Department of Psychiatry, School of Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan; Department of Psychiatry, University of Iowa, Iowa City, Iowa, USA.
Department of Psychiatry, University of Iowa, Iowa City, Iowa, USA; Department of Neurosurgery, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA; Iowa Neuroscience Institute, University of Iowa, Iowa City, Iowa, USA; Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, Iowa, USA.
J Affect Disord. 2020 Jul 1;272:417-422. doi: 10.1016/j.jad.2020.03.120. Epub 2020 Apr 29.
Child abuse is a risk factor for mood disorders, and linked to decreased DNA methylation (DNAm) of FKBP5 intron 7 through interactions with the single nucleotide polymorphism (SNP) rs1360780. However, no study has investigated which specific subtypes of child abuse are related to decreased DNAm of FKBP5 intron 7 in mood disorders. We therefore aimed to examine the relationship among various subtypes of child abuse, rs1360780, and the DNAm level of FKBP5 intron 7.
A total of 190 subjects (87 patients with major depressive disorder [MDD], 61 patients with bipolar disorder [BD], and 42 healthy controls) participated. The Child Abuse and Trauma Scale (CATS) was used to evaluate child abuse. Whole blood was processed for genotyping, and pyrosequencing was conducted to assess the DNAm level of FKBP5 intron 7. A multiple regression analysis was used to analyze the DNAm level as a dependent variable, and the CATS subtypes and rs1360780 were used as independent variables.
Emotional abuse/neglect, one of the specific subtypes of child abuse, was related to lower DNAm of FKBP5 intron 7 interacting with rs1360780 in the BD patients. There were no significant results in the MDD patients or the controls.
Since the study was limited to Japanese individuals, particularly those with MDD and BD, the findings are not generalizable. Furthermore, as child abuse was measured retrospectively, there may be recall bias.
This finding indicates that a specific subtype of child abuse may play an important role in the development of BD.
儿童虐待是心境障碍的一个风险因素，并且通过与单核苷酸多态性（SNP）rs1360780 的相互作用，导致 FKBP5 内含子 7 的 DNA 甲基化（DNAm）减少。然而，尚无研究调查哪种特定类型的儿童虐待与心境障碍中 FKBP5 内含子 7 的 DNAm 减少有关。因此，我们旨在研究各种类型的儿童虐待、rs1360780 与 FKBP5 内含子 7 的 DNAm 水平之间的关系。
共有 190 名受试者（87 名重性抑郁障碍 [MDD] 患者、61 名双相障碍 [BD] 患者和 42 名健康对照者）参与了研究。使用儿童虐待和创伤量表（CATS）评估儿童虐待情况。处理全血进行基因分型，并进行焦磷酸测序评估 FKBP5 内含子 7 的 DNAm 水平。采用多元回归分析将 DNAm 水平作为因变量，将 CATS 亚型和 rs1360780 作为自变量进行分析。
在 BD 患者中，一种特定类型的儿童虐待（情感虐待/忽视）与 FKBP5 内含子 7 的 DNAm 降低有关，并且与 rs1360780 相互作用。在 MDD 患者或对照组中未观察到显著结果。
由于该研究仅限于日本人群，特别是 MDD 和 BD 患者，因此发现不具有普遍性。此外，由于儿童虐待是通过回顾性测量的，因此可能存在回忆偏倚。
这一发现表明特定类型的儿童虐待可能在 BD 的发展中起重要作用。
