Cargando…

Evidence for Schizophrenia-Specific Pathophysiology of Nicotine Dependence

Tobacco use is the top preventable cause of early mortality in schizophrenia. Over 60% of people with schizophrenia smoke, three times the general prevalence. The biological basis of this increased risk is not understood, and existing interventions do not target schizophrenia-specific pathology. We...

Descripción completa

Detalles Bibliográficos
Autores principales: Ward, Heather Burrell, Beermann, Adam, Nawaz, Uzma, Halko, Mark A., Janes, Amy C., Moran, Lauren V., Brady, Roscoe O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829345/
https://www.ncbi.nlm.nih.gov/pubmed/35153877
http://dx.doi.org/10.3389/fpsyt.2022.804055
_version_ 1784648058338803712
author Ward, Heather Burrell
Beermann, Adam
Nawaz, Uzma
Halko, Mark A.
Janes, Amy C.
Moran, Lauren V.
Brady, Roscoe O.
author_facet Ward, Heather Burrell
Beermann, Adam
Nawaz, Uzma
Halko, Mark A.
Janes, Amy C.
Moran, Lauren V.
Brady, Roscoe O.
author_sort Ward, Heather Burrell
collection PubMed
description Tobacco use is the top preventable cause of early mortality in schizophrenia. Over 60% of people with schizophrenia smoke, three times the general prevalence. The biological basis of this increased risk is not understood, and existing interventions do not target schizophrenia-specific pathology. We therefore used a connectome-wide analysis to identify schizophrenia-specific circuits of nicotine addiction. We reanalyzed data from two studies: In Cohort 1, 35 smokers (18 schizophrenia, 17 control) underwent resting-state fMRI and clinical characterization. A multivariate pattern analysis of whole-connectome data was used to identify the strongest links between cigarette use and functional connectivity. In Cohort 2, 12 schizophrenia participants and 12 controls were enrolled in a randomized, controlled crossover study of nicotine patch with resting-state fMRI. We correlated change in network functional connectivity with nicotine dose. In Cohort 1, the strongest (p < 0.001) correlate between connectivity and cigarette use was driven by individual variation in default mode network (DMN) topography. In individuals with greater daily cigarette consumption, we observed a pathological expansion of the DMN territory into the identified parieto-occipital region, while in individuals with lower daily cigarette consumption, this region was external to the DMN. This effect was entirely driven by schizophrenia participants. Given the relationship between DMN topography and nicotine use we observed in Cohort 1, we sought to directly test the impact of nicotine on this network using an independent second cohort. In Cohort 2, nicotine reduced DMN connectivity in a dose-dependent manner (R = −0.50; 95% CI −0.75 to −0.12, p < 0.05). In the placebo condition, schizophrenia subjects had hyperconnectivity compared to controls (p < 0.05). Nicotine administration normalized DMN hyperconnectivity in schizophrenia. We here provide direct evidence that the biological basis of nicotine dependence is different in schizophrenia and in non-schizophrenia populations. Our results suggest the high prevalence of nicotine use in schizophrenia may be an attempt to correct a network deficit known to interfere with cognition.
format Online
Article
Text
id pubmed-8829345
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-88293452022-02-11 Evidence for Schizophrenia-Specific Pathophysiology of Nicotine Dependence Ward, Heather Burrell Beermann, Adam Nawaz, Uzma Halko, Mark A. Janes, Amy C. Moran, Lauren V. Brady, Roscoe O. Front Psychiatry Psychiatry Tobacco use is the top preventable cause of early mortality in schizophrenia. Over 60% of people with schizophrenia smoke, three times the general prevalence. The biological basis of this increased risk is not understood, and existing interventions do not target schizophrenia-specific pathology. We therefore used a connectome-wide analysis to identify schizophrenia-specific circuits of nicotine addiction. We reanalyzed data from two studies: In Cohort 1, 35 smokers (18 schizophrenia, 17 control) underwent resting-state fMRI and clinical characterization. A multivariate pattern analysis of whole-connectome data was used to identify the strongest links between cigarette use and functional connectivity. In Cohort 2, 12 schizophrenia participants and 12 controls were enrolled in a randomized, controlled crossover study of nicotine patch with resting-state fMRI. We correlated change in network functional connectivity with nicotine dose. In Cohort 1, the strongest (p < 0.001) correlate between connectivity and cigarette use was driven by individual variation in default mode network (DMN) topography. In individuals with greater daily cigarette consumption, we observed a pathological expansion of the DMN territory into the identified parieto-occipital region, while in individuals with lower daily cigarette consumption, this region was external to the DMN. This effect was entirely driven by schizophrenia participants. Given the relationship between DMN topography and nicotine use we observed in Cohort 1, we sought to directly test the impact of nicotine on this network using an independent second cohort. In Cohort 2, nicotine reduced DMN connectivity in a dose-dependent manner (R = −0.50; 95% CI −0.75 to −0.12, p < 0.05). In the placebo condition, schizophrenia subjects had hyperconnectivity compared to controls (p < 0.05). Nicotine administration normalized DMN hyperconnectivity in schizophrenia. We here provide direct evidence that the biological basis of nicotine dependence is different in schizophrenia and in non-schizophrenia populations. Our results suggest the high prevalence of nicotine use in schizophrenia may be an attempt to correct a network deficit known to interfere with cognition. Frontiers Media S.A. 2022-01-27 /pmc/articles/PMC8829345/ /pubmed/35153877 http://dx.doi.org/10.3389/fpsyt.2022.804055 Text en Copyright © 2022 Ward, Beermann, Nawaz, Halko, Janes, Moran and Brady. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Psychiatry
Ward, Heather Burrell
Beermann, Adam
Nawaz, Uzma
Halko, Mark A.
Janes, Amy C.
Moran, Lauren V.
Brady, Roscoe O.
Evidence for Schizophrenia-Specific Pathophysiology of Nicotine Dependence
title Evidence for Schizophrenia-Specific Pathophysiology of Nicotine Dependence
title_full Evidence for Schizophrenia-Specific Pathophysiology of Nicotine Dependence
title_fullStr Evidence for Schizophrenia-Specific Pathophysiology of Nicotine Dependence
title_full_unstemmed Evidence for Schizophrenia-Specific Pathophysiology of Nicotine Dependence
title_short Evidence for Schizophrenia-Specific Pathophysiology of Nicotine Dependence
title_sort evidence for schizophrenia-specific pathophysiology of nicotine dependence
topic Psychiatry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829345/
https://www.ncbi.nlm.nih.gov/pubmed/35153877
http://dx.doi.org/10.3389/fpsyt.2022.804055
work_keys_str_mv AT wardheatherburrell evidenceforschizophreniaspecificpathophysiologyofnicotinedependence
AT beermannadam evidenceforschizophreniaspecificpathophysiologyofnicotinedependence
AT nawazuzma evidenceforschizophreniaspecificpathophysiologyofnicotinedependence
AT halkomarka evidenceforschizophreniaspecificpathophysiologyofnicotinedependence
AT janesamyc evidenceforschizophreniaspecificpathophysiologyofnicotinedependence
AT moranlaurenv evidenceforschizophreniaspecificpathophysiologyofnicotinedependence
AT bradyroscoeo evidenceforschizophreniaspecificpathophysiologyofnicotinedependence