1Christine N. Vidal MS,
2Jay N. Giedd MD,
2Peter Gochman MA,
2Jonathan Blumenthal MA,
2Robert Nicolson MD,
1Arthur W. Toga PhD,
2Judith L. Rapoport MD,
1Paul M. Thompson PhD
1Laboratory of Neuro Imaging, Brain Mapping Division, Department of Neurology, UCLA School of Medicine, Los Angeles, CA
2Child Psychiatry Branch, National Institute of Mental Health, Bethesda, MD
Striking profiles of accelerated gray matter loss spread across the cortex in childhood-onset schizophrenia (COS; ). We developed a new mathematical method that maps in detail the spatial patterns of linkage between these brain changes and clinical and cognitive assessment.
12 COS, 12 healthy and 10 psychosis not-otherwise-specified matched subjects (PNOS; ) were imaged longitudinally over a 5-year time span. 3D maps localizing brain changes were derived from MRI scans at baseline and follow-up. High-dimensional elastic matching of cortical patterns  was used to associate measures of gray matter density from homologous cortical regions across subjects and across time. Annualized 4D maps of gray matter loss rates within each subject were subsequently elastically realigned for averaging and comparison across diagnostic groups. Statistical maps were generated indicating locally the degree to which gray matter loss rates were statistically linked with: 1) full-scale IQ (WAIS-R or WISC-R) , 2) saccadic eye movements (catch-up and anticipatory saccades), and 3) Children’s Global Assessment of Functioning Scale scores (CGAS) which provide a global assessment of function . Maps identifying these linkages were assessed statistically by permutation.
In COS, the greatly accelerated loss of gray matter (>5%/yr.) which was observed in a region encompassing frontal eye fields, supplementary motor, sensorimotor, parietal and temporal cortices bilaterally, was globally linked with the clinical and cognitive impairments. This suggests an overall deterioration of global functioning in COS, consistent with the progressive deterioration of structure. Rates of temporal, superior and anterior frontal gray matter loss were strongly correlated with CGAS scores at follow-up. Patients with fastest loss of gray matter in the temporal regions were most severely impaired in Full-Scale IQ (p<0.008, right hemisphere) including the Information (p<0.048, left hemisphere) and Comprehension (p<0.052, right hemisphere) subtests (raw scores), and catch-up saccades (p<0.045, right hemisphere; p<0.0001, left hemisphere). Patients with fastest gray matter loss in the superior frontal area were most severely impaired in IQ at final scan (p<0.038, right hemisphere; p<0.021, left hemisphere). Statistical maps on the cortical surface revealed regionally-specific, significant linkages between these losses and raw scores on the Information (p<0.053, right hemisphere), Comprehension (p<0.026, right hemisphere; p<0.033, left hemisphere) and Vocabulary (p<0.049, right hemisphere; p<0.058, left hemisphere) subtests.
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.
Thompson et al. PNAS 98(20):11650-11655(2001) Jacobsen & Rapoport JCPP 39(1):101-13(1998); Thompson et al. Cerebral Cortex 11:1-16(2001); Bedwell et al. Am J Psychiatry 156:1996-1997(1999); Shaffer et al. Arch. Gen. Psychiatry 40:1228-1231(1983).
Paul Thompson, Ph.D.
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