Psychedelic compounds: Mechanisms, circuits and behavioral outcomes of antidepressant treatment response

Mental health disorders affect 84 million Europeans and are associated with an economic burden of 100 billion SEK/year in Sweden alone.

Evidence from clinical trials suggests that a single psilocybin treatment can produce a fast and sustained antidepressant response.

However, many questions still remain about its mechanism of action, due to lack of knowledge of the brain cells and circuits where the effects are taking place and limitations of the behavioral tests used to examine antidepressant activity in rodents.

Combining advanced molecular, behavioral and computational tools, this project will establish a deep phenotyping system to deconstruct the behavioral “language” associated with treatment response.

This is refinement from the traditional assessment of single-behavior readouts to dynamic group behaviors in a translationally-relevant context that will cause a paradigm shift and improve the field of behavioral neuroscience.

To go beyond the state-of-the-art, I will combine activity-dependent labelling techniques and single-cell methods to identify the genes and cell circuits engaged during psilocybin treatment.

To address the multidimensional nature of psychiatric disorders, I will manipulate genes and networks related to the effects of psilocybin.

The ambitious and innovative studies proposed here have the potential to change our understanding of mental health disorders and impacting the development of fast-acting and efficacious treatments for psychiatric disorders.