Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ): Rationale and Study Design of the Largest Global Prospective Cohort Study of Clinical High Risk for Psychosis

Schizophrenia Bulletin, Journal Year: 2024, Volume and Issue: 50(3), P. 496 - 512

Published: March 7, 2024

Abstract This article describes the rationale, aims, and methodology of Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). is largest international collaboration to date that will develop algorithms predict trajectories outcomes individuals at clinical high risk (CHR) for psychosis advance development use novel pharmacological interventions CHR individuals. We present a description participating research networks data processing analysis coordination center, their processes harmonization across 43 sites from 13 countries (recruitment North America, Australia, Europe, Asia, South America), flow quality assessment processes, analyses, transfer National Institute Mental Health (NIMH) Data Archive (NDA) by community. In an expected sample approximately 2000 640 matched healthy controls, AMP SCZ collect clinical, environmental, cognitive along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech facial expression samples, measures derived digital health technologies smartphone-based daily surveys, passive sensing as well actigraphy. The study investigate range over 2-year period, transition psychosis, remission or persistence status, attenuated positive symptoms, persistent negative mood anxiety psychosocial functioning. global reach its harmonized innovative methods promise catalyze new treatments address critical unmet public needs in

Language: Английский

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The Underlying Neurobiological Mechanisms of Psychosis: Focus on Neurotransmission Dysregulation, Neuroinflammation, Oxidative Stress, and Mitochondrial Dysfunction

Antioxidants, Journal Year: 2024, Volume and Issue: 13(6), P. 709 - 709

Published: June 12, 2024

Psychosis, defined as a set of symptoms that results in distorted sense reality, is observed several psychiatric disorders addition to schizophrenia. This paper reviews the literature relevant underlying neurobiology psychosis. The dopamine hypothesis has been major influence study neurochemistry psychosis and development antipsychotic drugs. However, it became clear early on other factors must be involved dysfunction In current review, reported how these factors, namely dysregulation neurotransmitters [dopamine, serotonin, glutamate, γ-aminobutyric acid (GABA)], neuroinflammation, glia (microglia, astrocytes, oligodendrocytes), hypothalamic–pituitary–adrenal axis, gut microbiome, oxidative stress, mitochondrial contribute interact with one another. Research increased knowledge complexity psychotic disorders. Potential new pharmacotherapies, including combinations drugs (with pre- probiotics some cases) affecting mentioned above, have suggested. Similarly, putative biomarkers, particularly those related immune system, proposed. Future research both pharmacotherapy biomarkers will require better-designed studies conducted an all stages consider confounders such sex differences comorbidity.

Language: Английский

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Schizophrenia Synaptic Pathology and Antipsychotic Treatment in the Framework of Oxidative and Mitochondrial Dysfunction: Translational Highlights for the Clinics and Treatment

Antioxidants, Journal Year: 2023, Volume and Issue: 12(4), P. 975 - 975

Published: April 21, 2023

Schizophrenia is a worldwide mental illness characterized by alterations at dopaminergic and glutamatergic synapses resulting in global dysconnectivity within between brain networks. Impairments inflammatory processes, mitochondrial functions, energy expenditure, oxidative stress have been extensively associated with schizophrenia pathophysiology. Antipsychotics, the mainstay of pharmacological treatment all sharing common feature dopamine D2 receptor occupancy, may affect antioxidant pathways as well protein levels gene expression. Here, we systematically reviewed available evidence on antioxidants’ mechanisms antipsychotic action impact first- second-generation compounds functions stress. We further focused clinical trials addressing efficacy tolerability antioxidants an augmentation strategy treatment. EMBASE, Scopus, Medline/PubMed databases were interrogated. The selection process was conducted respect Preferred Reporting Items for Systematic Reviews Meta-Analyses (PRISMA) criteria. Several proteins involved cell viability, metabolism, regulation systems reported to be significantly modified differences drugs. Finally, cognitive psychotic symptoms patients schizophrenia, although only preliminary, results indicate that studies are warranted.

Language: Английский

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A systematic review of clozapine‐associated inflammation and related monitoring

Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy, Journal Year: 2023, Volume and Issue: 43(12), P. 1364 - 1396

Published: Oct. 16, 2023

Clozapine is an effective antipsychotic medication used for treatment-resistant schizophrenia. However, it underutilized due to rigorous hematologic monitoring requirements and many adverse drug reactions. Publications have highlighted the occurrence of inflammatory reactions, some life-threatening, particularly during early stages clozapine treatment. Although guidelines suggested processes initiation, screening in clinical practice not universal. This systematic review aimed investigate relationship between inflammation assess importance A comprehensive literature search yielded 6915 unique publication records after removal duplicates. After a process, 75 publications were included review, which focused on three main aspects: (i) impact markers, (ii) cardiac other organ function clozapine-associated processes, (iii) non-specific signs symptoms inflammation. Elevated levels C-reactive protein (CRP) several proinflammatory cytokines been observed association with practicality measuring specific markers remains uncertain. Current evidence supports CRP first 4-8 weeks treatment, especially facilitate myocarditis screening. Further research needed establish clinically relevant thresholds intervention. The implementation protocols phase treatment may mitigate reactions allow continued use clozapine. Future studies should also explore pneumonia, as well metabolism predict need dose adjustment. These endeavors development evidence-based

Language: Английский

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Advancing understanding of the mechanisms of antipsychotic-associated cognitive impairment to minimise harm: a call to action

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(8), P. 2571 - 2574

Published: March 7, 2024

Language: Английский

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Neuroinflammation and schizophrenia – is there a link?

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

Published: Feb. 8, 2024

Keywords: inflammation, schizophrenia, biomarkers, psychiatric genetics, neurobiology, neuroinflammation, psychotic disorders

Language: Английский

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Multimorbidity and the Etiology of Schizophrenia

Current Psychiatry Reports, Journal Year: 2024, Volume and Issue: 26(5), P. 253 - 263

Published: April 16, 2024

Language: Английский

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The kynurenine pathway in treatment-resistant schizophrenia at the crossroads between pathophysiology and pharmacotherapy

Schizophrenia Research, Journal Year: 2023, Volume and Issue: 264, P. 71 - 80

Published: Dec. 14, 2023

Language: Английский

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Developmental perspectives on the origins of psychotic disorders: The need for a transdiagnostic approach

Development and Psychopathology, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 11

Published: Feb. 26, 2024

Research on serious mental disorders, particularly psychosis, has revealed highly variable symptom profiles and developmental trajectories prior to illness-onset. As Dante Cicchetti pointed out decades before the term "transdiagnostic" was widely used, pathways psychopathology emerge in a system involving equifinality multifinality. Like most other psychological psychosis is associated with multiple domains of risk factors, both genetic environmental, there are many transdiagnostic that can lead psychotic syndromes. In this article, we discuss our current understanding heterogeneity etiology its implications for approaches conceptualizing research. We highlight need examining factors at levels increase emphasis as key etiologic subtypes. This will be increasingly feasible now large, longitudinal datasets becoming available researchers have access more sophisticated analytic tools, such machine learning, which identify homogenous subtypes ultimate goal enhancing options treatment preventive intervention.

Language: Английский

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Association between psychiatric admissions in patients with schizophrenia and IL-6 plasma levels polygenic score

European Archives of Psychiatry and Clinical Neuroscience, Journal Year: 2024, Volume and Issue: 274(7), P. 1671 - 1679

Published: March 16, 2024

Language: Английский

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