Richard K. Nakamura, Ph.D. Deputy Director National Institute of Mental Health

1. Science and Service: • Opening Pathways to • Better Mental Health • Complexities of Co-occurring Conditions Meeting Richard K. Nakamura, Ph.D. Deputy Director National Institute of Mental Health

2. NIMH Mission • Reduce the burden of mental and behavioral disorders through research on mind, brain and behavior

3. How do we do this? • NIMH budget is over $1.3 billion • 7th Largest Institute of the NIH • Most goes into 2000 research grants around the country based on expert review that funds less than 1/3 of applications.

4. The Burden of Mental Illness is Enormous

5. World Bank and the World Health Organization • Global Burden of Disease • To measure both premature death and disability, a single measure was developed: • Disability Adjusted Life Year • DALY • One DALY is one lost year of healthy life.

6. Disease Burden by Illness - DALY World, 2000All Ages Lower respiratory infections Perinatal conditions HIV/AIDS Unipolar depressive disorders Diarrhoeal diseases Ischaemic heart disease Cerebrovascular disease Road traffic accidents Malaria Tuberculosis 0 1 2 3 4 5 6 7 Percent of Total Source: World Health Organization – World Health Report, 2001

7. Disease Burden by Illness - DALY World, 200015-44 year olds HIV/AIDS Unipolar depressive disorders Road traffic accidents Tuberculosis Alcohol use disorders Self inflicted injuries Iron-deficiency anemia Schizophrenia Bipolar affective disorder Violence 0 2 4 6 8 10 12 Percent of Total Source: World Health Organization – World Health Report, 2001

8. Disease Burden by Illness - DALY United States, Canada and Western Europe, 200015 - 44 year olds Unipolar depressive disorders Alcohol use disorders Road traffic accidents Drug use disorders Self inflicted injuries Bipolar disorder Migraine Schizophrenia Hearing Loss, adult onset HIV/AIDS 0 2 4 6 8 10 12 14 16 18 Percent of Total Source: WHO – Burden of Disease Statistics, 2001

9. Cardiovascular diseases Mental Illness* Malignant neoplasms (cancer) Injuries (disabling) Alcohol and Drug Use Disorders All respiratory diseases Digestive diseases Musculoskeletal diseases 17.0 14.8 14.4 7.3 7.2 5.4 4.2 4.2 Disease Burden by Illness - DALY United States, Canada and Western Europe, 2000 All Ages Percent of Source: World Health Organization – Burden of Disease Statistics, 2001 total DALYs *Includes self-inflicted injuries

10. Mental Illness* Alcohol and Drug Use Disorders Alzheimer’s Disease and Dementias Musculoskeletal Diseases Respiratory Diseases Cardiovascular Diseases Sense organ Diseases Injuries (Disabling) 24.1 12.5 7.7 7.5 6.4 5.4 4.9 4.7 Causes of Disability United States, Canada and Western Europe, 2000 All Ages Percent of Source: World Health Organization – Burden of Disease Statistics, 2001 total YLDs *Includes self-inflicted injuries

11. Suicide in America • 11th Leading cause of death (1.3% of all deaths) • 30,662 in 2001 (undercounting likely) • 8th leading cause of death in men • 3rd leading cause of death in 15-24 year olds • Suicide outnumbered homicide by 3 to 2 • There are now twice as many deaths due to suicide than due to HIV/AIDS • 90% had a mental illness

12. Personality Disorders Antisocial Personality Disorder 84 29.6 Comorbidity of Mental Disorders with Any Substance Abuse Rank Order of Mental Disorders by Odds Ratio • % with Substance Odds • Axis / Disorders Abuse or Dependence Ratio Bipolar I 61 7.9 Bipolar II 48 4.7 Schizophrenia 47 4.6 Panic Disorder 36 2.9 Obsessive Compulsive Disorder 33 2.5 Dysthymia 31 2.4 Unipolar Depression 27 1.9 Phobia 23 1.6

13. The Brain Changes • We now understand that our genes specify a general plan with many options. Our brain changes its physical structure through behavior and interactions with the environment

14. A Revolution • Our new understanding of the brain integrates: • nature and nurture • mind and brain • genes and the environment

15. Neurogenesis in the Adult Human I II Source: Eriksson et al., 1999

16. Stress Impairs Neurogenesis Dentate Gyrus, Marmoset Monkey 400 300 p<.05 * BrdU Labeled Cells/mm3 200 100 Gould 1998 0 Control Stress Dentate Gyrus, Adult Rat 4000 3000 p<.05 * 2000 BrdU Labeled Cells 1000 Gould 2000 0 Dominant Subordinate

17. Physical Activity & Neurogenesis Source: van Praag et al., 1999

18. Science 301: 805-809, 2003

19. Source: Trachtenberg et al Nature, December 2002

20. Anxiety PTSD

21. Evidence in Humans: PTSD Patients Fail to Show mPFC Activation When Exposed to Traumatic Reminders Shin et al., Biological Psychiatry, 2001

22. Non-PTSD

23. PTSD

24. Science, 302: 386-388, 2003

27. Modulation of Cortical-Limbic Pathways in Major Depression Treatment-Specific Effects of Cognitive Behavior Therapy Kimberly Goldapple, MSc; Zindel Segal, PhD; Carol Garson,MA; Mark Lau, PhD; Peter Bieling, PhD; Sidney Kennedy, MD; Helen Mayberg, MD Arch Gen Psychiatry. 2004;61:34-41.

28. Summary: Modulation of Common ‘System’ Treatment-Specific Effects CBT SRI inverse SRI only CBT only attention-cognition pCg PF9 P40 - CBT hippocampus mF9/10 mood state Emotion-cognition integration thal bg aCg24 oF11 a-ins Cg25 - drug bs am hth vegetative-circadian

32. Anxiety PTSD

33. BEST BUYS IN MENTAL HEALTH Gavin Andrews, Cathy Issakidis, Kristy Sanderson, Justine Corry, Helen Lapsley Policy & Epidemiology Group, School of Psychiatry, UNSW & WHO Collaborating Centre, St Vincent’s Hospital Sydney

34. ‘Best Buys’ study: disorders covered • Affective: depression, dysthymia, bipolar disorder • Anxiety: panic/agoraphobia, social phobia, generalized anxiety disorder, post-traumatic stress disorder • Alcohol: abuse and dependence • Schizophrenia

35. Results: Current Treatment Coverage Effective Burden Efficiency coverage averted % % % $/YLD Depressive Disorders 60 34 15 20 000 Anxiety Disorders 35 20 13 15 000 Alcohol Disorders 11 6 2 98 000 Schizophrenia 100 ~ 13 196 000 Total 40 23 13 30 000

36. Results: Optimal Treatment Coverage Effective Burden Efficiency coverage averted % % % $/YLD Depressive Disorders 60 60 23 11 000 Anxiety Disorders 35 35 20 9 000 Alcohol Disorders 11 11 5 53 000 Schizophrenia 100 100 22 107 000 Total 40 40 20 18 000

37. www.nimh.nih.gov