Mapping Adolescent Brain Change Reveals Dynamic Profile of Accelerated Gray Matter Loss in Childhood-Onset Schizophrenia
Paul M. Thompson1,
Jay N. Giedd2,
Arthur W. Toga1,
Judith L. Rapoport2
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
Mapping Rates of Gray Matter Loss in Schizophrenia
We report the detection of striking profiles of accelerated gray matter loss in childhood-onset schizophrenia (COS), with deficits moving in a dynamic pattern across the cerebral cortex throughout adolescence. We developed a new mathematical method that creates detailed spatial maps of the rates of gray matter loss across the cortex over time. We set out to map rates of cortical gray matter loss in patients with COS, a rare but severe form of psychosis which is neurobiologically continuous with the adult disease . We also visualized corresponding gray matter changes in matched normal teenagers, and assessed whether the disease-specific changes intensified or enveloped more cortical territory as the disease progressed.
3D maps of brain changes were derived from high-resolution MRI scans acquired repeatedly from the same subjects over a 7-year time span . 12 schizophrenic subjects (aged 13.9±0.8 years at first scan) and a demographically-matched group of 12 healthy adolescents were imaged repeatedly over a 5-year time span (aged 13.5±0.7 years at initial scan). After affine alignment of individual data, gyral pattern and shape variations were encoded using high-dimensional elastic deformation mappings  driving each subject’s cortical anatomy into a group average configuration. The 3-dimensional distribution of gray matter in each subject’s brain was computed, and attached as an attribute field to a high-resolution 3D cortical model for that subject and time-point . Elastic matching was then used to associate gray matter measures 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 across diagnostic groups. The degree to which gray matter loss rates were accelerated in disease was computed pointwise across the cortex, visualized using color-coded maps, and assessed statistically by permutation.
In COS, a striking, greatly accelerated loss of gray matter (>5%/yr.) was observed in a broad anatomical region encompassing frontal eye fields, supplementary motor, sensorimotor, parietal, and temporal cortices bilaterally. At first scan, severe deficits (>20%; p<0.0005) encompassed parietal and motor cortices, at a rate that attenuated with age (p<0.05). Conversely, power maps revealed that the severe temporal lobe deficit observed later (>5%/yr.), was absent early in the disease (at age 13) despite being severely progressive after illness onset. Disease-specific profiles were independently replicated in both genders and were linked with profiles of positive and negative symptoms (see also Vidal et al., this volume).
This study is the first to uncover a dynamic wave of accelerated gray matter loss in COS, spreading from parietal cortices at disease onset to encompass temporal and frontal regions later in the disease, with a final profile consistent with the deficit pattern in adult schizophrenia. This dynamic progression of cortical deficits may suggest a structural basis for the neuromotor, sensory and associative deficits observed clinically, revealing the timing, rates and anatomical distribution of brain changes in the disease.
References:  Giedd et al. Biol. Psychiatry 46(7):892-8(1999);  Jacobsen & Rapoport JCPP 39(1):101-13(1998).  Thompson et al., Cerebral Cortex 11:1-16(2001).
Paul Thompson, Ph.D.
Assistant Professor of Neurology
4238 Reed Neurology
UCLA School of Medicine
710 Westwood Plaza
Westwood, Los Angeles CA 90095-1769, USA.