Principal Investigator: Gustavo Turecki, MD, PhD
Molecular changes associated with early-life adversity, mood disorders and their comorbidities, and suicide
- DNA modifications
- Histone modifications
- Noncoding RNAs (ncRNAs; lncRNAs, miRNAs, etc.)
Biomarkers of major depressive disorder treatment response or relapse and suicidal events
- Molecular biomarkers
- Neural correlates
Clinical phenotypes associated with suicidal behaviour
Suicide Brain Banking
Contributions to the Suicide section of the Douglas-Bell Canada Brain Bank
Single-cell changes associated with depression in postmortem human brains
- Nagy C, Maitra M, Tanti A, Suderman M, Théroux J-F, Davoli MA, Perlman K, Yerko V, Wang YC, Tripathy S, Pavlidis P, Mechawar N, Ragoussis J, Turecki G. Single-nucleus transcriptomics of the prefrontal cortex in major depressive disorder implicates oligodendrocyte precursor cells and excitatory neurons. Nature Neuroscience 2020;23(6):771-81. Note: This study optimized a protocol for single-nucleus sequencing in postmortem brain tissue and described one of the first large-scale single-cell transcriptomic study in mental disorders.
- Maitra M, Nagy C, Chawla A, Wang YC, Nascimento C, Suderman M, Théroux JF, Mechawar N, Ragoussis J, Turecki G. Extraction of nuclei from archived post-mortem tissues for single-nucleus sequencing applications. Nature Protocols. 2021;16(6):2788-801. PMID: 33972803. Note: This publication details the methodological approach for performing single-nucleus transcriptomics on post-mortem brain tissue, which has been developed and optimized by our lab.
Molecular mechanisms of response to antidepressant treatment
- Lopez JP, Lim R, Cruceanu C, Crapper L, Fasano C, Labonte B, Maussion G, Yang JP, Yerko V, Vigneault E, El Mestikawy S, Mechawar N, Pavlidis P, Turecki G. miR-1202 is a primate-specific and brain-enriched microRNA involved in major depression and antidepressant treatment. Nature Medicine 2014;20(7):764-8. Note: We identified a miRNA that is differentially expressed in subjects who respond to treatment for major depression and identified a new molecular target for antidepressant treatment.
- 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, Muller 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. MicroRNAs 146a/b-5 and 425-3p and 24-3p are markers of antidepressant response and regulate MAPK/Wnt-system genes. Nature Communications 2017;8:15497. Note: This article identified four miRNA that were consistent mediators of antidepressant response over different lines of evidence. We identified new molecular targets for antidepressant treatment.
- Belzeaux R, Gorgievski V, Fiori L, Lopez JP, Grenier J, Lin R, Nagy C, Ibrahim EC, Gascon E, Courtet P, Richard-Devantoy S, Berlim M, Chachamovich E, Théroux JF, Dumas S, Giros B, Rotzinger S, Soares C, Foster J, Mechawar N, Tall G, Tzavara E, Kennedy SH, Turecki G. GPR56/ADGRG1 is associated with response to antidepressant treatment. Nature Communications 2020;11(11):1635. Note: This investigation revealed a novel role for G protein-coupled receptor 56 (GPR56) in mediating the response to antidepressant treatment.
Early-life adversity associates with epigenetic changes in brain tissue
- McGowan PO, Sasaki A, D’Alessio AC, Dymov S, Labonte B, Szyf M*, Turecki G*, Meaney MJ*. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nature Neuroscience 2009;12(3):342-8. *shared senior authorship and corresponding authors.
Note: This work was the first to show biological mechanisms for the lasting impact of social trauma and received widespread media attention, as well as 2,700 citations.
- Labonte B, Suderman M, Maussion G, Navaro L, Yerko V, Mahar I, Bureau A, Mechawar N, Szyf M, Meaney MJ, Turecki G. Genome-wide epigenetic regulation by early-life trauma. Archives General Psychiatry 2012;69(7):722-31. Note: This was the first genome-wide study investigating epigenetic regulation of the brain by the early-life environment in humans.
- Lutz PE, Tanti A, Gasecka A, Barnett-Burns S, Kim JJ, Zhou Y, Chen GG, Wakid M, Shaw M, Almeida D, Chay MA, Yang J, Lariviere V, M’Boutchou MN, van Kempen LC, Yerko V, Prud’homme J, Davoli MA, Vaillancourt K, Theroux JF, Bramoulle A, Zhang TY, Meaney MJ, Ernst C, Cote D, Mechawar N, Turecki G. Association of a history of child abuse with impaired myelination in the anterior cingulate cortex: convergent epigenetic, transcriptional, and morphological evidence. The American Journal of Psychiatry 2017;174(12):1185-1194. Note: This investigation identified changes in DNA methylation in myelin-related genes that associated with child abuse, specifically in oligodendrocytes.
- Lutz PE, Chay MA, Pacis A, Chen GC, Aouabed Z, Maffioletti E, Théroux JF, Grenier JC, Yang J, Auirre M, Ernst C, Redensek A, van Kempen LC, Yalcin I, Kwan T, Mechawar N, Pastinen T, Turecki G. Non-CG methylation and multiple histone profiles associate child abuse with immune and small GTPase dysregulation. Nature Communications 2021;12(1):1132. Note: This study combined multiple layers of epigenomic data to understand molecular adaptations in the amygdala, a brain region that plays a critical role in the regulation of emotions, in individuals who were severely abused during childhood.
Relationship between behavioural traits and depression and suicide phenotypes
- Dumais A, Lesage AD, Alda M, Rouleau G, Dumont M, Chawky N, Roy M, Mann JJ, Benkelfat C, Turecki G. Risk factors for suicide completion in major depression: a case-control study of impulsive and aggressive behaviors in men The American Journal of Psychiatry 2005;162(11):2116-24. Note: This innovative study furthered our understanding of clinical and behavioral risk factors of suicide. The new methods and original design used here are now regarded as standards in the field.
- McGirr A, Alda M, Seguin M, Cabot S, Lesage A, Turecki G. Familial aggregation of suicide explained by cluster B traits: a three-group family study of suicide controlling for major depressive disorder. The American Journal of Psychiatry 2009;166(10):1124-34. Note: These studies used new methods and original study designs that are now regarded as standards in the field to better define depression and suicide phenotypes. In particular, we study how impulsive-aggressive behaviours contribute to suicide risk, and have published in several high-impact journals.
- Turecki G. The molecular bases of the suicidal brain. Nat Rev Neurosci 2014;15(12):802-16.
- Turecki G & Brent, DA. Suicide and suicidal behaviour. Lancet. 2016 19;387(10024):1227-39.
- Turecki G, Brent DA, Gunnell D, O’Connor RC, Oquendo MA, Pirkis J, Stanley BH. Suicide and suicide risk. Nat Rev Dis Primers. 2019;5(1):74.
Full publication list: G Turecki on PubMed