1 Christine N. Vidal, 2 Judith L. Rapoport MD, 2 Peter Gochman MA,

1. 3D MRI volume SUBJECTS & SCANS Extraction 12 COS 6 males + 6 females DSM-III-R Onset of psychotic sympt:12 12 NV 6 males + 6 females 10 PNOS 7 males + 3 females DSM-III-R Medication-matched group Tissue classification Alignment FEF, Sup M, Sens M parietal Raw sc: info…….L: P<0.048 3D T1-weighted MRI volumes 1.5-T Signa scanner (GE) NIMH 3D average anatomy Temporal MAP AVERAGE LOSS, RATES, SIGNIFICANCE before time first last after INVESTIGATE EFFECTS SCH: 18.6  1.0 years NV: 18.0  0.8 years SCH: 13.9  0.8 years NV: 13.5  0.7 years + + Cognitive & Clinical Evaluation 2: IQ, SANS, SAPS, Eye tracking, CGAS Rate of Gray Matter loss 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 METHODS Cognitive & Clinical Evaluation 1: 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 3) Mapping brain change in medication-matched subjects (PNOS) who don’t satisfy criteria for SCH. Temporal deficit: specific to SCH SCH Temporal loss Non SCH (medication- matched) No temporal loss DIFF Significant progressive GM loss in COS Ruling out Medication Effects 4) Dependencies between the rate of GM loss and the patient’s age are mapped 5) Linkage between loss of GM and clinical & cognitive changes correlation Catch-up saccades Full Scale IQ Subscales of IQ CGAS P-value P-value P<0.064 In temporal: R P< P< P<0.031 comp…..R: p<0.052 P<0.045 significance SAPS Top P<0.075 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<0.0001 P<0.010 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 thompson@loni.ucla.edu chvidal@loni.ucla.edu Email addresses: Visit the web site : www.loni.ucla.edu Ref: [1]. PNAS Sept 25, 2001 vol. 98 no. 20 pp. 10979-11836