Helena K Kim, Gwyneth Zai, Daniel J Müller, Muhammad I Husain, Raymond W Lam, Benicio N Frey, Claudio N Soares, Sagar V Parikh, Roumen Milev, Jane A Foster, Gustavo Turecki, Faranak Farzan, Benoit H Mulsant, Sidney H Kennedy, Shreejoy J Tripathy, Stefan Kloiber
{"title":"鉴定内源性大麻素对重度抑郁症治疗结果的预测:加拿大首个抑郁症生物标志物整合网络(CAN-BIND 1)研究的二次分析。","authors":"Helena K Kim, Gwyneth Zai, Daniel J Müller, Muhammad I Husain, Raymond W Lam, Benicio N Frey, Claudio N Soares, Sagar V Parikh, Roumen Milev, Jane A Foster, Gustavo Turecki, Faranak Farzan, Benoit H Mulsant, Sidney H Kennedy, Shreejoy J Tripathy, Stefan Kloiber","doi":"10.1055/a-1872-0844","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>Lower methylation of CpG islands of the diacylglycerol lipase alpha gene (<i>DAGLA</i>) was associated with non-remission at week 16 (<i>DAGLA</i>; OR=0.337, p<0.003, q=0.050). Methylation of <i>DAGLA</i> 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.</p><p><strong>Discussion: </strong>Methylation of <i>DAGLA</i> is a promising candidate as a marker of treatment outcomes for MDD and needs to be explored further.</p>","PeriodicalId":19783,"journal":{"name":"Pharmacopsychiatry","volume":null,"pages":null},"PeriodicalIF":3.6000,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":"{\"title\":\"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.\",\"authors\":\"Helena K Kim, Gwyneth Zai, Daniel J Müller, Muhammad I Husain, Raymond W Lam, Benicio N Frey, Claudio N Soares, Sagar V Parikh, Roumen Milev, Jane A Foster, Gustavo Turecki, Faranak Farzan, Benoit H Mulsant, Sidney H Kennedy, Shreejoy J Tripathy, Stefan Kloiber\",\"doi\":\"10.1055/a-1872-0844\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>Lower methylation of CpG islands of the diacylglycerol lipase alpha gene (<i>DAGLA</i>) was associated with non-remission at week 16 (<i>DAGLA</i>; OR=0.337, p<0.003, q=0.050). Methylation of <i>DAGLA</i> 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.</p><p><strong>Discussion: </strong>Methylation of <i>DAGLA</i> is a promising candidate as a marker of treatment outcomes for MDD and needs to be explored further.</p>\",\"PeriodicalId\":19783,\"journal\":{\"name\":\"Pharmacopsychiatry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2022-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmacopsychiatry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1055/a-1872-0844\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2022/7/6 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacopsychiatry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1055/a-1872-0844","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/7/6 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
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.
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.
期刊介绍：
Covering advances in the fi eld of psychotropic drugs, Pharmaco psychiatry provides psychiatrists, neuroscientists and clinicians with key clinical insights and describes new avenues of research and treatment. The pharmacological and neurobiological bases of psychiatric disorders are discussed by presenting clinical and experimental research.
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