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

Abstract

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.

Multi-omic modeling of antidepressant response implicates dynamic immune and inflammatory changes in individuals who respond to treatment

“…Although the brain represents the most relevant tissue for identifying biomarkers of AD response, due to its lack of accessibility, the majority of studies rely on the investigation of peripheral markers [10]. A number of high-throughput studies have been performed in the blood, including those investigating gene expression, DNA methylation, genetic variation, and metabolic profiling, and have identified a number of factors related to AD response [11][12][13][14][15][16][17]. While promising, many of these findings have yet to be replicated, nor is it clear how findings from these different studies may be related.…”

Multi-omic modeling of antidepressant response implicates dynamic immune and inflammatory changes in individuals who respond to treatment

“…Although the brain represents the most relevant tissue for identifying biomarkers of AD response, due to its lack of accessibility, the majority of studies rely on the investigation of peripheral markers 10 . A number of high-throughput studies have been performed in the blood, including those investigating gene expression, DNA methylation, genetic variation, and metabolic profiling, and have identified a number of factors related to AD response [11][12][13][14][15][16][17] . While promising, many of these findings have yet to be replicated, nor is it clear how findings from these different studies may be related.…”