NIMH Director discusses mental health research and the ARRA

1. Thomas R. Insel, M.D. Thomas R. Insel, M.D. Director, NIMH/NIH/DHHS Director, NIMH/NIH/DHHS The National Institute of Mental Health The National Institute of Mental Health and the and the American Recovery and Reinvestment Act American Recovery and Reinvestment Act July 10, 2009

2. NIMH Mission To transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery, and cure.

3. Source: WHO World Health Report 2002 Burden of Disease (DALYs) U.S., Canada, and Western Europe 15-44 years old

4. Public Health Impact: Early Mortality in Individuals with Major Mental Illness (MMI) Adapted from Colton and Manderscheid, 2006, Prev Chronic Dis • Average age at time of death : 56 years • Increased likelihood of heart disease and suicide

5. Direct and indirect components of the economic burden of serious mental disorders, excluding incarceration, homelessness, comorbid conditions and early mortality. ($ in billions) 1992 2002 Health Care Expenditures $62.91 $100.12 Loss of earning $76.71 $193.23 Disability (SSI + SSDI) $16.41 $24.34 Totals $156.0 B $317.6 B Matching Resources with Public Health Need Insel, Am J Psychiatry, 2008

6. Re-Thinking Re-Thinking “Mental Illness” “Mental Illness” Mental disorders are brain disorders. Mental disorders are developmental disorders. Mental disorders result from complex genetic risk plus experiential factors.

7. oF11 pACC24 mF9/10 PCC MCC PF9/46 Par40 PM6 sACC25 hth bstem a-ins amg mb-vta hc na-vst thal Salience Motivation Mood state Self-awareness insight Cognition (attention-appraisal-action) Interoception (drive-autonomic-circadian) Mental Disorders are Brain Disorders Response Pathways for Depression CBT PF MF MCC Meds PF P Cg25 PCC BS MEDS Br Med Bul 65:193-207, 2003 Arch Gen Psych 61:34-41-2004

8. Source: J Giedd, NIMH Prolonged Human Brain Development

9. 10 15 20 25 Age # of Cortical Synapses Normal Development Based on McGlashan and Hoffman (2000) A Developmental Brain Model for Schizophrenia Psychosis Threshold Possible Paths to Schizophrenia Intervention

10. McCarthy et al., Nat Rev Genetics 2008 Mendelian disease Frequency of DNA variation in population High Intermediate Modest Low Very rare Rare Uncommon Common 0.001 0.01 0.10 Complex Genetics of Mental Illness Penetrance 22q11.2 16p11.1 1q21.1 15q13.3 Disc-1 ANK3 CACNA1C HLA CAM10 New technology for sequencing Repository of DNA from pts/controls Needed: Funds for supporting large scale effort Rare Large effect Common Small effect

11. NIMH Strategic Plan (4 P’s) • Strategic Objective #1: Pathophysiology • Strategic Objective #2: Predictive medicine • Strategic Objective #3: Preemptive and Personalized Interventions • Strategic Objective #4: Public Health Impact – Participatory Research

12. Nice roadmap but is there any gas in the car?

13. American Recovery and Reinvestment Act (ARRA)- Impact of Economic Stimulus on NIH

14. American Recovery and Reinvestment Act (ARRA)- Objectives  Stimulate the economy  Create and preserve jobs  Advance biomedical research $10.4B to NIH $366M to NIMH

15. Scientific Research Approach - NIMH  Stimulate and accelerate biomedical research with existing mechanisms (33%) – Funding additional meritorious R01s, R21s and R03s that have been peer reviewed and approved by NIMH Council – Administrative supplements to accelerate ongoing research  Expand science with new programs (67%) – Revisions to extant programs (“Competitive supplements”) – New ARRA NIH-wide programs – New ARRA IC-specific programs

16. NIMH ARRA Priorities • Jumpstart: the NIMH Strategic Plan (4P’s) the NIH AIDS Res Strategic Plan • Increase training, faculty recruitment, diversity the Autism Research Strategic Plan • Support beaker-ready projects w 2 year outcomes • Process: transparent, careful, accountable

17. New ARRA NIH-wide Programs  Challenge Grants  Grand Opportunities (“GO” Grants)  Recruit new faculty to conduct research  Provide summer jobs for high school / college students and teachers in science labs  AREA (R15) Grants } Jumpstart Strategic Plans } Create and Retain Jobs } National effort On average, every NIH grant supports 6 -7 part-time or full-time jobs

18. Challenge Grants • 2 year $500k/yr awards – submitted April 27, 2009 • Received >21,000 proposals, 894 for NIMH • Reviewed June-July, Funded before 9/30/09 • NIH OD committed $200M; NIMH has committed $90M NIMH Challenge Areas: Biomarkers Genomic sequencing Schizophrenia interactome AIDS – behavior change Comparative Effectiveness Developing iPS cells

19. Grand Opportunity Grants • 2 year >$500K/yr awards – submitted May 24, 2009 • Received 104 proposals for NIMH ($470M) • Reviewed June; Funded before 9/30/09 • NIMH has committed $67M NIMH GO Grants: Genomic profiling of mental disorders Neurodevelopmental genomics Transcriptional map of developing human brain

20. ARRA NIMH RFA: Research to Address the Heterogeneity of Autism Spectrum Disorders 4 Different mechanisms to address heterogeneity of autism and focus on short-term objectives of IACC Strategic Plan 590 proposals ($500M) submitted May 12; Peer reviewed June 19; Scheduled for Council July 17 Combined commitment is $60M (NIMH, NICHD, NINDS, NIDCR, NIEHS)

21. Peer Review for ARRA  Rapid (initial mail reviews within 1 month)  Extensive (364 reviewers for NIMH GO and autism proposals)  Careful (Two tier review to ensure quality)  Public input (Autism review included consumers)

22. http://www.nih.gov/recovery Transparency:

23. Accountability: http://report.nih.gov/

25. NIMH Signature Project #1 Reducing Suicide in the Army Problem: Suicide rates in Army have doubled Army asked for assistance in assessing risk and resilience in soldiers NIMH commits ARRA funds ($10M) to collaborative effort for historic epidemiological study to follow 15,000 soldiers Study to provide actionable information to Army

26. NIMH Signature Project #2 Recovery After an Initial Schizophrenic Episode (RAISE) Problem: Schizophrenia associated with chronic disability RAISE will test aggressive, comprehensive treatment (medication, psychosocial, rehabilitation) to optimize outcomes RAISE developed with SSA, SAMHSA, and CMS for “hand off” from research to practice NIMH ARRA funds ($25M) will launch project in 2009

27. NIMH Signature Project #3 Neurogenomics Problem: Many leads but few genes for psychiatric illnesses (rare variants likely but difficult to detect) New techniques permit rapid, comprehensive sequencing, including detection of rare variants NIMH ARRA funds ($20 -30M) will support development of first comprehensive sequencing efforts Sequencing is feasible in 2 years

28. NIMH Signature Project #4 Developmental Human Brain Atlas Problem: Absence of a reference atlas for human brain development New techniques permit mapping regional gene expression in the developing human brain NIMH ARRA funds ($20M) will support development of the digital public resource Mapping is labor intensive but feasible in 2 years

29. NIMH Comparative Effectiveness Research ARRA Projects: • Leveraging existing healthcare networks for CER on Mental Disorders and Autism • Cost effectiveness of mental health interventions • Collaboration with AHRQ CER Program • Building ASD registries for use in Comparative Effectiveness Research

30. What Can We Accomplish With ARRA? Biomedical Progress: Creating a foundation for future progress Creating and Preserving Jobs: >50% of grant budget = personnel Economic Stimulus: Proposals from all 50 states

31. NIMH ARRA obligations actual and planned for FY2009 (all mechanisms)

32. Summary ARRA provides an unprecedented opportunity to advance biomedical research while participating in the nation’s economic recovery NIMH is using ARRA funds to jumpstart its strategic plan, support autism and AIDS research, and provide training and faculty positions. Specific signature projects focus on suicide in the Army, schizophrenia, and genomics. Demand for ARRA support high, success relatively low, but ARRA will build foundation for progress.

33. www.nimh.nih.gov www.nimh.nih.gov Paving the Way for Prevention, Recovery, and Cure

34. Select NIMH ARRA Funds – 7/10/09 Initiative Committed funding Due Date Proposals received Funding Date Expansion of payline $60M 2008- 2010 ----- 6/09 Supplements $10M adm. $10M comp. 4/09 $205M $ 64M 6/09 8/09 Challenge $90M 4/09 $578M 8/09 Grand Opportunity $67M 5/09 $470M 9/09 New faculty recruitment $5M 5/09 $25M 9/09 Autism RFA $30M 5/09 $500M 7/09 Army suicide & RAISE $35M 2009 $35M 7/09

35. What Happens After ARRA? Demand for research will increase: Success rate (# funded/# proposed) < 10% Many unsuccessful grants return in 2010 Both unsuccessful and successful grants return in 2011 Total # ARRA proposals = 1,703 Estimated success rate in 2011: If 50% return: 13.7% If 75% return: 12.2% If 90% return: 11.5% Required for 20% success rate: 7 -11% increase from FY10 PB