This application, in response to PAR-07-159 (National Cooperative Drug Discovery Groups for the Treatment of Mental Disorders, Drug or Alcohol Addiction), represents the resubmission of the competitive renewal application of """"""""The Emory-MSSM-GSK-NIMH Collaborative Mood and Anxiety Disorders Initiative"""""""", MH-069056. This unique opportunity to accelerate antidepressant and anxiolytic drug development brings together expertise of four complementary research groups: the Emory University School of Medicine Department of Psychiatry and Behavioral Sciences, the NIMH Intramural Mood and Anxiety Disorders Program, the Mt. Sinai School of Medicine Department of Psychiatry (MSSM) and the Center for Excellence in Drug Discovery (CEDD) in Psychiatry of GlaxoSmithKline (GSK), one of the largest multinational pharmaceutical companies. The two major goals of the current application are the development of innovative new models for basic and clinical research in mood and anxiety disorders and the intensive scrutiny of 3 novel GSK antidepressant/anxiolytic candidates [two structurally distinct CRP! receptor antagonists (GSK008 and CRF-002), and a 5-HTiA/IB/ID receptor antagonist (GSK-1), in preclinical and clinical paradigms. In addition to an Administrative and Genomics/Endocrine/Statistics Core, 5 research projects are proposed. The preclinical projects are based at Emory University and are led by established investigators including, Michael Davis, PhD (Rat Models of Anxiety), Donald Rainnie, PhD (Physiologic Actions of Novel Antidepressants/Anxiolytics in the Basolateral Amygdala), and Clinton D. Kilts, PhD and Mark Goodman, PhD, (CRFi receptor PET Ligand Development). One clinical project is based in the intramural NIMH program: Effects of novel antidepressants/anxiolytics on human startle in normal volunteers (Christian Grillon, PhD, PI). A placebo-controlled, double-blind trial (based at Emory: Barbara Rothbaum, PhD, PI and MSSM: Dennis Charney, MD, PI) will assess the efficacy of the CRFi receptor antagonist GSK008 in patients with post-traumatic stress disorder (PTSD). This proposal encompasses virtually all of the major goals outlined in the PAR, namely, development of new neurochemical tools including PET ligands, exploration of new models for drug development and facilitation of a partnership between academia, NIMH and industry.

Public Health Relevance

Mood and anxiety disorders are the most common of all psychiatric disorders and are associated with very significant morbidity and mortality. The primary goal of this NCDDG Center is to accelerate the development of novel drugs for the treatment of depression and anxiety.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19MH069056-08
Application #
8112734
Study Section
Special Emphasis Panel (ZMH1-ERB-S (05))
Program Officer
Brady, Linda S
Project Start
2003-08-11
Project End
2014-05-31
Budget Start
2011-06-01
Budget End
2012-05-31
Support Year
8
Fiscal Year
2011
Total Cost
$2,059,619
Indirect Cost
Name
Emory University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
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Hodgins, Gabrielle E; Blommel, Jared G; Dunlop, Boadie W et al. (2018) Placebo Effects Across Self-Report, Clinician Rating, and Objective Performance Tasks Among Women With Post-Traumatic Stress Disorder: Investigation of Placebo Response in a Pharmacological Treatment Study of Post-Traumatic Stress Disorder. J Clin Psychopharmacol 38:200-206
Dunlop, Boadie W; Binder, Elisabeth B; Iosifescu, Dan et al. (2017) Corticotropin-Releasing Factor Receptor 1 Antagonism Is Ineffective for Women With Posttraumatic Stress Disorder. Biol Psychiatry 82:866-874
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Grillon, Christian; Hale, Elizabeth; Lieberman, Lynne et al. (2015) The CRH1 antagonist GSK561679 increases human fear but not anxiety as assessed by startle. Neuropsychopharmacology 40:1064-71
Ridgewell, Caitlin; Bray, Allison; Curtis, Kaylah et al. (2015) Enhanced Olfactory Cortex Connectivity in a Patient With PTSD With Olfactory Hallucinations. J Neuropsychiatry Clin Neurosci 27:e170-1
Stehouwer, Jeffrey S; Bourke, Chase H; Owens, Michael J et al. (2015) Synthesis, binding affinity, radiolabeling, and microPET evaluation of 4-(2-substituted-4-substituted)-8-(dialkylamino)-6-methyl-1-substituted-3,4-dihydropyrido[2,3-b]pyrazin-2(1H)-ones as ligands for brain corticotropin-releasing factor type-1 (CRF1) rec Bioorg Med Chem Lett 25:5111-4

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