Possamai-Della Taise, Peper-Nascimento Jefté, Varela Roger B, Daminelli Thiani, Fries Gabriel R, Ceretta Luciane B, Juruena Mario F, Quevedo João, Valvassori Samira S
Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil.
Neuromodulation and Novel Therapeutics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
Eur Arch Psychiatry Clin Neurosci. 2024 Nov 14. doi: 10.1007/s00406-024-01917-6.
Childhood maltreatment may be linked to epigenetics and brain-derived neurotrophic factor (BDNF) changes, which are mechanisms altered in several psychiatric conditions, including bipolar disorder (BD). However, the specific mechanisms connecting childhood maltreatment to the pathophysiology of BD remain unclear. The present study aims to examine the effects of childhood maltreatment on epigenetic and neurotrophic outcomes in BD patients and health controls. History of childhood maltreatment was obtained using the Childhood Trauma Questionnaire (CTQ) from 36 BD outpatients and 46 healthy subjects. DNA methyltransferase (DNMT) activity, HMTH3K9 activity, histone 3 lysine 9 tri-methylation (H3K9me3) levels, histone deacetylase (HDAC)1 levels, HDAC2 levels, histone 3 lysine 14 acetylation (H3K14ac) levels, and mRNA of BDNF were evaluated in peripheral blood mononuclear cells. Plasma BDNF levels were also measured. Total scores of CTQ, as well as the subscale scores of emotional abuse, sexual abuse, and emotional neglect, were predictive of changes in DNMT and HMTh3k9 activity, H3K9m3 levels, BDNF mRNA expression, and BDNF levels. These findings were observed in all our samples and, in some cases, among BD patients. Emotional abuse was the main childhood maltreatment subtype associated with epigenetic alterations in BD. Our results elucidate some mechanisms by which childhood maltreatment can alter epigenetic and neurotrophic markers. Especially in BD subjects, our results suggest childhood maltreatment per se is not a direct cause for epigenetic alterations. In another way, we suppose that the effect of childhood maltreatment could be cumulative and interact with other factors associated with the pathophysiology of BD.
童年期受虐可能与表观遗传学及脑源性神经营养因子（BDNF）的变化有关，这些是在包括双相情感障碍（BD）在内的多种精神疾病中发生改变的机制。然而，将童年期受虐与BD病理生理学联系起来的具体机制仍不清楚。本研究旨在探讨童年期受虐对BD患者和健康对照者表观遗传学及神经营养结果的影响。通过儿童创伤问卷（CTQ）从36名BD门诊患者和46名健康受试者中获取童年期受虐史。对外周血单核细胞中的DNA甲基转移酶（DNMT）活性、HMTH3K9活性、组蛋白3赖氨酸9三甲基化（H3K9me3）水平、组蛋白去乙酰化酶（HDAC）1水平、HDAC2水平、组蛋白3赖氨酸14乙酰化（H3K14ac）水平以及BDNF的mRNA进行评估。还测量了血浆BDNF水平。CTQ的总分以及情感虐待、性虐待和情感忽视的子量表得分可预测DNMT和HMTh3k9活性、H3K9m3水平、BDNF mRNA表达和BDNF水平的变化。这些发现见于我们所有的样本中，在某些情况下，也见于BD患者中。情感虐待是与BD表观遗传学改变相关的主要童年期受虐亚型。我们的结果阐明了童年期受虐可改变表观遗传学和神经营养标志物的一些机制。特别是在BD受试者中，我们的结果表明童年期受虐本身并非表观遗传学改变的直接原因。另一方面，我们推测童年期受虐的影响可能是累积性的，并与BD病理生理学相关的其他因素相互作用。
