A voxel-level brain-wide association study of cortisol at 8 a.m.: Evidence from Cushing's disease

Cortisol, the end product of the hypothalamic–pituitary–adrenal axis, regulates cognitive function and emotion processing. Cushing's disease, which is characterized by a unique excess of cortisol upon clinical diagnosis, serve as an excellent in vivo “hyperexpression” model to investigate the n...

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Autores principales:	Yanyang Zhang, Tao Zhou, Shiyu Feng, Xinyun Liu, Fuyu Wang, Zhiqiang Sha, Xinguang Yu
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Cortisol Functional magnetic resonance imaging Gene expression Connectivity Cognition Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Neurophysiology and neuropsychology QP351-495
Acceso en línea:	https://doaj.org/article/a2ef2cd0987c468f914543490d2a808d
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spelling	oai:doaj.org-article:a2ef2cd0987c468f914543490d2a808d2021-11-06T04:30:07ZA voxel-level brain-wide association study of cortisol at 8 a.m.: Evidence from Cushing's disease2352-289510.1016/j.ynstr.2021.100414https://doaj.org/article/a2ef2cd0987c468f914543490d2a808d2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2352289521001223https://doaj.org/toc/2352-2895Cortisol, the end product of the hypothalamic–pituitary–adrenal axis, regulates cognitive function and emotion processing. Cushing's disease, which is characterized by a unique excess of cortisol upon clinical diagnosis, serve as an excellent in vivo “hyperexpression” model to investigate the neurobiological mechanisms of cortisol in the human brain. Previous studies have shown the association between cortisol and functional connectivity within an a priori brain network. However, the whole-brain connectivity pattern that accompanies endogenous cortisol variation is still unclear, as are its associated genetic underpinnings. Here, using resting-state functional magnetic resonance imaging in 112 subjects (60 patients with Cushing's disease and 52 healthy subjects), we performed a voxel-level brain-wide association analysis to investigate the functional connectivity pattern associated with a wide variation in cortisol levels at 8 a.m. The results showed that the regions associated with cortisol as of 8 a.m. were primarily distributed in brain functional hubs involved in self-referential processing, such as the medial prefrontal cortex, anterior and posterior cingulate cortex, and caudate. We also found that regions in the middle temporal, inferior parietal and ventrolateral prefrontal cortex, which is important for social communication tasks, and in the visual and supplementary motor cortex, which is involved in primary sensorimotor perception, were adversely affected by excessive cortisol. The connectivity between these regions was also significantly correlated with neuropsychiatric profiles, such anxiety and depression. Finally, combined neuroimaging and transcriptome analysis showed that functional cortisol-sensitive brain variations were significantly coupled to regional expression of glucocorticoid and mineralocorticoid receptors. These findings reveal cortisol-biased functional signatures in the human brain and shed light on the transcriptional regulation constraints on the cortisol-related brain network.Yanyang ZhangTao ZhouShiyu FengXinyun LiuFuyu WangZhiqiang ShaXinguang YuElsevierarticleCortisolFunctional magnetic resonance imagingGene expressionConnectivityCognitionNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429Neurophysiology and neuropsychologyQP351-495ENNeurobiology of Stress, Vol 15, Iss , Pp 100414- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cortisol Functional magnetic resonance imaging Gene expression Connectivity Cognition Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Neurophysiology and neuropsychology QP351-495
spellingShingle	Cortisol Functional magnetic resonance imaging Gene expression Connectivity Cognition Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Neurophysiology and neuropsychology QP351-495 Yanyang Zhang Tao Zhou Shiyu Feng Xinyun Liu Fuyu Wang Zhiqiang Sha Xinguang Yu A voxel-level brain-wide association study of cortisol at 8 a.m.: Evidence from Cushing's disease
description	Cortisol, the end product of the hypothalamic–pituitary–adrenal axis, regulates cognitive function and emotion processing. Cushing's disease, which is characterized by a unique excess of cortisol upon clinical diagnosis, serve as an excellent in vivo “hyperexpression” model to investigate the neurobiological mechanisms of cortisol in the human brain. Previous studies have shown the association between cortisol and functional connectivity within an a priori brain network. However, the whole-brain connectivity pattern that accompanies endogenous cortisol variation is still unclear, as are its associated genetic underpinnings. Here, using resting-state functional magnetic resonance imaging in 112 subjects (60 patients with Cushing's disease and 52 healthy subjects), we performed a voxel-level brain-wide association analysis to investigate the functional connectivity pattern associated with a wide variation in cortisol levels at 8 a.m. The results showed that the regions associated with cortisol as of 8 a.m. were primarily distributed in brain functional hubs involved in self-referential processing, such as the medial prefrontal cortex, anterior and posterior cingulate cortex, and caudate. We also found that regions in the middle temporal, inferior parietal and ventrolateral prefrontal cortex, which is important for social communication tasks, and in the visual and supplementary motor cortex, which is involved in primary sensorimotor perception, were adversely affected by excessive cortisol. The connectivity between these regions was also significantly correlated with neuropsychiatric profiles, such anxiety and depression. Finally, combined neuroimaging and transcriptome analysis showed that functional cortisol-sensitive brain variations were significantly coupled to regional expression of glucocorticoid and mineralocorticoid receptors. These findings reveal cortisol-biased functional signatures in the human brain and shed light on the transcriptional regulation constraints on the cortisol-related brain network.
format	article
author	Yanyang Zhang Tao Zhou Shiyu Feng Xinyun Liu Fuyu Wang Zhiqiang Sha Xinguang Yu
author_facet	Yanyang Zhang Tao Zhou Shiyu Feng Xinyun Liu Fuyu Wang Zhiqiang Sha Xinguang Yu
author_sort	Yanyang Zhang
title	A voxel-level brain-wide association study of cortisol at 8 a.m.: Evidence from Cushing's disease
title_short	A voxel-level brain-wide association study of cortisol at 8 a.m.: Evidence from Cushing's disease
title_full	A voxel-level brain-wide association study of cortisol at 8 a.m.: Evidence from Cushing's disease
title_fullStr	A voxel-level brain-wide association study of cortisol at 8 a.m.: Evidence from Cushing's disease
title_full_unstemmed	A voxel-level brain-wide association study of cortisol at 8 a.m.: Evidence from Cushing's disease
title_sort	voxel-level brain-wide association study of cortisol at 8 a.m.: evidence from cushing's disease
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/a2ef2cd0987c468f914543490d2a808d
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A voxel-level brain-wide association study of cortisol at 8 a.m.: Evidence from Cushing's disease

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