The synaptic hypothesis of schizophrenia version III: a master mechanism

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

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Evidence for embracing normative modeling

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

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

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

Published: Dec. 12, 2023

Language: Английский

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Schizophrenia: from neurochemistry to circuits, symptoms and treatments

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

Published: Dec. 18, 2023

Language: Английский

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New clues for the role of cerebellum in schizophrenia and the associated cognitive impairment

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

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Neurostructural subgroup in 4291 individuals with schizophrenia identified using the subtype and stage inference algorithm

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

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TRPV1 Channels in the Central Nervous System as Drug Targets

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

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Dysconnection in schizophrenia: Filling the dots from old to new evidence

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

Published: March 21, 2024

Language: Английский

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Cerebellum as a neural substrate for impoverishment in early psychosis

Neuropsychologia, Journal Year: 2025, Volume and Issue: unknown, P. 109094 - 109094

Published: Feb. 1, 2025

Language: Английский

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What traditional neuropsychological assessment got wrong about mild traumatic brain injury. IV: clinical applications and future directions

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

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