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Molecular Mechanisms of Schizophrenia and Novel Treatment Targets

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: 20 June 2025 | Viewed by 2753

Special Issue Editor


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Guest Editor
Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Interests: schizohprenia spectrum disorders; pathology; treatment; psychophysiology

Special Issue Information

Dear Colleagues,

Despite decades of research and impressive advancements, our contemporary understanding of the biological mechanisms underlying schizophrenia phenomenology and treatment response remains incomplete. Novel approaches to interrogating and targeting the molecular substrates of schizophrenia, ranging from the subcellular to anatomical order, require rigorous investigation aimed at characterizing such mechanisms and the development of treatments beyond what is currently available for individuals with schizophrenia. In this Special Issue, we aim to present a multidisciplinary collection of the latest advances in the molecular basis of schizophrenia and novel treatment targets. This Special Issue will cover molecular pharmacology, cellular signaling, immunology, metabolism, and genomics.

Dr. Jenifer Vohs
Guest Editor

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Keywords

  • schizophrenia and molecular pharmacology
  • cellular signaling
  • immunology
  • metabolism
  • genomics

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Published Papers (2 papers)

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Research

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20 pages, 3086 KiB  
Article
Molecular and Functional Analysis of TLR 1, 2 and 6 in Peripheral Blood Monocytes of Patients with Schizophrenia: A Pilot Study
by Carlo E. Sotelo-Ramírez, Marcela Valdés-Tovar, Julio Uriel Zaragoza-Hoyos, Leonardo Ortiz-López, Jesús Argueta, Mauricio Rosel-Vales, Roxana U. Miranda-Labra and Beatriz Camarena
Int. J. Mol. Sci. 2025, 26(3), 926; https://doi.org/10.3390/ijms26030926 - 23 Jan 2025
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Abstract
Schizophrenia (SZ) is a chronic disabling mental disorder with high heritability, and several immune-regulating genes have been implicated in its pathophysiology In this study, we investigated the expression of Toll-like receptors (TLRs) 1, 2, and 6 in peripheral blood monocytes from SZ patients [...] Read more.
Schizophrenia (SZ) is a chronic disabling mental disorder with high heritability, and several immune-regulating genes have been implicated in its pathophysiology In this study, we investigated the expression of Toll-like receptors (TLRs) 1, 2, and 6 in peripheral blood monocytes from SZ patients and healthy control subjects (HCSs) in the Mexican population, focusing on specific SZ-associated gene variants. Gene expressions were assessed by qPCR, and protein expression was measured using flow cytometry. The secretory profiles of MALP2-stimulated monocytes were evaluated through immunoproteomic arrays. Our results indicate that patients with SZ carrying the rs4833093/TLR1 GG genotype exhibited significantly lower TLR1 gene expression compared to TT carriers. Notably, HCSs with the TT genotype showed markedly higher TLR1 protein expression, while all patients with SZ exhibited significantly reduced protein levels regardless of genotype. Furthermore, monocytes from patients with SZ displayed altered secretion profiles upon TLR stimulation, with significant elevations in IL-18, uPAR, angiopoietin-2, and serpin E1, alongside reductions in MCP-1, IL-17A, IL-24, MIF, and myeloperoxidase compared to HCSs. These findings suggest a dysfunctional TLR-mediated innate immune response in SZ. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Schizophrenia and Novel Treatment Targets)
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Review

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12 pages, 585 KiB  
Review
Dysfunctional Parvalbumin Neurons in Schizophrenia and the Pathway to the Clinical Application of Kv3 Channel Modulators
by Masaya Yanagi and Mamoru Hashimoto
Int. J. Mol. Sci. 2024, 25(16), 8696; https://doi.org/10.3390/ijms25168696 - 9 Aug 2024
Cited by 1 | Viewed by 1428
Abstract
Based on the pathophysiological changes observed in schizophrenia, the gamma-aminobutyric acid (GABA) hypothesis may facilitate the development of targeted treatments for this disease. This hypothesis, mainly derived from postmortem brain results, postulates dysfunctions in a subset of GABAergic neurons, particularly parvalbumin-containing interneurons. In [...] Read more.
Based on the pathophysiological changes observed in schizophrenia, the gamma-aminobutyric acid (GABA) hypothesis may facilitate the development of targeted treatments for this disease. This hypothesis, mainly derived from postmortem brain results, postulates dysfunctions in a subset of GABAergic neurons, particularly parvalbumin-containing interneurons. In the cerebral cortex, the fast spike firing of parvalbumin-positive GABAergic interneurons is regulated by the Kv3.1 and Kv3.2 channels, which belong to a potassium channel subfamily. Decreased Kv3.1 levels have been observed in the prefrontal cortex of patients with schizophrenia, prompting the investigation of Kv3 channel modulators for the treatment of schizophrenia. However, biomarkers that capture the dysfunction of parvalbumin neurons are required for these modulators to be effective in the pharmacotherapy of schizophrenia. Electroencephalography and magnetoencephalography studies have demonstrated impairments in evoked gamma oscillations in patients with schizophrenia, which may reflect the dysfunction of cortical parvalbumin neurons. This review summarizes these topics and provides an overview of how the development of therapeutics that incorporate biomarkers could innovate the treatment of schizophrenia and potentially change the targets of pharmacotherapy. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Schizophrenia and Novel Treatment Targets)
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