Polygenic risk for obsessive-compulsive disorder (OCD) predicts brain response during working memory task in OCD, unaffected relatives, and healthy controls

Abstract Alterations in frontal and parietal neural activations during working memory task performance have been suggested as a candidate endophenotype of obsessive-compulsive disorder (OCD) in studies involving first-degree relatives. However, the direct link between genetic risk for OCD and neuro-...

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Autores principales:	Stephan Heinzel, Christian Kaufmann, Rosa Grützmann, Julia Klawohn, Anja Riesel, Katharina Bey, Stefanie Heilmann-Heimbach, Leonie Weinhold, Alfredo Ramirez, Michael Wagner, Norbert Kathmann
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/19edda6e47d94e4e8d34ab02204182a9
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spelling	oai:doaj.org-article:19edda6e47d94e4e8d34ab02204182a92021-12-02T17:27:02ZPolygenic risk for obsessive-compulsive disorder (OCD) predicts brain response during working memory task in OCD, unaffected relatives, and healthy controls10.1038/s41598-021-98333-w2045-2322https://doaj.org/article/19edda6e47d94e4e8d34ab02204182a92021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98333-whttps://doaj.org/toc/2045-2322Abstract Alterations in frontal and parietal neural activations during working memory task performance have been suggested as a candidate endophenotype of obsessive-compulsive disorder (OCD) in studies involving first-degree relatives. However, the direct link between genetic risk for OCD and neuro-functional alterations during working memory performance has not been investigated to date. Thus, the aim of the current functional magnetic resonance imaging (fMRI) study was to test the direct association between polygenic risk for OCD and neural activity during the performance of a numeric n-back task with four working memory load conditions in 128 participants, including patients with OCD, unaffected first-degree relatives of OCD patients, and healthy controls. Behavioral results show a significant performance deficit at high working memory load in both patients with OCD and first-degree relatives (p < 0.05). A whole-brain analysis of the fMRI data indicated decreased neural activity in bilateral inferior parietal lobule and dorsolateral prefrontal cortex in both patients and relatives. Most importantly, OCD polygenic risk scores predicted neural activity in orbitofrontal cortex. Results indicate that genetic risk for OCD can partly explain alterations in brain response during working memory performance, supporting the notion of a neuro-functional endophenotype for OCD.Stephan HeinzelChristian KaufmannRosa GrützmannJulia KlawohnAnja RieselKatharina BeyStefanie Heilmann-HeimbachLeonie WeinholdAlfredo RamirezMichael WagnerNorbert KathmannNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Stephan Heinzel Christian Kaufmann Rosa Grützmann Julia Klawohn Anja Riesel Katharina Bey Stefanie Heilmann-Heimbach Leonie Weinhold Alfredo Ramirez Michael Wagner Norbert Kathmann Polygenic risk for obsessive-compulsive disorder (OCD) predicts brain response during working memory task in OCD, unaffected relatives, and healthy controls
description	Abstract Alterations in frontal and parietal neural activations during working memory task performance have been suggested as a candidate endophenotype of obsessive-compulsive disorder (OCD) in studies involving first-degree relatives. However, the direct link between genetic risk for OCD and neuro-functional alterations during working memory performance has not been investigated to date. Thus, the aim of the current functional magnetic resonance imaging (fMRI) study was to test the direct association between polygenic risk for OCD and neural activity during the performance of a numeric n-back task with four working memory load conditions in 128 participants, including patients with OCD, unaffected first-degree relatives of OCD patients, and healthy controls. Behavioral results show a significant performance deficit at high working memory load in both patients with OCD and first-degree relatives (p < 0.05). A whole-brain analysis of the fMRI data indicated decreased neural activity in bilateral inferior parietal lobule and dorsolateral prefrontal cortex in both patients and relatives. Most importantly, OCD polygenic risk scores predicted neural activity in orbitofrontal cortex. Results indicate that genetic risk for OCD can partly explain alterations in brain response during working memory performance, supporting the notion of a neuro-functional endophenotype for OCD.
format	article
author	Stephan Heinzel Christian Kaufmann Rosa Grützmann Julia Klawohn Anja Riesel Katharina Bey Stefanie Heilmann-Heimbach Leonie Weinhold Alfredo Ramirez Michael Wagner Norbert Kathmann
author_facet	Stephan Heinzel Christian Kaufmann Rosa Grützmann Julia Klawohn Anja Riesel Katharina Bey Stefanie Heilmann-Heimbach Leonie Weinhold Alfredo Ramirez Michael Wagner Norbert Kathmann
author_sort	Stephan Heinzel
title	Polygenic risk for obsessive-compulsive disorder (OCD) predicts brain response during working memory task in OCD, unaffected relatives, and healthy controls
title_short	Polygenic risk for obsessive-compulsive disorder (OCD) predicts brain response during working memory task in OCD, unaffected relatives, and healthy controls
title_full	Polygenic risk for obsessive-compulsive disorder (OCD) predicts brain response during working memory task in OCD, unaffected relatives, and healthy controls
title_fullStr	Polygenic risk for obsessive-compulsive disorder (OCD) predicts brain response during working memory task in OCD, unaffected relatives, and healthy controls
title_full_unstemmed	Polygenic risk for obsessive-compulsive disorder (OCD) predicts brain response during working memory task in OCD, unaffected relatives, and healthy controls
title_sort	polygenic risk for obsessive-compulsive disorder (ocd) predicts brain response during working memory task in ocd, unaffected relatives, and healthy controls
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/19edda6e47d94e4e8d34ab02204182a9
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Polygenic risk for obsessive-compulsive disorder (OCD) predicts brain response during working memory task in OCD, unaffected relatives, and healthy controls

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