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

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.

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Publication Details

Journal
Translational Psychiatry
Published
2024-10-12
DOI
https://doi.org/10.1038/s41398-024-03151-z
Citations
10
Primary Topic
Cannabis and Cannabinoid Research
Type
article
Field-Weighted Citation Impact
4.48

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article

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

Gustavo Turecki, Stephen C. Strother, Katherine E. Wynne‐Edwards, Susan Rotzinger et al.
10 citations
Translational Psychiatry
Cannabis and Cannabinoid Research
4.48
article

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

Gustavo Turecki, Stephen C. Strother, Katherine E. Wynne‐Edwards, Susan Rotzinger, Jane Allyson Foster, Stephen R. Arnott, Scott Squires, Niclas Stensson, Roumen Milev, Sidney H. Kennedy, Raegan Mazurka, Nikita Nogovitsyn, Jordan Poppenk, Benicio Noronha Frey, Jessie Rowe, Stefanie Hassel, Kate Leslie Harkness, Raymond W. Lam, Leah M. Mayo
article en
10 citations

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.

Translational PsychiatryVol. 14(1)
Linköping University (SE), St. Michael's Hospital (CA), Dalhousie University (CA), Allen Institute for Brain Science (US), University of British Columbia (CA), University of Calgary (CA), University of Toronto (CA), Queen's University (CA), Douglas Mental Health University Institute (CA), Baycrest Hospital (CA), Southwestern Medical Center (US), Indoc Research (CA), Southwestern Medical Center (US), Hotchkiss Brain Institute (CA), McGill University (CA), St. Joseph’s Healthcare Hamilton (CA), The University of Texas Southwestern Medical Center (US), McMaster University (CA)
Ontario Brain Institute, Ontario Mental Health Foundation, Vetenskapsrådet
Openalex Percentile: Top 5%
Cannabis and Cannabinoid Research
4.48
DOIOpen Access PDFOpenAlex
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