Investigation of choroid plexus variability in schizophrenia-spectrum disorders – insights from a multimodal study DOI Creative Commons
Vladislav Yakimov, Joanna Moussiopoulou, Lukas Roell

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 18, 2023

Abstract Background and Hypothesis Previous studies have suggested that choroid plexus (ChP) enlargement occurs in individuals with schizophrenia-spectrum disorders (SSD) is associated peripheral inflammation. However, it unclear whether such an delineates a biologically defined subgroup of SSD. Moreover, remains elusive how ChP linked to brain regions, inflammation Study Design A cross-sectional cohort 132 SSD 107 age-matched healthy controls (HC) underwent magnetic resonance imaging (MRI) the clinical phenotyping investigate regions. Case-control comparison volumes was conducted structural variance analysed by employing variability ratio (VR). K-means clustering analysis used identify subgroups distinct patterns ventricular system clusters were compared terms demographic, immunological measures. The relationship between previously inflammation, investigated. Results We could not find significant HC but detected increased VR lateral ventricle volumes. Based on these regions we identified 3 differences age, symbol coding test scores possibly inflammatory markers. Larger volume higher hippocampus, putamen, thalamus SSD, HC. Conclusions This study suggests variability, mean volume,

Language: Английский

Immune Dysfunction in Schizophrenia Spectrum Disorders DOI
Shiral S. Gangadin, Anne-Sophie D. Enthoven,

Nico J.M. van Beveren

et al.

Annual Review of Clinical Psychology, Journal Year: 2024, Volume and Issue: 20(1), P. 229 - 257

Published: July 12, 2024

Evidence from epidemiological, clinical, and biological research resulted in the immune hypothesis: hypothesis that system dysfunction is involved pathophysiology of schizophrenia spectrum disorders (SSD). The promising implication this potential to use existing immunomodulatory treatment for innovative interventions SSD. Here, we provide a selective historical review important discoveries have shaped our understanding We first explain basic principles dysfunction, after which travel more than century back time. Starting journey with neurosyphilis-associated psychosis nineteenth century, continue by evaluating role infections autoimmunity SSD findings assessment function using new techniques, such as cytokine levels, microglia density, neuroimaging, gene expression. Drawing these findings, discuss anti-inflammatory SSD, conclude look into future.

Language: Английский

Citations

13
Neuroinflammation and schizophrenia – is there a link? DOI Creative Commons
Cristiano Chaves, Serdar Dursun, Massimo Tusconi

et al.

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

Citations

9
Neuroactive Kynurenines as Pharmacological Targets: New Experimental Tools and Exciting Therapeutic Opportunities DOI
Ana Pocivavsek, Robert Schwarcz, Sophie Erhardt

et al.

Pharmacological Reviews, Journal Year: 2024, Volume and Issue: 76(6), P. 978 - 1008

Published: Sept. 20, 2024

Both preclinical and clinical studies implicate functional impairments of several neuroactive metabolites the kynurenine pathway (KP), major degradative cascade essential amino acid tryptophan in mammals, pathophysiology neurologic psychiatric diseases. A number KP enzymes, such as 2,3-dioxygenase (TDO2), indoleamine 2,3-dioxygenases (IDO1 IDO2), aminotransferases (KATs), 3-monooxygenase (KMO), 3-hydroxyanthranilic oxygenase (3-HAO), quinolinic phosphoribosyltransferase (QPRT), control brain metabolism health disease are therefore increasingly considered to be promising targets for treatment disorders nervous system. Understanding distribution, cellular expression, regulation enzymes is critical conceptualization implementation successful therapeutic strategies. SIGNIFICANCE STATEMENT: Studies have implicated Key regulate both disease, making them treating these disorders. Therefore, understanding developing effective This review endeavors describe processes detail.

Language: Английский

Citations

9
From Clinic to Mechanisms: Multi-Omics Provide New Insights into Cerebrospinal Fluid Metabolites and the Spectrum of Psychiatric Disorders DOI
Jie Wen, Yingjie Li, Yu Chen

et al.

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 14, 2025

Language: Английский

Citations

1
Kynurenic Acid and Promotion of Activity-Dependent Synapse Elimination in Schizophrenia DOI
Funda Orhan, Susmita Malwade, Neda Khanlarkhani

et al.

American Journal of Psychiatry, Journal Year: 2025, Volume and Issue: 182(4), P. 389 - 400

Published: April 1, 2025

Schizophrenia is a neurodevelopmental disorder characterized by an excessive loss of synapses. Kynurenic acid (KYNA), neuroactive metabolite tryptophan along the kynurenine pathway, can induce schizophrenia-related phenotypes in rodents, and clinical studies have revealed elevated KYNA levels CNS individuals with schizophrenia. However, factors that cause schizophrenia, mechanisms which contributes to pathophysiology, remain largely elusive. The authors used patient-derived cellular modeling test hypothesis microglia-mediated synapse engulfment reducing neuronal activity. Patient-derived induced pluripotent stem cells were generate 2D cultures neurons microglia-like cells, as well forebrain organoids innately developing microglia, study how influences synaptic activity microglial uptake structures. To verify experimental data context, large-scale developmental postmortem brain tissue genetic datasets coexpression networks for KYNA-producing aminotransferases (KATs) regarding enrichment common schizophrenia risk variants functional annotations. In these models, structures inhibition endogenous production led decrease internalization synapses microglia. integrated transcriptomic showed KATs enriched genes governing Together, results link activity-dependent material while implicating pharmacological strategy avoid

Language: Английский

Citations

1
Association between psychiatric admissions in patients with schizophrenia and IL-6 plasma levels polygenic score DOI
Fernando Facal, Manuel Arrojo, Mario Páramo

et al.

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

Published: March 16, 2024

Language: Английский

Citations

5
Association of symptom severity and cerebrospinal fluid alterations in recent onset psychosis in schizophrenia-spectrum disorders – An individual patient data meta-analysis DOI Creative Commons
Mattia Campana, Vladislav Yakimov, Joanna Moussiopoulou

et al.

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 119, P. 353 - 362

Published: April 10, 2024

Neuroinflammation and blood-cerebrospinal fluid barrier (BCB) disruption could be key elements in schizophrenia-spectrum disorderś(SSDs) etiology symptom modulation. We present the largest two-stage individual patient data (IPD) meta-analysis, investigating association of BCB cerebrospinal (CSF) alterations with severity first-episode psychosis (FEP) recent onset psychotic disorder (ROP) individuals, a focus on sex-related differences. Data was collected from PubMed EMBASE databases. FEP, ROP high-risk syndromes for IPD were included if routine basic CSF-diagnostics reported. Risk bias studies evaluated. Random-effects meta-analyses mixed-effects linear regression models employed to assess impact severity. Published (6 studies) unpublished n = 531 individuals analyses. CSF altered 38.8 % individuals. No significant differences found between without (SMD -0.17, 95 %CI -0.55-0.22, p 0.341). However, males elevated CSF/serum albumin ratios or any alteration had significantly higher positive scores than those 0.34, 0.05-0.64, 0.037 SMD 0.29, 0.17-0.41p 0.005, respectively). Mixed-effects simple showed no (p > 0.1) parameters symptomatic outcomes. interaction sex 0.1). appears highly prevalent early involved symptomś males, indicating potential difficult-to-treat states. This work highlights need considering breakdownand SSDs clinical trials treatment strategies.

Language: Английский

Citations

4
MAPPING THE CEREBROSPINAL FLUID PROTEOME IN BIPOLAR DISORDER DOI Creative Commons
Andreas Göteson,

Jessica Holmén‐Larsson,

Hakan Hamdi Çelik

et al.

Biological Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Catecholamine Dysregulation in Former American Football Players DOI
Suzan van Amerongen, Elaine R. Peskind, Yorghos Tripodis

et al.

Neurology, Journal Year: 2025, Volume and Issue: 104(10)

Published: April 21, 2025

Disturbances in brain catecholamine activity may be associated with symptoms after exposure to repetitive head impacts (RHIs) or related chronic traumatic encephalopathy (CTE). In this article, we studied CSF catecholamines former professional and college American football players examined the relationship proxies of RHI exposure, CTE probability, cognitive performance, neuropsychiatric symptoms, parkinsonism. observational cross-sectional study, male players, ("PRO") ("COL") level, asymptomatic unexposed ("UE") individuals from DIAGNOSE Research Project. Catecholamines-norepinephrine (NE) its metabolite, 3,4-dihydroxyphenylglycol (DHPG), dopamine (DA) precursor, 3,4-dihydroxyphenylalanine (l-DOPA), 3,4-dihydroxyphenylacetic acid (DOPAC)-were measured high-performance liquid chromatography compared across groups analysis covariance. Multivariable linear regression models tested between (e.g., total years playing football), factor scores for cognition, neurobehavioral dysregulation (explosivity, emotional dyscontrol, impulsivity, affective lability), as well depressive/anxiety Beck Depression/Anxiety Inventories. probability parkinsonism were assessed using National Institute Neurological Disorders Stroke consensus diagnostic criteria syndrome (TES), biomarkers among different groups. The cohort consisted 120 (85 PRO 35 COL players) UE participants (age 45-75). Former had significantly lower levels NE (mean difference = -0.114, 95% CI -0.190 -0.038), l-DOPA (-0.121, -0.109 -0.027), DOPAC (-0.116, -0.177 -0.054) than participants. For DOPAC, these overall group differences primarily due cohorts. No significant found TES-CTE subgroups TES-parkinsonism Within cohort, post hoc analyses, higher scores, BAI score, worse executive functioning processing speed. DHPG impulsivity only subgroup. We observed reduced concentrations elite although degree clinical impact needs further study.

Language: Английский

Citations

0
Metabolic Syndrome and Schizophrenia: Adding a Piece to the Interplay Between the Kynurenine Pathway and Inflammation DOI Creative Commons
Jacopo Sapienza, Giulia Agostoni, Federica Repaci

et al.

Metabolites, Journal Year: 2025, Volume and Issue: 15(3), P. 176 - 176

Published: March 5, 2025

The biology of schizophrenia is highly complex and multifaceted. Numerous efforts have been made over the years to disentangle heterogeneity disease, gradually leading a more detailed understanding its underlying pathogenic mechanisms. Two cardinal elements in pathophysiology are neuroinflammation alterations neurotransmission. kynurenine (KYN) pathway (KP) particular importance because it inducted by systemic low-grade inflammation peripheral tissues, producing metabolites that neuroactive (i.e., modulating glutamatergic cholinergic neurotransmission), neuroprotective, or neurotoxic. Consequently, KP at crossroads between two primary systems involved pathogenesis schizophrenia. It bridges central nervous system (CNS) periphery, as can cross blood–brain barrier modulate neuronal activity. Metabolic syndrome plays crucial role this context, frequently co-occurs with schizophrenia, contributing sub-inflammatory state able activate KP. This narrative review provides valuable insights into these interactions, offering framework for developing targeted therapeutic interventions precision psychiatry approaches disorder.

Language: Английский

Citations

0