Transcriptional and neurochemical signatures of cerebral blood flow alterations in schizophrenia and the clinical high-risk state for psychosis

Sam Knight; Leyla Abbasova; Yashar Zeighami; Justine Y. Hansen; Daniel Martins; Fernando Zelaya; Ottavia Dipasquale; Thomas Liu; David Shin; Matthijs Bossong; Matilda Azis; Mathilde Antoniades; Oliver Howes; Ilaria Bonoldi; Alice Egerton; Paul Allen; Owen O'Daly; Philip McGuire; Gemma Modinos

doi:10.1101/2024.03.13.583894

Transcriptional and neurochemical signatures of cerebral blood flow alterations in schizophrenia and the clinical high-risk state for psychosis

Sam Knight^*, Leyla Abbasova, Yashar Zeighami, Justine Y. Hansen, Daniel Martins, Fernando Zelaya, Ottavia Dipasquale, Thomas Liu, David Shin, Matthijs Bossong, Matilda Azis, Mathilde Antoniades, Oliver Howes, Ilaria Bonoldi, Alice Egerton, Paul Allen, Owen O'Daly, Philip McGuire, Gemma Modinos

^*Corresponding author for this work

Research output: Working paper/Preprint › Preprint

Abstract

The brain integrates multiple scales of description, from the level of cells and molecules to large-scale networks and behaviour, and understanding the relationships between these layers may be fundamental to advancing our understanding of how the brain works in health and disease. Recent neuroimaging research has shown that alterations in brain function that are associated with schizophrenia spectrum disorders (SSD) are already present in young adults at clinical high-risk for psychosis (CHR-P), yet the cellular and molecular determinants of these alterations are not well understood. Here, combining regional cerebral blood flow (rCBF) data with existing transcriptomic and neurotransmitter data, we show that cell-types involved in stress response and inflammation, as well as the dopamine, acetylcholine, GABAA and NMDA receptor systems, align as shared and distinct cellular and neurochemical signatures of rCBF phenotypes in people with SSD and those at CHR-P. Decoding the biological pathways involved in neuroimaging-based psychosis phenotypes may provide a basis for the development of novel interventions.

Original language	English
DOIs	https://doi.org/10.1101/2024.03.13.583894
Publication status	Published - 14 Mar 2024

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Knight, S., Abbasova, L., Zeighami, Y., Hansen, J. Y., Martins, D., Zelaya, F., Dipasquale, O., Liu, T., Shin, D., Bossong, M., Azis, M., Antoniades, M., Howes, O., Bonoldi, I., Egerton, A., Allen, P., O'Daly, O., McGuire, P., & Modinos, G. (2024). Transcriptional and neurochemical signatures of cerebral blood flow alterations in schizophrenia and the clinical high-risk state for psychosis. https://doi.org/10.1101/2024.03.13.583894

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abstract = "The brain integrates multiple scales of description, from the level of cells and molecules to large-scale networks and behaviour, and understanding the relationships between these layers may be fundamental to advancing our understanding of how the brain works in health and disease. Recent neuroimaging research has shown that alterations in brain function that are associated with schizophrenia spectrum disorders (SSD) are already present in young adults at clinical high-risk for psychosis (CHR-P), yet the cellular and molecular determinants of these alterations are not well understood. Here, combining regional cerebral blood flow (rCBF) data with existing transcriptomic and neurotransmitter data, we show that cell-types involved in stress response and inflammation, as well as the dopamine, acetylcholine, GABAA and NMDA receptor systems, align as shared and distinct cellular and neurochemical signatures of rCBF phenotypes in people with SSD and those at CHR-P. Decoding the biological pathways involved in neuroimaging-based psychosis phenotypes may provide a basis for the development of novel interventions.",

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Knight, S , Abbasova, L, Zeighami, Y, Hansen, JY, Martins, D , Zelaya, F , Dipasquale, O, Liu, T, Shin, D, Bossong, M , Azis, M, Antoniades, M, Howes, O , Bonoldi, I , Egerton, A , Allen, P , O'Daly, O , McGuire, P & Modinos, G 2024 'Transcriptional and neurochemical signatures of cerebral blood flow alterations in schizophrenia and the clinical high-risk state for psychosis'. https://doi.org/10.1101/2024.03.13.583894

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T1 - Transcriptional and neurochemical signatures of cerebral blood flow alterations in schizophrenia and the clinical high-risk state for psychosis

AU - Knight, Sam

AU - Abbasova, Leyla

AU - Zeighami, Yashar

AU - Hansen, Justine Y.

AU - Martins, Daniel

AU - Zelaya, Fernando

AU - Dipasquale, Ottavia

AU - Liu, Thomas

AU - Shin, David

AU - Bossong, Matthijs

AU - Azis, Matilda

AU - Antoniades, Mathilde

AU - Howes, Oliver

AU - Bonoldi, Ilaria

AU - Egerton, Alice

AU - Allen, Paul

AU - O'Daly, Owen

AU - McGuire, Philip

AU - Modinos, Gemma

PY - 2024/3/14

Y1 - 2024/3/14

N2 - The brain integrates multiple scales of description, from the level of cells and molecules to large-scale networks and behaviour, and understanding the relationships between these layers may be fundamental to advancing our understanding of how the brain works in health and disease. Recent neuroimaging research has shown that alterations in brain function that are associated with schizophrenia spectrum disorders (SSD) are already present in young adults at clinical high-risk for psychosis (CHR-P), yet the cellular and molecular determinants of these alterations are not well understood. Here, combining regional cerebral blood flow (rCBF) data with existing transcriptomic and neurotransmitter data, we show that cell-types involved in stress response and inflammation, as well as the dopamine, acetylcholine, GABAA and NMDA receptor systems, align as shared and distinct cellular and neurochemical signatures of rCBF phenotypes in people with SSD and those at CHR-P. Decoding the biological pathways involved in neuroimaging-based psychosis phenotypes may provide a basis for the development of novel interventions.

AB - The brain integrates multiple scales of description, from the level of cells and molecules to large-scale networks and behaviour, and understanding the relationships between these layers may be fundamental to advancing our understanding of how the brain works in health and disease. Recent neuroimaging research has shown that alterations in brain function that are associated with schizophrenia spectrum disorders (SSD) are already present in young adults at clinical high-risk for psychosis (CHR-P), yet the cellular and molecular determinants of these alterations are not well understood. Here, combining regional cerebral blood flow (rCBF) data with existing transcriptomic and neurotransmitter data, we show that cell-types involved in stress response and inflammation, as well as the dopamine, acetylcholine, GABAA and NMDA receptor systems, align as shared and distinct cellular and neurochemical signatures of rCBF phenotypes in people with SSD and those at CHR-P. Decoding the biological pathways involved in neuroimaging-based psychosis phenotypes may provide a basis for the development of novel interventions.

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M3 - Preprint

BT - Transcriptional and neurochemical signatures of cerebral blood flow alterations in schizophrenia and the clinical high-risk state for psychosis

ER -

Transcriptional and neurochemical signatures of cerebral blood flow alterations in schizophrenia and the clinical high-risk state for psychosis

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