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Lower cholinergic basal forebrain volumes link with cognitive difficulties in schizophrenia
A potential pathophysiological mechanism of cognitive difficulties in schizophrenia is a dysregulated cholinergic system. Particularly, the cholinergic basal forebrain nuclei (BFCN), the source of cortical cholinergic innervation, support multiple cognitive functions, ranging from attention to decis...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8580980/ https://www.ncbi.nlm.nih.gov/pubmed/34188186 http://dx.doi.org/10.1038/s41386-021-01070-x |
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author | Avram, Mihai Grothe, Michel J. Meinhold, Lena Leucht, Claudia Leucht, Stefan Borgwardt, Stefan Brandl, Felix Sorg, Christian |
author_facet | Avram, Mihai Grothe, Michel J. Meinhold, Lena Leucht, Claudia Leucht, Stefan Borgwardt, Stefan Brandl, Felix Sorg, Christian |
author_sort | Avram, Mihai |
collection | PubMed |
description | A potential pathophysiological mechanism of cognitive difficulties in schizophrenia is a dysregulated cholinergic system. Particularly, the cholinergic basal forebrain nuclei (BFCN), the source of cortical cholinergic innervation, support multiple cognitive functions, ranging from attention to decision-making. We hypothesized that BFCN structural integrity is altered in schizophrenia and associated with patients’ attentional deficits. We assessed gray matter (GM) integrity of cytoarchitectonically defined BFCN region-of-interest in 72 patients with schizophrenia and 73 healthy controls, matched for age and gender, from the COBRE open-source database, via structural magnetic resonance imaging (MRI)–based volumetry. MRI-derived measures of GM integrity (i.e., volumes) were linked with performance on a symbol coding task (SCT), a paper-pencil-based metric that assesses attention, by correlation and mediation analysis. To assess the replicability of findings, we repeated the analyses in an independent dataset comprising 26 patients with schizophrenia and 24 matched healthy controls. BFCN volumes were lower in patients (t(139)=2.51, p = 0.01) and significantly associated with impaired SCT performance (r = 0.31, p = 0.01). Furthermore, lower BFCN volumes mediated the group difference in SCT performance. When including global GM volumes, which were lower in patients, as covariates-of-no-interest, these findings disappeared, indicating that schizophrenia did not have a specific effect on BFCN relative to other regional volume changes. We replicated these findings in the independent cohort, e.g., BFCN volumes were lower in patients and mediated patients’ impaired SCT performance. Results demonstrate lower BFCN volumes in schizophrenia, which link with patients’ attentional deficits. Data suggest that a dysregulated cholinergic system might contribute to cognitive difficulties in schizophrenia via impaired BFCN. |
format | Online Article Text |
id | pubmed-8580980 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-85809802021-11-15 Lower cholinergic basal forebrain volumes link with cognitive difficulties in schizophrenia Avram, Mihai Grothe, Michel J. Meinhold, Lena Leucht, Claudia Leucht, Stefan Borgwardt, Stefan Brandl, Felix Sorg, Christian Neuropsychopharmacology Article A potential pathophysiological mechanism of cognitive difficulties in schizophrenia is a dysregulated cholinergic system. Particularly, the cholinergic basal forebrain nuclei (BFCN), the source of cortical cholinergic innervation, support multiple cognitive functions, ranging from attention to decision-making. We hypothesized that BFCN structural integrity is altered in schizophrenia and associated with patients’ attentional deficits. We assessed gray matter (GM) integrity of cytoarchitectonically defined BFCN region-of-interest in 72 patients with schizophrenia and 73 healthy controls, matched for age and gender, from the COBRE open-source database, via structural magnetic resonance imaging (MRI)–based volumetry. MRI-derived measures of GM integrity (i.e., volumes) were linked with performance on a symbol coding task (SCT), a paper-pencil-based metric that assesses attention, by correlation and mediation analysis. To assess the replicability of findings, we repeated the analyses in an independent dataset comprising 26 patients with schizophrenia and 24 matched healthy controls. BFCN volumes were lower in patients (t(139)=2.51, p = 0.01) and significantly associated with impaired SCT performance (r = 0.31, p = 0.01). Furthermore, lower BFCN volumes mediated the group difference in SCT performance. When including global GM volumes, which were lower in patients, as covariates-of-no-interest, these findings disappeared, indicating that schizophrenia did not have a specific effect on BFCN relative to other regional volume changes. We replicated these findings in the independent cohort, e.g., BFCN volumes were lower in patients and mediated patients’ impaired SCT performance. Results demonstrate lower BFCN volumes in schizophrenia, which link with patients’ attentional deficits. Data suggest that a dysregulated cholinergic system might contribute to cognitive difficulties in schizophrenia via impaired BFCN. Springer International Publishing 2021-06-29 2021-12 /pmc/articles/PMC8580980/ /pubmed/34188186 http://dx.doi.org/10.1038/s41386-021-01070-x 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 Avram, Mihai Grothe, Michel J. Meinhold, Lena Leucht, Claudia Leucht, Stefan Borgwardt, Stefan Brandl, Felix Sorg, Christian Lower cholinergic basal forebrain volumes link with cognitive difficulties in schizophrenia |
title | Lower cholinergic basal forebrain volumes link with cognitive difficulties in schizophrenia |
title_full | Lower cholinergic basal forebrain volumes link with cognitive difficulties in schizophrenia |
title_fullStr | Lower cholinergic basal forebrain volumes link with cognitive difficulties in schizophrenia |
title_full_unstemmed | Lower cholinergic basal forebrain volumes link with cognitive difficulties in schizophrenia |
title_short | Lower cholinergic basal forebrain volumes link with cognitive difficulties in schizophrenia |
title_sort | lower cholinergic basal forebrain volumes link with cognitive difficulties in schizophrenia |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8580980/ https://www.ncbi.nlm.nih.gov/pubmed/34188186 http://dx.doi.org/10.1038/s41386-021-01070-x |
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