Although most neurologic diseases are associated with cell loss, the Yale group's study did not support that conclusion. Neuroimaging data suggest a smaller than normal cortex in schizophrenia, and from this and other information, the team concluded that the distance between neurons in the schizophrenic cortex is diminished, while the number of neurons probably remains the same. The space between the cells, called the neuropil, contains neuronal processes and synaptic contacts. They hypothesized that reduced neuropil is responsible for cognitive disturbances in schizophrenia, either due to atrophy of neuronal processes and connections, or a failure of them to develop. She thinks the relative sparsity of connections caused by reduced neuropil leads to the deficiencies in learning and memory found in schizophrenic patients.
Much work remains to determine the precise nature of the neuropil alterations.
Electron microscopy, the best technology for postmortem studies of synaptic contacts, is limited in the human brain because brains must be chemically fixed within two hours of death to ensure adequate preservation, she says. The longstanding question of whether, ultimately, schizophrenia is a neurodevelopmental or a neurodegenerative disease, or both, remains unresolved. The clinical significance of this debate is that if there is neurodegeneration, early intervention might help. You don't want to micromanage science too much, because you might be wrong. In recent years he has studied the mechanisms of normal forebrain development in mice, particularly the induction of proper cell organization and the role of a signaling molecule, the steroidlike hormone retinoic acid.