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Alprazolam modulates persistence energy during emotion processing in first-degree relatives of individuals with schizophrenia: a network control study

Schizophrenia is marked by deficits in facial affect processing associated with abnormalities in GABAergic circuitry, deficits also found in first-degree relatives. Facial affect processing involves a distributed network of brain regions including limbic regions like amygdala and visual processing a...

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Autores principales: Mahadevan, Arun S., Cornblath, Eli J., Lydon-Staley, David M., Zhou, Dale, Parkes, Linden, Larsen, Bart, Adebimpe, Azeez, Kahn, Ari E., Gur, Ruben C., Gur, Raquel E., Satterthwaite, Theodore D., Wolf, Daniel H., Bassett, Dani S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618098/
https://www.ncbi.nlm.nih.gov/pubmed/37353585
http://dx.doi.org/10.1038/s41380-023-02121-z
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author Mahadevan, Arun S.
Cornblath, Eli J.
Lydon-Staley, David M.
Zhou, Dale
Parkes, Linden
Larsen, Bart
Adebimpe, Azeez
Kahn, Ari E.
Gur, Ruben C.
Gur, Raquel E.
Satterthwaite, Theodore D.
Wolf, Daniel H.
Bassett, Dani S.
author_facet Mahadevan, Arun S.
Cornblath, Eli J.
Lydon-Staley, David M.
Zhou, Dale
Parkes, Linden
Larsen, Bart
Adebimpe, Azeez
Kahn, Ari E.
Gur, Ruben C.
Gur, Raquel E.
Satterthwaite, Theodore D.
Wolf, Daniel H.
Bassett, Dani S.
author_sort Mahadevan, Arun S.
collection PubMed
description Schizophrenia is marked by deficits in facial affect processing associated with abnormalities in GABAergic circuitry, deficits also found in first-degree relatives. Facial affect processing involves a distributed network of brain regions including limbic regions like amygdala and visual processing areas like fusiform cortex. Pharmacological modulation of GABAergic circuitry using benzodiazepines like alprazolam can be useful for studying this facial affect processing network and associated GABAergic abnormalities in schizophrenia. Here, we use pharmacological modulation and computational modeling to study the contribution of GABAergic abnormalities toward emotion processing deficits in schizophrenia. Specifically, we apply principles from network control theory to model persistence energy – the control energy required to maintain brain activation states – during emotion identification and recall tasks, with and without administration of alprazolam, in a sample of first-degree relatives and healthy controls. Here, persistence energy quantifies the magnitude of theoretical external inputs during the task. We find that alprazolam increases persistence energy in relatives but not in controls during threatening face processing, suggesting a compensatory mechanism given the relative absence of behavioral abnormalities in this sample of unaffected relatives. Further, we demonstrate that regions in the fusiform and occipital cortices are important for facilitating state transitions during facial affect processing. Finally, we uncover spatial relationships (i) between regional variation in differential control energy (alprazolam versus placebo) and (ii) both serotonin and dopamine neurotransmitter systems, indicating that alprazolam may exert its effects by altering neuromodulatory systems. Together, these findings provide a new perspective on the distributed emotion processing network and the effect of GABAergic modulation on this network, in addition to identifying an association between schizophrenia risk and abnormal GABAergic effects on persistence energy during threat processing.
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spelling pubmed-106180982023-11-02 Alprazolam modulates persistence energy during emotion processing in first-degree relatives of individuals with schizophrenia: a network control study Mahadevan, Arun S. Cornblath, Eli J. Lydon-Staley, David M. Zhou, Dale Parkes, Linden Larsen, Bart Adebimpe, Azeez Kahn, Ari E. Gur, Ruben C. Gur, Raquel E. Satterthwaite, Theodore D. Wolf, Daniel H. Bassett, Dani S. Mol Psychiatry Article Schizophrenia is marked by deficits in facial affect processing associated with abnormalities in GABAergic circuitry, deficits also found in first-degree relatives. Facial affect processing involves a distributed network of brain regions including limbic regions like amygdala and visual processing areas like fusiform cortex. Pharmacological modulation of GABAergic circuitry using benzodiazepines like alprazolam can be useful for studying this facial affect processing network and associated GABAergic abnormalities in schizophrenia. Here, we use pharmacological modulation and computational modeling to study the contribution of GABAergic abnormalities toward emotion processing deficits in schizophrenia. Specifically, we apply principles from network control theory to model persistence energy – the control energy required to maintain brain activation states – during emotion identification and recall tasks, with and without administration of alprazolam, in a sample of first-degree relatives and healthy controls. Here, persistence energy quantifies the magnitude of theoretical external inputs during the task. We find that alprazolam increases persistence energy in relatives but not in controls during threatening face processing, suggesting a compensatory mechanism given the relative absence of behavioral abnormalities in this sample of unaffected relatives. Further, we demonstrate that regions in the fusiform and occipital cortices are important for facilitating state transitions during facial affect processing. Finally, we uncover spatial relationships (i) between regional variation in differential control energy (alprazolam versus placebo) and (ii) both serotonin and dopamine neurotransmitter systems, indicating that alprazolam may exert its effects by altering neuromodulatory systems. Together, these findings provide a new perspective on the distributed emotion processing network and the effect of GABAergic modulation on this network, in addition to identifying an association between schizophrenia risk and abnormal GABAergic effects on persistence energy during threat processing. Nature Publishing Group UK 2023-06-23 2023 /pmc/articles/PMC10618098/ /pubmed/37353585 http://dx.doi.org/10.1038/s41380-023-02121-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Mahadevan, Arun S.
Cornblath, Eli J.
Lydon-Staley, David M.
Zhou, Dale
Parkes, Linden
Larsen, Bart
Adebimpe, Azeez
Kahn, Ari E.
Gur, Ruben C.
Gur, Raquel E.
Satterthwaite, Theodore D.
Wolf, Daniel H.
Bassett, Dani S.
Alprazolam modulates persistence energy during emotion processing in first-degree relatives of individuals with schizophrenia: a network control study
title Alprazolam modulates persistence energy during emotion processing in first-degree relatives of individuals with schizophrenia: a network control study
title_full Alprazolam modulates persistence energy during emotion processing in first-degree relatives of individuals with schizophrenia: a network control study
title_fullStr Alprazolam modulates persistence energy during emotion processing in first-degree relatives of individuals with schizophrenia: a network control study
title_full_unstemmed Alprazolam modulates persistence energy during emotion processing in first-degree relatives of individuals with schizophrenia: a network control study
title_short Alprazolam modulates persistence energy during emotion processing in first-degree relatives of individuals with schizophrenia: a network control study
title_sort alprazolam modulates persistence energy during emotion processing in first-degree relatives of individuals with schizophrenia: a network control study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618098/
https://www.ncbi.nlm.nih.gov/pubmed/37353585
http://dx.doi.org/10.1038/s41380-023-02121-z
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