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

• Type of Material: Article
• Authors: Shota Nishitani, University of Fukui; Takashi Fujisawa, Emory University; Daiki Hiraoka, University of Fukui; Kai Makita, University of Fukui; Shinichiro Takiguchi, University of Fukui Hospital; Shoko Hamamura, University of Fukui; Akiko Yao, University of Fukui; Koji Shimada, University of Fukui; Alicia Smith, Emory University; Akemi Tomoda, University of Fukui
• Language: English
• Date: 2021-11-18
• Publisher: SPRINGERNATURE
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2021
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41398-021-01714-y
• Title of Journal or Parent Work: TRANSLATIONAL PSYCHIATRY
• Volume: 11
• Issue: 1
• Start Page: 589
• End Page: 589
• Keywords: GRAY-MATTER VOLUME; ADULTS; ASSOCIATION; ABUSE; REACTIVE ATTACHMENT DISORDER; SCALE; Science & Technology; BEHAVIOR; Psychiatry; CHILDHOOD MALTREATMENT; Life Sciences & Biomedicine; OFFENDERS
• Research Categories: Health Sciences, Obstetrics and Gynecology

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.