Thomas R. Insel, M.D.

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Recovery How Research Will Change Practice
June 13, 2008
Thomas R. Insel, M.D. Director, NIMH
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Noah 36 months in a life

• Number of outpatient providers 80

Number of outpatient visits 326
Number of ER visits 84
Number of inpatient admissions 19
Number of inpatient diagnoses 22
Methadone and cocaine overdose 7/28/06
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Noah 36 months in a life
Number of psychotropic meds 20
Number of outpatient prescriptions 245
Insurance bill for inpt outpt care 235K
Cost of outpatient medications 19K
Methadone and cocaine overdose 7/28/06
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Coordination of Mental Health Services in the
U.S.
Medicare
Medicaid
CMHS
HUD
Education
SSA
SMHA
State Medicaid Agency
V.R.
CMHC
PHA
Case Mgt.
M.H. Care
Housing
Job Support
Consumer
M.D.
Meds
Income Support
Hogan, 2002
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Resources Matched with Public Health Need
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
Insel, Am J Psychiatry, 2008
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Disparities in Mental Health Care
Race/Ethnicity Not Receiving Minimally Adequate Treatment, Among Those with SMI
OR
Non-Hispanic black 3.3
Non-Hispanic white 1.0
Hispanic 0.8
Other 3.6
Adjusted for age, sex, income level, education,
urbanicity, region of the country, employment
status, and marital status.
Wang et al. Am J Public Health 2002
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Mental Disorders Mortality

• Over 30,000 suicides per year (in the U.S.)
• - 90 related to mental illness

• For context
• 18,000 homicides
• 20,000 AIDS deaths
• only 3 forms of cancer gt 30,000

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Public Health ImpactEarly Mortality in
Individuals with Major Mental Illness (MMI)

• Data from outpatient
• and inpatient clients
• diagnosed with MMI
• Average age at time
• of death 56 years
• Increased likelihood
• of dying from suicide
• Medical co-morbidities

Adapted from Colton and Manderscheid, 2006, Prev
Chronic Dis
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Where is the problem???
Family???
The Patient???
The system???
The doctors???
The Illness
Pharmaceutical companies???
Stigma???
Insurance companies???
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Disruptive Innovations For Preemption and Recovery
Mental disorders are brain disorders.
Mental disorders are developmental disorders.
Mental disorders result from complex genetic risk
plus experiential factors.
Current treatments may be necessary but not
sufficient for recovery.
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Mental disorders as brain disorders
PNAS, 2007
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Brain differences associated with depression
Area 25 altered metabolism and 39 (bipolar)
and 48 (unipolar) reduced grey matter volume
Cg25
Drevets et al., Nature, 1997
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Affect in Subgenual Cingulate (BA25)
Depressed Affect
increased CBF/Metb
Cg25
decreased CBF/Metb
Prefrontal 9
Cg25
R
Mayberg et al. Am J Psych 156675-82 1999
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Critical Role of Subcallosal Cingulate Cg25
TMS
SSRI
Placebo
SNRI
ECT
?Cg25
Nobler
George
Mayberg
Kennedy
Mayberg
Sad Memory
SERT SSltLL MRI
Depression ?Glia
Tryptophan Deplete
?Cg25 activity
Mayberg
Talbot
Pezewas
Ongur
Pre-CGT (FDG)
Pre-DBS (CBF)
Med NR (fMRI)
CBT/Med NR (FDG)
Ablation Targets
?Cg25 activity
Dougherty
Mayberg
Greicius
Mayberg
Bailey, Ballentine, Hunter-Brown, Laitenen
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Disruptive Innovations In Mental Health
Mental disorders are brain disorders.
Mental disorders are developmental disorders.
Mental disorders result from complex genetic risk
plus experiential factors.
Current treatments may be necessary but not
sufficient for recovery.
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Alzheimers A Developmental Disorder?
Lancet Neurol 2007
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Schizophrenia A Developmental Brain Disorder
Genetic risk Unusual thought content Suspicion/par
anoia Social impairment History of substance abuse
68-80 prediction
Arch Gen Psych, 2008
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Progressive Brain Structural Changes Mapped as
Psychosis Develops in At Risk Individuals
Sun et al, Schiz Res., 2008
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Schizophrenia Trajectory
Stage 1 Presymptomatic, Risk factors, Cognitive
deficit with challenge lt Age 15
Stage 2 Prodrome, cognitive deficits emerging,
minor disability
Age 15 18
Stage 3 Psychosis, acute disability, family
costs Age 18 24
Stage 4 Chronic illness, medical complications,
social costs gt Age 24
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Disruptive Innovations In Mental Health
Mental disorders are brain disorders.
Mental disorders are developmental disorders.
Mental disorders result from complex genetic risk
plus experiential factors.
Current treatments may be necessary but not
sufficient for recovery.
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The Genomics Revolution

• Human Genome Project (2003)
• Mapped 3 billion bases of DNA in human genome

CTAGGCTTAAGCGGACCTGCTCTAGGTCAGTC.
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Manolio, Brooks, Collins, in press.
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Why does genomics matter?

• Genes are not going to yield a diagnostic test
• Genes are not going to identify a cause

But

• Genetic variation can identify risk
• Genes can reveal mechanisms of disease

Thus, genes can point to new targets for
prevention and treatment
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Pathways to Pathophysiology
Meyer-Lindenberg Weinberger, Nature Rev
Neurosci, 2007
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Disruptive Innovations In Mental Health
Mental disorders are brain disorders.
Mental disorders are developmental disorders.
Mental disorders result from complex genetic risk
plus experiential factors.
Current treatments may be necessary but not
sufficient for recovery.
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Current Treatments How Good?
10,000 patients, 200 sites, 3 diseases, practical
trials

• CATIE (chronic schiz)

Real world setting Recovery of
function Practical questions
STARD (MDD)
STEP-BD (Bipolar)
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Current Treatments How Good?

• Schizophrenia 74 discontinuation of
  anti-psychotics, limited access to psychosocial
  Rxs

• Depression 31 remitted at 14 weeks, 67 at 1
  year, limited access to CBT

• Bipolar 21 stable for 8 weeks in first 6
  months, high rates of medical co-morbidity

• Childhood disorders dx prevalence increase
  10-fold for autism, 40-fold for bipolar, no
  selective meds and few proven behavioral
  approaches

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Practical Trials What Did We Learn?

• We can optimize care in real world settings

• With optimized care, outcomes are not optimal

• Current treatments help too few people get better
  and very few get well

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Research For Recovery

• Pathophysiology (genes to cells to circuits to
  behavior/cognition and back)

• Trajectory of mental disorders (predictive
  biomarkers, individual risk)

• New interventions (rational, preemptive,
  personalized therapeutics)

• Participatory efforts (reducing disparities,
  focus on recovery)

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Imagine (2018) Diagnosis Dimensional
Mechanism Genes to behavior
Treatment Personal pre-emptive
Now (2008) Diagnosis Categorical but
co-morbid Mechanism Brain circuit
dysfunction Treatment Second generation
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Research for Prevention, Recovery, and Cure
www.nimh.nih.gov