Cerebellar Cortical Circuitry in Schizophrenia: A Cellular Framework for Predictive Dysfunction and Psychosis
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| Natura: | Recurso digital |
| Lingua: | inglese |
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2026
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| author | Faris, Pawan Vergani, Alberto Arturo Heredia-Ortiz, Isabella Masoli, Stefano Fusar-Poli, Paolo D'ANGELO, EGIDIO UGO |
| author_facet | Faris, Pawan Vergani, Alberto Arturo Heredia-Ortiz, Isabella Masoli, Stefano Fusar-Poli, Paolo D'ANGELO, EGIDIO UGO |
| contents | <p><strong>Abstract</strong><br>Schizophrenia (SZ) is a neuropsychiatric disorder characterised by progressive alterations across distributed brain networks that emerge across clinical stages from at-risk states to chronic illness. While traditionally centred on cortical and subcortical regions, converging evidence implicates the cerebellum as a critical node in the pathophysiology of SZ in relation to cognitive dysfunction and impaired predictive processing. Advancing this framework requires moving beyond systems-level observation to define the cellular and microcircuit mechanisms underlying cerebellar involvement. Here, we synthesise evidence on cerebellar cellular alterations in SZ, based on a structured analysis of human postmortem studies, neuroimaging findings, and experimental models relevant to SZ pathophysiology. Across principal neuronal populations, including Purkinje cells, granule cells, and inhibitory interneurons, data reveal convergent microstructural and functional abnormalities rather than uniform neuronal loss. Purkinje cells exhibit reduced dendritic complexity, decreased spine density, and altered intrinsic and synaptic properties, indicating impaired integration and output signalling. In parallel, alterations in the granular layer, including disrupted development, synaptic organisation, and NMDA receptor–dependent plasticity, are likely to impair input processing. These changes are accompanied by widespread alterations in GABAergic, glutamatergic, serotonergic, and dopaminergic signalling, leading to disruption of E/I tone across the cerebellum. We hypothesise that the synergistic impairment of cerebellar input transformation and output represents a fundamental substrate in SZ. Within a predictive processing framework, these deficits are hypothesised to derail internal model formation and prediction error signalling, thereby precipitating impairments in cognitive coordination, multisensory integration, and salience processing. This multi-scale synthesis provides a mechanistic scaffold for understanding the cerebellar contribution to the cognitive and perceptual landscape of SZ, while highlighting the imperative for future research to integrate longitudinal, cellular, and computational approaches.</p> |
| format | Recurso digital |
| id | zenodo_https___doi_org_10_5281_zenodo_19337133 |
| institution | Zenodo |
| language | eng |
| publishDate | 2026 |
| publisher | Zenodo |
| record_format | zenodo |
| spellingShingle | Cerebellar Cortical Circuitry in Schizophrenia: A Cellular Framework for Predictive Dysfunction and Psychosis Faris, Pawan Vergani, Alberto Arturo Heredia-Ortiz, Isabella Masoli, Stefano Fusar-Poli, Paolo D'ANGELO, EGIDIO UGO Cerebellum Schizophrenia Purkinje Cells Granule cells <p><strong>Abstract</strong><br>Schizophrenia (SZ) is a neuropsychiatric disorder characterised by progressive alterations across distributed brain networks that emerge across clinical stages from at-risk states to chronic illness. While traditionally centred on cortical and subcortical regions, converging evidence implicates the cerebellum as a critical node in the pathophysiology of SZ in relation to cognitive dysfunction and impaired predictive processing. Advancing this framework requires moving beyond systems-level observation to define the cellular and microcircuit mechanisms underlying cerebellar involvement. Here, we synthesise evidence on cerebellar cellular alterations in SZ, based on a structured analysis of human postmortem studies, neuroimaging findings, and experimental models relevant to SZ pathophysiology. Across principal neuronal populations, including Purkinje cells, granule cells, and inhibitory interneurons, data reveal convergent microstructural and functional abnormalities rather than uniform neuronal loss. Purkinje cells exhibit reduced dendritic complexity, decreased spine density, and altered intrinsic and synaptic properties, indicating impaired integration and output signalling. In parallel, alterations in the granular layer, including disrupted development, synaptic organisation, and NMDA receptor–dependent plasticity, are likely to impair input processing. These changes are accompanied by widespread alterations in GABAergic, glutamatergic, serotonergic, and dopaminergic signalling, leading to disruption of E/I tone across the cerebellum. We hypothesise that the synergistic impairment of cerebellar input transformation and output represents a fundamental substrate in SZ. Within a predictive processing framework, these deficits are hypothesised to derail internal model formation and prediction error signalling, thereby precipitating impairments in cognitive coordination, multisensory integration, and salience processing. This multi-scale synthesis provides a mechanistic scaffold for understanding the cerebellar contribution to the cognitive and perceptual landscape of SZ, while highlighting the imperative for future research to integrate longitudinal, cellular, and computational approaches.</p> |
| title | Cerebellar Cortical Circuitry in Schizophrenia: A Cellular Framework for Predictive Dysfunction and Psychosis |
| topic | Cerebellum Schizophrenia Purkinje Cells Granule cells |
| url | https://doi.org/10.5281/zenodo.19337133 |