Cortical structural differences following repeated ayahuasca use hold molecular signatures

IntroductionSerotonergic psychedelics such as ayahuasca are reported to promote both structural and functional neural plasticity via partial 5-HT2A agonism. However, little is known about how these molecular mechanisms may extend to repeated psychedelic administration in humans, let alone neuroanato...
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Autor*in:	Pablo Mallaroni [verfasserIn] Natasha L. Mason [verfasserIn] Lilian Kloft [verfasserIn] Johannes T. Reckweg [verfasserIn] Kim van Oorsouw [verfasserIn] Johannes G. Ramaekers [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	ayahuasca psychedelics 5-HT2A transcriptomics morphometry ultra-high field MRI

Übergeordnetes Werk:	In: Frontiers in Neuroscience - Frontiers Media S.A., 2008, 17(2023)
Übergeordnetes Werk:	volume:17 ; year:2023

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fnins.2023.1217079

Katalog-ID:	DOAJ09673499X

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520			\|a IntroductionSerotonergic psychedelics such as ayahuasca are reported to promote both structural and functional neural plasticity via partial 5-HT2A agonism. However, little is known about how these molecular mechanisms may extend to repeated psychedelic administration in humans, let alone neuroanatomy. While early evidence suggests localised changes to cortical thickness in long-term ayahuasca users, it is unknown how such findings may be reflected by large-scale anatomical brain networks comprising cytoarchitecturally complex regions.MethodsHere, we examined the relationship between cortical gene expression markers of psychedelic action and brain morphometric change following repeated ayahuasca usage, using high-field 7 Tesla neuroimaging data derived from 24 members of an ayahuasca-using church (Santo Daime) and case-matched controls.ResultsUsing a morphometric similarity network (MSN) analysis, repeated ayahuasca use was associated with a spatially distributed cortical patterning of both structural differentiation in sensorimotor areas and de-differentiation in transmodal areas. Cortical MSN remodelling was found to be spatially correlated with dysregulation of 5-HT2A gene expression as well as a broader set of genes encoding target receptors pertinent to ayahuasca’s effects. Furthermore, these associations were similarly interrelated with altered gene expression of specific transcriptional factors and immediate early genes previously identified in preclinical assays as relevant to psychedelic-induced neuroplasticity.ConclusionTaken together, these findings provide preliminary evidence that the molecular mechanisms of psychedelic action may scale up to a macroscale level of brain organisation in vivo. Closer attention to the role of cortical transcriptomics in structural-functional coupling may help account for the behavioural differences observed in experienced psychedelic users.
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spelling	10.3389/fnins.2023.1217079 doi (DE-627)DOAJ09673499X (DE-599)DOAJb1873bef02474162bde87da84318ac71 DE-627 ger DE-627 rakwb eng RC321-571 Pablo Mallaroni verfasserin aut Cortical structural differences following repeated ayahuasca use hold molecular signatures 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier IntroductionSerotonergic psychedelics such as ayahuasca are reported to promote both structural and functional neural plasticity via partial 5-HT2A agonism. However, little is known about how these molecular mechanisms may extend to repeated psychedelic administration in humans, let alone neuroanatomy. While early evidence suggests localised changes to cortical thickness in long-term ayahuasca users, it is unknown how such findings may be reflected by large-scale anatomical brain networks comprising cytoarchitecturally complex regions.MethodsHere, we examined the relationship between cortical gene expression markers of psychedelic action and brain morphometric change following repeated ayahuasca usage, using high-field 7 Tesla neuroimaging data derived from 24 members of an ayahuasca-using church (Santo Daime) and case-matched controls.ResultsUsing a morphometric similarity network (MSN) analysis, repeated ayahuasca use was associated with a spatially distributed cortical patterning of both structural differentiation in sensorimotor areas and de-differentiation in transmodal areas. Cortical MSN remodelling was found to be spatially correlated with dysregulation of 5-HT2A gene expression as well as a broader set of genes encoding target receptors pertinent to ayahuasca’s effects. Furthermore, these associations were similarly interrelated with altered gene expression of specific transcriptional factors and immediate early genes previously identified in preclinical assays as relevant to psychedelic-induced neuroplasticity.ConclusionTaken together, these findings provide preliminary evidence that the molecular mechanisms of psychedelic action may scale up to a macroscale level of brain organisation in vivo. Closer attention to the role of cortical transcriptomics in structural-functional coupling may help account for the behavioural differences observed in experienced psychedelic users. ayahuasca psychedelics 5-HT2A transcriptomics morphometry ultra-high field MRI Neurosciences. Biological psychiatry. Neuropsychiatry Natasha L. Mason verfasserin aut Lilian Kloft verfasserin aut Johannes T. Reckweg verfasserin aut Kim van Oorsouw verfasserin aut Johannes G. Ramaekers verfasserin aut In Frontiers in Neuroscience Frontiers Media S.A., 2008 17(2023) (DE-627)55908109X (DE-600)2411902-7 1662453X nnns volume:17 year:2023 https://doi.org/10.3389/fnins.2023.1217079 kostenfrei https://doaj.org/article/b1873bef02474162bde87da84318ac71 kostenfrei https://www.frontiersin.org/articles/10.3389/fnins.2023.1217079/full kostenfrei https://doaj.org/toc/1662-453X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2023
allfields_unstemmed	10.3389/fnins.2023.1217079 doi (DE-627)DOAJ09673499X (DE-599)DOAJb1873bef02474162bde87da84318ac71 DE-627 ger DE-627 rakwb eng RC321-571 Pablo Mallaroni verfasserin aut Cortical structural differences following repeated ayahuasca use hold molecular signatures 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier IntroductionSerotonergic psychedelics such as ayahuasca are reported to promote both structural and functional neural plasticity via partial 5-HT2A agonism. However, little is known about how these molecular mechanisms may extend to repeated psychedelic administration in humans, let alone neuroanatomy. While early evidence suggests localised changes to cortical thickness in long-term ayahuasca users, it is unknown how such findings may be reflected by large-scale anatomical brain networks comprising cytoarchitecturally complex regions.MethodsHere, we examined the relationship between cortical gene expression markers of psychedelic action and brain morphometric change following repeated ayahuasca usage, using high-field 7 Tesla neuroimaging data derived from 24 members of an ayahuasca-using church (Santo Daime) and case-matched controls.ResultsUsing a morphometric similarity network (MSN) analysis, repeated ayahuasca use was associated with a spatially distributed cortical patterning of both structural differentiation in sensorimotor areas and de-differentiation in transmodal areas. Cortical MSN remodelling was found to be spatially correlated with dysregulation of 5-HT2A gene expression as well as a broader set of genes encoding target receptors pertinent to ayahuasca’s effects. Furthermore, these associations were similarly interrelated with altered gene expression of specific transcriptional factors and immediate early genes previously identified in preclinical assays as relevant to psychedelic-induced neuroplasticity.ConclusionTaken together, these findings provide preliminary evidence that the molecular mechanisms of psychedelic action may scale up to a macroscale level of brain organisation in vivo. Closer attention to the role of cortical transcriptomics in structural-functional coupling may help account for the behavioural differences observed in experienced psychedelic users. ayahuasca psychedelics 5-HT2A transcriptomics morphometry ultra-high field MRI Neurosciences. Biological psychiatry. Neuropsychiatry Natasha L. Mason verfasserin aut Lilian Kloft verfasserin aut Johannes T. Reckweg verfasserin aut Kim van Oorsouw verfasserin aut Johannes G. Ramaekers verfasserin aut In Frontiers in Neuroscience Frontiers Media S.A., 2008 17(2023) (DE-627)55908109X (DE-600)2411902-7 1662453X nnns volume:17 year:2023 https://doi.org/10.3389/fnins.2023.1217079 kostenfrei https://doaj.org/article/b1873bef02474162bde87da84318ac71 kostenfrei https://www.frontiersin.org/articles/10.3389/fnins.2023.1217079/full kostenfrei https://doaj.org/toc/1662-453X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2023
allfieldsGer	10.3389/fnins.2023.1217079 doi (DE-627)DOAJ09673499X (DE-599)DOAJb1873bef02474162bde87da84318ac71 DE-627 ger DE-627 rakwb eng RC321-571 Pablo Mallaroni verfasserin aut Cortical structural differences following repeated ayahuasca use hold molecular signatures 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier IntroductionSerotonergic psychedelics such as ayahuasca are reported to promote both structural and functional neural plasticity via partial 5-HT2A agonism. However, little is known about how these molecular mechanisms may extend to repeated psychedelic administration in humans, let alone neuroanatomy. While early evidence suggests localised changes to cortical thickness in long-term ayahuasca users, it is unknown how such findings may be reflected by large-scale anatomical brain networks comprising cytoarchitecturally complex regions.MethodsHere, we examined the relationship between cortical gene expression markers of psychedelic action and brain morphometric change following repeated ayahuasca usage, using high-field 7 Tesla neuroimaging data derived from 24 members of an ayahuasca-using church (Santo Daime) and case-matched controls.ResultsUsing a morphometric similarity network (MSN) analysis, repeated ayahuasca use was associated with a spatially distributed cortical patterning of both structural differentiation in sensorimotor areas and de-differentiation in transmodal areas. Cortical MSN remodelling was found to be spatially correlated with dysregulation of 5-HT2A gene expression as well as a broader set of genes encoding target receptors pertinent to ayahuasca’s effects. Furthermore, these associations were similarly interrelated with altered gene expression of specific transcriptional factors and immediate early genes previously identified in preclinical assays as relevant to psychedelic-induced neuroplasticity.ConclusionTaken together, these findings provide preliminary evidence that the molecular mechanisms of psychedelic action may scale up to a macroscale level of brain organisation in vivo. Closer attention to the role of cortical transcriptomics in structural-functional coupling may help account for the behavioural differences observed in experienced psychedelic users. ayahuasca psychedelics 5-HT2A transcriptomics morphometry ultra-high field MRI Neurosciences. Biological psychiatry. Neuropsychiatry Natasha L. Mason verfasserin aut Lilian Kloft verfasserin aut Johannes T. Reckweg verfasserin aut Kim van Oorsouw verfasserin aut Johannes G. Ramaekers verfasserin aut In Frontiers in Neuroscience Frontiers Media S.A., 2008 17(2023) (DE-627)55908109X (DE-600)2411902-7 1662453X nnns volume:17 year:2023 https://doi.org/10.3389/fnins.2023.1217079 kostenfrei https://doaj.org/article/b1873bef02474162bde87da84318ac71 kostenfrei https://www.frontiersin.org/articles/10.3389/fnins.2023.1217079/full kostenfrei https://doaj.org/toc/1662-453X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2023
allfieldsSound	10.3389/fnins.2023.1217079 doi (DE-627)DOAJ09673499X (DE-599)DOAJb1873bef02474162bde87da84318ac71 DE-627 ger DE-627 rakwb eng RC321-571 Pablo Mallaroni verfasserin aut Cortical structural differences following repeated ayahuasca use hold molecular signatures 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier IntroductionSerotonergic psychedelics such as ayahuasca are reported to promote both structural and functional neural plasticity via partial 5-HT2A agonism. However, little is known about how these molecular mechanisms may extend to repeated psychedelic administration in humans, let alone neuroanatomy. While early evidence suggests localised changes to cortical thickness in long-term ayahuasca users, it is unknown how such findings may be reflected by large-scale anatomical brain networks comprising cytoarchitecturally complex regions.MethodsHere, we examined the relationship between cortical gene expression markers of psychedelic action and brain morphometric change following repeated ayahuasca usage, using high-field 7 Tesla neuroimaging data derived from 24 members of an ayahuasca-using church (Santo Daime) and case-matched controls.ResultsUsing a morphometric similarity network (MSN) analysis, repeated ayahuasca use was associated with a spatially distributed cortical patterning of both structural differentiation in sensorimotor areas and de-differentiation in transmodal areas. Cortical MSN remodelling was found to be spatially correlated with dysregulation of 5-HT2A gene expression as well as a broader set of genes encoding target receptors pertinent to ayahuasca’s effects. Furthermore, these associations were similarly interrelated with altered gene expression of specific transcriptional factors and immediate early genes previously identified in preclinical assays as relevant to psychedelic-induced neuroplasticity.ConclusionTaken together, these findings provide preliminary evidence that the molecular mechanisms of psychedelic action may scale up to a macroscale level of brain organisation in vivo. Closer attention to the role of cortical transcriptomics in structural-functional coupling may help account for the behavioural differences observed in experienced psychedelic users. ayahuasca psychedelics 5-HT2A transcriptomics morphometry ultra-high field MRI Neurosciences. Biological psychiatry. Neuropsychiatry Natasha L. Mason verfasserin aut Lilian Kloft verfasserin aut Johannes T. Reckweg verfasserin aut Kim van Oorsouw verfasserin aut Johannes G. Ramaekers verfasserin aut In Frontiers in Neuroscience Frontiers Media S.A., 2008 17(2023) (DE-627)55908109X (DE-600)2411902-7 1662453X nnns volume:17 year:2023 https://doi.org/10.3389/fnins.2023.1217079 kostenfrei https://doaj.org/article/b1873bef02474162bde87da84318ac71 kostenfrei https://www.frontiersin.org/articles/10.3389/fnins.2023.1217079/full kostenfrei https://doaj.org/toc/1662-453X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2023
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However, little is known about how these molecular mechanisms may extend to repeated psychedelic administration in humans, let alone neuroanatomy. While early evidence suggests localised changes to cortical thickness in long-term ayahuasca users, it is unknown how such findings may be reflected by large-scale anatomical brain networks comprising cytoarchitecturally complex regions.MethodsHere, we examined the relationship between cortical gene expression markers of psychedelic action and brain morphometric change following repeated ayahuasca usage, using high-field 7 Tesla neuroimaging data derived from 24 members of an ayahuasca-using church (Santo Daime) and case-matched controls.ResultsUsing a morphometric similarity network (MSN) analysis, repeated ayahuasca use was associated with a spatially distributed cortical patterning of both structural differentiation in sensorimotor areas and de-differentiation in transmodal areas. Cortical MSN remodelling was found to be spatially correlated with dysregulation of 5-HT2A gene expression as well as a broader set of genes encoding target receptors pertinent to ayahuasca’s effects. Furthermore, these associations were similarly interrelated with altered gene expression of specific transcriptional factors and immediate early genes previously identified in preclinical assays as relevant to psychedelic-induced neuroplasticity.ConclusionTaken together, these findings provide preliminary evidence that the molecular mechanisms of psychedelic action may scale up to a macroscale level of brain organisation in vivo. 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callnumber-first	R - Medicine
author	Pablo Mallaroni
spellingShingle	Pablo Mallaroni misc RC321-571 misc ayahuasca misc psychedelics misc 5-HT2A misc transcriptomics misc morphometry misc ultra-high field MRI misc Neurosciences. Biological psychiatry. Neuropsychiatry Cortical structural differences following repeated ayahuasca use hold molecular signatures
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topic_title	RC321-571 Cortical structural differences following repeated ayahuasca use hold molecular signatures ayahuasca psychedelics 5-HT2A transcriptomics morphometry ultra-high field MRI
topic	misc RC321-571 misc ayahuasca misc psychedelics misc 5-HT2A misc transcriptomics misc morphometry misc ultra-high field MRI misc Neurosciences. Biological psychiatry. Neuropsychiatry
topic_unstemmed	misc RC321-571 misc ayahuasca misc psychedelics misc 5-HT2A misc transcriptomics misc morphometry misc ultra-high field MRI misc Neurosciences. Biological psychiatry. Neuropsychiatry
topic_browse	misc RC321-571 misc ayahuasca misc psychedelics misc 5-HT2A misc transcriptomics misc morphometry misc ultra-high field MRI misc Neurosciences. Biological psychiatry. Neuropsychiatry
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title	Cortical structural differences following repeated ayahuasca use hold molecular signatures
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title_full	Cortical structural differences following repeated ayahuasca use hold molecular signatures
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title_sort	cortical structural differences following repeated ayahuasca use hold molecular signatures
callnumber	RC321-571
title_auth	Cortical structural differences following repeated ayahuasca use hold molecular signatures
abstract	IntroductionSerotonergic psychedelics such as ayahuasca are reported to promote both structural and functional neural plasticity via partial 5-HT2A agonism. However, little is known about how these molecular mechanisms may extend to repeated psychedelic administration in humans, let alone neuroanatomy. While early evidence suggests localised changes to cortical thickness in long-term ayahuasca users, it is unknown how such findings may be reflected by large-scale anatomical brain networks comprising cytoarchitecturally complex regions.MethodsHere, we examined the relationship between cortical gene expression markers of psychedelic action and brain morphometric change following repeated ayahuasca usage, using high-field 7 Tesla neuroimaging data derived from 24 members of an ayahuasca-using church (Santo Daime) and case-matched controls.ResultsUsing a morphometric similarity network (MSN) analysis, repeated ayahuasca use was associated with a spatially distributed cortical patterning of both structural differentiation in sensorimotor areas and de-differentiation in transmodal areas. Cortical MSN remodelling was found to be spatially correlated with dysregulation of 5-HT2A gene expression as well as a broader set of genes encoding target receptors pertinent to ayahuasca’s effects. Furthermore, these associations were similarly interrelated with altered gene expression of specific transcriptional factors and immediate early genes previously identified in preclinical assays as relevant to psychedelic-induced neuroplasticity.ConclusionTaken together, these findings provide preliminary evidence that the molecular mechanisms of psychedelic action may scale up to a macroscale level of brain organisation in vivo. Closer attention to the role of cortical transcriptomics in structural-functional coupling may help account for the behavioural differences observed in experienced psychedelic users.
abstractGer	IntroductionSerotonergic psychedelics such as ayahuasca are reported to promote both structural and functional neural plasticity via partial 5-HT2A agonism. However, little is known about how these molecular mechanisms may extend to repeated psychedelic administration in humans, let alone neuroanatomy. While early evidence suggests localised changes to cortical thickness in long-term ayahuasca users, it is unknown how such findings may be reflected by large-scale anatomical brain networks comprising cytoarchitecturally complex regions.MethodsHere, we examined the relationship between cortical gene expression markers of psychedelic action and brain morphometric change following repeated ayahuasca usage, using high-field 7 Tesla neuroimaging data derived from 24 members of an ayahuasca-using church (Santo Daime) and case-matched controls.ResultsUsing a morphometric similarity network (MSN) analysis, repeated ayahuasca use was associated with a spatially distributed cortical patterning of both structural differentiation in sensorimotor areas and de-differentiation in transmodal areas. Cortical MSN remodelling was found to be spatially correlated with dysregulation of 5-HT2A gene expression as well as a broader set of genes encoding target receptors pertinent to ayahuasca’s effects. Furthermore, these associations were similarly interrelated with altered gene expression of specific transcriptional factors and immediate early genes previously identified in preclinical assays as relevant to psychedelic-induced neuroplasticity.ConclusionTaken together, these findings provide preliminary evidence that the molecular mechanisms of psychedelic action may scale up to a macroscale level of brain organisation in vivo. Closer attention to the role of cortical transcriptomics in structural-functional coupling may help account for the behavioural differences observed in experienced psychedelic users.
abstract_unstemmed	IntroductionSerotonergic psychedelics such as ayahuasca are reported to promote both structural and functional neural plasticity via partial 5-HT2A agonism. However, little is known about how these molecular mechanisms may extend to repeated psychedelic administration in humans, let alone neuroanatomy. While early evidence suggests localised changes to cortical thickness in long-term ayahuasca users, it is unknown how such findings may be reflected by large-scale anatomical brain networks comprising cytoarchitecturally complex regions.MethodsHere, we examined the relationship between cortical gene expression markers of psychedelic action and brain morphometric change following repeated ayahuasca usage, using high-field 7 Tesla neuroimaging data derived from 24 members of an ayahuasca-using church (Santo Daime) and case-matched controls.ResultsUsing a morphometric similarity network (MSN) analysis, repeated ayahuasca use was associated with a spatially distributed cortical patterning of both structural differentiation in sensorimotor areas and de-differentiation in transmodal areas. Cortical MSN remodelling was found to be spatially correlated with dysregulation of 5-HT2A gene expression as well as a broader set of genes encoding target receptors pertinent to ayahuasca’s effects. Furthermore, these associations were similarly interrelated with altered gene expression of specific transcriptional factors and immediate early genes previously identified in preclinical assays as relevant to psychedelic-induced neuroplasticity.ConclusionTaken together, these findings provide preliminary evidence that the molecular mechanisms of psychedelic action may scale up to a macroscale level of brain organisation in vivo. Closer attention to the role of cortical transcriptomics in structural-functional coupling may help account for the behavioural differences observed in experienced psychedelic users.
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title_short	Cortical structural differences following repeated ayahuasca use hold molecular signatures
url	https://doi.org/10.3389/fnins.2023.1217079 https://doaj.org/article/b1873bef02474162bde87da84318ac71 https://www.frontiersin.org/articles/10.3389/fnins.2023.1217079/full https://doaj.org/toc/1662-453X
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up_date	2024-07-03T21:49:36.960Z
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Cortical structural differences following repeated ayahuasca use hold molecular signatures

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