Antidepressive Agents; Depression; Molecular Biology; Neurobiology; Psychiatry; Stress, Psychological; Signal Transduction; Gene Expression
Psychiatry: Connecticut Mental Health Center | Molecular Psychiatry, Division of | Neuroscience Research Training Program (NRTP) | Stress & Addiction Clinical Research Program | VA National Center for PTSD | VA-Yale Clinical Neurosciences PTSD Research Program
Neuroscience Microarray Center, Yale
Studies in Dr. Duman's laboratory are focused on identifying the molecular and cellular adaptations that underlie the actions of antidepressant drugs and stress. This includes adaptations of receptors, signal transduction proteins, gene transcription factors, neurotrophic factors, and regulation of synaptic processes and even birth of new neurons (neurogenesis) in the adult brain. Preclinical and clinical studies support the hypothesis that neuronal atrophy and cell loss in response to stress contribute to mood disorders. Conversely, the therapeutic action of antidepressants may occur in part via blocking or reversing these damaging effects of stress. A variety of molecular approaches combined with cellular and behavioral studies are conducted to elucidate the basis of complex behavioral abnormalities.
Specialized Terms: Depression; Antidepressants; Stress; Molecular biology; Neuropharmacology Signal transduction pathways; Gene expression; Identifying the molecular and cellular adaptations that underlie the actions of psychotropic drugs and stress
Decreased expression of synapse-related genes and loss of synapses in major depressive disorder.
Kang H-J, B Voleti, T Hajszan, G Rajkowska, C Stockmeier P Licznerski, A Lepack, MS Majik, LS Jeong, M Banasr, H Son, and RS Duman (2012) Decreased expression of synapse-related genes and loss of synapses in major depressive disorder.
mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists.
Li N, BY Lee, R-J Liu, M Banasr, J Dwyer, M Iwata, C Greer, X-Y Li, G Aghajanian, and RS Duman (2010) Science 329:959-964.
Negative regulator of MAP kinase is increased in depression and is necessary and sufficient for depressive behavior.
Duric V, M Banasr, P Licznerski, H Schmidt, C Stockmeier, A Simen, SS Newton, and RS Duman (2010) Nature Medicine 16:1328-32.
Synaptic dysfunction in depression: potential therapeutic targets.
Duman RS and GK Aghajanian (2012) Science 338(6103):68-72.
REDD1 is essential for stress-induced synaptic loss and depressive behavior
Ota KT, RJ Liu, B Voleti, JG Maldonado-Aviles, V Duric, M Iwata, S Dutheil, C Duman, S Boikess, DA Lewis, CA Stockmeier, RJ DiLeone, C Rex, GK Aghajanian, RS Duman (2014) Nature Medicine 20:531-535.
Optogenetic stimulation of infralimbic PFC reproduces ketamine’s rapid and sustained antidepressant actions.
Fuchikami M, AM Thomas, RJ Liu, ES Wohleb, BB Land, RJ DiLeone, GK Aghajanian and RS Duman (2015) PNAS USA 112:8106-8111.
A synaptic hypothesis of depression: new insights from studies of stress systems and rapid-acting antidepressants.
Duman RS, GK Aghajanian, G Sanacora, and JH Krystal (2016) Nature Medicine 22:238-249.
GABA interneurons mediate the rapid antidepressant-like effects of scopolamine.
Wohleb ES, M Wu, DM Gerhard, SR Taylor, MR Picciotto, M Alreja, and RS Duman (2016) J Clinical Investigation 126(7):2482-94.
Integrating neuroimmune systems in the neurobiology of depression.
Wohleb ES, T Franklin, M Iwata, and RS Duman (2016) Nature Reviews Neuroscience 17(8):497-511.
Full List of PubMed Publications
- Tanis KQ, Duman RS, Newton SS: CREB binding and activity in brain: regional specificity and induction by electroconvulsive seizure. Biol Psychiatry. 2008 Apr 1; 2007 Oct 15. PMID: 17936724