A New Method for Mapping the Linkage between Abnormal Gray Matter Loss and the Clinical and Cognitive Deficits in Childhood-Onset Schizophrenia 1 Christine N. Vidal, 2 Judith L. Rapoport MD, 2 Peter Gochman MA, 2 Jay N. Giedd MD, 2 Jonathan Blumenthal MA, 2 Robert Nicolson MD, 1 Arthur W. Toga PhD, 1 Paul M. Thompson PhD 1 Laboratory of Neuro Imaging, Brain Mapping Division, Department of Neurology, UCLA School of Medicine 2 Child 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 COS 6 males + 6 females DSM-III-R Onset of psychotic sympt:12 12 NV 6 males + 6 females SUBJECTS & SCANS 10 PNOS 7 males + 3 females DSM-III-R Medication-matched group 3D T1-weighted MRI volumes 1.5-T Signa scanner (GE) NIMH time first SCH: 13.9  0.8 years NV: 13.5  0.7 years last SCH: 18.6  1.0 years NV: 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 METHODS INVESTIGATE EFFECTS MAP AVERAGE LOSS, RATES, SIGNIFICANCE 3D MRI volume Extraction Alignment Tissue 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 ) 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< 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, vocab…. L/R: P<0.058, In temporal: Full Scale IQ Subscales of IQ In frontal: CGAS P<0.064 P<0.031 P-value SAPS P<0.005 Catch-up saccades P<0.045 P< significance Regions where loss rates depend on age correlation 4) Dependencies between the rate of GM loss and the patient’s age are mapped addresses: Visit the web site : 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.