Corpus callosum volumes in the 5 years following the first-episode of schizophrenia: Effects of antipsychotics, chronicity and maturation

Abstract

Background: White matter (WM) structural changes, particularly affecting the corpus callosum (CC), seem to be critically implicated in psychosis. Whether such abnormalities are progressive or static is still a matter of debate in schizophrenia research. Aberrant maturation processes might also influence the longitudinal trajectory of age-related CC changes in schizophrenia patients. We investigated whether patients with first-episode schizophrenia-related psychoses (FESZ) would present longitudinal CC and whole WM volume changes over the 5 years after disease onset. Method: Thirty-two FESZ patients and 34 controls recruited using a population-based design completed a 5-year assessment protocol, including structural MRI scanning at baseline and follow-up. The linear effects of disease duration, clinical outcome and antipsychotic (AP) use over time on WM and CC volumes were studied using both voxelwise and volume-based morphometry analyses. We also examined maturation/aging abnormalities through cross-sectional analyses of age-related trajectories of total WM and CC volume changes. Results: No interaction between diagnosis and time was observed, and clinical outcome did not influence CC volumes in patients. On the other hand, FESZ patients continuously exposed to AP medication showed volume increase over time in posterior CC. Curve-estimation analyses revealed a different aging pattern in FESZ patients versus controls: while patients displayed a linear decline of total WM and anterior CC volumes with age, a non-linear trajectory of total WM and relative preservation of CC volumes were observed in controls. Conclusions: Continuous AP exposure can influence CC morphology during the first years after schizophrenia onset. Schizophrenia is associated with an abnormal pattern of total WM and anterior CC aging during non-elderly adulthood, and this adds complexity to the discussion on the static or progressive nature of structural abnormalities in psychosis. Keywords: Schizophrenia, Psychosis, Corpus callosum, White matter, Magnetic resonance imaging