Rising Star Award Research Update – Ian Maze, PhD
Assistant Professor, Departments of Neuroscience and Pharmacological Sciences at Icahn School of Medicine at Mount Sinai
2017 Rising Star Early Diagnostics Basic Research Award winner
Major Depressive Disorder (MDD) afflicts over 300 million people worldwide, but current antidepressant medications work to relieve symptoms in only a fraction of these individuals, often only after weeks to months of treatment. What if a simple blood test could be developed 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 begins? Such a test could promote 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 treatments.
Recent research from Dr. Ian Maze, a 2017 Rising Star Early Diagnostics Basic Research Awardee, suggests that a protein called histone H3 serotonylation (H3K4me3Q5ser) may be the key to developing such a blood test. To further investigate its potential as a blood biomarker for predicting depression vulnerability, Dr. Maze and his team are using a rodent model of depression, called chronic social defeat stress (CSDS). This experimental model repeatedly exposes a cohort of mice to a larger, more aggressive mouse. The resulting social stress can serve as a trigger for some of the mice (noted as “susceptible”) to develop depressive-like symptoms. They are testing blood levels of H3K4me3Q5ser in these mice before, within, and after a period of repeated CSDS sessions and are correlating these levels at each time point with the evolution of the mice’s depressive-like behaviors. This experiment is revealing whether changes in H3K4me3Q5ser expression precede, coincide with, or follow changes in behavior— and is resolving 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 their second aim, Dr. Maze and his team are using a similar process to evaluate whether measuring H3K4me3Q5ser levels in blood can be used to predict responses to antidepressant treatments. By measuring blood levels of H3K4me3Q5ser 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 and his team are discovering whether such measurements can help to predict antidepressant efficacy.
In addition to the mice studies, they are also tracking H3K4me3Q5ser blood levels in humans. 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 and compared to changes in H3Q5ser expression levels. These observations promise to shed invaluable light on the relationship between H3K4me3Q5ser expression, the presence/absence of MDD, and efficacy of medications for individual patients.
One Mind is strongly supportive of this important research and are enthusiastic about the potential to improve the early identification and treatments for MDD. We gratefully acknowledge the donors for making this research possible.To learn more about Dr. Maze’s research, please watch the presentation he gave at our 2017 Music Festival for Brain Health (shown below) as well as the October 2018 Brain Waves interview he participated in.
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