Etienne Sibille, Ph.D.


Etienne Sibille, PhD, is the scientific lead of the NDA program, Chair of the Campbell Family Mental Health Research Institute at CAMH, senior scientist at CAMH and Professor of Psychiatry, and of Pharmacology and Toxicology at the University of Toronto. Dr. Sibille obtained his PhD and training Cornell and Columbia universities in New York. Prior to moving to CAMH in 2014, he was tenured faculty at the University of Pittsburg, USA.

Our Research Focus


The goals of my research program are to investigate the cellular and molecular mechanisms underlying major depressive disorders (MDD), life-long maturation or aging of the brain, and their respective interactions and, to use this knowledge to develop strategies for novel therapeutic approaches. To reach these goals, we use large-scale genomic, molecular and biostatistical approaches to characterize the primary pathology in human postmortem brain samples. We then use relevant genetic and environmental mouse models to investigate causal links between the identified pathologies (e.g. BDNF/GABA dysregulations) and mood regulatory mechanisms. Finally we test novel therapeutic strategies at the behavioral and molecular/cellular levels.

Meet the team

Publication List


The full detail can be found on Google Scholar. Below is a list of significant contributions to the field.

Characterization of the primary molecular pathology of depression in human postmortem subjects

My research group focuses on translational research aimed at identifying the cellular and molecular bases of major depression. We have provided direct evidence for BDNF- and GABA-related pathologies in depression and showed they contribute to mood and cognitive symptoms. These studies link two major hypotheses of depression, namely the reduced neurotrophic support and altered excitation/inhibition balance. These findings have led to novel models of brain disorders, linking molecular, cellular, biochemical, neural network and behavioral levels, and to the development of novel therapeutics for mood and cognitive symptoms occurring in depression and in age-related disorders. (~50 publications)

    1. Seney ML, Huo Z, Cahill K., French L., Puralewski R., Zhang J., Logan RW, Tseng G., Lewis D.A, Sibille E. Opposite molecular signatures of depression in men and women. Biol Psychiatry. 2018 Feb 19. pii: S0006-3223(18)30065-9. doi: 10.1016/j.biopsych.2018.01.017. PMID: 29548746.
    2. Scifo E, Pabba M, Kapadia F, Ma T, Lewis DA, Tseng GC, Sibille E. Sustained Molecular Pathology Across Episodes and Remission in Major Depressive Disorder. Biol Psychiatry. 2018 Jan 1;83(1):81-89. PMID: 28935211; PMCID: PMC5705452.
    3. Ding Y, Chang LC, Wang X, Guilloux JP, Parrish J, Oh H, French BJ, Lewis DA, Tseng GC, Sibille E. Molecular and Genetic Characterization of Depression: Overlap with other Psychiatric Disorders and Aging. Mol Neuropsychiatry. 2015 May;1(1):1-12. PMID: 26213687; PMCID: PMC4512183.
    4. Tripp A, Oh H, Guilloux JP, Martinowich K, Lewis DA, Sibille E. Brain-derived neurotrophic factor signaling and subgenual anterior cingulate cortex dysfunction in major depressive disorder. Am J Psychiatry. 2012 Nov;169(11):1194-202. PMID: 23128924; PMCID: PMC3638149.
    5. Guilloux JP, Douillard-Guilloux G, Kota R, Wang X, Gardier AM, Martinowich K, Tseng GC, Lewis DA, Sibille E. Molecular evidence for BDNF- and GABA-related dysfunctions in the amygdala of female subjects with major depression. Mol Psychiatry. 2012 Nov;17(11):1130-42. PMID: 21912391; PMCID: PMC3237836.

Altered SST+ neuron-mediated information processing in depression and aging

We have shown that SST+ GABAergic interneuron targeting pyramidal cell dendrites are affected in depression and other brain disorders (human postmortem studies), are vulnerable to biological stress, and contribute to behavioral (mood and cognition) and physiological symptoms in brain disorders (rodent studies). These studies have led to a model of reduced signal-to-noise ratio and altered information processing by cortical microcircuits in depression and other brain disorders, and to a novel therapeutic drug development program.s)

    1. Prévot T, Sibille E. Altered GABA-mediated information processing and cognitive dysfunctions in depression and other brain disorders. Mol Psychiatry. 2020 Apr 28. doi: 10.1038/s41380-020-0727-3. Online ahead of print.PMID: 32346158
    2. Prévot TD, Li G, Vidojevic A, Misquitta KA, Fee C, Santrac A, Knutson DE, Stephen MR, Kodali R, Zahn NM, Arnold LA, Scholze P, Fisher JL, Marković BD, Banasr M, Cook JM, Savic M, Sibille E*. Novel Benzodiazepine-Like Ligands with Various Anxiolytic, Antidepressant, or Pro-Cognitive Profiles. Mol Neuropsychiatry. 2019 Apr;5(2):84-97. doi: 10.1159/000496086. PMID: 31192221, PMCID: PMC6528097
    3. Fee C, Banasr M, Sibille E. Somatostatin-Positive Gamma-Aminobutyric Acid Interneuron Deficits in Depression: Cortical Microcircuit and Therapeutic Perspectives. Biol Psychiatry. 2017 Oct 15;82(8):549-559. PubMed PMID: 28697889; PubMed Central PMCID: PMC5610074.
    4. Lin LC, Sibille E. Somatostatin, neuronal vulnerability and behavioral emotionality. Mol Psychiatry. 2015 Mar;20(3):377-87. PubMed PMID: 25600109; PubMed Central PMCID: PMC4355106.
    5. Soumier A, Sibille E. Opposing Effects of Acute Versus Chronic Blockade of Frontal Cortex Somatostatin-Positive Inhibitory Neurons on Behavioral Emotionality in Mice. Neuropsychopharmacology. 2014 Aug;39(9):2252-62. PMID: 24690741, PMCID: PMC4104344

Investigating the role of reduced BDNF in depression and aging

We have provided evidence of reduced BDNF signaling in postmortem brain of depressed subjects and of aged controls, and confirmed that low BDNF contributes to the molecular and behavioural changes associated with these conditions using mouse genetic models. (10+ publications).

  1. Oh H, Piantadosi SC, Rocco BR, Lewis DA, Watkins SC, Sibille E. The role of dendritic brain-derived neurotrophic factor transcripts on altered inhibitory circuitry in depression. Biological Psychiatry. 2019 Mar 15;85(6):517-26. DOI: 1016/j.biopsych.2018.09.026
  2. Oh H, Lewis DA, Sibille E. The Role of BDNF in Age-Dependent Changes of Excitatory and Inhibitory Synaptic Markers in the Human Prefrontal Cortex. Neuropsychopharmacology. 2016 Dec;41(13):3080-3091. PubMed PMID: 27417517; PubMed Central PMCID: PMC5101556.
  3. McKinney BC, Lin CW, Oh H, Tseng GC, Lewis DA, Sibille E. Hypermethylation of BDNF and SST Genes in the Orbital Frontal Cortex of Older Individuals: A Putative Mechanism for Declining Gene Expression with Age. Neuropsychopharmacology. 2015 Oct;40(11):2604-13. PubMed PMID: 25881116; PubMed Central PMCID: PMC4569950.
  4. Guilloux JP, Douillard-Guilloux G, Kota R, Wang X, Gardier AM, Martinowich K, Tseng GC, Lewis DA, Sibille E. Molecular evidence for BDNF- and GABA-related dysfunctions in the amygdala of female subjects with major depression. Mol Psychiatry. 2012 Nov;17(11):1130-42. PubMed PMID: 21912391; PubMed Central PMCID: PMC3237836.

Age by Disease molecular interactions

We have shown that aging represents the largest source of biological variability in transcriptome in the human postmortem brain, and have now characterized its nature, extent and gene/ pathway specificities. Recent findings from our group demonstrate that these age-related changes include neuropsychiatric and neurodegenerative disease pathways and may promote disease. These experimental findings have been conceptualized in a novel age-by-disease interaction hypothesis, which we are testing at the genetic levels, using a combined human postmortem brain and epidemiological cohort research approach. (15+ publications)

  1. Pabba M, Scifo E, Kapadia F, Nikolova YS, Ma T, Mechawar N, Tseng GC, Sibille E. Resilient protein co-expression network in male orbitofrontal cortex layer 2/3 during human aging. Neurobiol Aging. 2017 Oct;58:180-190. PubMed PMID: 28750307; PubMed Central PMCID: PMC5581682.
  2. Ding Y, Chang LC, Wang X, Guilloux JP, Parrish J, Oh H, French BJ, Lewis DA, Tseng GC, Sibille E. Molecular and Genetic Characterization of Depression: Overlap with other Psychiatric Disorders and Aging. Mol Neuropsychiatry. 2015 May;1(1):1-12. PubMed PMID: 26213687; PubMed Central PMCID: PMC4512183.
  3. Douillard-Guilloux G, Guilloux JP, Lewis DA, Sibille E. Anticipated brain molecular aging in major depression. Am J Geriatr Psychiatry. 2013 May;21(5):450-60. PubMed PMID: 23570888; PubMed Central PMCID: PMC3615087.
  4. Sibille E. Molecular aging of the brain, neuroplasticity, and vulnerability to depression and other brain-related disorders. Dialogues Clin Neurosci. 2013 Mar;15(1):53-65. PubMed PMID: 23576889; PubMed Central PMCID: PMC3622469.