Transcript No Slide Title

Families: Causing or Preventing
the Onset of Psychosis?
Fifth Annual Grampians Mental Health
Conference
March 1-2, 2005
William R. McFarlane, M.D.
Center for Psychiatric Research
Maine Medical Center
Portland, Maine
University of Vermont
A biosocial hypothesis
Major psychiatric disorders are the
result of the continuous interaction of
specific brain defects with specific
social and environmental inputs.
Functioning as an effect of psychotic
episodes
120
100
Functioning
80
60
40
20
0
0
1
2
3
Number of episodes
4
5
6
Effects of multiple relapses
140
120
130
Days to
remission
100
76.5
80
60
47
40
20
0
1st
2nd
Adapted from Lieberman, J., et al., J Clin, Psychiatry, 1996; 57: 5-9
3rd
Biologic risk factors
• Genetic risk
– 80-85% heritability
• Non-genetic biologic risk
–
–
–
–
–
Prenatal infections (influenza)
Prenatal toxic exposure (lead)
Obstetrical complications
Traumatic (head trauma, perinatal to adolescence)
Autoimmune (Rh incompatibility, increasing risk with multiple
births)
– Nutrition (starvation, omega-3 deficiency)
– Heavy cannabis, other psychotogenic drug exposure
• Non-heritable genetic risk
– Age of father >50; probably natural mutations in spermatogenesis
Cortical volume reduction, in childhoodonset schizophrenia, ages 14-19
Effects of genetic risk and family functioning on
eventual schizophrenia-spectrum disorders
% of sub-sample
40
36.8
35
Low OPAS ratings
High OPAS ratings
30
25
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
Effects of EE and medication on
relapse in schizophrenia
57.7
60
50
44.3
AP Meds
No meds.
40
27.9
30
18.4
20
10
0
High EE
Bebbington and Kuipers, 1994
Low EE
Effects of EE and contact on
relapse in schizophrenia
60
58.8
50
41.7
40
High contact
Low contact
30
23.9
18.3
20
10
0
High EE
Bebbington and Kuipers, 1994
Low EE
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
Mothers’ Protectiveness and Fusion
over Time during Prodrome
Fathers’ Protectiveness and Fusion over
Time during Prodrome
Role of Family Assessment
• To identify interpersonal stressors in the family relationships of
prodromal young people
– Determine young person and family members’ contributions to
these dynamics
• To identify relationships that might buffer stressors from within
and outside the family
• To determine what specific components of the family system are
affected by treatment
– If even one person is affected by treatment, the whole system will
change to accommodate
Biosocial causal interactions in late
schizophrenic prodrome
Early prodrome
Late prodrome
Critical
comments
CD, EOI
Anxiety
Panic
Misattribution
High EE
Illusions
Dread
Insomnia
Anorexia
Psychosis
Withdrawal
"Oddness"
Functional
deterioration
Social &
Social
performance
deficits
deficits
Perceptual
distortions
Pervasive
anxiety
Acute onset
Quantitative behavioral genetics:
Evocative gene-environment interaction
“The parental response to the child in early adolescence appears
to have the effect of protecting the child from a pathway to
“full–blown” antisocial characteristics”
“Knowledge of an individual’s genotype, combined with early
intervention at the level of the family environment, may well
prove to be the critical combination for preventing serious
psychopathology”
Towers, Spotts and Reiss, 2002
Portland Identification and Early
Referral
(PIER)
Reducing the incidence of
major psychotic disorders in
a defined population
Project Overview
PIER
Education
Clinical Work
Research
Material
Development
Assessment
Professionals
Psychosocial
Treatment
General
Public
Pharmacological
Treatment
Professional and Public Education
• Reducing stigma
• Information about modern concepts of
psychotic disorders
• Increasing understanding of early stages of
mental illness and prodromal symptoms
and signs
• How to get consultation, specialized
assessments and treatment quickly
• Ongoing inter-professional collaboration
Clinical Strategies
Signs of prodromal psychosis
Schedule of Prodromal Syndrome (SOPS), McGlashan, et al
A clustering of the following:
1. Changes in behavior, thoughts and emotions, with preservation of
insight, such as:
• Unusual perceptual experiences
• “Presence”, imaginary friends, fleeting apparitions, odd sounds
• Heightened perceptual sensitivity
• To light, noise, touch, interpersonal distance
• Magical thinking
• Derealization, depersonalization, grandiose ideas, child-like logic
• 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
• 2. A 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. Withdrawal from family and friends
– Loss of interest in friends, extracurriculars, sports/hobbies
– Increasing sense of disconnection, alienation
– Family alienation, resentment, increasing hostility, paranoia
Other entry criteria
• Ages 12-35
• Brief psychotic episode (< 1 month)
• Prodromal symptoms or recent deterioration
(>30% GAF decrease) in youth with a first or
second degree relative with a psychotic disorder.
• Schizotypal personality disorder combined with
recent deterioration (>30% GAF decrease) are
also at risk.
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
Cognitive assessments used in school or job
Low-dose atypical antipsychotic medication
– 10-20 mg aripiprazole, 2.5-7.5 mg olanzapine, 0.25-3 mg risperidone
• Mood stabilizers, as indicated by symptoms:
– SSRIs, with caution, especially with aripiprazole, family history of manic
episodes
– Antimanic drugs: lamotrigine 50-150 mg, valproate, 500-1500mg, lithium
Key clinical strategies in family intervention
specific to prodromal psychosis
• More individualized, multidimensional family assessment
• Thorough orientation regarding psychosis onset
• Education about psychosis, stress and emotional
moderation
• Maximum social support for all members of the family
• Psychoeducational MFG for stress reduction, optimal
problem solving, CD reduction, social support, sharing,
cross-parenting, buddy development
• Solving developmental, family, vocational, educational,
social and romantic problems that threaten stability
Key clinical strategies in family intervention
specific to prodromal psychosis
• Strengthening relationships and creating an optimal,
protective home environment:
– Reducing intensity
– Adjusting expectations and performance demands
– Minimizing internal family stressors
• Marital stress
• Sibling hostility
• Conceptual and attributional confusion and disagreement
– 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
• Treatment for parents and siblings, if psychiatric disorders present,
especially depression and bipolar disorder
• Single family PE, if necessary, because of logistics or extreme family
distress, negativity, and/or abuse
• PRN single family crisis intervention as needed
• PRN family or marital therapy in rare instances
• Creating reduced-stimuli environments for school and work
• Collaborative clarification of normal adolescent issues vs. symptoms
and disability
• Adapting school and work characteristics to current cognitive
functioning
• Focusing more on symptoms and functioning, less on diagnosis
PIER: Twelve month outcomes
Preliminary data for SOPS-positive prodromal cases
from the first 24 months of intake:
n = 44
Intake: May 7, 2001- May 6, 2003
Outcome: May 7, 2002- May 6, 2004
PIER referral sources
Referral sources (n = 390)
%
Family
24
School, college professionals
20
Mental health agencies
17
In-house (MMC, SHH)
21
Community physicians, therapists
14
Self
Other
1
2
Demographics of referred and treated
cases
Gender and Age
Male (age range 12-27 yrs)
21
53.8%
Female (age range 12-24 yrs)
18
46.2%
Mean age of referrals
Mean age, SOPS + prodromal cases
390
15.4
39
17.4
Screening and treatment entry
Referrals
SIPS Completed
390
100
25.6%
44
44.0%
Declined treatment
4
9.1%
Dropped out <3 Months
1
2.3%
Treated sample
39
88.6%
Met SOPS Criteria
Conversions
Scoring 6 on SOPS, at any time, year 1
n=39
•
•
•
•
Cases not converted
Cases converted, 1-6 days
Cases converted, 7-30 days
SOPS conversions
34 87.2%
2
5.1%
2
5.1%
1
2.6%
– Scoring 6, 4 days/week for >30 days
• Schizophreniform disorder
• Total days in conversion
14,235)
0
0.0%
75 (of
Course of conversion
n = 8, year 1 and 2, to date
7
SIPS P scale
6
Current status
5
Schizophrenia
4
3
?
Not hospitalized
2
1
Asymptomatic
0
Baseline
*mean interval = 32 weeks
SIPS
before
episode*
Highest
SIPS
SIPS after SIPS one
episode
month
later
Current
SIPS
PACE, PRIME and PIER
12 month outcome
40
%
c
o
n
v
e
r
t
i
n
g
35 36
30
25
20
15
38
19
16
12.8
10
5
0
2.6
PACE
PRIME
PIER
NBI
SPI
Control
Olanzapine
FACT-All
FACT-SOPS
Relapse outcomes in clinical trials
1980-1997
70
65
60
50
41
40
30
20
9
10
0
No medication
Individual therapy &
medication
PEMFG & medication
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=.000
p=.000
p=.000
p=.000
0.5
0
Positive
Negative
Disorganized
SOPS Subscale
General
GAF: Baseline and 12 month
70
57.2
60
50
36.9
40
30
20
10
0
Baseline
n=36; t=5.236; p=.000
12 month
Estimated treated incident
population for schizophrenia
•
•
•
•
•
•
•
Population
260,000
ECA incidence rate
1 / 10,000
Expected incident population
52
Mood disorders & false positives 8
De facto schizophrenia spectrum 31
Treated population, maximum <60%
Identified population, maximum <67%
Clinical observations
•
Family types
– None observed to date.
•
Great variety
– Majority are loving, supportive, some with one parent with CD.
– A few are highly dysfunctional, some with untreated bipolar disorders.
•
•
High proportion of relatives with psychiatric disorders.
Most prodromal young people develop hostility and irritability.
– Many begin to be extremely frightened, distracted and increasingly disorganized.
•
•
Almost all family members are anxious, frightened, confused; some are
annoyed, resentful, critical and impatient with increasing failures and social
withdrawal.
Misattribution often leads to disagreements along stereotypical gender lines,
leading in turn to increasing marital distress, leading to increasing general
tension in relationships, anxiety at psychological level and increasing and
persisting arousal at the psychophysiological level.
• The nodal and essential family element is ignorance about the
prodromal state, which is, by definition, all but universal at
present in lay and professional cultures .
Conclusions
• Public education is beginning to influence attitudes,
knowledge and behavior.
• Increasingly accurate referrals are coming from outside
the mental health system.
• May be affecting the final common pathway to psychosis
for many cases
• Medication at low doses is adequate but appears essential
for prevention of imminent, and perhaps later, psychosis.
• Very low conversion rates accompany evidence-based,
comprehensive treatment (~10%; 0% for schizophrenia).
• A substantial, though presently unknown, proportion of
the incident population can be identified and prevented
from developing psychosis, in the short term.
Conclusions
• Family intervention, at least, is accompanied by high
treatment acceptance and retention, including
medication.
• Family and psychosocial intervention may be having an
effect on functioning beyond medication effects.
• Deficiencies for family-based treatment
– Variety of family realities
– Other unknown variables not targeted
– Other known variables not targeted: CD
PIER Sponsors
PIER has been made possible with the generous support of:
•
•
•
•
•
•
•
•
•
•
•
Center for Mental Health Services
NIMH
Robert Wood Johnson Foundation
Maine Health Access Foundation
Bingham Fund
Betterment Fund
Brain Foundation
State of Maine
American Psychiatric Foundation
UnumProvident Foundation
Wrendy Haines Fund