Dr. Ian Maze: Predicting Depression Risk and Treatment Response through Blood Chemistry

Rising Star Awardee Dr. Maze aims to determine whether testing the blood for reduced levels of a serotonin-modified protein could help to predict susceptibility to depression under stress, to diagnose major depressive disorder, and/or to predict whether antidepressant medications might help specific patients.

Major Depressive Disorder (MDD) afflicts over 300 million people worldwide, but current antidepressant medications work to relieve symptoms in only a fraction of these, and then, generally only after weeks to months of treatment. What if a simple blood test were available that could not only indicate whether a person would respond favorably to medications, but could also reveal someone’s individual level of vulnerability to MDD under stress before it even begins? Such a test could potentiate proactive lifestyle changes to help at-risk people ward off MDD, while potentially saving newly-diagnosed patients months of trying different medications in favor of alternative (e.g. psychosocial) treatments that might help them more efficiently.

Recent research in the lab of Ian Maze, Ph.D., Assistant Professor, Departments of Neuroscience and Pharmacological Sciences at the Icahn School of Medicine at Mount Sinai, suggests that the expression of a chemically modified protein (called histone H3 serotonylation; H3Q5ser) involved in serotonergic neuronal activity in the brain displays characteristics that make it opportune to assess in just such a blood test: H3Q5ser is not only expressed differently in the brains of people with MDD vs. non-afflicted people in a way that correlates with responsiveness to antidepressants, but it also shows up in concordant proportions in the blood. Now, Dr. Maze has won the 2017 One Mind Rising Star Early Diagnostics Basic Research Award for his ambitious proposal to investigate this modified protein as a potential blood biomarker that could help doctors to eventually predict depression vulnerability, and antidepressant responsiveness, in individual patients.

To test this possibility, Dr. Maze proposes a sequence of three research aims. First, Dr. Maze and his team will ascertain whether H3Q5ser can serve as a biomarker to predict stress susceptibility in a rodent model. In a model called “chronic social defeat stress” (CSDS), where each member of a cohort of experimental mice is exposed to a larger, more aggressive mouse repeatedly, the resulting social stress can serve as a trigger for some of the mice (noted as “susceptible” to stress) to develop depression-like symptoms. Dr. Maze’s team will test the blood levels of H3Q5ser in these mice before, within, and after a period of repeated CSDS sessions, and correlate these levels at each time point with the evolution of the mice’s depressive-like behaviors. This experiment should reveal whether changes in H3Q5ser expression precede, coincide with, or follow changes in behavior—and resolve the question of whether a blood test for this modified protein’s expression can be used to predict the development of depression-like behavior in this mouse model.

In their second aim, Maze and his team will use a similar process on this same mouse model to evaluate whether measuring H3Q5ser expression in the blood can be used to predict the susceptible mice’s response to antidepressant treatment. By measuring the blood levels of H3Q5ser in these mice before, during, and after treatment with antidepressant medications, and observing whether changes in this protein’s expression precede, coincide with, or follow ameliorations in the animals’ behavior, Dr. Maze’s team will discover whether such H3Q5ser measurement can help to predict antidepressant efficacy in this mouse model.

Third, Dr. Maze will track H3Q5ser expression in humans over time: 100 each of healthy controls, untreated MDD patients, and MDD patients taking antidepressants will undergo blood tests regularly over a few months. The treated MDD patients will concurrently be assessed for changes in symptoms, with these changes analyzed against their H3Q5ser expression levels. These observations should shed invaluable light on the relationships between H3Q5ser expression, the presence/absence of MDD, and the efficacy of medications for individual patients.

Says Dr. Maze, “Our studies aim to fully test the hypothesis that H3Q5ser may be used as a biomarker for MDD and/or antidepressant efficacy in human patients. If true, the existence of such a marker will prove useful in both the diagnosis of MDD and in its treatment.”

From a patient’s perspective, such a discovery could help to bring about recovery faster. We at One Mind Institute are excited to watch how Dr. Maze’s research will play out, and we extend our heartfelt appreciation to our donors for enabling us to support this Rising Star’s work.

"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."
"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."
"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."
"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."
"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."
"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. "
"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 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!"

Stay Connected

Sign up and receive e-newsletters and more

One Mind Institute is a 501(c)3 nonprofit, Tax ID # 68-0359707

 

X