Perlman Kelly, Chouinard-Watkins Raphaël, Tanti Arnaud, Cisbani Giulia, Orri Massimiliano, Turecki Gustavo, Bazinet Richard P, Mechawar Naguib
McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, Québec, Canada.
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Transl Psychiatry. 2021 Oct 18;11(1):535. doi: 10.1038/s41398-021-01657-4.
Child abuse (CA) strongly increases the lifetime risk of suffering from major depression and predicts an unfavorable course for the illness. Severe CA has been associated with a specific dysregulation of oligodendrocyte function and thinner myelin sheaths in the human anterior cingulate cortex (ACC) white matter. Given that myelin is extremely lipid-rich, it is plausible that these findings may be accompanied by a disruption of the lipid profile that composes the myelin sheath. This is important to explore since the composition of fatty acids (FA) in myelin phospholipids can influence its stability, permeability, and compactness. Therefore, the objective of this study was to quantify and compare FA concentrations in postmortem ACC white matter in the choline glycerophospholipid pool (ChoGpl), a key myelin phospholipid pool, between adult depressed suicides with a history of CA (DS-CA) matched depressed suicides without CA (DS) and healthy non-psychiatric controls (CTRL). Total lipids were extracted from 101 subjects according to the Folch method and separated into respective classes using thin-layer chromatography. FA methyl esters from the ChoGpl fraction were quantified using gas chromatography. Our analysis revealed specific effects of CA in FAs from the arachidonic acid synthesis pathway, which was further validated with RNA-sequencing data. Furthermore, the concentration of most FAs was found to decrease with age. By extending the previous molecular level findings linking CA with altered myelination in the ACC, these results provide further insights regarding white matter alterations associated with early-life adversity.
儿童虐待（CA）会显著增加患重度抑郁症的终生风险，并预示该病的不良病程。严重的儿童虐待与人类前扣带回皮质（ACC）白质中少突胶质细胞功能的特定失调以及髓鞘变薄有关。鉴于髓鞘富含脂质，这些发现可能伴随着构成髓鞘的脂质谱的破坏，这一点似乎是合理的。这一点很值得探究，因为髓鞘磷脂中脂肪酸（FA）的组成会影响其稳定性、通透性和紧密性。因此，本研究的目的是对有儿童虐待史的成年抑郁自杀者（DS-CA）、与之匹配的无儿童虐待史的抑郁自杀者（DS）以及健康非精神科对照者（CTRL）的死后ACC白质中胆碱甘油磷脂池（ChoGpl）（一个关键的髓鞘磷脂池）中的脂肪酸浓度进行定量和比较。根据Folch方法从101名受试者中提取总脂质，并使用薄层色谱法将其分离成各自的类别。使用气相色谱法定量ChoGpl组分中的脂肪酸甲酯。我们的分析揭示了儿童虐待对花生四烯酸合成途径中的脂肪酸有特定影响，这一结果通过RNA测序数据得到了进一步验证。此外，发现大多数脂肪酸的浓度会随着年龄的增长而降低。通过扩展先前将儿童虐待与ACC中髓鞘形成改变联系起来的分子水平研究结果，这些结果为与早期生活逆境相关的白质改变提供了进一步的见解。
