Progressive Brain Volume Loss in Schizophrenia Over the Course of the Illness: Evidence of Maturational Abnormalities in Early Adulthood

Background: Considering the magnitude of the reported changes in brain volume over time in first-episode patients it is unlikely that these changes are constant over the life-span of the schizophrenic illness. Thus, one would expect the progression in brain volume change in schizophrenia to follow a more complex trajectory over time. Methods: Two magnetic resonance imaging brain scans were obtained over a 5-year interval of 96 schizophrenia patients and 113 healthy subjects between ages 16 to 56. Results: The trajectory of brain volume change differed between patients with schizophrenia and healthy individuals. Before the age of 45 years cerebral and gray matter loss and lateral ventricle increase were excessive in patients relative to controls, representing approximately the first 20 years of illness. Patients showed an excessive third ventricle volume increase over time. In addition, poor outcome patients showed more brain tissue loss during the follow-up interval than good outcome patients. Conclusions: Cerebral (gray) matter volume loss in the patients was mainly characterized by the absence of the normal curved trajectory of volume change with age that was present in healthy subjects. Later in life, the degree of volume change in patients is similar to that observed with normal aging. Independently of age, larger brain volume changes appear clinically relevant.