IMPRO
VIN
G TH
E DETEC
TION
OF YO
UTH
S AT RISK OF
PSYCH
OSIS IN
THE C
OM
MU
NITY: A
NEU
ROD
EVELO
PMEN
TAL
PERSPECTIV
E
PEPPNET W
ebinar
Monica E C
alkins, Ph.D. A
ssociate Professor of Psychology D
irector, Clinical Research A
ssessment
Associate D
irector, Penn Psychosis Evaluation and Recovery C
enter (PERC)
Neuropsychiatry Section, D
epartment of Psychiatry
Perelman School of M
edicine
University of Pennsylvania
Oct 17, 2018
Jerome Taylor, M
.D. C
hild, Adolescent &
Adult Psychiatrist
Children’s H
ospital of Philadelphia
Disclosures
¨ N
one
Background
¨
Subthreshold psychotic-like experiences
¤
Are relatively com
mon in the general population of children and adolescents.
¤
Develop into distressing and im
pairing psychotic disorders in a minority of youths.
¨
Increasing our ability to identify youth at risk of psychosis in the general public is a key step tow
ards an improved ability to prevent the disorder.
¨
Clinical challenges in screening/Identifying P
S sym
ptoms in children/
adolescents ¤
Little normative/base rate data – Is this just a “norm
al” experience? Is this just an “adaptive” response to circum
stances? n
Related – child’s conflation of “norm
al” childhood experience with “abnorm
al”
¤
Com
orbidities - Is this just “due to/manifestation” of [other thing/disorder]?
¤
Ability/w
illingness to disclose ¤
Limited collateral inform
ant knowledge of subthreshold positive sym
ptoms
Background
¨
The Philadelphia N
eurodevelopmental C
ohort (PN
C) w
as founded to characterize clinical and neurobehavioral phenotypes of genotyped youths. ¤ A
llowed com
munity screening to identify the earliest em
ergence of psychosis spectrum
symptom
s in young people. ¤ C
omplem
entary to investigations of clinically help-seeking individuals.
¨
Through the PN
C, w
e aimed to prospectively investigate predictors and
trajectories of psychosis spectrum features in a com
munity sam
ple of U
.S. youths.
¤ Findings inform
understanding of significance of early subthreshold sym
ptoms
(2015) J Child Psychology and Psychiatry
• A
merican Recovery and
Reinvestment A
ct (ARRA
) Funded
• Available in the public dom
ain (dbG
ap) – 199 approved requests to date
• A
ge 8-21 •
Mean age = 14.2 (s.d.=3.7)
• Fem
ale = 52 %; A
A/O
ther = 44%
• N
=9,498 •
Time 1 recruitm
ent = 2009-2011 •
In-home = 66%
PH
EN
OTY
PIN
G
(n=9,498)
Clinical A
ssessment
Neurocognitive
Testing N
euroimaging
(n=1,445)
CA
G
(50,293) E
MR
Center for A
pplied Genom
ics
T1: Psychosis Spectrum
Assessm
ent
• P
ositive Threshold P
sychosis: H
allucinations/ D
elusions (K-
SA
DS
) •
Positive S
ub-threshold P
sychosis (PR
IME
S
creen, Miller et al.
2004)
• N
egative/ D
isorganized (6 S
cale of Prodrom
al S
ymptom
s items)
Younger children endorsed higher levels of subthreshold positive sym
ptoms – led to “norm
ing” the psychosis spectrum
Symptom
s
• Youngest and oldest males had higher total scores than fem
ales
• Minority youth endorsed m
ore symptom
s at all age bins (p’s <0.01)
• Calculated z-scores based on m
eans and standard deviations within each age year for
the total sample, m
ales, females, E
uropean-Am
erican and African-A
merican/O
ther
groups.
“Norm
ing” the psychosis spectrum Sym
ptoms
• O
nline look up table (in development):
https://pil.med.upenn.edu/prim
e
• Standard (T) score tables w
ere
generated for each reference
group, where T=50+10(z). T
scores have a mean of 50 and
a standard deviation of 10.
• Age, sex and race norm
ative
references for PS
-R can inform
interpretation of individual
responses in research, clinical
and comm
unity settings.
T-score<6060-6970-7980-8990-99100+
• A
mong m
edically healthy youth, age 11-21 (mean 15 y.o.):
• psychotic sym
ptoms: 3.7%
• sub-psychotic sym
ptoms: 12.3%
• only subthreshold negative sym
ptoms: 2.3%
• P
S sym
ptoms predicted by m
ale sex, younger age, non-EA race
• P
sychosis spectrum sym
ptoms associated w
ith •
Reduced neurocognitive accuracy and global functioning
• Increased odds of depression, anxiety, behavioral disorders, substance use, suicidal ideation
“Validation” of the Psychosis Spectrum C
onstruct
“Validation” of the Psychosis Spectrum C
onstruct
Interviewer O
bservations
Global A
ssessment of Functioning (G
AF)
Family Interview
for Genetics S
tudies (FIG
S) – B
rief
Sem
i-Structured P
sychopathology A
ssessment
K-S
AD
S M
ood, AD
HD
, S
ubstance S
tructured Interview for
Prodrom
al Syndrom
es (S
IPS
)
Dem
ographics and Medical H
istory
Timeline
Interviewer O
bservations
Global A
ssessment of Functioning (G
AF)
Sem
i-Structured P
sychopathology A
ssessment
K-S
AD
S M
ood, AD
HD
, S
ubstance S
tructured Interview for
Prodrom
al Syndrom
es (S
IPS
)
Timeline
Adult P
roband (age 18-21) and C
ollateral Informant (of youths 9-17)
Middle P
roband (age 11-17)
• 2-year Follow
-up: Psychosis S
pectrum=249, N
on-Spectrum
=254 •
Assessm
ents conducted blind to Time 1 risk status
At 2-year follow-up (m
ean 17 y.o.), PS symptom
s persisted or w
orsened in 51% of baseline PS, w
ith remaining classified as
”resilient”. PS symptom
s emerged in 16%
of baseline Non-PS.
Persistent group had increased concurrent comorbid
psychopathology in most dom
ains, and a higher rate of psychosis fam
ily history.
Symptom
persistence predicted by baseline higher severity of subclinical psychosis, low
er global functioning, and prior psychiatric medication
PNC$$
9,498$
Psychosis$Spectrum
$153$
Persist$$87$
(57%)$
Psycho=c$Disorder$
13$(8%
)$
SubApsychosis$$74$
(48%)$
Resilient$66$
(43%)$
NonAPsychosis$Spectrum
$$230$
Emerge$56$
(24%)$
Psycho=c$Disorder$
4$(2%
)$
SubApsychosis$52$
(22%)$
$$
Typically$Developing$$174$(76%
)$
Time 1
Time 3
Figure 1. .
At 4-year follow-up (n=383, m
ean 19 y.o.), using methods
identical to Time 2, psychosis spectrum
features persisted or w
orsened in 57% of youths classified as PS at baseline
Persistent Resilient
Emergent
Typically D
eveloping
N
87 66
56 212
Female (%
) 48.3
62.1 51.8
55.2
African-A
merican/
Other %
73.6
60.6 75.0
44.3
T1 PRIME-Screen – Revised Total (m
ean±
SD)
6.7 (5.1) 4.0 (4.0)
2.0 (2.5) 1.3 (1.7)
T1 PRIME-Screen
Revised, Age
Norm
ed (mean
±SD
)
1.3 (1.4) 1.0 (1.1)
-0.1 (0.8) -0.4 (0.5)
T1 SOPS N
egative/D
isorganized A
ge Norm
ed (m
ean±SD
)
1.4 (1.7) 0.5 (1.2)
-0.2 (0.8) -0.4 (0.6)
T1 Global A
ssessment
Scale (mean
±SD
)
68.3 (12.8) 76.4 (12.8)
77.5 (10.8) 84.8 (9.5) PN
C$$9,498$
Psychosis$Spectrum
$104$
Persist$$58$
(56%)$
Persist$42$
(41%)$
Remit$
16$(15%
)$
Remit$
46$(44%
)$
Re?occur$14$
(14%)$
Remit$
32$(31%
)$
Non?Psychosis$Spectrum
$$116$
Emerge$20$
(17%)$
Persist$12$
(10%)$
Remit$
8$(7%
)$$
Non?PS$$96$
(83%)$
Emerge$9$
(8%)$$
Non?PS$87$
(75%)$$$
Time 1
Time 2
Time 3
Figure 2.
Am
ong youths assessed at all three time-points (n=220),
56% show
ed temporal stability in presence or absence of
psychosis spectrum
sym
ptoms,
while
the rem
ainder exhibited
varying patterns
of sym
ptom
remission,
re-occurrence and em
ergence over time (see Figure 2).
Am
ong youths assessed at all three time-points (n=220),
56% show
ed temporal stability in presence or absence of
psychosis spectrum
sym
ptoms,
while
the rem
ainder exhibited
varying patterns
of sym
ptom
remission,
re-occurrence and em
ergence over time (see Figure 2).
In youth assessed at all three time-points (n=220),
59% (n=129) show
ed temporal stability in presence or
absence of psychosis spectrum sym
ptoms
Rem
ainder exhibited fluctuating patterns of symptom
rem
ission, re-occurrence and emergence over tim
e (“flux”).
Conclusions
¨
Varying courses of psychosis spectrum sym
ptoms are evident early in U
.S. youth
representative of the comm
unity. ¤ P
sychosis spectrum persistence, em
ergence, and resilience are dynamic
developmental processes.
¤ A
ge must be considered – both in interpretation of self-reported sym
ptoms and
because youth are still passing through risk period n To our know
ledge, first effort to provide normative, standardized reference scores for
a psychosis spectrum screening tool across age range.
n R
esults underscore the need to interpret endorsements of com
munity youths in the
context of age, sex and race. n S
tandard scores developed here can facilitate assessment of the “norm
alcy” of individual responses according to these dem
ographic parameters
n N
ow 6 year follow
-up (mean 21 y.o.) - concurrent validation via screening and S
IPS
¨
A majority (70-75%
) of youth with persistent P
S sym
ptoms reported speaking w
ith a professional about m
ental health concerns n R
eflects a
critically im
portant opportunity
for sim
ple screening
to identify
and intervene early w
here warranted.
PNC
Collaborators and Support
Raquel E
. Gur, M
D P
hD
Ruben C
. Gur, P
hD
Kathleen M
erikangas, PhD
Theodore S
atterthwaite, M
D
Daniel W
olf, MD
, PhD
Jam
es Yi, MD
, PhD
Tyler M
oore, PhD
K
osha Ruparel, M
S
Marcy B
urstein, PhD
D
avid Roalf, P
hD
Christian K
ohler, MD
B
ruce Turetsky, MD
H
akon Hakonarson, M
D
W
e thank the participants and their families. S
upported by RC
2MH
089983 (RE
G);
K08M
H079364 (M
EC
); K23M
H098130 (TD
S); D
owshen P
rogram for N
euroscience; and the Lifespan B
rain Institute M
onica E. Calkins, PhD
Jerom
e H. Taylor, M
D