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The relationship between childhood trauma, dopamine release and dexamphetamine-induced positive psychotic symptoms: a [(11)C]-(+)-PHNO PET study
Childhood trauma is a risk factor for psychosis. Amphetamine increases synaptic striatal dopamine levels and can induce positive psychotic symptoms in healthy individuals and patients with schizophrenia. Socio-developmental hypotheses of psychosis propose that childhood trauma and other environmenta...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6848217/ https://www.ncbi.nlm.nih.gov/pubmed/31712556 http://dx.doi.org/10.1038/s41398-019-0627-y |
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author | Dahoun, Tarik Nour, Matthew M. McCutcheon, Robert A. Adams, Rick A. Bloomfield, Michael A. P. Howes, Oliver D. |
author_facet | Dahoun, Tarik Nour, Matthew M. McCutcheon, Robert A. Adams, Rick A. Bloomfield, Michael A. P. Howes, Oliver D. |
author_sort | Dahoun, Tarik |
collection | PubMed |
description | Childhood trauma is a risk factor for psychosis. Amphetamine increases synaptic striatal dopamine levels and can induce positive psychotic symptoms in healthy individuals and patients with schizophrenia. Socio-developmental hypotheses of psychosis propose that childhood trauma and other environmental risk factors sensitize the dopamine system to increase the risk of psychotic symptoms, but this remains to be tested in humans. We used [(11)C]-(+)-PHNO positron emission tomography to measure striatal dopamine-2/3 receptor (D(2/3)R) availability and ventral striatal dexamphetamine-induced dopamine release in healthy participants (n = 24). The relationships between dexamphetamine-induced dopamine release, dexamphetamine-induced positive psychotic symptoms using the Positive and Negative Syndrome Scale (PANSS), and childhood trauma using the Childhood Trauma Questionnaire (CTQ) were assessed using linear regression and mediation analyses, with childhood trauma as the independent variable, dexamphetamine-induced dopamine release as the mediator variable, and dexamphetamine-induced symptoms as the dependent variable. There was a significant interaction between childhood trauma and ventral striatal dopamine release in predicting dexamphetamine-induced positive psychotic symptoms (standardized β = 1.83, p = 0.003), but a mediation analysis was not significant (standardized β = −0.18, p = 0.158). There were no significant effects of dopamine release and childhood trauma on change in negative (p = 0.280) or general PANSS symptoms (p = 0.061), and there was no relationship between ventral striatal baseline D(2/3)R availability and positive symptoms (p = 0.368). This indicates childhood trauma and dopamine release interact to influence the induction of positive psychotic symptoms. This is not consistent with a simple sensitization hypothesis, but suggests that childhood trauma moderates the cognitive response to dopamine release to make psychotic experiences more likely. |
format | Online Article Text |
id | pubmed-6848217 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-68482172019-11-14 The relationship between childhood trauma, dopamine release and dexamphetamine-induced positive psychotic symptoms: a [(11)C]-(+)-PHNO PET study Dahoun, Tarik Nour, Matthew M. McCutcheon, Robert A. Adams, Rick A. Bloomfield, Michael A. P. Howes, Oliver D. Transl Psychiatry Article Childhood trauma is a risk factor for psychosis. Amphetamine increases synaptic striatal dopamine levels and can induce positive psychotic symptoms in healthy individuals and patients with schizophrenia. Socio-developmental hypotheses of psychosis propose that childhood trauma and other environmental risk factors sensitize the dopamine system to increase the risk of psychotic symptoms, but this remains to be tested in humans. We used [(11)C]-(+)-PHNO positron emission tomography to measure striatal dopamine-2/3 receptor (D(2/3)R) availability and ventral striatal dexamphetamine-induced dopamine release in healthy participants (n = 24). The relationships between dexamphetamine-induced dopamine release, dexamphetamine-induced positive psychotic symptoms using the Positive and Negative Syndrome Scale (PANSS), and childhood trauma using the Childhood Trauma Questionnaire (CTQ) were assessed using linear regression and mediation analyses, with childhood trauma as the independent variable, dexamphetamine-induced dopamine release as the mediator variable, and dexamphetamine-induced symptoms as the dependent variable. There was a significant interaction between childhood trauma and ventral striatal dopamine release in predicting dexamphetamine-induced positive psychotic symptoms (standardized β = 1.83, p = 0.003), but a mediation analysis was not significant (standardized β = −0.18, p = 0.158). There were no significant effects of dopamine release and childhood trauma on change in negative (p = 0.280) or general PANSS symptoms (p = 0.061), and there was no relationship between ventral striatal baseline D(2/3)R availability and positive symptoms (p = 0.368). This indicates childhood trauma and dopamine release interact to influence the induction of positive psychotic symptoms. This is not consistent with a simple sensitization hypothesis, but suggests that childhood trauma moderates the cognitive response to dopamine release to make psychotic experiences more likely. Nature Publishing Group UK 2019-11-11 /pmc/articles/PMC6848217/ /pubmed/31712556 http://dx.doi.org/10.1038/s41398-019-0627-y Text en © The Author(s) 2019 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/. |
spellingShingle | Article Dahoun, Tarik Nour, Matthew M. McCutcheon, Robert A. Adams, Rick A. Bloomfield, Michael A. P. Howes, Oliver D. The relationship between childhood trauma, dopamine release and dexamphetamine-induced positive psychotic symptoms: a [(11)C]-(+)-PHNO PET study |
title | The relationship between childhood trauma, dopamine release and dexamphetamine-induced positive psychotic symptoms: a [(11)C]-(+)-PHNO PET study |
title_full | The relationship between childhood trauma, dopamine release and dexamphetamine-induced positive psychotic symptoms: a [(11)C]-(+)-PHNO PET study |
title_fullStr | The relationship between childhood trauma, dopamine release and dexamphetamine-induced positive psychotic symptoms: a [(11)C]-(+)-PHNO PET study |
title_full_unstemmed | The relationship between childhood trauma, dopamine release and dexamphetamine-induced positive psychotic symptoms: a [(11)C]-(+)-PHNO PET study |
title_short | The relationship between childhood trauma, dopamine release and dexamphetamine-induced positive psychotic symptoms: a [(11)C]-(+)-PHNO PET study |
title_sort | relationship between childhood trauma, dopamine release and dexamphetamine-induced positive psychotic symptoms: a [(11)c]-(+)-phno pet study |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6848217/ https://www.ncbi.nlm.nih.gov/pubmed/31712556 http://dx.doi.org/10.1038/s41398-019-0627-y |
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