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Pharmacopsychiatry 2022; 55(06): 297-303
DOI: 10.1055/a-1872-0844
Original Paper

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

Helena K. Kim
1   Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada
,
Gwyneth Zai
1   Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada
2   Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Canada
3   Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Canada
,
Daniel J. Müller
1   Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada
2   Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Canada
,
Muhammad I. Husain
1   Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada
2   Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Canada
,
Raymond W. Lam
4   Department of Psychiatry, University of British Columbia, Vancouver, Canada
,
Benicio N. Frey
5   Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Canada
6   Mood Disorders Program and Women’s Health Concerns Clinic, St. Joseph’s Healthcare, Hamilton, Canada
,
Claudio N. Soares
7   Department of Psychiatry, Queen’s university School of Medicine, Kingston, Canada
,
Sagar V. Parikh
8   Department of Psychiatry, University of Michigan, Ann Arbor, United States of America
,
Roumen Milev
7   Department of Psychiatry, Queen’s university School of Medicine, Kingston, Canada
9   Department of Psychiatry, Providence care, Kingston, Canada
,
Jane A. Foster
5   Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Canada
,
Gustavo Turecki
10   Douglas Institute, Department of Psychiatry, McGill University, Montreal, Canada
,
Faranak Farzan
11   eBrain Lab, School of Mechatronic Systems Engineering, Simon Fraser University, Surrey, Canada
,
Benoit H. Mulsant
1   Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada
2   Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Canada
3   Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Canada
,
Sidney H. Kennedy
1   Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada
3   Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Canada
,
Shreejoy J. Tripathy
1   Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada
2   Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Canada
3   Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Canada
12   Krembil Center for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, Canada
13   Department of Physiology, University of Toronto, Toronto, Canada
,
Stefan Kloiber
1   Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada
2   Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Canada
3   Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Canada
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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.

Key words

endocannabinoid - major depressive disorder - methylation - DAGLA - antidepressant

Supplementary Material



Publication History

Received: 26 April 2022
Received: 31 May 2022

Accepted: 27 May 2022

Article published online:
06 July 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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