The Center's faculty conducting pre-clinical research has led to many advancements in our understanding of depression.
Jay A. Gingrich, MD, PhD
Dr. Gingrich and his research group use a systems approach to better understand normal and abnormal brain function; in particular, the mechanisms that underlie neuropsychiatric disorders such as schizophrenia, depression, and anxiety disorders. Their goal is to understand how genetic and epigenetic factors affect behavior and intervening systems such as circuitry, anatomy, and physiology. His group exploits the ability to genetically modify mice—either to mimic known human susceptibility factors or to use conditional gene modifications—to further investigate their hypotheses regarding circuitry and physiology. Towards that end, Dr. Gingrich is pursuing several lines of research related to the role of serotonin-signaling in the cortex. These studies have demonstrated an important role for cortical influence on behaviors related to schizophrenia and anxiety. His group also has an active program examining the role of the neurotransmitter serotonin on the development of brain circuits that modulate affective and anxiety states. Additionally, his group has developed a mouse model of epigenetic effects of paternal age on behavior and brain function.
1. Serotonin and the Modulation of Brain Development
Grant: R01 MH080116
Role: Principal Investigator
Description: This project studies the mechanisms underlying the impact of early SSRI exposure on adult emotional function in mice.
2. A Multi-Cohort Assessment of Gestational SSRI Exposure on Long-Term Psychiatric Outcomes
Grant: R01 MH114967
Role: Co-Investigator (Principal Investigator: Ardesheer Talati, PhD)
Description: The overall goal of this three-year project is to test the long-term effects of maternal antidepressant use on offspring mental health in adolescence. This is an important public health question, as antidepressant use in pregnancy has been increasing. Although previous work had suggested there may be increased psychiatric problems in adolescents who were exposed to SSRIs, this study will be able to confirm these findings definitively using three different populations.
3. Effects of Prenatal Maternal Depression and Antidepressant Exposures on Offspring Neurodevelopmental Trajectories: A Birth Cohort Study
Grant: R01 MH119510
Description: This study addresses the potential effects of antidepressant medication use during pregnancy on infant neurodevelopment. Pregnant women with and without depression will be enrolled to determine the impact of their antidepressant medication use on brain development and associated cognitive and behavioral functioning over the first two years of life.
Grieve, P. G., Fifer, W. P., Cousy, N. P., Monk, C. E., Stark, R. I., Gingrich, J. A., & Myers, M. M. (2019). Neonatal infant EEG bursts are altered by prenatal maternal depression and serotonin selective reuptake inhibitor use. Clinical Neurophysiology, 130(11), 2019-2025.
Fanibunda, S. E., Deb, S., Maniyadath, B., Tiwari, P., Ghai, U., Gupta, S., Figueiredo, D., Weisstaub, N., Gingrich, J. A., Vaidya, A., Kolthur-Seetharam, U., & Vaidya, V. A. (2019). Serotonin regulates mitochondrial biogenesis and function in rodent cortical neurons via the 5-HT2A receptor and SIRT1-PGC-1α axis. Proceedings of the National Academy of Sciences of the United States of America, 116(22), 110280-11037.
Jaggar, M., Banerjee, T., Weisstaub, N., Gingrich, J. A., & Vaidya, V. A. (2019). 5-HT2A receptor loss does not alter acute fluoxetine-induced anxiety and exhibit sex-dependent regulation of cortical immediate early gene expression. Neuronal Signaling, 3(1), NS20180205.
Office Address: 1051 Riverside Drive, Unit 40, New York, NY 10032
René Hen, PhD
Dr. Hen received his PhD from University Louis Pasteur under the mentorship of Pierre Chambon. After completing postdoctoral training in Richard Axel's laboratory at Columbia University, Hen then became an assistant professor in Strasbourg. Presently, he is a professor of pharmacology, psychiatry, and neuroscience. His laboratory uses animal models to elucidate the neural substrates that underlie mood and anxiety disorders. He has been studying the mechanism of action of antidepressant medications as well as hippocampal neurogenesis for the past 25 years and has a strong background in molecular biology, pharmacology, gene targeting technologies, and behavioral studies. Dr. Hen is also director of the Division of Systems Neuroscience at New York State Psychiatric Institute, which focuses on identifying brain circuits that are dysfunctional in psychiatric disorders as well as the targets of current and novel medications. Areas of specialized expertise include the serotonergic system, the response to stress, the hippocampus, adult neural stem cells as well as their contributions to mood and anxiety disorders. Additionally, Dr. Hen serves as director of a T32 training grant and has mentored numerous students, postdocs, and residents.
1. Adult Hippocampal Neuroplasticity and Depression
Grant: R01 MH083862
Role: Co-Investigator (Principal Investigator: Maura Boldrini, MD, PhD)
Description: This study aims to study the effect of Major Depression and antidepressants on human neurogenesis. The study will characterize human adult neurogenesis in postmortem samples of individuals with mood disorders and suicide and the effects of antidepressants treatment on human adult neurogenesis.
2. A Circuit and Endophenotype-based Approach to Stratify and Treat Depression
Grant: Hope for Depression Research Foundation (RGA-13-003)
Role: Principal Investigator
Description: The major goal of this proposal is to explore novel mechanisms of antidepressant action, specifically within the opiate system.
3. Endogenous Opioid System Contributions to Antidepressant Action
Grant: R21 MH116462
Role: Multiple Principal Investigator (with John E. Pintar, PhD)
Description: This study is aimed at studying the contribution of enkephalin and its receptors to antidepressant action.
Jimenez, J. C., Berry, J. E., Lim, S. C., Ong, S. K., Kheirbek, M. A., & Hen, R. (2020). Contextual fear memory retrieval by correlated ensembles of ventral CA1 neurons. Nature Communications, 11(1), 3492.
Luna, V. M., Anacker, C., Burghardt, N. S., Khandaker, H., Andreu, V., Millette, A., Leary, P., Ravenelle, R., Jimenez, J. C., Mastrodonato, A., Denny, C. A., Fenton, A. A., Scharfman, H. E., & Hen, R. (2019). Adult-born hippocampal neurons bidirectionally modulate entorhinal inputs into the dentate gyrus. Science, 364(6440), 578-583.
Anacker, C., Luna, V. M., Stevens, G. S., Millette, A., Shores, R., Jimenez, J. C., Chen, B., & Hen, R. (2018). Hippocampal neurogenesis confers stress resilience by inhibiting the ventral dentate gyrus. Nature, 559(7712), 98-102.
Office Address: 40 Haven Avenue, Kolb Annex 767, New York, NY 10032
Bradley Miller, MD, PhD
Dr. Miller is an assistant professor in the Department of Psychiatry at Columbia University. He attended New York University as an undergraduate and then completed the MD/PhD program at Washington University, St. Louis. As a graduate student, he discovered a signaling pathway that drives axonal degeneration. This work led to new treatment avenues that are currently under investigation. He then joined Columbia University to complete the Psychiatry Residency Program, after which he completed postdoctoral training through the T32 Affective Disorders Research Fellowship program under the mentorship of René Hen and Sander Markx. Dr. Miller’s lab now focuses on bringing precision medicine to the treatment of major depression. He uses mouse models to investigate the circuit mechanisms of normal emotional behavior, and to determine how depression associated mutations alter these circuits. His work has been recognized and supported by a BBRF NARSAD Young Investigator Award, the Hope for Depression Research Foundation, and the NIMH.
1. Circuit Mechanisms of GPR156 Mutation Effects on Emotional Behavior
Grant: Hope for Depression Research Foundation
Role: Principal Investigator
Description: This project builds on a discovery that a rare mutation in a receptor expressed in the brain called GPR156 increases the risk of major depression threefold. Dr. Miller’s laboratory is investigating how this mutation alters cell signaling, gene expression, and neuronal activity in the brain and leads to enhanced sensitivity to stress.
2. Mapping Serotonergic Activity During Emotional Behaviors in the Healthy and Stressed Brain
Grant: K08 MH116368
Role: Principal Investigator
Description: Serotonin is the target of the most widely used antidepressants. It is unclear what leads to serotonin release and what the impact of serotonin release is on target brain areas. Using miniature microscopy imaging in freely behaving mice, Dr. Miller’s lab discovered that a wide range of emotionally salient stimuli, both pleasurable and aversive, trigger serotonin release throughout the brain. His lab is now determining how this serotonin release influences brain activity in target areas. Clarifying how serotonin release regulates emotional behaviors could lead to improvements on current serotonergic antidepressant medications.
Office Address: 40 Haven Avenue, Kolb Annex 759, New York, NY 10032