Clement Zai

Dr. Zai completed his MSc in Medical Biophysics generating a conditional transgenic mouse model of colorectal cancer. He completed his PhD in Medical Science conducting genetics and pharmacogenetics of schizophrenia.

He became a project scientist at the Centre for Addiction and Mental Health (CAMH) and Assistant Professor at the University of Toronto in 2015. He completed his MPH in Epidemiology at Harvard Chan School of Public Health in 2021. He was promoted to Associate Professor in 2022.

Research Synopsis

Dr. Zai has been conducting a number of pharmacogenetics studies in schizophrenia patients since 2004, including the antipsychotic-induced side effect of tardive dyskinesia. He is continuing with pharmacogenetic studies as a staff scientist in a federally funded randomized controlled three-arm pharmacogenetic clinical trial. His research portfolio has expanded to include genetic studies of suicidal ideation and behaviour, PTSD, childhood-onset high aggression, and bipolar disorder.

His main research goal is to elucidate the mechanism of psychiatric disorders and suicidal behaviour. His multidisciplinary research strategies (from high-throughput genetic analyses, animal behavioral models, to interactions with social and environmental factors in large datasets) will yield findings that can potentially be translated to suicide prevention, reduced medication side effects, and better outcomes for psychiatric patients.

Selected Publications

Senior author. Piras IS, Huentelman MJ, Pinna F, Paribello P, Solmi M, Murru A, Carpiniello B, Manchia M, Zai CC. A review and meta-analysis of gene expression profiles in suicide. European Neuropsychopharmacology. 2022 March; 56:39-49. [DOI: 10.1016/j.euroneuro.2021.12.003]. PMID: 34923210

Primary author. Zai CC, Fabbri C, Hosang GM, Zhang RS, Koyama E, de Luca V, Tiwari AK, King N, Strauss J, Jones I, Jones L, Breen G, Farmer AE, McGuffin P, Vincent JB, Kennedy JL, Lewis CM. Genome-wide association study of suicidal behaviour severity in mood disorders. World Journal of Biological Psychiatry. 2021 Nov; 22(9):722-731. [DOI: 10.1080/15622975.2021.1907711]. Epub 2021 Jun 3. PMID: 33783297

Co-primary author.  Tiwari AK*, Zai CC*, Altar CA, Tanner J-A, Davies P, Traxler P, Li J, Cogan E, Kucera M, Gugila A, Braganza N, Emmerson H, Zai GC, Mueller DJ, Levitan R, Kloiber S, Daskalakis ZJ, Frey B, Bowen J, Tarride J-E, Tytus R, Chandrasena R, Voudouris N, Taylor V, Tempier R, Sharma V, Vasudev A, Dzongowski P, Pliamm L, Greenspoon T, Dechairo B.  Clinical utility of combinatorial pharmacogenomic testing in depression: A Canadian patient- and rater-blinded, randomized, controlled trial.  Translational Psychiatry.  2022 Mar 14; 12(1):101. [DOI: 10.1038/s41398-022-01847-8]. Correction: Transl Psychiatry. May 30, 2022; 12(1):214. doi: 10.1038/s41398-022-01963-5. PMID: 35288545

Co-author. Maihofer AX, Choi KW, Coleman JRI, Daskalakis NP, Denckla CA, Ketema E, Morey RA, Polimanti R, Ratanatharathorn A, Torres K, Wingo AP, Zai CC, Aiello AE, Almli LM, Amstadter AB, Andersen SB, Andreassen OA, Arbisi PA, Ashley-Koch AE, Austin SB, Avdibegović E, Borglum AD, Babić D, Bækvad-Hansen M, Baker DG, Beckham JC, Bierut LJ, Bisson JI, Boks MP, Bolger EA, Bradley B, Brashear M, Breen G, Bryant RA, Bustamante AC, Bybjerg-Grauholm J, Calabrese JR, Caldas-de-Almeida JM, Chen CY, Dale AM, Dalvie S, Deckert J, Delahanty DL, Dennis MF, Disner SG, Domschke K, Duncan LE, Džubur Kulenović A, Erbes CR, Evans A, Farrer LA, Feeny NC, Flory JD, Forbes D, Franz CE, Galea S, Garrett ME, Gautam A, Gelaye B, Gelernter J, Geuze E, Gillespie CF, Goçi A, Gordon SD, Guffanti G, Hammamieh R, Hauser MA, Heath AC, Hemmings SMJ, Hougaard DM, Jakovljević M, Jett M, Johnson EO, Jones I, Jovanovic T, Qin XJ, Karstoft KI, Kaufman ML, Kessler RC, Khan A, Kimbrel NA, King AP, Koen N, Kranzler HR, Kremen WS, Lawford BR, Lebois LAM, Lewis C, Liberzon I, Linnstaedt SD, Logue MW, Lori A, Lugonja B, Luykx JJ, Lyons MJ, Maples-Keller JL, Marmar C, Martin NG, Maurer D, Mavissakalian MR, McFarlane A, McGlinchey RE, McLaughlin KA, McLean SA, Mehta D, Mellor R, Michopoulos V, Milberg W, Miller MW, Morris CP, Mors O, Mortensen PB, Nelson EC, Nordentoft M, Norman SB, O'Donnell M, Orcutt HK, Panizzon MS, Peters ES, Peterson AL, Peverill M, Pietrzak RH, Polusny MA, Rice JP, Risbrough VB, Roberts AL, Rothbaum AO, Rothbaum BO, Roy-Byrne P, Ruggiero KJ, Rung A, Rutten BPF, Saccone NL, Sanchez SE, Schijven D, Seedat S, Seligowski AV, Seng JS, Sheerin CM, Silove D, Smith AK, Smoller JW, Sponheim SR, Stein DJ, Stevens JS, Teicher MH, Thompson WK, Trapido E, Uddin M, Ursano RJ, van den Heuvel LL, Van Hooff M, Vermetten E, Vinkers C, Voisey J, Wang Y, Wang Z, Werge T, Williams MA, Williamson DE, Winternitz S, Wolf C, Wolf EJ, Yehuda R, Young KA, Young RM, Zhao H, Zoellner LA, Haas M, Lasseter H, Provost AC, Salem RM, Sebat J, Shaffer RA, Wu T, Ripke S, Daly MJ, Ressler KJ, Koenen KC, Stein MB, Nievergelt CM. Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information. Biological Psychiatry. 2021 Sep 28;S0006-3223(21)01632-2. [DOI: 10.1016/j.biopsych.2021.09.020]. Online ahead of print. PMID: 34865855

Co-author. Mullins N, Kang J, Campos AI, Coleman JRI, Edwards AC, Galfalvy H, Levey DF, Lori A, Shabalin A, Starnawska A, Su MH, Watson HJ, Adams M, Awasthi S, Gandal M, Hafferty JD, Hishimoto A, Kim M, Okazaki S, Otsuka I, Ripke S, Ware EB, Bergen AW, Berrettini WH, Bohus M, Brandt H, Chang X, Chen WJ, Chen HC, Crawford S, Crow S, DiBlasi E, Duriez P, Fernández-Aranda F, Fichter MM, Gallinger S, Glatt SJ, Gorwood P, Guo Y, Hakonarson H, Halmi KA, Hwu HG, Jain S, Jamain S, Jiménez-Murcia S, Johnson C, Kaplan AS, Kaye WH, Keel PK, Kennedy JL, Klump KL, Li D, Liao SC, Lieb K, Lilenfeld L, Liu CM, Magistretti PJ, Marshall CR, Mitchell JE, Monson ET, Myers RM, Pinto D, Powers A, Ramoz N, Roepke S, Rozanov V, Scherer SW, Schmahl C, Sokolowski M, Strober M, Thornton LM, Treasure J, Tsuang MT, Witt SH, Woodside DB, Yilmaz Z, Zillich L, Adolfsson R, Agartz I, Air TM, Alda M, Alfredsson L, Andreassen OA, Anjorin A, Appadurai V, Soler Artigas M, Van der Auwera S, Azevedo MH, Bass N, Bau CHD, Baune BT, Bellivier F, Berger K, Biernacka JM, Bigdeli TB, Binder EB, Boehnke M, Boks MP, Bosch R, Braff DL, Bryant R, Budde M, Byrne EM, Cahn W, Casas M, Castelao E, Cervilla JA, Chaumette B, Cichon S, Corvin A, Craddock N, Craig D, Degenhardt F, Djurovic S, Edenberg HJ, Fanous AH, Foo JC, Forstner AJ, Frye M, Fullerton JM, Gatt JM, Gejman PV, Giegling I, Grabe HJ, Green MJ, Grevet EH, Grigoroiu-Serbanescu M, Gutierrez B, Guzman-Parra J, Hamilton SP, Hamshere ML, Hartmann A, Hauser J, Heilmann-Heimbach S, Hoffmann P, Ising M, Jones I, Jones LA, Jonsson L, Kahn RS, Kelsoe JR, Kendler KS, Kloiber S, Koenen KC, Kogevinas M, Konte B, Krebs MO, Landén M, Lawrence J, Leboyer M, Lee PH, Levinson DF, Liao C, Lissowska J, Lucae S, Mayoral F, McElroy SL, McGrath P, McGuffin P, McQuillin A, Medland SE, Mehta D, Melle I, Milaneschi Y, Mitchell PB, Molina E, Morken G, Mortensen PB, Müller-Myhsok B, Nievergelt C, Nimgaonkar V, Nöthen MM, O'Donovan MC, Ophoff RA, Owen MJ, Pato C, Pato MT, Penninx BWJH, Pimm J, Pistis G, Potash JB, Power RA, Preisig M, Quested D, Ramos-Quiroga JA, Reif A, Ribasés M, Richarte V, Rietschel M, Rivera M, Roberts A, Roberts G, Rouleau GA, Rovaris DL, Rujescu D, Sánchez-Mora C, Sanders AR, Schofield PR, Schulze TG, Scott LJ, Serretti A, Shi J, Shyn SI, Sirignano L, Sklar P, Smeland OB, Smoller JW, Sonuga-Barke EJS, Spalletta G, Strauss JS, Świątkowska B, Trzaskowski M, Turecki G, Vilar-Ribó L, Vincent JB, Völzke H, Walters JTR, Shannon Weickert C, Weickert TW, Weissman MM, Williams LM, Wray NR, Zai CC, Ashley-Koch AE, Beckham JC, Hauser ER, Hauser MA, Kimbrel NA, Lindquist JH, McMahon B, Oslin DW, Qin X; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; Bipolar Disorder Working Group of the Psychiatric Genomics Consortium; Eating Disorders Working Group of the Psychiatric Genomics Consortium; German Borderline Genomics Consortium; MVP Suicide Exemplar Workgroup; VA Million Veteran Program, Agerbo E, Børglum AD, Breen G, Erlangsen A, Esko T, Gelernter J, Hougaard DM, Kessler RC, Kranzler HR, Li QS, Martin NG, McIntosh AM, Mors O, Nordentoft M, Olsen CM, Porteous D, Ursano RJ, Wasserman D, Werge T, Whiteman DC, Bulik CM, Coon H, Demontis D, Docherty AR, Kuo PH, Lewis CM, Mann JJ, Rentería ME, Smith DJ, Stahl EA, Stein MB, Streit F, Willour V, Ruderfer DM. Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors. Biological Psychiatry. 2022 Feb 1; 91(3):313-327. Epub 2021 Sep 9. [DOI: 10.1016/j.biopsych.2021.05.029]. PMID: 34861974

Co-author. Ni G, Zeng J, Revez JA, Wang Y, Zheng Z, Ge T, Restuadi R, Kiewa J, Nyholt DR, Coleman JRI, Smoller JW; Schizophrenia Working Group of the Psychiatric Genomics Consortium; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Yang J, Visscher PM, Wray NR. A Comparison of Ten Polygenic Score Methods for Psychiatric Disorders Applied Across Multiple Cohorts. Biological Psychiatry. 2021 May 4:S0006-3223(21)01263-4. [DOI: 10.1016/j.biopsych.2021.04.018]. PMID: 34304866

Senior author. Lu JY, Tiwari AK, Freeman N, Zai GC, Luca V, Müller DJ, Tampakeras M, Herbert D, Emmerson H, Cheema SY, King N, Voineskos AN, Potkin SG, Lieberman JA, Meltzer HY, Remington G, Kennedy JL, Zai CC. Liver enzyme CYP2D6 gene and tardive dyskinesia. Pharmacogenomics. 2020 Oct;21(15):1065-1072. [DOI: 10.2217/pgs-2020-0065]. PMID: 32969762

Senior author. Maes MS, Lu JY, Tiwari AK, Freeman N, de Luca V, Müller DJ, Voineskos AN, Potkin SG, Lieberman JA, Meltzer HY, Remington G, Kennedy JL, Zai CC. Schizophrenia-associated gene dysbindin-1 and tardive dyskinesia. Drug Development Research. 2021 Aug;82(5):678-684. [DOI: 10.1002/ddr.21681]. PMID: 32394511

Senior author. Cheung S, Woo J, Maes MS, Zai CC. Suicide epigenetics, a review of recent progress. Journal of Affective Disorders. 2020 Mar 15; 265:423-438. [DOI: 10.1016/j.jad.2020.01.040]. Epub 2020 Jan 15. Review. PMID: 32090769

Co-senior author. Melhuish Beaupre LM, Tiwari AK, Gonçalves VF, Lisoway AJ, Harripaul RS, Müller DJ, Zai CC, Kennedy JL. Antidepressant-Associated Mania in Bipolar Disorder: A Review and Meta-analysis of Potential Clinical and Genetic Risk Factors. Journal of Clinical Psychopharmacology. 2020 Mar/Apr; 40(2):180-185. [DOI: 10.1097/JCP.0000000000001186.] PMID: 32134853

Primary author. Zai CC, Tiwari AK, Zai GC, Freeman N, Pouget JG, Greco J, Tampakeras M, Shaikh SA, Herbert D, Emmerson H, Cheema SY, Braganza N, Mueller DJ, Voineskos AN, Remington G, Kennedy JL. Association Study of the Complement Component C4 Gene in Tardive Dyskinesia. Frontiers in Pharmacology - Neuropharmacology. 2019 Nov 26; 10:1339. [DOI: 10.3389/fphar.2019.01339] PMID: 31849639.

Co-author. Kamitaki N, Sekar A, Handsaker RE, de Rivera H, Tooley K, Morris DL, Taylor KE, Whelan CW, Tombleson P, Loohuis LMO; Schizophrenia Working Group of the Psychiatric Genomics Consortium, Boehnke M, Kimberly RP, Kaufman KM, Harley JB, Langefeld CD, Seidman CE, Pato MT, Pato CN, Ophoff RA, Graham RR, Criswell LA, Vyse TJ, McCarroll SA. Complement genes contribute sex-biased vulnerability in diverse disorders. Nature. 2020 Jun;582(7813):577-581. [DOI: 10.1038/s41586-020-2277-x]. 2020 May 11. PMID: 32499649

Primary author. Zai CC, George J, Cheema SY, Zai GC, Fonseka TM, Danesi M, Shaikh SA, Irwin D, Tampakeras M, Freeman N, Rehm J, Wells S, Kennedy JL. An examination of genes, stress and suicidal behavior in two First Nations communities: The role of the brain-derived neurotropic factor gene. Psychiatry Research. 2019 Feb 18; 275:247-252. [DOI: 10.1016/j.psychres.2019.02.034]. PMID: 30933702

Appointments

Staff Scientist, Tanenbaum Centre for Pharmacogenetics, Molecular Brain Science Department, Campbell Family Mental Health Institute, Centre for Addiction and Mental health

Associate Professor, Department of Psychiatry, Institute of Medical Science, University of Toronto

Visiting Scientist, Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard

Honours and Awards

The International College of Neuropsychopharmacology Max Hamilton Memorial Prize (2023)

Young Investigator Travel Awards

American Society of Clinical Psychopharmacology (2014, 2018)

American Foundation for Suicide Prevention (2017)

World Federation of Societies of Biological Psychiatry (2017)

 American College of Neuropsychopharmacology (2014)

International Society for Bipolar Disorders (2013)