Dr. Conor Liston: Neurobiologically Distinguishing Depression Subtypes

Dr. Liston's research has identified four neurobiologically distinct subtypes of depression, so that soon, clinicians can offer their patients more personalized diagnoses and treatments.

Each individual who lives with depression lives a unique struggle. Causes and symptoms of the diagnosis differ from case to case, making it impossible to treat and to study effectively using a “one size fits all” approach. Although a more refined set of diagnoses accurately distinguishing depression subtypes would be a huge boon to patients, as of 2015 scientists still had only a rudimentary understanding of the neurobiological bases underlying such prospective subtypes.

Casting brilliant light on the topic in a paper published in the prestigious journal Nature Medicine in January 2017 is Conor Liston, MD, PhD, Assistant Professor of Neuroscience and Psychiatry at the Brain and Mind Research Institute and Department of Psychiatry, Weill Cornell Medical College. With funding from his 2015 One Mind Institute / Janssen Rising Star Translational Research Award, Dr. Liston and his team have begun to tease apart the neurobiological differences between different types of depressive disorders.

In their 2017 paper, Liston’s team identified four discrete depression subtypes by looking for patterns in brain biology (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 four clear, never-before-distinguished subtypes. As Liston says, “These subtypes cannot be diagnosed based solely on clinical symptoms, but they are associated with contrasting clinical profiles feature subtype-specific differences in anhedonia, anxiety, insomnia, fatigue, and psychomotor slowing. Importantly, they also predict individual response rates to transcranial magnetic stimulation of the dorsomedial prefrontal cortex, a neurostimulation-based antidepressant therapy.”

If Liston’s success continues this trajectory, not only might doctors soon be able to use neuroimaging to diagnose different forms of depression much more specifically than ever before, they may also soon be able to prescribe just the right treatment strategy for each patient, without the weeks of trial and error that often accompanies finding helpful treatments now—potentially saving countless lives.

Coming soon, Liston’s team plans to extend their discoveries into even more useful results for patients through three research aims:

  1. Learn more from these biomarkers for classifying depression, by studying a prospective 75-patient cohort with brain imaging, to evaluate how specific connectivity patterns generate specific depression symptoms and behaviors.
  2. Model the deficits of the stress-related subtype in the brains of mice, to 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 the calming effects of interneuron activity—can work to improve prefrontal cortex dysfunction and combat depression-like behaviors in chronically stressed mice. Very interestingly, the team has already discovered a key mechanism for ketamine’s antidepressant effect: brain plasticity enhancement. By accelerating the restoration of synapses lost in the prefrontal cortex to depression, ketamine is able to rapidly rescue depressive behaviors. By isolating this ketamine mechanism, Liston’s team has lit the way for researchers to develop even better rapid antidepressants.

These discoveries have helped Dr. Liston earn several major awards from the U.S. government and other sources to expand his research to help more people. We at One Mind Institute thank Dr. Liston for his commitment to brain health, and thank our donors for enabling us to fund his constructive work.

[photo credit: Carlos Rene Perez]

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

"The support of One Mind Institute has been absolutely essential to all of the psychosis prediction and prevention efforts of CAPPS and the NAPLS. On behalf of the patients and families who have received high quality clinical services in our program regardless of their ability to pay, and on behalf of the numerous dedicated members of our research and clinical treatment teams, I am so incredibly grateful for One Mind Institute’s generous contributions. On a personal note, it is very inspiring to see the huge gains made for mental health research and awareness over the past several years, which have been sparked in large part by the efforts of the Staglin family."
"As a family member of someone living with schizoaffective disorder, I am proud to support One Mind Institute’s profoundly important work. One Mind Institute allows those touched in some way by psychiatric illness to take action and work toward solutions by helping to spur early stage research. One Mind Institute’s audacious mission to find a cure for psychiatric illness in one generation is what it will take to make meaningful progress, and holds the promise of changing millions of lives around the globe. "
"One Mind Institute, thank you again for funding CAPPS/ABBRC. Our daughter, Anna, participated in the program 2012-2013 and just received her final assessment. While this research helps others, know how much we appreciated participating with such genuinely dedicated people (very well selected to work with adolescents). It was very helpful for us as well, and provides us with even more hope. We're so impressed with the program."
"One Mind Institute is an organization equal parts compassion and science. A critical component of their work is advocacy and voice for millions of people who live with mental illnesses. Equally important is the incredible efforts they provide to further research in learning more about the brain and identifying effective treatments for brain diseases. One Mind Institute is a leader in the field of mental illness!"
"From the moment I found One Mind Institute and met the amazing Staglin family I knew that my advocacy would grow by leaps and bounds. Through their dedication and commitment I found a community of brilliant scientists, passionate philanthropists, music lovers and a new mental health family to call my own. I cherish the work One Mind Institute does every day to advance the research on brain disorders, to increase the awareness around mental illness and mental health and to create a community of love and support for advocates everywhere. I would not be the person I am today without the inspiration One Mind Institute has provided me."
"One Mind Institute has distinguished itself as a leader in the fight against brain disease. One Mind Institute’s vision of a world without mental illness seems beyond reach only to those who have not seen firsthand the intensity of One Mind Institute’s dedication and focus. These folks are not giving up until they’ve won. The Saks Institute is delighted to be One Mind Institute’s partner in the fight."
"Having struggled with schizophrenia since a young woman, I am deeply grateful for what One Mind Institute does. One Mind Institute’s unwavering commitment to support research is an inspiration to those of us who long for the day when a cure for serious mental illness is found. I think of One Mind Institute as a good friend and kindly mentor who has taken up my cause and fights for my mental health each and every day."
"When I heard of the groundbreaking work the Staglins were doing through their organization One Mind Institute, such as research into preventing schizophrenia from ever occurring, I hoped to meet them. When I did I was amazed by their non-stop energy and complete devotion to the cause. But most of all, I was moved by their sincere desire to share ideas with people from all backgrounds and fields. As I continue to create films to inspire empathy for those with mental illness, I remain inspired by the Staglins and what One Mind Institute has done to transform mental health research and improve lives. "

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