Developmental morphology of the corpus callosum in healthy and first-break schizophrenic subjects

Corpus callosum (CC) is one of the highest order neural commissures of the brain, and is among the last structures to complete postnatal maturation. In normals the size of the CC increases into the mid 20s, in parallel with expansion of cognitive abilities and the maturation of the association cortex. Several MRI studies have suggested reduced size of the corpus callosum (CC) in schizophrenia, a disorder presumed to have a neurodevelopmental pathophysiology. We hypothesized alterations in regions of CC connecting association cortices in schizophrenia. We also predicted that the normal age related increases in CC size would be absent in schizophrenia. We performed MRI studies of the CC in a series of 30 first-break schizophrenic patients, 13 nonschizophrenic psychotic subjects and 82 healthy controls. The cross-sectional area of the genu, anterior body, posterior body, isthmus, and the splenium were measured separately on the midsagittal MRI slice, using a semiautomated computerized algorithm. There was a strong correlation between total CC area and age in the healthy controls after intracranial area was partialled out (n=82; partial r=0.38, p=0.00001). This relation strongly persisted in the subgroup of controls matched for the schizophrenic group (n=32; partial r=0.46; p=0.005) but this relationship did not exist in the schizophrenic group (n=30; partial r=0.241, p=0.20). Schizophrenics had smaller splenii than both control groups (p=0.005), and showed a trend for reductions in both anterior genu (p=0.085) and anterior body (p=0.067) (MANCOVA with age and cranial size as covariates). All three of these areas are known to have a high relative density of small diameter axonal projections connecting associational cortices. Reductions in these specific areas of the CC may reflect abnormalities in the associational cortices that give rise to them. Our findings also suggest that callosal development may be retarded or incomplete in schizophrenia.