Department of Psychiatry, Dalhousie University, Halifax, NS, Canada.
Department of Psychology, Queen's University, Kingston, ON, Canada.
Transl Psychiatry. 2024 Oct 12;14(1):431. doi: 10.1038/s41398-024-03151-z.
Evidence from preclinical animal models suggests that the stress-buffering function of the endocannabinoid (eCB) system may help protect against stress-related reductions in hippocampal volume, as is documented in major depressive disorder (MDD). However, stress exposure may also lead to dysregulation of this system. Thus, pathways from marked stress histories, such as childhood maltreatment (CM), to smaller hippocampal volumes and MDD in humans may depend on dysregulated versus intact eCB functioning. We examined whether the relation between MDD and peripheral eCB concentrations would vary as a function of CM history. Further, we examined whether eCBs moderate the relation of CM/MDD and hippocampal volume. Ninety-one adults with MDD and 62 healthy comparison participants (HCs) were recruited for a study from the Canadian Biomarker Integration Network in Depression program (CAN-BIND-04). The eCBs, anandamide (AEA) and 2-arachidonylglycerol (2-AG), were assessed from blood plasma. Severe CM history was assessed retrospectively via contextual interview. MDD was associated with eCBs, though not all associations were moderated by CM or in the direction expected. Specifically, MDD was associated with higher AEA compared to HCs regardless of CM history, a difference that could be attributed to psychotropic medications. MDD was also associated with higher 2-AG, but only for participants with CM. Consistent with hypotheses, we found lower left hippocampal volume in participants with versus without CM, but only for those with lower AEA, and not moderate or high AEA. Our study presents the first evidence in humans implicating eCBs in stress-related mechanisms involving reduced hippocampal volume in MDD.
来自临床前动物模型的证据表明，内源性大麻素（eCB）系统的应激缓冲功能可能有助于防止与应激相关的海马体积减少，这在重度抑郁症（MDD）中已有记载。然而，应激暴露也可能导致该系统失调。因此，从明显的应激史（如儿童虐待（CM））到人类较小的海马体积和 MDD 的途径可能取决于 eCB 功能的失调或完整。我们研究了 MDD 与外周 eCB 浓度之间的关系是否会因 CM 病史而异。此外，我们还研究了 eCB 是否调节 CM/MDD 和海马体积之间的关系。91 名患有 MDD 的成年人和 62 名健康对照组（HCs）参加了加拿大抑郁生物标志物综合网络计划（CAN-BIND-04）的一项研究。通过血液血浆评估 eCBs，即花生四烯酸乙醇胺（AEA）和 2-花生四烯酰甘油（2-AG）。通过情景访谈回顾性评估严重的 CM 病史。尽管并非所有关联都受到 CM 或预期方向的调节，但 MDD 与 eCB 相关。具体而言，与 HCs 相比，无论 CM 病史如何，MDD 与较高的 AEA 相关，这种差异可以归因于精神药物。MDD 还与较高的 2-AG 相关，但仅与 CM 参与者有关。与假设一致，我们发现与 CM 参与者相比，无 CM 参与者的左海马体积较低，但仅在 AEA 较低的参与者中，而不是在中等或高水平的 AEA 中。我们的研究首次在人类中提出了 eCB 参与与应激相关的机制的证据，这些机制涉及 MDD 中海马体积的减少。
