“Circuit Biomarkers for Diagnosing and Treating Neurophysiological Subtypes of Depression”
Dr. Liston is striving to identify different depression subtypes by looking for patterns in the brain (biomarkers). Collaborating with investigators at multiple institutions, Dr. Liston has compiled an unprecedentedly large dataset of resting state fMRI scans for over 1,000 depressed patients and matched controls. Dr. Liston’s lab has analyzed these scans to identify distinct patterns of abnormal brain connectivity that define each of three apparent subtypes. Interestingly, the deficient availability of the “calming” neurotransmitter GABA in the prefrontal cortex characterizes the subtype that closely resembles the debilitating result of chronic stress.
Now, Liston’s team plans to extend these discoveries into useful results for patients through three research aims:
1. Validate the accuracy of these biomarkers for classifying depression, studying a prospective 75-patient cohort with brain imaging, and assessments comparing stress resiliency and reactivity. In this portion, Liston’s team will also seek to confirm the specific GABA and connectivity deficits in the prefrontal cortex as were discovered in the stress-related subtype.
2. Modeling the deficits of the stress-related subtype in the brains of mice, test whether these can cause the mice to display deficits in cognitive control, reward processing, and depression-related behaviors, as observed in humans with this subtype.
3. Test whether two different strategies—ketamine treatment, and optogenetically enhancing (GABA-producing) interneuron activity—can work to improve prefrontal cortex dysfunction and combat depression-like behaviors in chronically stressed mice. In parallel, the team will test whether ketamine works especially effectively to treat the stress-related subtype in humans.
Dr. Liston states, “successful achievement of our aims will establish neuroimaging biomarkers with the long-term potential to transform clinical practice by providing, for the first time, an objective means of diagnosing subtypes of depression and predicting response to a rapid-acting antidepressant.”
About the award
The IMHRO/Janssen Rising Star Translational Research Award seeks to fund novel therapies for psychiatric illness with the objective to advance the translation of scientific knowledge of underlying disease mechanisms in bipolar disorder, schizophrenia, and major depression toward benefits to patients and the healthcare system.
Chosen by IMHRO's Scientific Advisory Board, each Rising Star recipient will receive up to $250,000 to fund research for their studies.