TY - JOUR
T1 - Association between the expression of lncRNA BASP-AS1 and volume of right hippocampal tail moderated by episode duration in major depressive disorder
T2 - a CAN-BIND 1 report
AU - Yrondi, Antoine
AU - Fiori, Laura M.
AU - Nogovitsyn, Nikita
AU - Hassel, Stefanie
AU - Théroux, Jean François
AU - Aouabed, Zahia
AU - Frey, Benicio N.
AU - Lam, Raymond W.
AU - Milev, Roumen
AU - Müller, Daniel J.
AU - Foster, Jane A.
AU - Soares, Claudio
AU - Rotzinger, Susan
AU - Strother, Stephen C.
AU - MacQueen, Glenda M.
AU - Arnott, Stephen R.
AU - Davis, Andrew D.
AU - Zamyadi, Mojdeh
AU - Harris, Jacqueline
AU - Kennedy, Sidney H.
AU - Turecki, Gustavo
N1 - Funding Information:
AY: has received speaker honoraria from AstraZeneca, Janssen, Lundbeck, Otsuka, Servier unrelated to this work. BF: has received a research grant from Pfizer. GM: has received consulting fees from Pfizer, Lundbeck, Janssen, Johnson&Johnson; disclosed honoraria for lectures for Lundbeck and Allergen; and has received research funding from the Ontario Brain Institute, Brain Canada, the Hotchkiss Brain Institute and Canadian Institutes of Health Research. RM: has received consulting and speaking honoraria from Allergan, Janssen, KYE, Lundbeck, Otsuka, Pfizer and Sunovion, and research grants from CAN-BIND, CIHR, Janssen, Lallemand, Lundbeck, Nubiyota, OBI, OMHF and Pfizer. SK: has received research funding or honoraria from the following sources: Abbott, Alkermes, Allergan, BMS, Brain Canada, Canadian Institutes for Health Research (CIHR), Janssen, Lundbeck, Lundbeck Institute, Ontario Brain Institute, Ontario Research Fund (ORF), Otsuka, Pfizer, Servier, Sunovion, and Xian-Janssen. LMF, NN, SH, JFT, ZA, RL, DM, JF, CS, SR, SCS, SRA, ADD, MZ, JH, GT: declare no competing interests.
Funding Information:
CAN-BIND is an Integrated Discovery Program carried out in partnership and with financial support from the Ontario Brain Institute, an independent non-profit corporation, funded partially by the Ontario government. The opinions, results and conclusions are those of the authors and no endorsement by the Ontario Brain Institute is intended or should be inferred. Additional funding is provided by the Canadian Institutes of Health Research (CIHR), Lundbeck, Bristol-Myers Squibb, Pfizer, and Servier. Funding and/or in kind support is also provided by the investigators’ universities and academic institutions. All study medications are independently purchased at wholesale market values.
Funding Information:
GT holds a Canada Research Chair (Tier 1) and is supported by grants from the Canadian Institute of Health Research (CIHR) (FDN148374, EGM141899, ENP161427), and by the Fonds de recherche du Québec -Santé (FRQS) through the Quebec Network on Suicide, Mood Disorders and Related Disorders.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41398-021-01592-4
DO - 10.1038/s41398-021-01592-4
M3 - Article
C2 - 34508068
AN - SCOPUS:85114764292
SN - 2158-3188
VL - 11
JO - Translational psychiatry
JF - Translational psychiatry
IS - 1
M1 - 469
ER -