Abstract: Both, clinical diagnostics of MDD and measures of antidepressant drug response are based upon subjective patient reports or clinical observations. The lack of biological definitions within diagnostics and therapy response poses a significant hurdle for the discovery of disease and therapy mechanisms.
This issue has successfully been addressed in Imaging Genetics studies by utilizing an intermediate phenotype approach, which is not dependent on the phenomenological operationalization of MDD. Resulting associations between genes and brain circuitries have clearly led to a deeper understanding of the neural underpinnings of MDD. Yet, it became evident that single gene effects are small and therefore clinically irrelevant. Additionally, recent research emphasizes the enormous complexity how genes and environment shape the development and function of depression circuitries by involving epistatic, epigenetic, gene-environment, and developmental mechanisms.
To move acquired diagnosis-related knowledge to a clinical level, several hurdles have to be taken, such as reproducibility and comparability of imaging studies as well as a far more complex modeling of genetic effects including the transcriptome and gene-regulation networks. Additionally, to better characterize neurobiological antidepressant treatment mechanisms on a brain systems level, more sophisticated statistical analyses techniques need to be applied, which specifically support the identification of treatment-related mechanisms or subgroups of MDD patients varying in drug-response.
Previous work of my lab as well as possible future strategies will be presented during this lecture.