Identification of Endocannabinoid Predictors of Treatment Outcomes in
Major Depressive Disorder: A Secondary Analysis of the First Canadian Biomarker
Integration Network in Depression (CAN-BIND 1) Study
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Abstract
Introduction An increasing number of studies are examining the link
between the endocannabinoidome and major depressive disorder (MDD). We conducted
an exploratory analysis of this system to identify potential markers of
treatment outcomes.
Methods The dataset of the Canadian Biomarker Integration Network in
Depression-1 study, consisting of 180 patients with MDD treated for eight weeks
with escitalopram followed by eight weeks with escitalopram alone or augmented
with aripiprazole was analyzed. Association between response Montgomery-Asberg
Depression Rating Scale (MADRS; score reduction≥50%) or
remission (MADRS score≤10) at weeks 8 and 16 and single nucleotide
polymorphisms (SNPs), methylation, and mRNA levels of 33 endocannabinoid markers
were examined. A standard genome-wide association studies protocol was used for
identifying SNPs, and logistic regression was used to assess methylation and
mRNA levels.
Results Lower methylation of CpG islands of the diacylglycerol lipase
alpha gene (DAGLA) was associated with non-remission at week 16
(DAGLA; OR=0.337, p<0.003, q=0.050).
Methylation of DAGLA was correlated with improvement in Clinical Global
Impression (p=0.026), Quick Inventory of Depressive Symptomatology
(p=0.010), and Snaith-Hamilton Pleasure scales (p=0.028). We did
not find any association between SNPs or mRNA levels and treatment outcomes.
Discussion Methylation of DAGLA is a promising candidate as a
marker of treatment outcomes for MDD and needs to be explored further.
