A New Method for Mapping the Linkage between
Abnormal Gray Matter Loss and the Clinical and
Cognitive Deficits in Childhood-Onset Schizophrenia
1Christine
N. Vidal, 2Judith L. Rapoport MD, 2Peter Gochman MA,
2Jay N. Giedd MD, 2Jonathan Blumenthal MA, 2Robert Nicolson MD,
1Arthur W. Toga PhD, 1Paul M. Thompson PhD
1Laboratory
of Neuro Imaging, Brain Mapping Division,
Department of Neurology, UCLA School of Medicine
2Child Psychiatry Branch, National Institute of Mental Health, NIH,
Bethesda, MD
INTRODUCTION
Striking profiles of accelerated gray matter loss spread across the cortex in childhood-onset schizophrenia (COS; [1]). We
developed a new mathematical method that maps in detail the spatial patterns of linkage between these brain changes and
clinical and cognitive assessment.
METHODS
3D MRI
volume
SUBJECTS & SCANS
12 COS
12 NV
10 PNOS
6 males + 6 females
DSM-III-R
Onset of psychotic sympt:12
6 males + 6 females
7 males + 3 females
DSM-III-R
Medication-matched group
METHODS
Extraction
Tissue classification
Alignment
3D T1-weighted MRI volumes
1.5-T Signa scanner (GE)
NIMH
3D average anatomy
first
last
SCH: 13.9  0.8 years
NV: 13.5  0.7 years
SCH: 18.6  1.0 years
NV: 18.0  0.8 years
+
+
MAP AVERAGE LOSS,
RATES, SIGNIFICANCE
time
before
after
INVESTIGATE EFFECTS
Cognitive & Clinical Evaluation 1:
Cognitive & Clinical Evaluation 2:
IQ, SANS, SAPS, Eye tracking,
CGAS
IQ, SANS, SAPS, Eye tracking,
CGAS
RESULTS
2) The significance of
disease-specific
change can be
established
1) Striking accelerated GM loss in COS : peak value > 5% / year
FEF, Sup M, Sens M
parietal
3) Mapping brain change in medication-matched subjects (PNOS)
who don’t satisfy criteria for SCH. Temporal deficit: specific to SCH
SCH
Temporal loss
Temporal
Non SCH
(medicationmatched)
No temporal loss
DIFF
Rate of Gray Matter loss
Significant progressive GM loss in COS
4) Dependencies between the rate of GM loss and the patient’s age
are mapped
correlation
Ruling out Medication Effects
5) Linkage between loss of GM and clinical & cognitive changes
Full Scale IQ
P-value
R
P<
P<
significance
Top
Catch-up
saccades
Subscales of IQ
P<0.075
P<0.010
P-value
CGAS
P<0.064
In temporal:
Raw sc:info…….L: P<0.048
comp…..R: p<0.052
P<0.045
SAPS
In frontal:
Raw sc: info……R: p<0.053
comp…..L/R: P<0.033, 0.026
vocab….L/R: P<0.058, 0.049
P<0.031
P<0.0001
P<0.005
L
Regions where loss rates depend on age
Rates of right temporal GM loss were strongly correlated with Full Scale IQ including the Information (Info) and Comprehension
(Comp) subtest raw scores. Faster loss rates in frontal cortex were also strongly correlated with IQ including the Info, Comp and
Vocabulary raw scores. The linkage in frontal superior areas was highly significant in both hemispheres, in temporal and frontal
anterior regions especially. The IQ test requires multiple brain systems to be intact, so extreme loss of tissue may lead to worse
performance. At final scan, rates of temporal GM loss in COS were strongly correlated with positive symptoms, CGAS, and scores
on catch-up saccades. Rates of right anterior frontal loss also correlated with CGAS and positive symptoms.
CONCLUSION
This study is the first to spatially map the degree of statistical linkage between cortical gray matter loss in adolescents with
schizophrenia and their clinical and cognitive impairments. These investigations show promise in isolating regional components
of gray matter deficits that may be differentially linked with key aspects of cognition and symptom severity.
More Information & Contact
Email addresses: [email protected] [email protected]
Ref: [1]. PNAS Sept 25, 2001 vol. 98 no. 20 pp. 10979-11836
Visit the web site :
www.loni.ucla.edu