A multi-modal MRI analysis of brain structure and function in relation to OXT methylation in maltreated children and adolescents

Abstract Child maltreatment dysregulates the brain’s oxytocinergic system, resulting in dysfunctional attachment patterns. However, how the oxytocinergic system in children who are maltreated (CM) is epigenetically affected remains unknown. We assessed differences in salivary DNA methylation of the...

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Autores principales:	Shota Nishitani, Takashi X. Fujisawa, Daiki Hiraoka, Kai Makita, Shinichiro Takiguchi, Shoko Hamamura, Akiko Yao, Koji Shimada, Alicia K. Smith, Akemi Tomoda
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/d62096f3e93e49ccbdef704675743504
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spelling	oai:doaj.org-article:d62096f3e93e49ccbdef7046757435042021-11-21T12:07:50ZA multi-modal MRI analysis of brain structure and function in relation to OXT methylation in maltreated children and adolescents10.1038/s41398-021-01714-y2158-3188https://doaj.org/article/d62096f3e93e49ccbdef7046757435042021-11-01T00:00:00Zhttps://doi.org/10.1038/s41398-021-01714-yhttps://doaj.org/toc/2158-3188Abstract Child maltreatment dysregulates the brain’s oxytocinergic system, resulting in dysfunctional attachment patterns. However, how the oxytocinergic system in children who are maltreated (CM) is epigenetically affected remains unknown. We assessed differences in salivary DNA methylation of the gene encoding oxytocin (OXT) between CM (n = 24) and non-CM (n = 31), alongside its impact on brain structures and functions using multi-modal brain imaging (voxel-based morphometry, diffusion tensor imaging, and task and resting-state functional magnetic resonance imaging). We found that CM showed higher promoter methylation than non-CM, and nine CpG sites were observed to be correlated with each other and grouped into one index (OXTmi). OXTmi was significantly negatively correlated with gray matter volume (GMV) in the left superior parietal lobule (SPL), and with right putamen activation during a rewarding task, but not with white matter structures. Using a random forest regression model, we investigated the sensitive period and type of maltreatment that contributed the most to OXTmi in CM, revealing that they were 5–8 years of age and physical abuse (PA), respectively. However, the presence of PA (PA+) was meant to reflect more severe cases, such as prolonged exposure to multiple types of abuse, than the absence of PA. PA+ was associated with significantly greater functional connectivity between the right putamen set as the seed and the left SPL and the left cerebellum exterior. The results suggest that OXT promoter hypermethylation may lead to the atypical development of reward and visual association structures and functions, thereby potentially worsening clinical aspects raised by traumatic experiences.Shota NishitaniTakashi X. FujisawaDaiki HiraokaKai MakitaShinichiro TakiguchiShoko HamamuraAkiko YaoKoji ShimadaAlicia K. SmithAkemi TomodaNature Publishing GrouparticleNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENTranslational Psychiatry, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Shota Nishitani Takashi X. Fujisawa Daiki Hiraoka Kai Makita Shinichiro Takiguchi Shoko Hamamura Akiko Yao Koji Shimada Alicia K. Smith Akemi Tomoda A multi-modal MRI analysis of brain structure and function in relation to OXT methylation in maltreated children and adolescents
description	Abstract Child maltreatment dysregulates the brain’s oxytocinergic system, resulting in dysfunctional attachment patterns. However, how the oxytocinergic system in children who are maltreated (CM) is epigenetically affected remains unknown. We assessed differences in salivary DNA methylation of the gene encoding oxytocin (OXT) between CM (n = 24) and non-CM (n = 31), alongside its impact on brain structures and functions using multi-modal brain imaging (voxel-based morphometry, diffusion tensor imaging, and task and resting-state functional magnetic resonance imaging). We found that CM showed higher promoter methylation than non-CM, and nine CpG sites were observed to be correlated with each other and grouped into one index (OXTmi). OXTmi was significantly negatively correlated with gray matter volume (GMV) in the left superior parietal lobule (SPL), and with right putamen activation during a rewarding task, but not with white matter structures. Using a random forest regression model, we investigated the sensitive period and type of maltreatment that contributed the most to OXTmi in CM, revealing that they were 5–8 years of age and physical abuse (PA), respectively. However, the presence of PA (PA+) was meant to reflect more severe cases, such as prolonged exposure to multiple types of abuse, than the absence of PA. PA+ was associated with significantly greater functional connectivity between the right putamen set as the seed and the left SPL and the left cerebellum exterior. The results suggest that OXT promoter hypermethylation may lead to the atypical development of reward and visual association structures and functions, thereby potentially worsening clinical aspects raised by traumatic experiences.
format	article
author	Shota Nishitani Takashi X. Fujisawa Daiki Hiraoka Kai Makita Shinichiro Takiguchi Shoko Hamamura Akiko Yao Koji Shimada Alicia K. Smith Akemi Tomoda
author_facet	Shota Nishitani Takashi X. Fujisawa Daiki Hiraoka Kai Makita Shinichiro Takiguchi Shoko Hamamura Akiko Yao Koji Shimada Alicia K. Smith Akemi Tomoda
author_sort	Shota Nishitani
title	A multi-modal MRI analysis of brain structure and function in relation to OXT methylation in maltreated children and adolescents
title_short	A multi-modal MRI analysis of brain structure and function in relation to OXT methylation in maltreated children and adolescents
title_full	A multi-modal MRI analysis of brain structure and function in relation to OXT methylation in maltreated children and adolescents
title_fullStr	A multi-modal MRI analysis of brain structure and function in relation to OXT methylation in maltreated children and adolescents
title_full_unstemmed	A multi-modal MRI analysis of brain structure and function in relation to OXT methylation in maltreated children and adolescents
title_sort	multi-modal mri analysis of brain structure and function in relation to oxt methylation in maltreated children and adolescents
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/d62096f3e93e49ccbdef704675743504
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A multi-modal MRI analysis of brain structure and function in relation to OXT methylation in maltreated children and adolescents

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