Detail

Keywords

Antidepressive Agents; Biomarkers, Pharmacological; Depression; Depressive Disorder, Treatment-Resistant; Digital Medicine; Functional Magnetic Resonance; Functional Neuroimaging; Genetics; Genetics, Behavioral; Ketamine; Magnetic Resonance Imaging; Neuroimaging

Research group(s)

• Clinical Neurimaging & Digital Health
  Research Area: Research focuses on affective disorders, particularly unipolar depression, spanning clinical diagnosis, pharmacotherapy, and underlying neurobiological mechanisms. A major emphasis has been structural and functional neuroimaging and imaging genetics linking variants to brain phenotypes. More recently, my work has expanded to digital therapeutics, including the development and clinical evaluation of the CBT-based digital therapeutic edupression.com®.
  Members:
  Lukas Pezawas

Research interests

My research has focused consistently on affective disorders — predominantly unipolar depression — encompassing clinical diagnosis, pharmacological therapy, and the biological mechanisms underlying these conditions. A broad range of biological and methodological approaches has been applied throughout my career. A major emphasis has been functional and structural neuroimaging, including task-based and resting-state fMRI as well as voxel-based morphometry, used to characterise neural circuits implicated in depression vulnerability and antidepressant drug response. Imaging genetics studies linking common genetic polymorphisms (5-HTTLPR, BDNF Val66Met, COMT Val158Met) to brain phenotypes have been a particular strength of this research programme and have generated findings of high scientific impact. In recent years, my research has extended to digital therapeutics. I played a leading role in the development and clinical evaluation of edupression.com, a CBT-based digital therapeutic for depression. Following a successful Phase III randomised controlled trial, edupression received approval as a reimbursable Digitale Gesundheitsanwendung (DiGA) in Germany — one of the first evidence-based digital health applications for a psychiatric indication to achieve this status in a major European healthcare system.

Techniques, methods & infrastructure

Structural and functional MRI formed the core methodological platform, encompassing resting-state fMRI, task-based paradigms (n-back working memory, emotional face processing), and voxel-based morphometry. Imaging genetics approaches linked common genetic polymorphisms to brain phenotypes using general linear models, seed-based functional connectivity analyses, and multivariate methods including partial least squares regression and independent component analysis. EEG-based electrophysiology and actigraphy complemented neuroimaging assessments in clinical populations. Clinical research was based at the TRD Clinic and the Main Outpatient Clinic of the Clinical Division of General Psychiatry, Medical University of Vienna, providing access to well-characterised patient cohorts included in a patient registry. Randomised controlled trials — including active sham-controlled designs — and longitudinal pharmacological studies were conducted using established clinical trial infrastructure; longitudinal fMRI designs were applied to characterise neuroplasticity during antidepressant pharmacotherapy and esketamine treatment. Data analysis was performed in R, MATLAB (SPM, FSL), and Python. International research collaborations with Stanford University School of Medicine, the National Institute of Mental Health (NIH/NIMH), TU Dresden, and the IMAGEN European consortium as well as other consortia provided access to large-scale multi-site neuroimaging datasets.

Grants

• Entwicklung und Aufbau einer umfassenden digitalen Plattform für Depressionspatienten als digitale Dienstleistung (2019)
  Source of Funding: FFG (Austrian Research Promotion Agency), Auftragsforschung
  Principal Investigator
• Cognition and Functional Connectivity after Elective Treatment of Brain Aneurysms (2016)
  Source of Funding: FWF (Austrian Science Fund), Klininische Forschung (KLIF)
  Coordinator of the collaborative project
• Neural Correlates of SSRI Drug Response: Impact of Stress System Genes (2012)
  Source of Funding: FWF (Austrian Science Fund), Klininische Forschung (KLIF)
  Principal Investigator
• Impact of Serotonergic Haplotypes on Structural and Functional Neural Circuitries in Depression (2010)
  Source of Funding: OeNB (Oesterreichische Nationalbank), Jubiläumsfonds
  Coordinator of the collaborative project
• Neural, Genetic, and Peripheral Correlates of SSRI Pharmaco-Response (2010)
  Source of Funding: OeNB (Oesterreichische Nationalbank), Jubiläumsfonds
  Principal Investigator
• Genetically Driven Variance in Glutamate Signaling Impacts Brain Circuitries of Depression and Related Behavior (2008)
  Source of Funding: Medical University of Vienna, Research-Grant
  Principal Investigator
• P3514: Multimodal Imaging of human Brain Monoamine Transporters, SFB F35-B11: Transmembrane transporters in health and disease (2007)
  Source of Funding: FWF (Austrian Science Fund), Sonderforschungsbereich (SFB)
  Principal Investigator
• Epistase von 5-HTTLPR und val66met BDNF: Ein genetischer Suszeptibilismechanismus der Depression (2006)
  Source of Funding: OeNB (Oesterreichische Nationalbank), Jubiläumsfonds
  Principal Investigator
• Epistase von 5-HTTLPR und val66met BDNF: Ein genetischer Suszeptibilismechanismus der Depression (2005)
  Source of Funding: Medical University of Vienna, MUW-Prämie
  Principal Investigator
• Epistasis of SERT, COMT &. BDNF: A Mechanistic Model of Depression (2005)
  Source of Funding: Bundesministerium für Soziales, Gesundheit, Pflege und Konsumentenschutz, Anbahnungsfinanzierung
  Principal Investigator
• A [123I]-IBZM SPECT Investigation of Genetic Variants of the Human D2DR-Gene that Impact on in vivo Striatal Dopamine Receptor Density of Schizophrenic Patients and Normal Controls (2001)
  Source of Funding: FWF (Austrian Science Fund), Schroedinger-Award
  Principal Investigator

Selected publications

1. Pezawas, L. et al. (2005) ‘5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression’, Nature Neuroscience, 8(6), pp. 828–834. Available at: https://doi.org/10.1038/nn1463.
2. Pezawas, L. et al. (2004) ‘The Brain-Derived Neurotrophic Factor val66met Polymorphism and Variation in Human Cortical Morphology’, The Journal of Neuroscience, 24(45), pp. 10099–10102. Available at: https://doi.org/10.1523/jneurosci.2680-04.2004.
3. Pezawas, L. et al. (2008) ‘Evidence of biologic epistasis between BDNF and SLC6A4 and implications for depression’, Molecular Psychiatry, 13(7), pp. 709–716. Available at: https://doi.org/10.1038/mp.2008.32.
4. Bartova, L. et al. (2015) ‘Reduced default mode network suppression during a working memory task in remitted major depression’, Journal of Psychiatric Research, 64, pp. 9–18. Available at: https://doi.org/10.1016/j.jpsychires.2015.02.025.
5. Rabl, U. et al. (2025) ‘HPA axis in psychotic and non-psychotic major depression: Cortisol plasma levels and hippocampal volume’, Journal of Affective Disorders, 377, pp. 14–22. Available at: https://doi.org/10.1016/j.jad.2025.02.014.