A New Method for Mapping the Linkage between Abnormal Gray Matter Loss and the Clinical and

Cognitive Deficits in Childhood-Onset Schizophrenia1Christine 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

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.

INTRODUCTION

METHODS

RESULTS

CONCLUSION

More Information & Contact

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.

12 COS6 males + 6 females

DSM-III-ROnset of psychotic sympt:12

12 NV6 males + 6 females

SUBJECTS & SCANSSUBJECTS & SCANS

10 PNOS7 males + 3 females

DSM-III-RMedication-matched group

3D T1-weighted MRI volumes1.5-T Signa scanner (GE)

NIMH

timefirst

SCH: 13.9 0.8 yearsNV: 13.5 0.7 years

last

SCH: 18.6 1.0 yearsNV: 18.0 0.8 years

+Cognitive & Clinical Evaluation 2:

IQ, SANS, SAPS, Eye tracking,CGAS

+Cognitive & Clinical Evaluation 1:

IQ, SANS, SAPS, Eye tracking,CGAS

METHODSMETHODS

INVESTIGATE EFFECTS

MAP AVERAGE LOSS,RATES, SIGNIFICANCE

3D MRI volume

Extraction

AlignmentTissue classification

3D average anatomy

before

after

Rate of Gray Matter loss

1) Striking accelerated GM loss in COS : peak value > 5% / year

Temporal

parietal

FEF, Sup M, Sens M

Significant progressive GM loss in COS

2) The significance of disease-specific change can be established

Ref: [1]. PNAS Sept 25, 2001 vol. 98 no. 20 pp. 10979-11836

3) Mapping brain change in medication-matched subjects (PNOS) who don’t satisfy criteria for SCH. Temporal deficit: specific to SCH

DIFF

Ruling out Medication Effects

SCH

Temporal loss

Non SCH(medication-matched)No temporal loss

5) Linkage between loss of GM and clinical & cognitive changes

P<0.075

P<0.010

P<

P<R

Top

L

P-value

Raw sc: info…….L: P<0.048

comp…..R: p<0.052

Raw sc: info……R: p<0.053

comp…..L/R: P<0.033, 0.026 vocab….L/R: P<0.058, 0.049

In temporal:

Full Scale IQ Subscales of IQ

In frontal:

CGAS

P<0.064

P<0.031

P-value

SAPS

P<0.005

Catch-upsaccades

P<0.045

P<0.0001

significance

Regions where loss rates depend on age

correlation

4) Dependencies between the rate of GM loss and the patient’s age are mapped

chvidal@loni.ucla.edu thompson@loni.ucla.eduEmail addresses: Visit the web site :www.loni.ucla.edu

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.