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

Mariana T.M De Moura,Marcus V Zanetti,Mauricio H Serpa,Paulo R Menezes,Fabio L.S Duran,Geraldo F Busatto,Marcia Scazufca,Maristela S Schaufelberger

doi:10.1016/j.nicl.2018.03.015

Abstract

BackgroundWhite 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.MethodThirty-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.ResultsNo 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.ConclusionsContinuous 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.

Highlights

The neurobiology of schizophrenia is not yet fully elucidated
In addition to structural MRI investigations, post-mortem studies found reductions in size and density of oligodendrocytes and abnormal myelin structure and compactness in the White matter (WM) of schizophrenia patients, which may interact with synaptic abnormalities to produce disrupted brain connectivity (Davis et al, 2003; Walterfang et al, 2006)
While no significant changes in corpus callosum (CC) volumes were observed in first-episode schizophreniarelated psychoses (FESZ) patients relative to controls, continuous AP use was associated with greater increase of the posterior CC region over the 5 years of follow-up

Summary

Introduction

The neurobiology of schizophrenia is not yet fully elucidated. In the last decades, neuroimaging studies have reported several structural and functional brain abnormalities associated with the disorder (Innocenti et al, 2003; Arnone et al, 2008; Bora et al, 2011), some of which seem to be directly related to clinical course and symptom dimensions (Ellison-Wright and Bullmore, 2009; Bora et al, 2011; Asami et al, 2012; Jääskeläinen et al, 2014; Rosa et al, 2015). In addition to structural MRI investigations, post-mortem studies found reductions in size and density of oligodendrocytes and abnormal myelin structure and compactness in the WM of schizophrenia patients, which may interact with synaptic abnormalities to produce disrupted brain connectivity (Davis et al, 2003; Walterfang et al, 2006). Such findings are in line with the notion that abnormal integration of brain networks is central to the neurobiology of schizophrenia, as postulated in the disconnection hypothesis (Davis et al, 2003; Walterfang et al, 2006; Schmitt et al, 2011; Kochunov and Hong, 2014). Schizophrenia is associated with an abnormal pattern of total WM and anterior CC aging during nonelderly adulthood, and this adds complexity to the discussion on the static or progressive nature of structural abnormalities in psychosis

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