Progressive brain changes in schizophrenia related to antipsychotic treatment? A meta-analysis of longitudinal MRI studies

P Fusar-Poli, R Smieskova, M J Kempton, B C Ho, N C Andreasen, S Borgwardt, P Fusar-Poli, R Smieskova, M J Kempton, B C Ho, N C Andreasen, S Borgwardt

Abstract

Context: Antipsychotic treatment is the first-line treatment option for schizophrenia. Individual studies suggested they can significantly affect brain structure and account for progressive brain changes observed during the illness.

Objectives: To quantitatively examine the effect of antipsychotics as compared to illness related factors on progressive brain changes in schizophrenia.

Data sources: Electronic databases were searched until April 2012. All magnetic resonance imaging studies reporting progressive brain changes in schizophrenia subjects and antipsychotic exposure were retrieved.

Study selection: 30 longitudinal MRI studies with antipsychotic administration in schizophrenia patients met the inclusion criteria.

Data extraction: Brain volumes before and after antipsychotic exposure, duration of illness, severity of psychotic symptoms as well as demographic, clinical, and methodological variables were extracted from each publication, or obtained directly from its authors.

Data synthesis: The overall sample was of 1046 schizophrenia patients and 780 controls for a median duration of follow-up of 72.4 weeks. At baseline, patients showed significant whole brain volume reductions and enlarged lateral ventricle (LV) volumes compared to controls. No baseline volumetric abnormalities were detected in the gray matter volumes (GMV), white matter volumes, cerebrospinal fluid and caudate nucleus. Longitudinally, there were progressive GMV decreases and LV enlargements in patients but not in controls. The GMV decreases were inversely correlated with cumulative exposure to antipsychotic treatments, while no effects were observed for duration of illness or illness severity.

Conclusions: Schizophrenia is characterized by progressive gray matter volume decreases and lateral ventricular volume increases. Some of these neuroanatomical alterations may be associated with antipsychotic treatment.

Keywords: Antipsychotic; Dopamine; MRI; Neuroimaging; Psychosis; Schizophrenia; Structural.

Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Figures

Fig. 1
Fig. 1
PRISMA Flow Diagram of literature search. All full-text excluded studies together with the reason why they were excluded are listed in the supplementary Table 3. Abbreviations: Cd, caudate nucleus; CSF, cerebrospinal fluid; GMV, gray matter volume; LV, lateral ventricles; VBM, voxel-based morphometry; WBV, whole brain volume; WMV, white matter volume.
Fig. 2
Fig. 2
Meta-regression analysis: (a) progressive GMV changes and cumulative exposure to antipsychotics (β = −0.013, CI 95% from −0.033 to −0.001, Q = 8.598, p = 0.048); (b) progressive GMV changes and duration of illness (DOI, β = 0.001, CI 95% from −0.001 to 0.001, p = 0.653); (c) progressive GMV changes and psychotic symptoms change over follow-up time (β = 0.002, CI 95% from −0.011 to 0.016, p = 0.732). The size of the circle reflects the sample size of the study. Negative vaules on the y axis indicate brain volume reductions at follow-up as compared to baseline. Cumulative exposure to antipsychotics unit was defined in Chlorpromazine Equivalent per day (CPZ-EQ/d) multiplied by the duration of the medication treatment in days (for details see Supplementary material study protocol para. 9). Change in psychotic symptom unit: percentage of baseline per item score (positive values indicate improvement of symptoms at follow-up as compared to baseline; for details see supplementary materials section 8).
Fig. 3
Fig. 3
Meta-regression analysis showing no significant (p > 0.05) correlations between: progressive LV volume changes and duration of illness (DOI) within the schizophrenia patients. The size of the circle reflects the sample size of the study. Positive values on the y axis reflect brain volume increases at follow-up as compared to baseline.

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