Preventing Psychotic Disorders by
Early Detection and Intervention
William R. McFarlane, M.D., Director
Early Detection, Intervention and Prevention of Psychosis Program
(EDIPPP)
National Program Office
Robert Wood Johnson Foundation
Center for Psychiatric Research
Maine Medical Center Research Institute
and
Spring Harbor Hospital
Portland, Maine
University of Vermont
Tufts University
Columbia University, College of Physicians and Surgeons
Collaborators
• William L. Cook, PhD
• Donna Downing, MS,
OTR/L
• Anita Ruff, MPH
• Brenda Joly, PhD
• Kimberly Pukstas
• Diane Parham, O.T.R./L
•
•
•
•
•
Karen Milner, MD
Cameron Carter, MD
Barbara Cornblatt, PhD
Steven Adelsheim, MD
Bentson McFarland, MD,
PhD
Early detection and prevention in another illness
“If you catch cancer at Stage 1 or 2, almost
everybody lives. If you catch it at Stage 3 or
4, almost everybody dies.
We know from cervical cancer that by
screening you can reduce cancer up to 70
percent. We’re just not spending enough of
our resources working to find markers for
early detection.”
---Lee Hartwell, MD
Nobel Laureate, Medicine
President and Director,
Hutchinson Center
New York Times Magazine
December 4, 2005, p. 56
Shortened productive lives
Cardiovascular disease
Mental illness
Cancer
Respiratory disease
Alcohol use
Infectious disease
Drug abuse
0
5
10
Productive years lost
Source: Mental Health Report of the Surgeon General
15
20
$10 million
Lifetime costs for each new case of
schizophrenia
25
Years of life lost by people with
schizophrenia due to all causes,
including heart disease, cancer and
suicide
Functioning as an effect of number of
psychotic episodes
100
90
Functioning (GAF)
80
70
60
50
40
30
20
10
0
0
1
2
3
Number of episodes
4
5
6
Empirical evidence for a relationship
between a long DUP and a poor prognosis
• Johnstone et al. 1986: Many psychotic patients did not get
appropriate treatment early, even when they sought help.
• Crow et al. 1986: DUP more important for the course than
maintenance medication.
• Rabiner et al 1986: Long DUP was related to a poor one year
outcome.
• Wyatt 1991,Opjordsmoen 1991: Earlier treatment predicted
better course.
Effects of untreated initial psychosis
• Being psychotic is a personal disaster and the longer it lasts,
the more it can become traumatic and stigmatizing.
• Being psychotic reduces cognitive and social function. They
may lose contact with family and friends, fail school, or drop
out of work.
• The longer the psychosis lasts, the more difficult it may be
for the therapist to establish a good therapeutic relationship
with the patient.
• Neurobiological deficit processes linked to symptom
formation may possibly proceed unlimited as long as the
patient is untreated.
High
Validity of diagnosis across phases of illness
Premorbid
period
Prodromal
period
Defined
Diagnosis
Neurological disease (Cerebral
AIDS, SLE, MS. etc.)
Chronic undifferentiated
schizophrenia
Paranoid schizophrenia
Schizo-obsessive disorder.
0
Schizo-affective disorder
“NRG-1 disorder”
Psychotic bipolar disorder
Psychotic depressive disorder
High
Validity of clinical differential diagnosis
Dementia praecox, deficit
schizophrenia
Severe agoraphobia
time
Early Insults
e.g. Disease
Genes, Possibly
Viral Infections,
Environmental
Toxins
Social and
Environmental
Triggers
Biological Vulnerability: CASIS
Brain
Abnormalities
Cognitive
Deficits
Affective Sx:
Depression
Social
Isolation
Disability
School
Failure
Structural
Biochemical
Functional
After Cornblatt, et al., 2005
NP Profile of Clinical High Risk (CHR) sample
relative to Healthy Comparisons (HC)
Non-genetic biologic and psychosocial
risk factors
• Prenatal infections (influenza, rubella, toxoplasma,
herpes s.)
• Winter birth
• Prenatal toxic exposure (lead)
• Obstetrical complications
• Head trauma (perinatal to adolescence)
• Autoimmune (Rh incompatibility, thyroid, type 1 diabetes,
celiac disease)
• Nutrition (starvation, omega-3 deficiency)
• Heavy metal exposure, maternal/fetal
• Heavy cannabis, other drug exposure
• Urban residence
• Exposure to trauma, with PTSD
• Negative emotional experience
Cortical volume reduction, in childhood-onset
schizophrenia, ages 14-19
Expressed emotion
•
•
•
•
Critical comments
Hostility
Over-involvement
Warmth
Proportion of families with high EE
in years following onset
50%
50%
35%
40%
30%
20%
14%
10%
0%
> 1 year
1-3 years
>5 years
Hooley, et al, 1995
Effects of genetic risk and family
functioning on eventual schizophreniaspectrum disorders
% of sub-sample
40
36.8
35
30
Low OPAS ratings
25
High OPAS ratings
20
15
10
5.8
5
4.8
5.3
0
High-risk, spectrum (n=145)*
* p < 0.001
**p = 0.582
G X E interaction: p=0.018
Low-risk, spectrum (n=158)**
Tienari, Wynne, et al, BJM, 2004
Mutual causal effects:
Patient symptoms and family interaction
Biosocial causal interactions in late schizophrenic
prodrome
Perceptual
distortions
Pervasive
anxiety
Acute onset
Withdrawal
"Oddness"
Functional
deterioration
Social &
performance
Social deficits
deficits
Family/Social
Physiological
Late prodrome
Critical
comments
CD, EOI
Anxiety
Panic
Misattribution
High EE
Illusions
Dread
Insomnia
Anorexia
Psychosis
Structural
Early prodrome
Social networks in schizophrenia
• Family network size
– diminishes with length of illness
– decreases in the period immediately following a
first episode
– is smaller at the time of first admission
• Networks
– buffer stress and adverse events
– determine treatment compliance
– predict relapse rate
– correlate with coping skills and burden.
Is early intervention indicated
prevention of psychotic
disorders?
Probably
“Yes, we can?”
Trials of Indicated Prevention
• Buckingham, UK
• EDIE, UK
• German Research Network
• OPUS, Denmark
• TIPS, Norway, Denmark
• PACE, Australia
• PRIME, North America
• Omega-3 FAs, Austria
• PIER, Maine
• EDIPPP, USA
% converting to psychosis
Psychosis prevention studies:
One year rates for conversion to
psychosis
40
32
35
30
25
20
15
9.9
10
5
0
Controls
Experimental
PACE
PRIME
OPUS
PIER
EDIE
Amminger
Mean rate
Portland Identification and Early Referral
(PIER)
Reducing the incidence of major
psychotic disorders in a defined
population, by early detection and
treatment:
Indicated prevention
Project Overview
PIER
Education
Clinical Work
Research
Material
Development
Assessment
Professionals
Psychosocial
Treatment
General
Public
Pharmacological
Treatment
Greater Portland
Area
BIOLOGICAL
RISK FACTORS
Population 33O,OOO
Experimental Catchment Area:
Vital statistics
Population, 2007
~340,000
Expected incidence, schizophrenia
34 (10/100,000)
Expected incidence, psychosis
116 (34/100,000)
Towns
28
Public high schools
25
Public middle schools
23
Private schools, all types
38
Colleges and universities
4
Psychiatric inpatient beds
134
Professional and Public Education
• Reducing stigma
• Information about modern concepts of
psychotic disorders
• Increasing understanding of early stages of
mental illness and prodromal symptoms
• How to get consultation, specialized
assessments and treatment quickly
• Ongoing inter-professional collaboration
Youth Education
• Public service announcements by mainstream television and
health information programs
• Interviews and spot announcements by youth television cable
network
• 2-3 sessions on early warning signs as part of the obligatory
10th grade health curriculum
• Widespread distribution of bookmarks and posters throughout
catchment area schools, colleges, bookstores
• Art and literature contest
• Major publicity events during Mental Illness Awareness Week
• Youth oriented website:
www.preventmentalillness.org
MentalPIER
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help
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Family practitioners
College health
services
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clinicians
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School teachers,
guidance counselors,
nurses, social workers
PIER
Team
Clergy
Employers
Advertising
Emergency and crisis services
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Family practitioners
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services
Pediatricians
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counselors, nurses, social
workers
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clinicians
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Team
Employers
Clergy
Emergency and crisis services
General Public
Clinical Strategies
Signs of prodromal psychosis
Schedule of Prodromal Syndrome (SOPS), McGlashan, et al
A clustering of the following:
Changes in behavior, thoughts and emotions, with preservation of
insight, such as:
Heightened perceptual sensitivity
To light, noise, touch, interpersonal distance
Magical thinking
Derealization, depersonalization, grandiose ideas, child-like logic
Unusual perceptual experiences
“Presence”, imaginary friends, fleeting apparitions, odd sounds
Unusual fears
Avoidance of bodily harm, fear of assault (cf. social phobia)
Disorganized or digressive speech
Receptive and expressive aphasia
Uncharacteristic, peculiar behavior
Satanic preoccupations, unpredictability, bizarre appearance
Reduced emotional or social responsiveness
“Depression”, alogia, anergia, mild dementia
Signs of prodromal psychosis
Changes in behavior, thoughts and emotions, with preservation of
insight, such as:
Unusual perceptual experiences
“Presence”, shadows, visual trails, ghosts
Imaginary friends
Fleeting apparitions
Odd sounds
Somatic illusions or hallucinations
Heightened or dulled perceptions
Vivid sensory experiences
Sensations and thoughts located outside the body
Frequent distortions or illusions
Brief but frank hallucinations, minimal effect on behavior or thinking
Signs of prodromal psychosis
Changes in behavior, thoughts and emotions, with preservation of
insight, such as:
Unusual fears
Marked guardedness, distrustful
Fear of assault (not social phobia)
Avoidance of bodily harm
Somatic delusions
Severe nihilism
Persistent persecutory self-referential thoughts
Paranoia
Extreme guilt, fear of harming others
Bizarre obsessional preoccupations
Fears of mind-reading
Frank delusions, without full conviction
Signs of prodromal psychosis
Changes in behavior, thoughts and emotions, with preservation of
insight, such as:
Disorganized or digressive speech and thoughts
Receptive aphasia: “Can’t understand others.”
Expressive aphasia: “Can’t be understood.”
Odd, circumstantial, tangential, paralogical speech
Overly simple speech
Loss of gist of conversation, poor abstracting
Rigid, concrete, almost autistic thinking
Loosening of associations
Marked vagueness, lack of clarity of subjects and objects
Racing speech
Stereotyped ideas, speech
Over-elaborate speech
Poor problem-solving
Signs of prodromal psychosis
• 2. Significant deterioration in functioning
–
–
–
–
Unexplained decrease in work or school performance
Decreased concentration and motivation
Decrease in personal hygiene
Decrease in the ability to cope with life events and stressors
• 3. Social withdrawal
– Loss of interest in friends, extracurricular sports/hobbies
– Increasing sense of disconnection, alienation
– Family alienation, resentment, increasing hostility, paranoia
Family-aided Assertive Community Treatment
(FACT):
Clinical and functional intervention
• Rapid, crisis-oriented initiation of treatment
• Psychoeducational multifamily groups
• Case management using key Assertive Community Treatment
methods
– Integrated, multidisciplinary team; outreach PRN; rapid response;
continuous case review
• Supported employment and education
– Collaboration with schools, colleges and employers
Family-aided Assertive Community Treatment
(FACT):
Clinical and functional intervention
• Cognitive assessments used in school or job
• Low-dose atypical antipsychotic medication
– aripiprazole 10-20 mg, quetiapine 300-600 mg, olanzapine 2.5-7.5
mg, risperidone 0.25-3 mg
• Mood stabilizers, as indicated by symptoms:
– Mood stabilizing drugs: lamotrigine 50-150 mg, valproate 5001500mg, lithium by blood level
• SSRIs, with caution, especially with aripiprazole and/or a family
history of manic episodes
Key clinical strategies in family intervention
specific to prodromal psychosis
• Strengthening relationships and creating an
optimal, protective home environment:
–
–
–
–
Reducing intensity, anxiety and over-involvement
Preventing onset of negativity and criticism
Adjusting expectations and performance demands
Minimizing internal family stressors
• Marital stress
• Sibling hostility
• Conceptual and attributional confusion and
disagreement
Key clinical strategies in family intervention
specific to prodromal psychosis
• Strengthening relationships and creating an
optimal, protective home environment:
– Buffering external stressors
• Academic and employment stress
• Social rejection at school or work
• Cultural taboos
• Entertainment stress
• Romantic and sexual complications
Key clinical strategies in family intervention
specific to prodromal psychosis
• Individualized, responsive education for single
families
• Little discussion of atrophic aspects of brain
functioning emphasis on transient, stress-induced
hyperactivity in some brain areas and some
biochemical systems
• Accelerated recovery, reentry and rehabilitation
• Emphasis on careful forward progress.
– "Slow down personal and career advancement, until
stability and motivation returns."
PIER: Outcomes after one year of
treatment
Data for 148 at-risk cases from the first 6 years
intake:
May 7, 2001- September 6, 2007
Community Education and Training:
Results
Outreach events
325
Public schools and colleges trained
100%
Professionals trained
7270
Bookmarks distributed
>70,000
Resource guides distributed
>1400
Website hits (2005-2007)
1,071/day
Website sessions (2005-2007)
56.3/day
Total hits (2005-2007)
>500,000
Surveys: Awareness of PIER in area, 2001
vs. 2007
8% vs. 19%
Figure 1. Disposition of all contacts with PIER,
5/7/2001-9/1/2007
All contacts
N=1333
Request for information
Case Referrals
N=180
N=1103
Request for
presentation
N=50
In catchment area
N=921
Age 12-35
N=780
Referred
Elsewhere
N=240 (30.8%)
No further
contact required
N=51 (6.5%)
Screened for formal assessment
N=404 (51.8%)
Contact
withdrawn
N=85 (10.9%)
Referred
Elsewhere
N= 74 (18.3%)
Presumed
Psychotic
N=47 (11.6%)
Completed
SIPS
N=271 (67.1%)
Contact withdrawn or did not
complete SIPS
N=9 (2.2%)
Psychotic by POPS criteria
Met SOPS criteria
N=32 (11.8%)
N=148 (54.6%)
Did not meet SOPS criteria
N=94(34.7%)
Declined treatment
Treated > 3 months
N=10 (6.8%)
N=118 (79.7%)
Dropped out in
< 3 months
N=22 (14.9%)
Efficiency of identification:
Diagnosis for those screened as at risk
n = 780
Referred for another disorder
314
40.2%
Prodromal
148
19.0%
Psychosis
79
10.1%
Any psychiatric illness
589
69.4%
Referral sources: Distribution
Non-mental health sources
52.3%
Tertiary sources
21.5%
Mental health sources
26.2%
Screening and treatment entry
Referrals
780
100.0%
SIPS Completed
271
34.8%
Met SOPS Criteria
148
54.6%
Declined treatment
10
6.8%
Dropped out <3 Months
22
14.9%
116
78.4%
Treated sample
Demographics of the treated sample
Males (age range 12 - 27)
Females (age range 12 - 24)
53.4%
46.6%
Average age
16.5
DSM-IV Substance abuse
disorder
15%
Treated cases converting to psychosis
within 12 months (n = 93)
• Cases not converted
72
77.4%
• Cases converted, 1-6 days
5
5.4%
• Cases converted, 7-30 days
7
7.5%
• SOPS psychosis conversions
5
5.4%
• Schizophrenic disorder
4
4.3%
• Total SOPS conversions
9
9.7%
SOPS scores at baseline and 12 months
3
S
u
b
s
c
a
l
e
Baseline
12 months
2.5
s
2
c
o 1.5
r
1
e
p<.001
p<.001
p<.001
p<.001
0.5
0
Positive
n=94
Negative
Disorganized
SOPS Subscale
General
Overall functioning:
Baseline and 12 months
70
56.5
60
50
38.1
40
30
20
10
0
Baseline
N=94; p<.01
12 month
Components of expressed emotion:
Prodromal vs. chronic phase
7
Scale score
6
5
4
3
2
1
Chronic
schizophrenia 1
Warmth
Chronic
schizophrenia 2
Rejection
Prodromal
Mothers
Protectiveness
All differences, prodromal vs. chronic: p<0.01
Fusion
Prodromal
Fathers
Difference in Initial Admissions
Portland vs. 3 Maine Urban Areas, Ages 12-25
10
Admissions/100,000
0
6.3
-10
-20
-30
Incidence difference, mean:
Portland vs 3 urban areas: 65/100,000
% of Portland baseline:
60%
-58.5
-40
-50
-60
1994-2000
2001-2007
Admissions/100,000
Difference in Initial Admissions Rates for Psychosis
Portland minus 3 Maine urban areas, Ages 12-25
80
60
40
20
0
-20
-40
-60
-80
-100
-120
1994
1995
1996
1997
1998
1999
2000
2001
PIER begins
2002
2003
2004
2005
2006
2007
Differences In Initial Admission Rates/100,000 For All
Psychoses, Ages 12-35, 1994-2000 Vs. 2001-2007:
Portland Vs. Control Catchment Areas In Maine
Central
46.1
Eastern
40
19.4
20
-0.2
Western
27.5
Mean, 3 areas
6.6
Rest of Maine
0
-20
-22.9
-40
-41.9
-60
-35.5
-42.1
-51.8
1994-2000
2001-2007
Difference in incidence/100,000
60
Incidence in Portland and 3 urban areas
All Psychosis, ages 12-25
80
y = 1.4x + 35.9
Admissions/100,000
70
60
y = 0.7x + 30.4
50
40
30
20r = -0.53
2001
2002
2003
2004
Portland
Urban Control
2005
2006
2007
Admissions/100,000
First admissions to Maine hospitals for a
psychotic or major mood disorder, 1990-2007
Ages 12-25
50
45
40
35
30
25
20
15
10
5
0
1991
1993
1995
1997
1999
2001
2003
2005
2007
Source: MHDO data, analyzed by Maine Health Information Center and Maine Medical Center Research Institute
Hospitalization costs avoided*
Portland vs. 3 other Maine cities
2002
Average:
2001-2007
2007
Cases not
admitted
Days in
hospital
Hospital
daily rate
Annual costs
avoided
36.8
10
$900
$331,200
36.8
13
$1,600
$765,440
62.7
10
$900
$564,300
62.7
13
$1,600
$1,304,160
89.5
10
$900
$805,500
89.5
13
$1,600
$1,861,600
*Savings from avoided initial hospitalizations in Portland. Cost estimates based on incidence rate differences (i.e., resulting fewer cases) between
greater Portland and the other 3 Maine urban areas. Amounts are based on time period—2002, 2007 or the average for 2001-2007—days in
hospital for first admission and daily rate in dollars. Population based on US Census estimates for the respective years.
Differences between treated prodromal
and post-psychotic states
Prodromal young persons have manifested:
• Maintenance of insight (prevention of loss)
• Continued ego-dystonic response to psychotic symptoms
• High acceptance of, and adherence to, treatment
• Low rates of substance abuse
• More open to discontinuing heavy drug and alcohol abuse
• Less resistance to family inclusion by patient
• Higher motivation to continue schooling and/or work
• More trusting and grateful therapeutic relationships
• Higher sensitivity to treatments
• Higher likelihood of improving course of functioning
Conclusions
• Public education is influencing attitudes, knowledge and behavior.
• Accurate referrals are coming from outside the mental health system.
• Treatment is blocking the final common pathway to psychosis.
• Medication at low doses is adequate but appears essential for
prevention of imminent, and perhaps later, psychosis.
• Very low conversion rates and functional improvement accompany
comprehensive treatment (~15%; ~5% for schizophrenic disorders).
• A substantial proportion of the incident population can be identified
and prevented from developing psychosis.
PIER Sponsors
PIER has been made possible with the generous support of:
Robert Wood Johnson Foundation
National Institute of Mental Health
Center for Mental Health Services (SAMHSA)
State of Maine
Maine Health Access Foundation
Bingham Fund
Betterment Fund
Brain Foundation
American Psychiatric Foundation
UnumProvident Foundation
Wrendy Haines Fund