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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., Competing Interests: There was no role of the following granting agencies/sponsors in the design, collection of data, analysis, interpretation of data, writing of this paper, and decision to submit the paper for publication. Muhammad I. Husain receives research support from the Brain and Behavior Research Foundation, Canadian Institutes of Health Research, CAMH Foundation, the PSI Foundation, and the University of Toronto. He has provided consultancy to Mindset Pharma, PsychEd Therapeutics, and Wake Network. He holds stock/stock options in Mindset Pharma. Raymond W. Lam has received honoraria for ad hoc speaking or advising/consulting or received research funds from: Asia-Pacific Economic Cooperation, BC Leading Edge Foundation, Canadian Institutes of Health Research, Canadian Network for Mood and Anxiety Treatments, Grand Challenges Canada, Healthy Minds Canada, Janssen, Lundbeck, Lundbeck Institute, Medscape, Michael Smith Foundation for Health Research, MITACS, Myriad Neuroscience, Ontario Brain Institute, Otsuka, Pfizer, Sanofi, Unity Health, Vancouver Coastal Health Research Institute, and VGH-UBCH Foundation. Claudio N. Soares received/has pending grants that include Canadian Institutes for Health Research, Ontario Brain Institute, Ontario Research Fund, and Eisai. He also receives consulting feed or honorarium from Lundbeck, Otsuka, Pfizer, Bayer, and Eisai. Sagar V. Parikh reports research support in the past three years from Takeda, Sage, Janssen, Merck, the Ontario Brain Institute, and the Canadian Institutes for Health Research; honoraria from Aifred, Assurex, Janssen, Lundbeck, Mensante, Neonmind, Otsuka, and Sage; and shares in Neonmind and Mensante. Roumen Milev has received consulting and speaking honoraria from AbbVie, Allergan, Eisai, Janssen, KYE, Lallemand, Lundbeck, Neonmind, Otsuka, and Sunovion, and research grants from CAN-BIND, CIHR, Janssen, Lallemand, Lundbeck, Nubiyota, OBI and OMHF. Jane A. Foster receives consulting and speaking fees from Takeda Canada and RBH. Faranak Farzan received funding from CIHR, NSER, and Michael Smith Foundation for Health Research. Benoit H. Mulsant holds and receives support from the Labatt Family Chair in Biology of Depression in Late-Life Adults at the University of Toronto. He currently receives research support from Brain Canada, the Canadian Institutes of Health Research, the CAMH Foundation, the Patient-Centered Outcomes Research Institute, the US National Institute of Health, Capital Solution Design LLC (software used in a study funded by CAMH Foundation), and HAPPYneuron (software used in a study funded by Brain Canada). He has been an unpaid consultant to Myriad Neuroscience. Sidney Kennedy received grants/has pending grants, including Abbott, Allergan, Brain Canada, Canadian Institutes for Health Research, Janssen, Lundbeck, Ontario Brain Institute, Ontario Research Fund, Otsuka, Pfizer, Servier, Sunovion, and Xian-Janssen. He also receives consulting fees or honorarium from Abbott, Alkermes, Allergan, Boehringer Ingelheim, Brain Canada, Canadian Institutes for Health Research, Janssen, Lundbeck, Lundbeck Institute, Ontario Brain Institute, Ontario Research Fund, Otsuka, Pfizer, Servier, Sunovion and Xian-Janssen. He has stock/stock options from Field Trip Health. Stefan Kloiber’s work has been supported by the Academic Scholar Award and the Labatt Family Innovation Fund in Brain Health, Department of Psychiatry, University of Toronto. DJM’s research work is supported by the Canadian Institutes of Health Research, the Ontario Brain Foundation, the Alternate Funding Plan of Ontario, and the Centre for Addiction and Mental Health Foundation. GZ’s work has been supported by the Academic Scholar Award and the Labatt Family Innovation Fund in Brain Health, Department of Psychiatry, University of Toronto, in addition to the Brain & Behavior Research Foundation, International Obsessive-Compulsive Disorder Foundation, and the Physicians’ Services Incorporated Foundation in Ontario, Canada. SK has received an honorarium for past consultation from EmpowerPharm. All other authors declare no conflict of interest. Helena K. Kim, Gwyneth Zai, Daniel J. Müller, Benicio N. Frey, Gustavo Turecki, and Shreejoy J. Tripathy have no conflicts to disclose., (Thieme. All rights reserved.)

The pharmacological treatment of depression consists of stages of trial and error, with less than 40% of patients achieving remission during first medication trial. However, in a large, randomized-controlled trial (RCT) in the U.S. ("GUIDED"), significant improvements in response and remission rates were observed in patients who received treatment guided by combinatorial pharmacogenomic testing, compared to treatment-as-usual (TAU). Here we present results from the Canadian "GAPP-MDD" RCT. This 52-week, 3-arm, multi-center, participant- and rater-blinded RCT evaluated clinical outcomes among patients with depression whose treatment was guided by combinatorial pharmacogenomic testing compared to TAU. The primary outcome was symptom improvement (change in 17-item Hamilton Depression Rating Scale, HAM-D17) at week 8. Secondary outcomes included response (≥50% decrease in HAM-D17) and remission (HAM-D17 ≤ 7) at week 8. Numerically, patients in the guided-care arm had greater symptom improvement (27.6% versus 22.7%), response (30.3% versus 22.7%), and remission rates (15.7% versus 8.3%) compared to TAU, although these differences were not statistically significant. Given that the GAPP-MDD trial was ultimately underpowered to detect statistically significant differences in patient outcomes, it was assessed in parallel with the larger GUIDED RCT. We observed that relative improvements in response and remission rates were consistent between the GAPP-MDD (33.0% response, 89.0% remission) and GUIDED (31.0% response, 51.0% remission) trials. Together with GUIDED, the results from the GAPP-MDD trial indicate that combinatorial pharmacogenomic testing can be an effective tool to help guide depression treatment in the context of the Canadian healthcare setting (ClinicalTrials.gov NCT02466477)., (© 2022. The Author(s).)

Introduction: Pharmacogenetics attempts to identify inter-individual genetic differences that are predictive of variable drug response and propensity to side effects, with the prospect of assisting physicians to select the most appropriate drug and dosage for treatment. However, many concerns regarding genetic tests exist. We sought to test the opinions of undergraduate science and medical students in southern Ontario universities toward pharmacogenetic testing., Methods and Results: Questionnaires were completed by 910 undergraduate medicine and science students from 2005 to 2007. Despite students' concerns that the results of genetic tests may be used for other purposes without consent (71%) or lead to discrimination (78%), an overwhelming number of students were in favor of pharmacogenetic testing (90%)., Discussion: To our knowledge, this study is the first to survey a large sample for their attitude toward pharmacogenetic testing for psychotropic medications. Our results indicate that, although concerns remain and scientific advancements are required, respondents were in support of pharmacogenetic testing for medications used to treat schizophrenia. © 2014 The Authors. Human Psychopharmacology: Clinical and Experimental published by John Wiley & Sons, Ltd., (© 2014 The Authors. Human Psychopharmacology: Clinical and Experimental published by John Wiley & Sons, Ltd.)

Obsessive-compulsive disorder (OCD) is a severe neuropsychiatric disorder with a strong genetic component, and may involve autoimmune processes. Support for this latter hypothesis comes from the identification of a subgroup of children, described by the term pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS), with onset of OCD symptoms following streptococcal infections. Genes involved in immune response therefore represent possible candidate genes for OCD, including the myelin oligodendrocyte glycoprotein (MOG) gene, which plays an important role in mediating the complement cascade in the immune system. Four polymorphisms in the MOG gene, a dinucleotide CA repeat (MOG2), a tetranucleotide TAAA repeat (MOG4), and 2 intronic single nucleotide polymorphisms, C1334T and C10991T, were investigated for the possibility of association with OCD using 160 nuclear families with an OCD proband. We examined the transmission of alleles of these four polymorphisms with the transmission disequilibrium test (TDT). A biased transmission of the 459-bp allele (allele 2: chi2 = 5.255, P = 0.022) of MOG4 was detected, while MOG2, C1334T, and C10991T showed no statistically significant bias in the transmission of alleles. The transmission of the C1334T.MOG2.C10991T.MOG4 haplotype 1.13.2.2 (chi2 = 6.426, P = 0.011) was also significant. Quantitative analysis using the family-based association test (FBAT) was significant for MOG4 in total Yale-Brown Obsessive-Compulsive Scale severity score (allele 2: z = 2.334, P = 0.020). Further investigations combining genetic, pathological, and pharmacological strategies, are warranted., (Copyright 2004 Wiley-Liss, Inc.)