Psilocybin therapy increases cognitive and neural flexibility in patients with major depressive disorder

Abstract Psilocybin has shown promise for the treatment of mood disorders, which are often accompanied by cognitive dysfunction including cognitive rigidity. Recent studies have proposed neuropsychoplastogenic effects as mechanisms underlying the enduring therapeutic effects of psilocybin. In an ope...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Manoj K. Doss, Michal Považan, Monica D. Rosenberg, Nathan D. Sepeda, Alan K. Davis, Patrick H. Finan, Gwenn S. Smith, James J. Pekar, Peter B. Barker, Roland R. Griffiths, Frederick S. Barrett
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/86a0e8c36d244f1fa71b11da3c3a46b2
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:86a0e8c36d244f1fa71b11da3c3a46b2
record_format	dspace
spelling	oai:doaj.org-article:86a0e8c36d244f1fa71b11da3c3a46b22021-11-14T12:11:20ZPsilocybin therapy increases cognitive and neural flexibility in patients with major depressive disorder10.1038/s41398-021-01706-y2158-3188https://doaj.org/article/86a0e8c36d244f1fa71b11da3c3a46b22021-11-01T00:00:00Zhttps://doi.org/10.1038/s41398-021-01706-yhttps://doaj.org/toc/2158-3188Abstract Psilocybin has shown promise for the treatment of mood disorders, which are often accompanied by cognitive dysfunction including cognitive rigidity. Recent studies have proposed neuropsychoplastogenic effects as mechanisms underlying the enduring therapeutic effects of psilocybin. In an open-label study of 24 patients with major depressive disorder, we tested the enduring effects of psilocybin therapy on cognitive flexibility (perseverative errors on a set-shifting task), neural flexibility (dynamics of functional connectivity or dFC via functional magnetic resonance imaging), and neurometabolite concentrations (via magnetic resonance spectroscopy) in brain regions supporting cognitive flexibility and implicated in acute psilocybin effects (e.g., the anterior cingulate cortex, or ACC). Psilocybin therapy increased cognitive flexibility for at least 4 weeks post-treatment, though these improvements were not correlated with the previously reported antidepressant effects. One week after psilocybin therapy, glutamate and N-acetylaspartate concentrations were decreased in the ACC, and dFC was increased between the ACC and the posterior cingulate cortex (PCC). Surprisingly, greater increases in dFC between the ACC and PCC were associated with less improvement in cognitive flexibility after psilocybin therapy. Connectome-based predictive modeling demonstrated that baseline dFC emanating from the ACC predicted improvements in cognitive flexibility. In these models, greater baseline dFC was associated with better baseline cognitive flexibility but less improvement in cognitive flexibility. These findings suggest a nuanced relationship between cognitive and neural flexibility. Whereas some enduring increases in neural dynamics may allow for shifting out of a maladaptively rigid state, larger persisting increases in neural dynamics may be of less benefit to psilocybin therapy.Manoj K. DossMichal PovažanMonica D. RosenbergNathan D. SepedaAlan K. DavisPatrick H. FinanGwenn S. SmithJames J. PekarPeter B. BarkerRoland R. GriffithsFrederick S. BarrettNature Publishing GrouparticleNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENTranslational Psychiatry, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Manoj K. Doss Michal Považan Monica D. Rosenberg Nathan D. Sepeda Alan K. Davis Patrick H. Finan Gwenn S. Smith James J. Pekar Peter B. Barker Roland R. Griffiths Frederick S. Barrett Psilocybin therapy increases cognitive and neural flexibility in patients with major depressive disorder
description	Abstract Psilocybin has shown promise for the treatment of mood disorders, which are often accompanied by cognitive dysfunction including cognitive rigidity. Recent studies have proposed neuropsychoplastogenic effects as mechanisms underlying the enduring therapeutic effects of psilocybin. In an open-label study of 24 patients with major depressive disorder, we tested the enduring effects of psilocybin therapy on cognitive flexibility (perseverative errors on a set-shifting task), neural flexibility (dynamics of functional connectivity or dFC via functional magnetic resonance imaging), and neurometabolite concentrations (via magnetic resonance spectroscopy) in brain regions supporting cognitive flexibility and implicated in acute psilocybin effects (e.g., the anterior cingulate cortex, or ACC). Psilocybin therapy increased cognitive flexibility for at least 4 weeks post-treatment, though these improvements were not correlated with the previously reported antidepressant effects. One week after psilocybin therapy, glutamate and N-acetylaspartate concentrations were decreased in the ACC, and dFC was increased between the ACC and the posterior cingulate cortex (PCC). Surprisingly, greater increases in dFC between the ACC and PCC were associated with less improvement in cognitive flexibility after psilocybin therapy. Connectome-based predictive modeling demonstrated that baseline dFC emanating from the ACC predicted improvements in cognitive flexibility. In these models, greater baseline dFC was associated with better baseline cognitive flexibility but less improvement in cognitive flexibility. These findings suggest a nuanced relationship between cognitive and neural flexibility. Whereas some enduring increases in neural dynamics may allow for shifting out of a maladaptively rigid state, larger persisting increases in neural dynamics may be of less benefit to psilocybin therapy.
format	article
author	Manoj K. Doss Michal Považan Monica D. Rosenberg Nathan D. Sepeda Alan K. Davis Patrick H. Finan Gwenn S. Smith James J. Pekar Peter B. Barker Roland R. Griffiths Frederick S. Barrett
author_facet	Manoj K. Doss Michal Považan Monica D. Rosenberg Nathan D. Sepeda Alan K. Davis Patrick H. Finan Gwenn S. Smith James J. Pekar Peter B. Barker Roland R. Griffiths Frederick S. Barrett
author_sort	Manoj K. Doss
title	Psilocybin therapy increases cognitive and neural flexibility in patients with major depressive disorder
title_short	Psilocybin therapy increases cognitive and neural flexibility in patients with major depressive disorder
title_full	Psilocybin therapy increases cognitive and neural flexibility in patients with major depressive disorder
title_fullStr	Psilocybin therapy increases cognitive and neural flexibility in patients with major depressive disorder
title_full_unstemmed	Psilocybin therapy increases cognitive and neural flexibility in patients with major depressive disorder
title_sort	psilocybin therapy increases cognitive and neural flexibility in patients with major depressive disorder
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/86a0e8c36d244f1fa71b11da3c3a46b2
work_keys_str_mv	AT manojkdoss psilocybintherapyincreasescognitiveandneuralflexibilityinpatientswithmajordepressivedisorder AT michalpovazan psilocybintherapyincreasescognitiveandneuralflexibilityinpatientswithmajordepressivedisorder AT monicadrosenberg psilocybintherapyincreasescognitiveandneuralflexibilityinpatientswithmajordepressivedisorder AT nathandsepeda psilocybintherapyincreasescognitiveandneuralflexibilityinpatientswithmajordepressivedisorder AT alankdavis psilocybintherapyincreasescognitiveandneuralflexibilityinpatientswithmajordepressivedisorder AT patrickhfinan psilocybintherapyincreasescognitiveandneuralflexibilityinpatientswithmajordepressivedisorder AT gwennssmith psilocybintherapyincreasescognitiveandneuralflexibilityinpatientswithmajordepressivedisorder AT jamesjpekar psilocybintherapyincreasescognitiveandneuralflexibilityinpatientswithmajordepressivedisorder AT peterbbarker psilocybintherapyincreasescognitiveandneuralflexibilityinpatientswithmajordepressivedisorder AT rolandrgriffiths psilocybintherapyincreasescognitiveandneuralflexibilityinpatientswithmajordepressivedisorder AT fredericksbarrett psilocybintherapyincreasescognitiveandneuralflexibilityinpatientswithmajordepressivedisorder
_version_	1718429415827832832

Psilocybin therapy increases cognitive and neural flexibility in patients with major depressive disorder

Ejemplares similares