The objective of this new Conte Center is to take maximal advantage of recent advances in chromatin biology, so-called epigenetics, to fundamentally increase our understanding of the long-lasting abnormalities in the brain that cause depression and that mediate antidepressant responses. Our work will focus on key limbic brain regions, nucleus accumbens (NAc) and several areas of prefrontal cortex (PFC), which have been implicated directly in the control of mood in health and disease. The Center is composed of four Projects at four different universities. The four PIs, Eric Nestler (Mount Sinai), Schahram Akbarian (UMass), David Allis (Rockefeller), and Carol Tamminga (UT Southwestern), are leaders in their fields who have an established history of effective collaboration and will use their complementary expertise and approaches to chart a multidisciplinary course in the proposed research. Projects 1, 2, and 3, lead by Drs. Nestler, Akbarian, and Allis, respectively, will characterize the role of epigenetic mechanisms within the brain's limbic regions in a range of animal models of depression over the life cycle of the animals. Project 4, lead by Dr. Tamminga, will translate these findings in animals to human postmortem brain tissue and thereby provide essential validation of the basic research for human depression. The Center is supported by three Cores, an Administrative Core to oversee and coordinate the Center's operations;a Chromatin and Gene Analysis Core to provide advanced state-of-the-art methods and bioinformatics to characterize genome-wide regulation of chromatin modifications in limbic regions in depression and antidepressant action;and an Animal Models Core to provide the most sophisticated animal models of depression along with the advanced tools (viral-mediated gene transfer and inducible mutations in mice) to manipulate individual genes of interest within limbic structures and thereby provide causal evidence for the involvement of epigenetic regulation in depression-related phenomena. We are very excited about this novel and pioneering investigation of the epigenetic underpinnings of depression, which we believe will help drive the field toward dramatically better treatments and diagnostic tests for depression and other stress-related illnesses. PUBLIC HEALTH REVELENCE: Depression has a lifetime risk of ~15% for the U.S. general population, yet available antidepressant therapies are based on serendipitous discoveries over 6 decades ago, and fully treat <50% of all affected individuals. An improved understanding of the molecular basis of depression will lead to improved treatments and diagnostic tests - a high priority for the National Institutes of Health.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Specialized Center (P50)
Project #
Application #
Study Section
Special Emphasis Panel (ZMH1)
Program Officer
Zalcman, Steven J
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Icahn School of Medicine at Mount Sinai
Schools of Medicine
New York
United States
Zip Code
Labonté, Benoit; Engmann, Olivia; Purushothaman, Immanuel et al. (2017) Sex-specific transcriptional signatures in human depression. Nat Med 23:1102-1111
Zhao, Jian-Yuan; Liang, Lingli; Gu, Xiyao et al. (2017) DNA methyltransferase DNMT3a contributes to neuropathic pain by repressing Kcna2 in primary afferent neurons. Nat Commun 8:14712
Nätt, Daniel; Barchiesi, Riccardo; Murad, Josef et al. (2017) Perinatal Malnutrition Leads to Sexually Dimorphic Behavioral Responses with Associated Epigenetic Changes in the Mouse Brain. Sci Rep 7:11082
Loh, Yong-Hwee Eddie; Feng, Jian; Nestler, Eric et al. (2017) Bioinformatic Analysis for Profiling Drug-induced Chromatin Modification Landscapes in Mouse Brain Using ChlP-seq Data. Bio Protoc 7:
Peña, Catherine J; Kronman, Hope G; Walker, Deena M et al. (2017) Early life stress confers lifelong stress susceptibility in mice via ventral tegmental area OTX2. Science 356:1185-1188
Lopez, Juan Pablo; Fiori, Laura M; Cruceanu, Cristiana et al. (2017) MicroRNAs 146a/b-5 and 425-3p and 24-3p are markers of antidepressant response and regulate MAPK/Wnt-system genes. Nat Commun 8:15497
Jiang, C; Lin, W-J; Sadahiro, M et al. (2017) VGF function in depression and antidepressant efficacy. Mol Psychiatry :
Ménard, Caroline; Pfau, Madeline L; Hodes, Georgia E et al. (2017) Immune and Neuroendocrine Mechanisms of Stress Vulnerability and Resilience. Neuropsychopharmacology 42:62-80
Brancato, Anna; Bregman, Dana; Ahn, H Francisica et al. (2017) Sub-chronic variable stress induces sex-specific effects on glutamatergic synapses in the nucleus accumbens. Neuroscience 350:180-189
Feng, Jian; Pena, Catherine J; Purushothaman, Immanuel et al. (2017) Tet1 in Nucleus Accumbens Opposes Depression- and Anxiety-Like Behaviors. Neuropsychopharmacology 42:1657-1669

Showing the most recent 10 out of 192 publications