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Differentiating the effect of antipsychotic medication and illness on brain volume reductions in first-episode psychosis: A Longitudinal, Randomised, Triple-blind, Placebo-controlled MRI Study

Changes in brain volume are a common finding in Magnetic Resonance Imaging (MRI) studies of people with psychosis and numerous longitudinal studies suggest that volume deficits progress with illness duration. However, a major unresolved question concerns whether these changes are driven by the under...

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Autores principales: Chopra, Sidhant, Fornito, Alex, Francey, Shona M., O’Donoghue, Brian, Cropley, Vanessa, Nelson, Barnaby, Graham, Jessica, Baldwin, Lara, Tahtalian, Steven, Yuen, Hok Pan, Allott, Kelly, Alvarez-Jimenez, Mario, Harrigan, Susy, Sabaroedin, Kristina, Pantelis, Christos, Wood, Stephen J., McGorry, Patrick
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209146/
https://www.ncbi.nlm.nih.gov/pubmed/33637835
http://dx.doi.org/10.1038/s41386-021-00980-0
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author Chopra, Sidhant
Fornito, Alex
Francey, Shona M.
O’Donoghue, Brian
Cropley, Vanessa
Nelson, Barnaby
Graham, Jessica
Baldwin, Lara
Tahtalian, Steven
Yuen, Hok Pan
Allott, Kelly
Alvarez-Jimenez, Mario
Harrigan, Susy
Sabaroedin, Kristina
Pantelis, Christos
Wood, Stephen J.
McGorry, Patrick
author_facet Chopra, Sidhant
Fornito, Alex
Francey, Shona M.
O’Donoghue, Brian
Cropley, Vanessa
Nelson, Barnaby
Graham, Jessica
Baldwin, Lara
Tahtalian, Steven
Yuen, Hok Pan
Allott, Kelly
Alvarez-Jimenez, Mario
Harrigan, Susy
Sabaroedin, Kristina
Pantelis, Christos
Wood, Stephen J.
McGorry, Patrick
author_sort Chopra, Sidhant
collection PubMed
description Changes in brain volume are a common finding in Magnetic Resonance Imaging (MRI) studies of people with psychosis and numerous longitudinal studies suggest that volume deficits progress with illness duration. However, a major unresolved question concerns whether these changes are driven by the underlying illness or represent iatrogenic effects of antipsychotic medication. In this study, 62 antipsychotic-naïve patients with first-episode psychosis (FEP) received either a second-generation antipsychotic (risperidone or paliperidone) or a placebo pill over a treatment period of 6 months. Both FEP groups received intensive psychosocial therapy. A healthy control group (n = 27) was also recruited. Structural MRI scans were obtained at baseline, 3 months and 12 months. Our primary aim was to differentiate illness-related brain volume changes from medication-related changes within the first 3 months of treatment. We secondarily investigated long-term effects at the 12-month timepoint. From baseline to 3 months, we observed a significant group x time interaction in the pallidum (p < 0.05 FWE-corrected), such that patients receiving antipsychotic medication showed increased volume, patients on placebo showed decreased volume, and healthy controls showed no change. Across the entire patient sample, a greater increase in pallidal grey matter volume over 3 months was associated with a greater reduction in symptom severity. Our findings indicate that psychotic illness and antipsychotic exposure exert distinct and spatially distributed effects on brain volume. Our results align with prior work in suggesting that the therapeutic efficacy of antipsychotic medications may be primarily mediated through their effects on the basal ganglia.
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spelling pubmed-82091462021-07-01 Differentiating the effect of antipsychotic medication and illness on brain volume reductions in first-episode psychosis: A Longitudinal, Randomised, Triple-blind, Placebo-controlled MRI Study Chopra, Sidhant Fornito, Alex Francey, Shona M. O’Donoghue, Brian Cropley, Vanessa Nelson, Barnaby Graham, Jessica Baldwin, Lara Tahtalian, Steven Yuen, Hok Pan Allott, Kelly Alvarez-Jimenez, Mario Harrigan, Susy Sabaroedin, Kristina Pantelis, Christos Wood, Stephen J. McGorry, Patrick Neuropsychopharmacology Article Changes in brain volume are a common finding in Magnetic Resonance Imaging (MRI) studies of people with psychosis and numerous longitudinal studies suggest that volume deficits progress with illness duration. However, a major unresolved question concerns whether these changes are driven by the underlying illness or represent iatrogenic effects of antipsychotic medication. In this study, 62 antipsychotic-naïve patients with first-episode psychosis (FEP) received either a second-generation antipsychotic (risperidone or paliperidone) or a placebo pill over a treatment period of 6 months. Both FEP groups received intensive psychosocial therapy. A healthy control group (n = 27) was also recruited. Structural MRI scans were obtained at baseline, 3 months and 12 months. Our primary aim was to differentiate illness-related brain volume changes from medication-related changes within the first 3 months of treatment. We secondarily investigated long-term effects at the 12-month timepoint. From baseline to 3 months, we observed a significant group x time interaction in the pallidum (p < 0.05 FWE-corrected), such that patients receiving antipsychotic medication showed increased volume, patients on placebo showed decreased volume, and healthy controls showed no change. Across the entire patient sample, a greater increase in pallidal grey matter volume over 3 months was associated with a greater reduction in symptom severity. Our findings indicate that psychotic illness and antipsychotic exposure exert distinct and spatially distributed effects on brain volume. Our results align with prior work in suggesting that the therapeutic efficacy of antipsychotic medications may be primarily mediated through their effects on the basal ganglia. Springer International Publishing 2021-02-26 2021-07 /pmc/articles/PMC8209146/ /pubmed/33637835 http://dx.doi.org/10.1038/s41386-021-00980-0 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Chopra, Sidhant
Fornito, Alex
Francey, Shona M.
O’Donoghue, Brian
Cropley, Vanessa
Nelson, Barnaby
Graham, Jessica
Baldwin, Lara
Tahtalian, Steven
Yuen, Hok Pan
Allott, Kelly
Alvarez-Jimenez, Mario
Harrigan, Susy
Sabaroedin, Kristina
Pantelis, Christos
Wood, Stephen J.
McGorry, Patrick
Differentiating the effect of antipsychotic medication and illness on brain volume reductions in first-episode psychosis: A Longitudinal, Randomised, Triple-blind, Placebo-controlled MRI Study
title Differentiating the effect of antipsychotic medication and illness on brain volume reductions in first-episode psychosis: A Longitudinal, Randomised, Triple-blind, Placebo-controlled MRI Study
title_full Differentiating the effect of antipsychotic medication and illness on brain volume reductions in first-episode psychosis: A Longitudinal, Randomised, Triple-blind, Placebo-controlled MRI Study
title_fullStr Differentiating the effect of antipsychotic medication and illness on brain volume reductions in first-episode psychosis: A Longitudinal, Randomised, Triple-blind, Placebo-controlled MRI Study
title_full_unstemmed Differentiating the effect of antipsychotic medication and illness on brain volume reductions in first-episode psychosis: A Longitudinal, Randomised, Triple-blind, Placebo-controlled MRI Study
title_short Differentiating the effect of antipsychotic medication and illness on brain volume reductions in first-episode psychosis: A Longitudinal, Randomised, Triple-blind, Placebo-controlled MRI Study
title_sort differentiating the effect of antipsychotic medication and illness on brain volume reductions in first-episode psychosis: a longitudinal, randomised, triple-blind, placebo-controlled mri study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209146/
https://www.ncbi.nlm.nih.gov/pubmed/33637835
http://dx.doi.org/10.1038/s41386-021-00980-0
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