents facilitate an early diagnosis these diseases. Thus, their selective inhibition or degradation basis therapies. This is supported by fact HDAC inhibitors (HDACis) currently under clinical research therapy, Food Drug Administration (FDA) has already approved some them. In this review, we will focus on recent advances latest discoveries innovative strategies applications compounds demonstrate inhibitory activity against HDACs, such PROteolysis-TArgeting Chimeras (PROTACs), tumor-targeted HDACis (e.g., folate conjugates nanoparticles), probes (positron emission tomography (PET) fluorescent ligands).

Language: Английский

Citations

45
Dissecting the Relationship Between Neuropsychiatric and Neurodegenerative Disorders DOI

Rohan Gupta,

Dia Advani, Divya Yadav

et al.

Molecular Neurobiology, Journal Year: 2023, Volume and Issue: 60(11), P. 6476 - 6529

Published: July 17, 2023

Language: Английский

Citations

23
Advances toward precision medicine for bipolar disorder: mechanisms & molecules DOI
Stephen J. Haggarty, Rakesh Karmacharya, Roy H. Perlis

et al.

Molecular Psychiatry, Journal Year: 2020, Volume and Issue: 26(1), P. 168 - 185

Published: July 7, 2020

Language: Английский

Citations

63