Association between the expression of lncRNA BASP-AS1 and volume of right hippocampal tail moderated by episode duration in major depressive disorder: a CAN-BIND 1 report

Author:

Yrondi Antoine,Fiori Laura M.,Nogovitsyn NikitaORCID,Hassel Stefanie,Théroux Jean François,Aouabed Zahia,Frey Benicio N.ORCID,Lam Raymond W.ORCID,Milev Roumen,Müller Daniel J.ORCID,Foster Jane A.ORCID,Soares Claudio,Rotzinger Susan,Strother Stephen C.ORCID,MacQueen Glenda M.,Arnott Stephen R.,Davis Andrew D.,Zamyadi Mojdeh,Harris Jacqueline,Kennedy Sidney H.ORCID,Turecki GustavoORCID

Abstract

AbstractThe 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.

Funder

Gouvernement du Canada | Instituts de Recherche en Santé du Canada | CIHR Skin Research Training Centre

Publisher

Springer Science and Business Media LLC

Subject

Biological Psychiatry,Cellular and Molecular Neuroscience,Psychiatry and Mental health

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