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The Effects of Psychosis Risk Variants on Brain Connectivity: A Review
In light of observed changes in connectivity in schizophrenia and the highly heritable nature of the disease, neural connectivity may serve as an important intermediate phenotype for schizophrenia. However, how individual variants confer altered connectivity and which measure of brain connectivity i...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Research Foundation
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3299399/ https://www.ncbi.nlm.nih.gov/pubmed/22416237 http://dx.doi.org/10.3389/fpsyt.2012.00018 |
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author | Mothersill, Omar Kelly, Sinead Rose, Emma Jane Donohoe, Gary |
author_facet | Mothersill, Omar Kelly, Sinead Rose, Emma Jane Donohoe, Gary |
author_sort | Mothersill, Omar |
collection | PubMed |
description | In light of observed changes in connectivity in schizophrenia and the highly heritable nature of the disease, neural connectivity may serve as an important intermediate phenotype for schizophrenia. However, how individual variants confer altered connectivity and which measure of brain connectivity is more proximal to the underlying genetic architecture (i.e., functional or structural) has not been well delineated. In this review we consider these issues and the relative sensitivity of imaging methodologies to schizophrenia-related changes in connectivity. We searched PubMed for studies considering schizophrenia risk genes AND functional or structural connectivity. Where data was available, summary statistics were used to determine an estimate of effect size (i.e., Cohen’s d). A random-effects meta-analysis was used to consider (1) the largest effect and (2) all significant effects between functional and structural studies. Schizophrenia risk variants involved in neurotransmission, neurodevelopment and myelin function were found to be associated with altered neural connectivity. On average, schizophrenia risk genes had a large effect on functional (mean d = 0.76) and structural connectivity (mean d = 1.04). The examination of the largest effect size indicated that the outcomes of functional and structural studies were comparable (Q = 2.17, p > 0.05). Conversely, consideration of effect size estimates for all significant effects suggest that reported effect sizes in structural connectivity studies were more variable than in functional connectivity studies, and that there was a significant lack of homogeneity across the modalities (Q = 6.928, p = 0.008). Given the more variable profile of effect sizes associated with structural connectivity, these data may suggest that structural imaging methods are more sensitive to a wider range of effects, as opposed to functional studies which may only be able to determine large effects. These conclusions are limited by methodological considerations, and require further investigation involving larger samples, multiple genes, and novel analysis techniques for confirmation. |
format | Online Article Text |
id | pubmed-3299399 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Frontiers Research Foundation |
record_format | MEDLINE/PubMed |
spelling | pubmed-32993992012-03-13 The Effects of Psychosis Risk Variants on Brain Connectivity: A Review Mothersill, Omar Kelly, Sinead Rose, Emma Jane Donohoe, Gary Front Psychiatry Psychiatry In light of observed changes in connectivity in schizophrenia and the highly heritable nature of the disease, neural connectivity may serve as an important intermediate phenotype for schizophrenia. However, how individual variants confer altered connectivity and which measure of brain connectivity is more proximal to the underlying genetic architecture (i.e., functional or structural) has not been well delineated. In this review we consider these issues and the relative sensitivity of imaging methodologies to schizophrenia-related changes in connectivity. We searched PubMed for studies considering schizophrenia risk genes AND functional or structural connectivity. Where data was available, summary statistics were used to determine an estimate of effect size (i.e., Cohen’s d). A random-effects meta-analysis was used to consider (1) the largest effect and (2) all significant effects between functional and structural studies. Schizophrenia risk variants involved in neurotransmission, neurodevelopment and myelin function were found to be associated with altered neural connectivity. On average, schizophrenia risk genes had a large effect on functional (mean d = 0.76) and structural connectivity (mean d = 1.04). The examination of the largest effect size indicated that the outcomes of functional and structural studies were comparable (Q = 2.17, p > 0.05). Conversely, consideration of effect size estimates for all significant effects suggest that reported effect sizes in structural connectivity studies were more variable than in functional connectivity studies, and that there was a significant lack of homogeneity across the modalities (Q = 6.928, p = 0.008). Given the more variable profile of effect sizes associated with structural connectivity, these data may suggest that structural imaging methods are more sensitive to a wider range of effects, as opposed to functional studies which may only be able to determine large effects. These conclusions are limited by methodological considerations, and require further investigation involving larger samples, multiple genes, and novel analysis techniques for confirmation. Frontiers Research Foundation 2012-03-09 /pmc/articles/PMC3299399/ /pubmed/22416237 http://dx.doi.org/10.3389/fpsyt.2012.00018 Text en Copyright © 2012 Mothersill, Kelly, Rose and Donohoe. http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited. |
spellingShingle | Psychiatry Mothersill, Omar Kelly, Sinead Rose, Emma Jane Donohoe, Gary The Effects of Psychosis Risk Variants on Brain Connectivity: A Review |
title | The Effects of Psychosis Risk Variants on Brain Connectivity: A Review |
title_full | The Effects of Psychosis Risk Variants on Brain Connectivity: A Review |
title_fullStr | The Effects of Psychosis Risk Variants on Brain Connectivity: A Review |
title_full_unstemmed | The Effects of Psychosis Risk Variants on Brain Connectivity: A Review |
title_short | The Effects of Psychosis Risk Variants on Brain Connectivity: A Review |
title_sort | effects of psychosis risk variants on brain connectivity: a review |
topic | Psychiatry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3299399/ https://www.ncbi.nlm.nih.gov/pubmed/22416237 http://dx.doi.org/10.3389/fpsyt.2012.00018 |
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