Neuroinflammation and schizophrenia – is there a link?

Chaves, Cristiano; Dursun, Serdar M.; Tusconi, Massimo; Hallak, Jaime E. C.

doi:10.3389/fpsyt.2024.1356975

Front. Psychiatry

2024

DOI: 10.3389/fpsyt.2024.1356975

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Neuroinflammation and schizophrenia – is there a link?

Cristiano Chaves,

Serdar M. Dursun,

Massimo Tusconi

et al.

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Cited by 3 publications

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“…These are categorically identified as positive, negative, and cognitive symptoms ( 2 ). Moreover, recent discoveries regarding inherent biomarkers ( 3 ) and neurodevelopmental disease progression ( 4 ) increasingly suggest possible overlap with other psychiatric disorders, such as bipolar disorder ( 5 – 7 ). This overlap ranges from genetic ( 5 ) and environmental ( 6 , 7 ) risk factors to pathophysiological mechanisms and symptoms ( 8 , 9 ).…”

mentioning

confidence: 99%

Editorial: Reviews in psychiatry 2023: schizophrenia

Tusconi,

Kätzel,

Sánchez-Gutiérrez

2024

Front. Psychiatry

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mentioning

confidence: 99%

Editorial: Reviews in psychiatry 2023: schizophrenia

Tusconi,

Kätzel,

Sánchez-Gutiérrez

2024

Front. Psychiatry

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Effects of positive mGlu5 modulation on D₂ signaling and nicotine-conditioned place preference: Mechanisms of epigenetic inheritance in a transgenerational model of drug abuse vulnerability in psychosis

Peeters,

Wills,

Cuozzo

et al. 2024

J Psychopharmacol

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Background: The metabotropic glutamate type 5 (mGlu5) receptor has emerged as a potential target for the treatment of psychosis that is suggested to have greater efficacy than antipsychotic medications that are currently utilized. Aims: This study sought to elucidate mechanisms of therapeutic action associated with the modulation of the mGlu5 receptor in a disordered system marked by dopamine dysfunction. We further explored epigenetic mechanisms contributing to heritable transmission of a psychosis-like phenotype in a novel heritable model of drug abuse vulnerability in psychosis. Methods: F1 generation male and female Sprague-Dawley rats that were the offspring of two neonatal quinpirole-treated (QQ) or two saline-treated (SS) animals were tested on nicotine-conditioned place preference (CPP). Regulators of G protein signaling 9 (RGS9) and β-arrestin 2 (βA2), which mediate dopamine (DA) D2 signaling, were measured in the nucleus accumbens shell, prelimbic and infralimbic cortices. Reduced Representation Bisulfite Sequencing (RRBS) was used to analyze the cytosine methylation in these brain regions. Results: Pretreatment with the mGlu5-positive allosteric modulator 3-Cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) 20 min prior to conditioning trials blocked enhanced nicotine CPP and mitigated aberrant G protein-dependent and -independent signaling in QQ animals. RRBS analysis revealed region-specific changes in several pathways, including nicotine addiction, dopamine synapses, and neural connectivity. Conclusions: These results reveal an important region-specific mechanism of action for CDPPB in a system marked by enhanced DAD2 receptor signaling. Results additionally reveal DNA methylation as an epigenetic mechanism of heritability, further validating the current model as a useful tool for the study of psychosis and comorbid nicotine use.

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What Remains to Be Discovered in Schizophrenia Therapeutics: Contributions by Advancing the Molecular Mechanisms of Drugs for Psychosis and Schizophrenia

Correll,

Tusconi,

Carta

et al. 2024

Biomolecules

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

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Neuroinflammation and schizophrenia – is there a link?

Cited by 3 publications

References 95 publications

Editorial: Reviews in psychiatry 2023: schizophrenia

Editorial: Reviews in psychiatry 2023: schizophrenia

Effects of positive mGlu5 modulation on D₂ signaling and nicotine-conditioned place preference: Mechanisms of epigenetic inheritance in a transgenerational model of drug abuse vulnerability in psychosis

What Remains to Be Discovered in Schizophrenia Therapeutics: Contributions by Advancing the Molecular Mechanisms of Drugs for Psychosis and Schizophrenia

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Neuroinflammation and schizophrenia – is there a link?

Cited by 3 publications

References 95 publications

Editorial: Reviews in psychiatry 2023: schizophrenia

Editorial: Reviews in psychiatry 2023: schizophrenia

Effects of positive mGlu5 modulation on D2 signaling and nicotine-conditioned place preference: Mechanisms of epigenetic inheritance in a transgenerational model of drug abuse vulnerability in psychosis

What Remains to Be Discovered in Schizophrenia Therapeutics: Contributions by Advancing the Molecular Mechanisms of Drugs for Psychosis and Schizophrenia

Contact Info

Product

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Effects of positive mGlu5 modulation on D₂ signaling and nicotine-conditioned place preference: Mechanisms of epigenetic inheritance in a transgenerational model of drug abuse vulnerability in psychosis