Validation of a new therapeutic avenue for the treatment of depression and anxiety

Depression and anxiety are a significant cause of disability globally. Treatment resistant depression and comorbid anxiety account for 50% of sufferers. Lack of effective treatments indicates that the etiology of depression is incompletely understood. These disorders result from circuit level maladaptation involving multiple brain regions. Our lab has shown that JNK modulates anxiety in mice and that JNK inhibition in a subset of cells in hippocampus alleviates anxiety.

This project will test the usefulness of cell-specific JNK inhibition for clinical depression using early life stress models. We will use fiber photometry to precisely define how JNK alters neural connectivity to control mood. Single cell transcriptomics will define JNK-regulated genes that confer susceptibility to anxiety and depression. This will establish the validity of targeting JNK as a new therapeutic avenue for treatment resistant depression and anxiety, while gaining insight on the underlying mechanism.