The pathophysiology of major depressive disorder (MDD) encompasses an array of changes at molecular and neurobiological levels. As chronic stress promotes neurotoxicity there are alterations in the expression of genes and gene-regulatory molecules. The hippocampus is particularly sensitive to the effects of stress and its posterior volumes can deliver clinically valuable information about the outcomes of antidepressant treatment. In the present work, we analyzed individuals with MDD (N = 201) and healthy controls (HC = 104), as part of the CAN-BIND-1 study. We used magnetic resonance imaging (MRI) to measure hippocampal volumes, evaluated gene expression with RNA sequencing, and assessed DNA methylation with the (Infinium MethylationEpic Beadchip), in order to investigate the association between hippocampal volume and both RNA expression and DNA methylation. We identified 60 RNAs which were differentially expressed between groups. Of these, 21 displayed differential methylation, and seven displayed a correlation between methylation and expression. We found a negative association between expression of Brain Abundant Membrane Attached Signal Protein 1 antisense 1 RNA (BASP1-AS1) and right hippocampal tail volume in the MDD group (β = −0.218, p = 0.021). There was a moderating effect of the duration of the current episode on the association between the expression of BASP1-AS1 and right hippocampal tail volume in the MDD group (β = −0.48, 95% C.I. [−0.80, −0.16]. t = −2.95 p = 0.004). In conclusion, we found that overexpression of BASP1-AS1 was correlated with DNA methylation, and was negatively associated with right tail hippocampal volume in MDD.

重度抑郁症 (MDD) 的病理生理学包括一系列分子和神经生物学水平的变化。由于慢性压力会促进神经毒性，因此基因和基因调控分子的表达会发生变化。海马体对压力的影响特别敏感，其后部体积可以提供有关抗抑郁治疗结果的具有临床价值的信息。在目前的工作中，我们分析了患有 MDD 的个体（N = 201) 和健康对照 (HC = 104)，作为 CAN-BIND-1 研究的一部分。我们使用磁共振成像 (MRI) 测量海马体积，通过 RNA 测序评估基因表达，并使用 (Infinium MethylationEpic Beadchip) 评估 DNA 甲基化，以研究海马体积与 RNA 表达和 DNA 甲基化之间的关联。我们确定了 60 个在组间差异表达的 RNA。其中，21 个显示差异甲基化，7 个显示甲基化和表达之间的相关性。我们发现 MDD 组中脑富集膜附着信号蛋白 1 反义 1 RNA (BASP1-AS1) 的表达与右海马尾体积呈负相关 ( β  = -0.218, p = 0.021）。当前发作的持续时间对 MDD 组中 BASP1-AS1 的表达与右海马尾体积之间的关联有调节作用（β  = -0.48, 95% CI [-0.80, -0.16] 。t  = −2.95 p  = 0.004）。总之，我们发现 BASP1-AS1 的过表达与 DNA 甲基化相关，并且与 MDD 中的右尾海马体积呈负相关。