Youth Mental Health and 22q11
Cameron S. Carter M.D.
Director Center for Neuroscience U.C. Davis
Early Diagnosis & Preventative Treatment Clinic (EDAPT)
UC Davis Department of Psychiatry
of Mental Health
Psychiatric Disorders are Common •  Up to one third of all adults will have a life9me experience of mental disorder •  Less that 30% will get treatment Psychiatric disorders are “developmental” •  80% will have earliest signs and symptoms before 18 years •  Children with developmental disorders have increased rates of psychiatric symptoms •  The symptoms are part of their developmental disorder and will respond to evidence based treatments rders were
ose with the
ention deficit,
early half
tic experiences.
y and disrupted
common.Poor
associated with
was more
.
etion syndrome
nt
adulthood.
pected to
orted psychotic
s imply a
tal disruption in
associated with
early adulthood.
t
None.
For the same reason, we did not recruit participants for either group from clinical ser11 5 ^ 1 2 0
vices where referral was for behavioural
or learning difficulties. Psychiatric disorder
and behavioural problems were not exclusion criteria for comparison participants
Adolescents and young adults
with
22q11
because
this would
havedeletion
biased the results
METHOD
towards a low rate of psychopathological
Study
participants
disruption,
of adolescents
syndrome: psychopathology
in an unrepresentative
at-risk group
and young adults with learning disabilities.
This study received ethical approval from
the KATE
Great Ormond
Street
D. BAKER
andHospital
DAVID National
H. SKUSE To counterbalance self-selection biases,
literature about the study provided to
Health Service Trust research ethics compotential cases and controls stated that it
mittee. Written informed consent was
tion syndrome is associated with specific
developmental
psychopathology similar to
B R I T I S H J O U R N A L O F P S YC H I AT RY ( 2 0 0 5 ) , 1 8 6 ,
that seen in idiopathic schizophrenia,
owing to shared genetic and pathophysiological mechanisms.
Table 1 Study populations
Microdeletions at chromosome 22q11.2
Background 22q11deletion syndrome
Group
t or w2 1
(22q11 deletion syndrome, velo-cardiois associated with high rates of psychiatric
DiGeorge
22q11 deletion syndrome (n
(nfacial
¼25)
25) syndrome,
Controls
(n
(n¼25)
25)syndrome; premorbidity, especially schizophrenia.
valence *1 in 4000) can cause heart and
If common neurodevelopmental
palate malformations,
Gender (male : female)
15 : 10
17 : 8 mild to moderate
0.351
trajectories characterise 22q11deletion
learning disability and communication1 imAge in years : mean (s.d.)
16.4 (2.0)
16.0 (2.9)
1.2
pairments (Scambler, 2000). Schizophrenia
syndrome and idiopathic schizophrenia,
Estimated IQ : mean (s.d.)
66 (15)
74 (16)
1.91
is
a
late
manifestation
in
around
30%
of
then similar‘premorbid’features would
cases, on a par with the risk to offspring
1. All P40.05.
be predicted.
Aims To define psychopathology in
adolescents and young adults with 22q11
deletion syndrome.
of two parents with schizophrenia (Murphy
et al,
al, 1999). People with schizophrenia
have an 80-fold increased prevalence of
the microdeletion relative to the general
11 5
population (Karayiorgou et al,
al, 1995). Individuals with schizophrenia and a 22q11.2
obtained from
participants age
with 22q11 de
cruited with t
22q11 Group (a
and informatio
informati
disciplinary clin
average genera
learning disabi
logical conditi
major sensory
be comparison
these volunteer
(64%), colleg
(12%) and org
services for you
abilities (24%)
current placem
deletion syndro
were recruited
groups were w
gender, age (ra
and estimated I
Given the s
similar to previ
dition), it is
study volunteer
scores. A symptom was counted as present
for dimensional scoring if the participant
met intensity criteria, regardless of whether
frequency or duration criteria were met for
T
Table
able 2
occur with neurocognitive dysfunctions
(Nuechterlein et al,
al, 2002). In this study,
dimensional schizotypy ratings were derived from CAPA interviews according to
control groups and the average symptom
counts for each dimension investigated.
Odds ratios for the risk of obtaining a diagnosis, given membership of the 22q11
DSM^IV diagnoses and dimensional symptom counts
Disorder
Number of diagnoses
w2
22q11 deletion syndrome
Controls
ADHD, inattentive subtype
12
4
Anxiety disorder
10
2
Separation anxiety
0
0
Social anxiety
0
1
Overanxious
8
1
Phobia
Mean dimensional symptom count (s.d.)
Mann^ Whitney U
22q11 deletion syndrome
Controls
6.8*
6.6 (3.1)
3.4 (3.2)
3.1**
6.7*
1.2 (2.0)
0.2 (0.9)
2.8*
11.1**
2.7 (2.4)
0.3 (0.9)
4.4**
2
0
Mood disorder
9
0
Dysthymia
4
0
Major depression
3
0
Hypomania
2
0
Manic episode
0
0
Obsessive^compulsive disorder
2
0
2.0
0.7 (1.5)
0.1 (0.4)
2.0*
Conduct disorder
0
0
0
0.1 (0.4)
0.3 (0.6)
1.4
ADHD, attention-deficit/hyperactivity disorder.
*P50.05; **P
**P50.01.
11 6
From: High Rates of Schizophrenia in Adults With Velo-Cardio-Facial Syndrome
Arch Gen Psychiatry. 1999;56(10):940-945. doi:10.1001/archpsyc.56.10.940
Date of download: 5/16/2014
Copyright © 2014 American Medical Association.
All rights reserved.
What is Psychosis?
•  A Brain Based Neurodevelopmental Disorder •  Can be related to a serious mood disorder (depression, bipolar disorder) or a primary psycho9c disorder •  Most Striking are the Posi9ve Symptoms -­‐ Hallucina9ons, Delusions, Thought Disorder •  However, there are also Nega9ve Symptoms -­‐ Loss of interest, energy, pleasure, withdrawal •  And Cogni9ve Impairments -­‐ problems in aRen9on, problem solving and memory
•  That Predict Func9onal Outcome -­‐ not responsive to current medica9on -­‐ poten9al for cogni9ve remedia9on How does Psychosis Develop?
Positive symptoms
Negative symptoms
Risk for
relapse
At Risk
phase
Acute
psychosis
Recovery
phase
1 week-1 year
1 week-1 month
6-36 months
Biological Complexity
•  Multiple systems impacted at multiple
levels!
•  Structural-Anatomical: cortical gray
matter reduction, subcortical changes,
sulcal & ventricular enlargement
•  Functional-Physiologic: reduced or
irregular activation during various
cognitive tasks
•  Cellular-Molecular: NT systems
abnormalities à altered receptor
distributions, increased cell density,
decreased/aberrant connections
between cells
Early Intervention Rationale
•  Duration of untreated psychosis is associated with
poor outcome
•  Early in illness treatment response is robust
•  Loss of function and treatment resistance follow
repeated relapses
•  Early intervention can improve functional outcome
•  Tailored treatment pathways and therapies for early
treatment and rehabilitation
The EDAPT & SacEDAPT Programs
% Patients
Relapse-Free
Duration of Untreated Psychosis
and Rate of Relapse
90
80
70
60
50
40
30
20
10
0
Short DUP, N=31 (treatment <1 year after psychosis onset)
Long DUP, N=22 (treatment >1 year after psychosis onset)
6
12
18
# Months after treatment entry
24
Adapted from Crow
et al. (1986). Brit J.
Psychiatry, 148,
120-127.
Psychosis Prodrome
•  Period of early clinical signs that individual is
at higher risk, but not always destined, for
psychosis
•  Typically occurs during adolescence or early
adulthood – between ages 15-25
(average age 17-18)
•  Average duration of 1-3 years
•  Likely association with brain maturation
•  Onset may be earlier for men than women
Non-specific signs of prodromal
psychosis
A clustering of the following:
•  A significant deterioration in the ability to cope with life events and
stressors
–  Decrease in work or school performance
–  Decreased concentration and motivation
•  Withdrawal from family and friends
•  Decrease in personal hygiene
Specific signs of risk for psychosis
Attenuated/subthreshold psychotic symptoms
Marked changes in behavior, thoughts and emotions, such as:
•  Unusual perceptual experiences
•  Heightened perceptual sensitivity
•  Magical thinking
•  Unusual fears
•  Disorganized or digressive speech
•  Uncharacteristic, peculiar behavior
•  a “whiff” of psychosis…
The EDAPT & SacEDAPT Programs
Careful Assessment is Needed
These symptoms CAN look similar to:
•  Depression or Anxiety
•  Substance Abuse
•  Reaction to abuse or trauma
•  Attention Deficit Hyperactivity Disorder
•  Reaction to family stress
•  Learning Disabilities
•  Pervasive Developmental Disorders
PS Criteria of
presence of a
t a 3–5 severity
report Global
ed on the SIPS
he Schedule for
Aged Children,
al., 1997) was
morbid mental
assess autistic
mental disorder
al Manual, 4th
ychiatric Asso-
•  eted live clinical
ew tailored to
eligible psychiording to their
view. JS and RH
nterview, and
es. Interviewer
(for JS and TN)
(Miller, et al.,
occurring at least once per week. Notably, no other positive
symptom score was above
the Research
“questionably
present” level for
Schizophrenia
118 (2010) 118–121
these two individuals, their total positive symptom scores were
Contents lists available at ScienceDirect
4 and 5. In contrast, six of the remaining seven 22q11.2DS
SchizophreniaAPS
Research
individuals reported long-standing
symptoms and therefore did not meet
syndrome.
j o u r n acriteria
l h o m e p a g e :for
w w w.a
e l s CHR
ev i e r. c o m
/ l o c a t e / s c h r e s These six
included those with the highest positive symptom total scores,
Brief
13,report
13, and 14.
SOPS positive
total scores
across
the fourin domains
Attenuated
symptoms
of psychosis
adolescentswere
with not
chromosome
deletion
syndrome
associated 22q11.2
with age
or intelligence.
SES was inversely
Joel Stoddard a,⁎, Tara Niendam b, Robert Hendren c, Cameron Carter b, Tony J. Simon a
a
Department of Psychiatry and Behavioral Sciences and the Medical Investigation of Neurodevelopmental Disorders (M.I.N.D.) Institute, University of California at Davis
Health System (UCDHS), United States
b
Department of Psychiatry and Behavioral Sciences and the Imaging Research Center, UCDHS, United States
c
Department of Psychiatry, University of California at San Francisco, United States
Table 1
Participant characteristics.
a r t i c l e
i n f o
Age (years)
Median (IQR), range
Female
Keywords:
SES
Chromosome 22q11.2 deletion syndrome
Mean (SD)
VCFS
Schizophrenia
FSIQ
Prodromal
psychosis
Clinical-high-risk psychosis
Mean (SD)
GAF
Mean (SD)
Article history:
Received 22 August 2009
Received in revised form 10 December 2009
Accepted 14 December 2009
Available online 6 January 2010
a b s t r a c t
22q11.2DS n = 20
15.1 (4.3), 12–22
Thirty percent of individuals with chromosome 22q11.2 deletion syndrome (22q11.2DS)
develop a psychotic disorder, particularly schizophrenia. We assessed attenuated positive,
negative and disorganized symptoms of psychosis and clinical-high-risk syndromes in 20
adolescents with 22q11.2DS (median age 15.1 years) using the Structured Interview for
Prodromal Symptoms (SIPS). Two participants met criteria for the Attenuated Positive
Symptom Syndrome, while nine participants (45%) experienced positive symptoms rated in
the “moderate” to “severe and psychotic” range on the SIPS. Almost all presented with
moderate to severe symptoms in the negative, disorganized, and general symptom domains.
© 2009 Elsevier B.V. All rights reserved.
1. Introduction
Mental disorders are common in chromosome 22q11.2
deletion syndrome (22q11.2DS), which is caused by a
microdeletion at chromosomal region 22q11.2 (OMIM accession nos. 188400, 192430, and 145410). Psychotic disorders,
especially schizophrenia, have a lifetime prevalence of about
30% (Murphy and Owen, 2001), which is disproportionately
high with respect to other neurodevelopmental disorders
70%
48.9 (14.0)
76.2 (10.9)
58.8 (10.8)
youth with 22q11.2DS (Baker and Skuse, 2005; Debbane,
et al., 2006; Feinstein, et al., 2002; Vorstman, et al., 2006).
However, examining subclinical psychotic-like symptoms
may yield additional information about the presentation of
psychosis in this at-risk population. Consequently, Baker and
Skuse (2005) studied schizotypal personality disorder
symptoms in adolescents with 22q11.2DS. While 48%
(n = 12/25) reported transient psychotic-like symptoms,
84% (n = 21/25) endorsed at least one schizotypal symptom.
Table 2
KSADS-PL determined mental disorders. a
Table 3
Presentation of SIPS
22q11.2DS n = 20
Diagnosis
Current n (%)
Lifetime n (%)
Any disorder
PDD NOS
ADHD
ODD
Tourette's disorder
Enuresis
Alcohol dependence
Any anxiety
SAD
GAD
OCD
Panic disorder
PTSD
ASD
Social phobia
Specific phobia
Anxiety disorder NOS
Any mood
MDD
Depressive disorder NOS
Adj. disorder with depressed mood
15 (75)
5 (25)
6 (30)
1 (5)
1 (5)
2 (10)
1 (5)
11 (55)
1 (5)
4 (20)
1 (5)
0 (0)
1 (5)
1 (5)
2 (10)
6 (30)
2 (10)
3 (15)
2 (10)
1 (5)
0 (0)
18 (90)
5 (25)
7 (35)
1 (5)
1 (5)
6 (30)
1 (5)
12 (60)
4 (20)
4 (20)
4 (5)
1 (5)
1 (5)
2 (5)
5 (25)
7 (35)
2 (10)
5 (25)
4 (20)
1 (5)
1 (5)
a
Data are presented as the number of adolescents who met criteria for a
diagnosis. Current refers to disorder present or partially remitted within
2 months prior to assessment. Lifetime refers to any history of the disorder.
Abbreviations refer to the following disorders: NOS = not otherwise
Positive symptom
Unusual thought
Persecutory delus
Grandiosity
Perceptual abnorm
Disorganized com
Negative symptom
Social anhedonia
Avolition
Expressions of em
Experience of em
Ideational richnes
Occupational func
Disorganized sym
Odd behavior or a
Bizarre thinking
Problems with at
Impairment in hy
General symptom
Sleep disturbance
Dysphoric mood
Motor disturbanc
Impaired toleranc
stress
Stoddard et al 2010 •  2 (10%) met aRenuated posi9ve syndrome criteria •  8 more had some evidence of aRenuated symptoms but we do not know the significance of this What are effec*ve treatments? •  Biological Factors
–  Medication
–  Substance use management
•  Cognitive/Psychological Factors
–  Cognitive Therapy
–  Cognitive Remediation
–  Skills Training
–  Supported Education/Employment
–  Peer/Family Support
•  Environmental/Family Factors
–  Family Therapy
Entry Criteria for EDAPT Clinic
•
•
Ages 12-25, IQ> 70 , no medical illness/injury affecting cognition
Drug use Ok, but no dependence
•
Recent onset of psychosis (within the past year) includes affective
and non-affective psychosis
or
Attenuated positive symptoms
or
Recent deterioration in youth with a parent/sibling with a psychotic
disorder
•
•
•
Also serve Mood/Bipolar Disorder (with attenuated or psychotic
features)
EDAPT Offers:
•  Phone consultation
–  Support for professionals like you!
•  Comprehensive Psychiatric Assessment
•  Case Management
–  Psychoeducation
–  Crisis management & Problem Solving
•  Groups:
•
•
•
•
–
–
–
–
Multifamily Group
Family Support Group
SAMM
Peer Support Group
Support from Peer & Family Advocate
Supported Education/Employment
Medication Management
Monitoring and support for 2 years
The EDAPT & SacEDAPT Programs
Contact Information
EDAPT & SacEDAPT
Phone Consultation Hours:
9:00am – 5:00pm M-F
EDAPT referrals:
Jane Dube – 916-734-2964
SacEDAPT Referrals:
Markie – 916-734-7251
http://earlypsychosis.ucdavis.edu