Endocannabinoid concentrations in major depression: effects of childhood maltreatment and relation to hippocampal volume.

IF 5.8 1区 医学 Q1 PSYCHIATRY
Raegan Mazurka, Kate L Harkness, Stefanie Hassel, Niclas Stensson, Nikita Nogovitsyn, Jordan Poppenk, Jane A Foster, Scott D Squires, Jessie Rowe, Roumen V Milev, Katherine E Wynne-Edwards, Gustavo Turecki, Stephen C Strother, Stephen R Arnott, Raymond W Lam, Susan Rotzinger, Sidney H Kennedy, Benicio N Frey, Leah M Mayo
{"title":"Endocannabinoid concentrations in major depression: effects of childhood maltreatment and relation to hippocampal volume.","authors":"Raegan Mazurka, Kate L Harkness, Stefanie Hassel, Niclas Stensson, Nikita Nogovitsyn, Jordan Poppenk, Jane A Foster, Scott D Squires, Jessie Rowe, Roumen V Milev, Katherine E Wynne-Edwards, Gustavo Turecki, Stephen C Strother, Stephen R Arnott, Raymond W Lam, Susan Rotzinger, Sidney H Kennedy, Benicio N Frey, Leah M Mayo","doi":"10.1038/s41398-024-03151-z","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.8000,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11470058/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational Psychiatry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41398-024-03151-z","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}
引用次数: 0

Abstract

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.

重度抑郁症患者的内源性大麻素浓度:童年虐待的影响以及与海马体体积的关系。
来自临床前动物模型的证据表明,内源性大麻素(eCB)系统的压力缓冲功能可能有助于防止与压力相关的海马体积缩小,这在重度抑郁障碍(MDD)中得到了证实。然而,压力暴露也可能导致该系统失调。因此,从明显的压力史(如童年虐待(CM))到较小的海马体积和人类MDD的路径可能取决于eCB功能失调还是完好。我们研究了 MDD 与外周 eCB 浓度之间的关系是否会因 CM 历史而变化。此外,我们还研究了 eCB 是否会缓和 CM/MDD 与海马体积之间的关系。我们从加拿大抑郁症生物标记物整合网络项目(CAN-BIND-04)中招募了 91 名患有 MDD 的成人和 62 名健康对比参与者(HCs)进行研究。研究人员从血浆中评估了 eCBs、anandamide (AEA) 和 2-arachidonylglycerol (2-AG)。严重中风病史通过背景访谈进行回顾性评估。多发性抑郁症与 eCBs 有关,但并非所有的关联都会受到 CM 的调节,也并非所有的关联都会朝着预期的方向发展。具体而言,与 HCs 相比,无论是否有 CM 史,MDD 都与较高的 AEA 相关,这种差异可能是由于精神药物所致。MDD 也与较高的 2-AG 相关,但仅针对有 CM 史的参与者。与假设一致的是,我们发现患有CM的参与者与未患有CM的参与者相比,左侧海马体积较小,但只有那些AEA较低的参与者才会出现这种情况,而中度或高度AEA的参与者则不会出现这种情况。我们的研究首次在人类中提出证据,证明 eCB 与压力相关机制有关,涉及 MDD 患者海马体积的缩小。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
11.50
自引率
2.90%
发文量
484
审稿时长
23 weeks
期刊介绍: Psychiatry has suffered tremendously by the limited translational pipeline. Nobel laureate Julius Axelrod''s discovery in 1961 of monoamine reuptake by pre-synaptic neurons still forms the basis of contemporary antidepressant treatment. There is a grievous gap between the explosion of knowledge in neuroscience and conceptually novel treatments for our patients. Translational Psychiatry bridges this gap by fostering and highlighting the pathway from discovery to clinical applications, healthcare and global health. We view translation broadly as the full spectrum of work that marks the pathway from discovery to global health, inclusive. The steps of translation that are within the scope of Translational Psychiatry include (i) fundamental discovery, (ii) bench to bedside, (iii) bedside to clinical applications (clinical trials), (iv) translation to policy and health care guidelines, (v) assessment of health policy and usage, and (vi) global health. All areas of medical research, including — but not restricted to — molecular biology, genetics, pharmacology, imaging and epidemiology are welcome as they contribute to enhance the field of translational psychiatry.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信