Novel Insights into Psychosis and Antipsychotic Interventions: From Managing Symptoms to Improving Outcomes DOI Open Access
Adonis Sfera,

Hassan Imran,

Dan O. Sfera

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 5904 - 5904

Published: May 28, 2024

For the past 70 years, dopamine hypothesis has been key working model in schizophrenia. This contributed to development of numerous inhibitors dopaminergic signaling and antipsychotic drugs, which led rapid symptom resolution but only marginal outcome improvement. Over decades, there limited research on quantifiable pathological changes schizophrenia, including premature cellular/neuronal senescence, brain volume loss, attenuation gamma oscillations electroencephalograms, oxidation lipids plasma mitochondrial membranes. We surmise that aberrant activation aryl hydrocarbon receptor by toxins derived from gut microbes or environment drives cellular neuronal a hallmark Early aging promotes secondary changes, impairment loss mitochondria, gray matter depletion, decreased oscillations, compensatory metabolic shift lactate lactylation. The aim this narrative review is twofold: (1) summarize what known about senescence schizophrenia schizophrenia-like disorders, (2) discuss novel strategies for improving long-term outcomes severe mental illness with natural senotherapeutics, membrane lipid replacement, transplantation, microbial phenazines, antioxidant phenothiazines, glycogen synthase kinase-3 beta, antagonists.

Language: Английский

The synaptic hypothesis of schizophrenia version III: a master mechanism DOI Creative Commons
Oliver Howes, Ellis Chika Onwordi

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(5), P. 1843 - 1856

Published: April 11, 2023

Abstract The synaptic hypothesis of schizophrenia has been highly influential. However, new approaches mean there a step-change in the evidence available, and some tenets earlier versions are not supported by recent findings. Here, we review normal development from structural functional imaging post-mortem studies that this is abnormal people at risk with schizophrenia. We then consider mechanism could underlie changes update hypothesis. Genome-wide association have identified number variants converging on pathways regulating elimination, formation plasticity, including complement factors microglial-mediated pruning. Induced pluripotent stem cell demonstrated patient-derived neurons show pre- post-synaptic deficits, signalling alterations, elevated, complement-dependent elimination structures compared to control-derived lines. Preclinical data environmental linked schizophrenia, such as stress immune activation, can lead synapse loss. Longitudinal MRI patients, prodrome, divergent trajectories grey matter volume cortical thickness controls, PET shows vivo for lower density patients Based evidence, propose version III This multi-hit model, whereby genetic and/or render synapses vulnerable excessive glia-mediated triggered during later neurodevelopment. loss disrupts pyramidal neuron function cortex contribute negative cognitive symptoms disinhibits projections mesostriatal regions dopamine overactivity psychosis. It accounts typical onset adolescence/early adulthood, its major factors, symptoms, identifies potential synaptic, microglial targets treatment.

Language: Английский

Citations

92
Evidence for embracing normative modeling DOI Creative Commons
Saige Rutherford,

Pieter Barkema,

Ivy F. Tso

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: March 13, 2023

In this work, we expand the normative model repository introduced in Rutherford et al., 2022a to include models charting lifespan trajectories of structural surface area and brain functional connectivity, measured using two unique resting-state network atlases (Yeo-17 Smith-10), an updated online platform for transferring these new data sources. We showcase value with a head-to-head comparison between features output by modeling raw several benchmarking tasks: mass univariate group difference testing (schizophrenia versus control), classification regression (predicting general cognitive ability). Across all benchmarks, show advantage features, strongest statistically significant results demonstrated tasks. intend accessible resources facilitate wider adoption across neuroimaging community.

Language: Английский

Citations

78
The schizophrenia syndrome, circa 2024: What we know and how that informs its nature DOI Open Access

Rajiv Tandon,

Henry A. Nasrallah, Schahram Akbarian

et al.

Schizophrenia Research, Journal Year: 2023, Volume and Issue: 264, P. 1 - 28

Published: Dec. 12, 2023

Language: Английский

Citations

60
Schizophrenia: from neurochemistry to circuits, symptoms and treatments DOI
Oliver Howes, Bernard R Bukala, Katherine Beck

et al.

Nature Reviews Neurology, Journal Year: 2023, Volume and Issue: 20(1), P. 22 - 35

Published: Dec. 18, 2023

Language: Английский

Citations

54
New clues for the role of cerebellum in schizophrenia and the associated cognitive impairment DOI Creative Commons
Pawan Faris, Doris Pischedda, Fulvia Palesi

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: May 10, 2024

Schizophrenia (SZ) is a complex neuropsychiatric disorder associated with severe cognitive dysfunction. Although research has mainly focused on forebrain abnormalities, emerging results support the involvement of cerebellum in SZ physiopathology, particularly Cognitive Impairment Associated (CIAS). Besides its role motor learning and control, implicated cognition emotion. Recent suggests that structural functional changes are linked to deficits various domains including attention, working memory, decision-making. Moreover, cerebellar dysfunction related altered circuit activities connectivity brain regions processing. This review delves into CIAS. We initially consider major alterations CIAS, addressing impairments neurotransmitter systems, synaptic plasticity, connectivity. then focus recent findings showing several mechanisms also communication impaired. evidence implicates as key component circuits underpinning CIAS physiopathology. Further studies warranted might open new perspectives toward understanding physiopathology effective treatment these disorders.

Language: Английский

Citations

11
Neurostructural subgroup in 4291 individuals with schizophrenia identified using the subtype and stage inference algorithm DOI Creative Commons
Yuchao Jiang, Cheng Luo,

Jijun Wang

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 17, 2024

Abstract Machine learning can be used to define subtypes of psychiatric conditions based on shared biological foundations mental disorders. Here we analyzed cross-sectional brain images from 4,222 individuals with schizophrenia and 7038 healthy subjects pooled across 41 international cohorts the ENIGMA, non-ENIGMA public datasets. Using Subtype Stage Inference (SuStaIn) algorithm, identify two distinct neurostructural subgroups by mapping spatial temporal ‘trajectory’ gray matter change in schizophrenia. Subgroup 1 was characterized an early cortical-predominant loss enlarged striatum, whereas subgroup 2 displayed subcortical-predominant hippocampus, striatum other subcortical regions. We confirmed reproducibility various sample sites, including Europe, North America East Asia. This imaging-based taxonomy holds potential neurobiological attributes, thereby suggesting viability redefining existing disorder constructs factors.

Language: Английский

Citations

9
What traditional neuropsychological assessment got wrong about mild traumatic brain injury. IV: clinical applications and future directions DOI
Erin D. Bigler,

Steven Allder,

Benjamin T. Dunkley

et al.

Brain Injury, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 17

Published: April 3, 2025

Part IV concludes this four-part review of 'What Traditional Neuropsychological Assessment Got Wrong About Mild Traumatic Brain Injury,' with a focus on clinical applications and future directions. These reviews have highlighted the limitations traditional neuropsychological assessment methods, particularly in evaluation patient mild traumatic brain injury (mTBI), especially within context all 21st Century advances neuroimaging, quantification network neuroscience. How advanced neuroimaging technology contemporary neuroscience can be applied to assessing mTBI at time along are reviewed. The current status computerized test (CNT) development is reviewed as it applies assessment. Likewise, how various types virtual reality (VR), artificial intelligence (AI), wearable sensors, markerless gaming could enhance CNT tool box some aspirational statements about improvements novel methods developed integrated technologies tailored meet needs patient.

Language: Английский

Citations

1
Dysconnection in schizophrenia: Filling the dots from old to new evidence DOI
Jacopo Sapienza, Federico Pacchioni, Marco Spangaro

et al.

Clinical Neurophysiology, Journal Year: 2024, Volume and Issue: 162, P. 226 - 228

Published: March 21, 2024

Language: Английский

Citations

7
TRPV1 Channels in the Central Nervous System as Drug Targets DOI Creative Commons

Loris A. Chahl

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(6), P. 756 - 756

Published: June 7, 2024

TRPV1 channels are polymodal cation located predominantly on primary afferent neurons that activated by inflammatory mediators, capsaicin (the active component in chili peppers), and noxious heat. channel antagonists potential new analgesic agents, but their development has been hindered the finding they also produce loss of thermal homeostasis response to Results from recent studies indicate it might be possible develop inhibit pain without affecting heat sensation. present central nervous system (CNS) have implicated learning, memory, behaviour. modulators proposed therapeutic treatment neurological psychiatric conditions. However, further understanding role CNS is required before advances neuropsychiatric conditions with can made.

Language: Английский

Citations

6
Neuroinflammation and kynurenines in schizophrenia: Impact on cognition depending on cognitive functioning and modulatory properties in relation to cognitive remediation and aerobic exercise DOI Creative Commons
Jacopo Sapienza, Giulia Agostoni, Stefano Comai

et al.

Schizophrenia Research Cognition, Journal Year: 2024, Volume and Issue: 38, P. 100328 - 100328

Published: Aug. 29, 2024

Background: In the last decade, kynurenine pathway (KP) has gained attention in pathogenesis of cognitive impairment schizophrenia being at croassroad between neuroinflammation and glutamatergic cholinergic neurotransmission.However, clinical findings are scarse conflicting, specific contributions these two systems to neurobiology symptoms far from elucidated.Furthermore, little is known about molecular underpinnings non-pharmacological interventions for improvement, including rehabilitation strategies.Methods: The current study examined 72 patients with schizophrenia, divided clusters depending on severity impairment, aim evaluate impact inflammatory biomarkers KP metabolites functioning.Moreover, we studied their possible link outcome relation sessions remediation therapy (CRT) aerobic exercise (AE) a longitudinal arm 42 patients.Results: Neuroinflammation appeared exert more pronounced influence cognition exhibiting higher functioning, contrasting activation KP, which had greater individuals lower profile.Cognitive improvements after treatments were negatively predicted by levels TNF-α positively 3-hydroxykynurenine (3-HK)/kynurenine (KYN) ratio, an index kynurenine-3-monooxygenase (KMO) enzyme activity.Conclusion: Overall, add novel evidence biological pointing differential role inducing deficits reserve predicting outcomes rehabilitation.

Language: Английский

Citations

6