Neurobiological mechanisms in the prevention and treatment of major depressive disorder

Research

We investigate the neurobiological mechanisms that underlie major depressive disorder and influence the response to antidepressant treatment. Our aim is to improve prevention and treatment by applying a pathophysiological perspective.

Our research centres around the neurobiological mechanisms of major depressive disorder (MDD) and how these can be reversed with traditional (i.e., monoaminergic antidepressants) and novel (i.e., ketamine, psilocybin) antidepressant treatment. We investigate how central processes in the brain are reflected in blood to identify markers that can be used to advance the prevention and treatment of MDD from a pathophysiological perspective. Our translational approach includes clinical research aimed at the identification and validation of blood-based biomarkers of antidepressant response and individual depressive symptoms as well as preclinical research investigating the neurobiological effects of traditional and novel antidepressant agents in both blood and brain tissue using animal models of MDD.

Main objectives of our research:

The identification and validation of blood-based biomarkers of the antidepressant and antisuicidal efficacy of traditional and novel antidepressant treatment.
Compare the antidepressant efficacy of traditional and novel antidepressant agents from a pathophysiological perspective.
Investigate the involvement of sleep and circadian rhythmicity in the antidepressant efficacy of different antidepressant treatments.
Elucidate how individual symptoms of MDD influence pathophysiological mechanisms to uncover novel approaches for prevention and treatment.

Relevance

How our research benefits to society

MDD represents one of the most prevalent psychiatric disorders. With a 12-month prevalence estimated at 5% and a lifetime prevalence of around 15%, MDD has been classified as one of the primary causes of disability worldwide. This coincides with a considerable societal impact, including a significant contribution to healthcare costs and work absenteeism. Despite the application of evidence-based treatment strategies, research indicates that around 20-30% of the patients does not respond to multiple steps of antidepressant treatment. These patients are classified as treatment-resistant depression (TRD), which is responsible for the largest contribution to the individual and societal impact of MDD.

The pathophysiology of MDD involves a diverse range of neurobiological mechanisms. This includes alterations in the expression of various genes and proteins that regulate brain structure and function, especially in areas involved in mood regulation. Investigating how traditional (i.e., monoaminergic antidepressants) and novel (i.e., ketamine, psilocybin) antidepressant agents influence these neurobiological processes facilitates the positioning in the current treatment landscape. Elucidating how central processes in the brain are reflected in blood enables the identification of biomarkers to predict and monitor treatment outcomes, to personalize treatment with targeted interventions. Research evaluating the relationship between individual symptoms of MDD and neurobiological mechanisms sheds light on the causes or consequences of pathophysiological alterations. Together, our line of research provides valuable opportunities to inform and advance the prevention and treatment from a pathophysiological perspective, reducing the individual and societal burden of MDD and TRD.