Progressive and Interrelated Functional and Structural Evidence of Post-Onset Brain Reduction in Schizophrenia

Abstract

Schizophrenia is a chronically debilitating disease, typically striking during young adulthood. Approximately 50% of patients will not remain employed even part-time after their first hospitalization.¹ With the cost of treatment and care factored in, the disease has an enormous impact on society. Although most now agree that the bizarre manifestations of schizophrenia stem from brain abnormalities, disagreement about its course exists. Whether schizophrenia includes progressive brain degeneration has been controversial since Kraepelin² first chose the name dementia praecox, or precocious dementia, for the syndrome. Kraepelin conceived of an early-onset dementing disorder with progressive mental deterioration due to degeneration of the frontal and temporal neocortices. Shortly thereafter Bleuler,³ renaming the syndrome schizophrenia, disagreed with invariable cognitive and structural decline, emphasizing cases with recovery. More than 100 years later, the issue has not been resolved. Whether schizophrenia involves progressive brain change is more than an esoteric issue: Progressive change presupposes an active process that can be targeted pharmacologically before it has completed its insidious attack, whereas static brain lesions reflect the end stage of completed deterioration.