More precise diagnostics for depression and individualized treatments

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Conor Liston, a 2015 One Mind/Janssen Translational Research Rising Star Awardee, continues to make exciting progress on understanding the biological causes of depression and ways to promote recovery.  His overarching hypothesis is that there are multiple subtypes of depression and that therapies need to specifically target these subtypes to be effective.   This aligns with the concept of “personalized medicine”, which is currently transforming health care.

In 2016, Dr. Liston and a team of scientists compared resting state functional magnetic resonance imaging (rsfMRI) in individuals with and without a diagnosis of depression.  rsfMRI is proving to be a valuable tool for studying functional connections of specific brain regions and local networks, as well as for understanding overall brain function.  Using statistical and computational methods to analyze the brain scans, Dr. Liston identified and described 4 different subtypes of depression. They then applied this knowledge to predict which patients would respond favorably to repetitive transcranial magnetic stimulation (rTMS) of specific brain regions. This major scientific advance toward personalized medicine for depression was published in the prestigious journal Nature Medicine last year (Drysdale et al., 2017).

Building on these clinical imaging studies, Dr. Liston went on to investigate the cellular and molecular changes in the brain using a mouse model of depression.  The model appears to replicate the features associated with at least one of the clinical subtypes, which is important for translation of knowledge from mice to humans. To accelerate the research, he and his team developed a user-friendly, high-throughput system for training and studying multiple mice at the same time. The system includes high-resolution infrared cameras that record the mouse’s behavior and an Arduino-supported system for simultaneously recording responses in the brain. Using this system, they have collected preliminary data demonstrating that the onset of depression-related behavior is associated with a decrease in dendritic spines in the prefrontal cortex.  Dendritic spines are where nerve cells (neurons) form many of their connections. Thus, their new data provides a biological explanation for the loss of prefrontal cortex connectivity and subsequent disruption in brain functions such as decision-making, social behavior and personality. New publications based on these findings are anticipated in 2018.

Dr. Liston’s research is remarkable in its innovation and impact. Depression is the second most disabling medical condition worldwide.  He and his collaborators are making major strides in lessening the burden of depression by developing tools for identifying likely responders to targeted treatments.  Dr. Liston’s team is also designing new systems and strategies to accelerate therapeutic development.  We at One Mind applaud his efforts and look forward to his continued success.

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Dr. Liston’s talk at Music Festival for Brain Health 2015: