Genomics of Antidepressant Response

Precision medicine will allow us to personalize antidepressant treatment to optimize patient outcomes. We’re searching for genetic biomarkers which will help us understand who will respond better to which antidepressant. We’re also part of The Canadian Biomarker Integration Network in Depression (CAN-BIND) — a national program of research and learning.

 

Image credit: Freepik

 

Did you know?

Among psychiatric disorders, depression is the number one cause of disability worldwide.

Major Depressive Disorder (MDD) is a leading cause of Global Burden of Disease, and is associated with substantial societal costs (World Health Organization, 2008). At this time, there are no objective tests to confirm the diagnosis of MDD, such as brain scans or blood draws. There is also no method to predict treatment outcome based on an individual’s unique clinical, physiological and environmental circumstances.

CAN-BIND 2: A validation study

The objective of this study is to integrate detailed clinical, neuroimaging, EEG, and molecular data to predict outcome for patients experiencing a Major Depressive Episode (MDE), and receiving pharmacotherapy reflective of standard practice. Stool samples will also be collected to integrate microbiota measures into data analyses, as well as blood samples for genomic profiling.

The CAN-BIND 2 validation cohort will consist of 200 participants who are diagnosed with clinical depression and are currently experiencing a depressive episode. Participants will receive standard, open-label treatment over 16 weeks. For the first eight weeks, patients will receive evidence-based, open label antidepressant treatment with Cipralex® (escitalopram) (10-20mg). After eight weeks, patients who responded to the medication will continue on their effective dose and will be followed for a further 8 weeks. Those who did not respond to treatment will receive open-label, add-on medication with Rexulti® (brexpiprazole) (0.5-2mg). Clinical, neurophysiology, molecular biomarker, and neuroimaging evaluations will be conducted regularly for the duration of treatment.

 
 
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Selected Publications

FROM OUR GROUP

ABCB1 gene variants and Antidepressant Treatment Outcomes: A Systematic Review and Meta-analysis including results from the CAN-BIND-1 Study

Magarbeh, L., Hassel, C., Choi, M., Islam, F., Marshe, V. S., Zai, C. C., Zuberi, R., Gammal, R. S., Men, X., Scherf-Clavel, M., Enko, D., Frey, B. N., Milev, R., Soares, C. N., Parikh, S. V., Placenza, F., Strother, S. C., Hassel, S., Taylor, V. H., Leri, F., … Müller, D. J. (2023).Clinical pharmacology and therapeutics, 10.1002/cpt.2854

Effects of CYP2C19 and CYP2D6 gene variants on escitalopram and aripiprazole treatment outcome and serum levels: results from the CAN-BIND 1 study

Islam, F., Marshe, V. S., Magarbeh, L., Frey, B. N., Milev, R. V., Soares, C. N., Parikh, S. V., Placenza, F., Strother, S. C., Hassel, S., Taylor, V. H., Leri, F., Blier, P., Uher, R., Farzan, F., Lam, R. W., Turecki, G., Foster, J. A., Rotzinger, S., Kennedy, S. H., Müller, D. J. (2022). Translational psychiatry, 12(1), 366.

Validation study of microRNAs previously associated with antidepressant response in older adults treated for late-life depression with venlafaxine.

Marshe VS, Islam F, Maciukiewicz M, Fiori LM, Yerko V, Yang J, Turecki G, Foster JA, Kennedy SH, Blumberger DM, Karp JF, Kennedy JL, Mulsant BH, Reynolds CF 3rd, Lenze EJ, Müller DJ.Prog Neuropsychopharmacol Biol Psychiatry. 2020 Jun 8;100:109867.

GWAS-based machine learning approach to predict duloxetine response in major depressive disorder.

Maciukiewicz M, Marshe VS, Hauschild AC, Foster JA, Rotzinger S, Kennedy JL, Kennedy SH, Müller DJ, Geraci J. J Psychiatr Res. 2018 Apr;99:62-68.

Genetic variation in IL-1β, IL-2, IL-6, TSPO and BDNF and response to duloxetine or placebo treatment in major depressive disorder.

Maciukiewicz M, Marshe VS, Tiwari AK, Fonseka TM, Freeman N, Rotzinger S, Foster JA, Kennedy JL, Kennedy SH, Müller DJ. Pharmacogenomics. 2015 Nov;16(17):1919-29.

FROM THE CAN-BIND TEAM

Symptom Dimension of Interest-Activity Indicates Need for Aripiprazole Augmentation of Escitalopram in Major Depressive Disorder: A CAN-BIND-1 Report.

Uher R, Frey BN, Quilty LC, Rotzinger S, Blier P, Foster JA, Müller DJ, Ravindran AV, Soares CN, Turecki G, Parikh SV, Milev R, MacQueen G, Lam RW, Kennedy SH; CAN-BIND Investigator Team. J Clin Psychiatry. 2020 Jun 16;81(4):20m13229.

Ketamine Treatment in Depression: A Systematic Review of Clinical Characteristics Predicting Symptom Improvement.

Lowe DJE, Müller DJ, George TP. Curr Top Med Chem. 2020;20(15):1398-1414.

Reverse translation of major depressive disorder symptoms: A framework for the behavioural phenotyping of putative biomarkers.

Daniels S, Horman T, Lapointe T, Melanson B, Storace A, Kennedy SH, Frey BN, Rizvi SJ, Hassel S, Mueller DJ, Parikh SV, Lam RW, Blier P, Farzan F, Giacobbe P, Milev R, Placenza F, Soares CN, Turecki G, Uher R, Leri F. J Affect Disord. 2020 Feb 15;263:353-366.

Escitalopram ameliorates differences in neural activity between healthy comparison and major depressive disorder groups on an fMRI Emotional conflict task: A CAN-BIND-1 study.

Alders GL, Davis AD, MacQueen G, Strother SC, Hassel S, Zamyadi M, Sharma GB, Arnott SR, Downar J, Harris JK, Lam RW, Milev R, Müller DJ, Ravindran A, Kennedy SH, Frey BN, Minuzzi L, Hall GB; CAN-BIND Investigator Team. J Affect Disord. 2020 Mar 1;264:414-424.

Association Between Side Effects and Blood microRNA Expression Levels and Their Targeted Pathways in Patients With Major Depressive Disorder Treated by a Selective Serotonin Reuptake Inhibitor, Escitalopram: A CAN-BIND-1 Report.

Yrondi A, Fiori LM, Frey BN, Lam RW, MacQueen GM, Milev R, Müller DJ, Foster JA, Kennedy SH, Turecki G. Int J Neuropsychopharmacol. 2020 Feb 1;23(2):88-95.

Use of Machine Learning for Predicting Escitalopram Treatment Outcome From Electroencephalography Recordings in Adult Patients With Depression.

Zhdanov A, Atluri S, Wong W, Vaghei Y, Daskalakis ZJ, Blumberger DM, Frey BN, Giacobbe P, Lam RW, Milev R, Mueller DJ, Turecki G, Parikh SV, Rotzinger S, Soares CN, Brenner CA, Vila-Rodriguez F, McAndrews MP, Kleffner K, Alonso-Prieto E, Arnott SR, Foster JA, Strother SC, Uher R, Kennedy SH, Farzan F. JAMA Netw Open. 2020 Jan 3;3(1):e1918377.

Integrated genome-wide methylation and expression analyses reveal functional predictors of response to antidepressants.

Ju C, Fiori LM, Belzeaux R, Theroux JF, Chen GG, Aouabed Z, Blier P, Farzan F, Frey BN, Giacobbe P, Lam RW, Leri F, MacQueen GM, Milev R, Müller DJ, Parikh SV, Rotzinger S, Soares CN, Uher R, Li Q, Foster JA, Kennedy SH, Turecki G. Transl Psychiatry. 2019 Oct 8;9(1):254.

Early change in reward and punishment sensitivity as a predictor of response to antidepressant treatment for major depressive disorder: a CAN-BIND-1 report.

Allen TA, Lam RW, Milev R, Rizvi SJ, Frey BN, MacQueen GM, Müller DJ, Uher R, Kennedy SH, Quilty LC. Psychol Med. 2019 Jul;49(10):1629-1638.

Symptomatic and Functional Outcomes and Early Prediction of Response to Escitalopram Monotherapy and Sequential Adjunctive Aripiprazole Therapy in Patients With Major Depressive Disorder: A CAN-BIND-1 Report.

Kennedy SH, Lam RW, Rotzinger S, Milev RV, Blier P, Downar J, Evans KR, Farzan F, Foster JA, Frey BN, Giacobbe P, Hall GB, Harkness KL, Hassel S, Ismail Z, Leri F, McInerney S, MacQueen GM, Minuzzi L, Müller DJ, Parikh SV, Placenza FM, Quilty LC, Ravindran AV, Sassi RB, Soares CN, Strother SC, Turecki G, Vaccarino AL, Vila-Rodriguez F, Yu J, Uher R; CAN-BIND Investigator Team. J Clin Psychiatry. 2019 Feb 5;80(2):18m12202.

The comparative effectiveness of electroencephalographic indices in predicting response to escitalopram therapy in depression: A pilot study.

Baskaran A, Farzan F, Milev R, Brenner CA, Alturi S, Pat McAndrews M, Blier P, Evans K, Foster JA, Frey BN, Giacobbe P, Lam RW, Leri F, MacQueen GM, Müller DJ, Parikh SV, Rotzinger S, Soares CN, Strother SC, Turecki G, Kennedy SH; CAN-BIND Investigators Team. J Affect Disord. 2018 Feb;227:542-549.

MicroRNAs 146a/b-5 and 425-3p and 24-3p are markers of antidepressant response and regulate MAPK/Wnt-system genes.

Lopez JP, Fiori LM, Cruceanu C, Lin R, Labonte B, Cates HM, Heller EA, Vialou V, Ku SM, Gerald C, Han MH, Foster J, Frey BN, Soares CN, Müller DJ, Farzan F, Leri F, MacQueen GM, Feilotter H, Tyryshkin K, Evans KR, Giacobbe P, Blier P, Lam RW, Milev R, Parikh SV, Rotzinger S, Strother SC, Lewis CM, Aitchison KJ, Wittenberg GM, Mechawar N, Nestler EJ, Uher R, Kennedy SH, Turecki G. Nat Commun. 2017 May 22;8:15497.

Discovering biomarkers for antidepressant response: protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort.

Lam RW, Milev R, Rotzinger S, Andreazza AC, Blier P, Brenner C, Daskalakis ZJ, Dharsee M, Downar J, Evans KR, Farzan F, Foster JA, Frey BN, Geraci J, Giacobbe P, Feilotter HE, Hall GB, Harkness KL, Hassel S, Ismail Z, Leri F, Liotti M, MacQueen GM, McAndrews MP, Minuzzi L, Müller DJ, Parikh SV, Placenza FM, Quilty LC, Ravindran AV, Salomons TV, Soares CN, Strother SC, Turecki G, Vaccarino AL, Vila-Rodriguez F, Kennedy SH; CAN-BIND Investigator Team. BMC Psychiatry. 2016 Apr 16;16:105.