Dynamically spreading frontal and cingulate deficits mapped in adolescents with schizophrenia

Context: We previously detected a dynamic wave of gray matter loss in childhood-onset schizophrenia that started in parietal association cortices and proceeded frontally to envelop dorsolateral prefrontal and temporal cortices, including superior temporal gyri. Objective: To map gray matter loss rates across the medial hemispheric surface, including the cingulate and medial frontal cortex, in the same cohort studied previously. Design: Five-year longitudinal study. Setting: National Institute of Mental Health, Bethesda, Md. Subjects: Twelve subjects with childhood-onset schizophrenia, 12 healthy controls, and 9 medication- and IQ matched subjects with psychosis not otherwise specified. Interventions: Three-dimensional magnetic resonance imaging at baseline and follow-up. Main Outcome Measures: Gyral pattern and shape variations encoded by means of high-dimensional elastic deformation mappings driving each subject's cortical anatomy onto a group average; changes in cortical gray matter mapped by computing warping fields that matched sulcal patterns across hemispheres, subjects, and time. Results: Selective, severe frontal gray matter loss occurred bilaterally in a dorsal-to-ventral pattern across the medial hemispheric surfaces in the schizophrenic subjects. A sharp boundary in the pattern of gray matter loss separated frontal regions and cingulate-limbic areas. Conclusion: Frontal and limbic regions may not be equally vulnerable to gray matter attrition, which is consistent with the cognitive, metabolic, and functional vulnerability of the frontal cortices in schizophrenia.