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Intrinsic functional connectivity in families genetically enriched for social anxiety disorder – an endophenotype study

BACKGROUND: Social anxiety disorder (SAD) is a serious psychiatric condition with a high prevalence, and a typical onset during childhood/adolescence. The condition runs in families, but it is largely unknown which neurobiological characteristics transfer this genetic vulnerability (‘endophenotypes’...

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Autores principales: Bas-Hoogendam, Janna Marie, van Steenbergen, Henk, Cohen Kadosh, Kathrin, Westenberg, P. Michiel, van der Wee, Nic J.A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237289/
https://www.ncbi.nlm.nih.gov/pubmed/34161885
http://dx.doi.org/10.1016/j.ebiom.2021.103445
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author Bas-Hoogendam, Janna Marie
van Steenbergen, Henk
Cohen Kadosh, Kathrin
Westenberg, P. Michiel
van der Wee, Nic J.A.
author_facet Bas-Hoogendam, Janna Marie
van Steenbergen, Henk
Cohen Kadosh, Kathrin
Westenberg, P. Michiel
van der Wee, Nic J.A.
author_sort Bas-Hoogendam, Janna Marie
collection PubMed
description BACKGROUND: Social anxiety disorder (SAD) is a serious psychiatric condition with a high prevalence, and a typical onset during childhood/adolescence. The condition runs in families, but it is largely unknown which neurobiological characteristics transfer this genetic vulnerability (‘endophenotypes’). Using data from the Leiden Family Lab study on SAD, including two generations of families genetically enriched for SAD, we investigated whether social anxiety (SA) co-segregated with changes in intrinsic functional connectivity (iFC), and examined heritability. METHODS: Functional MRI data were acquired during resting-state in 109 individuals (56 males; mean age: 31·5, range 9·2-61·5 years). FSL's tool MELODIC was used to perform independent component analysis. Six networks of interest (default mode, dorsal attention, executive control, frontoparietal, limbic and salience) were identified at the group-level and used to generate subject-specific spatial maps. Voxel-wise regression models, with SA-level as predictor and voxel-wise iFC as candidate endophenotypes, were performed to investigate the association with SA, within masks of the networks of interest. Subsequently, heritability was estimated. FINDINGS: SA co-segregated with iFC within the dorsal attention network (positive association in left middle frontal gyrus and right postcentral gyrus) and frontoparietal network (positive association within left middle temporal gyrus) (cluster-forming-threshold z>2·3, cluster-corrected extent-threshold p<0·05). Furthermore, iFC of multiple voxels within these clusters was at least moderately heritable. INTERPRETATION: These findings provide initial evidence for increased iFC as candidate endophenotype of SAD, particularly within networks involved in attention. These changes might underlie attentional biases commonly present in SAD. FUNDING: Leiden University Research Profile ‘Health, Prevention and the Human Lifecycle’.
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spelling pubmed-82372892021-06-29 Intrinsic functional connectivity in families genetically enriched for social anxiety disorder – an endophenotype study Bas-Hoogendam, Janna Marie van Steenbergen, Henk Cohen Kadosh, Kathrin Westenberg, P. Michiel van der Wee, Nic J.A. EBioMedicine Research Paper BACKGROUND: Social anxiety disorder (SAD) is a serious psychiatric condition with a high prevalence, and a typical onset during childhood/adolescence. The condition runs in families, but it is largely unknown which neurobiological characteristics transfer this genetic vulnerability (‘endophenotypes’). Using data from the Leiden Family Lab study on SAD, including two generations of families genetically enriched for SAD, we investigated whether social anxiety (SA) co-segregated with changes in intrinsic functional connectivity (iFC), and examined heritability. METHODS: Functional MRI data were acquired during resting-state in 109 individuals (56 males; mean age: 31·5, range 9·2-61·5 years). FSL's tool MELODIC was used to perform independent component analysis. Six networks of interest (default mode, dorsal attention, executive control, frontoparietal, limbic and salience) were identified at the group-level and used to generate subject-specific spatial maps. Voxel-wise regression models, with SA-level as predictor and voxel-wise iFC as candidate endophenotypes, were performed to investigate the association with SA, within masks of the networks of interest. Subsequently, heritability was estimated. FINDINGS: SA co-segregated with iFC within the dorsal attention network (positive association in left middle frontal gyrus and right postcentral gyrus) and frontoparietal network (positive association within left middle temporal gyrus) (cluster-forming-threshold z>2·3, cluster-corrected extent-threshold p<0·05). Furthermore, iFC of multiple voxels within these clusters was at least moderately heritable. INTERPRETATION: These findings provide initial evidence for increased iFC as candidate endophenotype of SAD, particularly within networks involved in attention. These changes might underlie attentional biases commonly present in SAD. FUNDING: Leiden University Research Profile ‘Health, Prevention and the Human Lifecycle’. Elsevier 2021-06-20 /pmc/articles/PMC8237289/ /pubmed/34161885 http://dx.doi.org/10.1016/j.ebiom.2021.103445 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
Bas-Hoogendam, Janna Marie
van Steenbergen, Henk
Cohen Kadosh, Kathrin
Westenberg, P. Michiel
van der Wee, Nic J.A.
Intrinsic functional connectivity in families genetically enriched for social anxiety disorder – an endophenotype study
title Intrinsic functional connectivity in families genetically enriched for social anxiety disorder – an endophenotype study
title_full Intrinsic functional connectivity in families genetically enriched for social anxiety disorder – an endophenotype study
title_fullStr Intrinsic functional connectivity in families genetically enriched for social anxiety disorder – an endophenotype study
title_full_unstemmed Intrinsic functional connectivity in families genetically enriched for social anxiety disorder – an endophenotype study
title_short Intrinsic functional connectivity in families genetically enriched for social anxiety disorder – an endophenotype study
title_sort intrinsic functional connectivity in families genetically enriched for social anxiety disorder – an endophenotype study
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237289/
https://www.ncbi.nlm.nih.gov/pubmed/34161885
http://dx.doi.org/10.1016/j.ebiom.2021.103445
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