Abstract
BackgroundThe results of multiple studies on the association between antipsychotic use and structural brain changes in schizophrenia have been assessed only in qualitative literature reviews to date. We aimed to perform a meta-analysis of voxel-based morphometry (VBM) studies on this association to quantitatively synthesize the findings of these studies.MethodsA systematic computerized literature search was carried out through MEDLINE/PubMed, EMBASE, ISI Web of Science, SCOPUS and PsycINFO databases aiming to identify all VBM studies addressing this question and meeting predetermined inclusion criteria. All studies reporting coordinates representing foci of structural brain changes associated with antipsychotic use were meta-analyzed by using the activation likelihood estimation technique, currently the most sophisticated and best-validated tool for voxel-wise meta-analysis of neuroimaging studies.ResultsTen studies (five cross-sectional and five longitudinal) met the inclusion criteria and comprised a total of 548 individuals (298 patients on antipsychotic drugs and 250 controls). Depending on the methodologies of the selected studies, the control groups included healthy subjects, drug-free patients, or the same patients evaluated repeatedly in longitudinal comparisons (i.e., serving as their own controls). A total of 102 foci associated with structural alterations were retrieved. The meta-analysis revealed seven clusters of areas with consistent structural brain changes in patients on antipsychotics compared to controls. The seven clusters included four areas of relative volumetric decrease in the left lateral temporal cortex [Brodmann area (BA) 20], left inferior frontal gyrus (BA 44), superior frontal gyrus extending to the left middle frontal gyrus (BA 6), and right rectal gyrus (BA 11), and three areas of relative volumetric increase in the left dorsal anterior cingulate cortex (BA 24), left ventral anterior cingulate cortex (BA 24) and right putamen.ConclusionsOur results identify the specific brain regions where possible associations between antipsychotic drug usage and structural brain changes in schizophrenia patients are more consistently reported. Additional longitudinal VBM studies including larger and more homogeneous samples of schizophrenia patients may be needed to further disentangle such alterations from those possibly linked to the intrinsic pathological progressive process in schizophrenia.
Highlights
The results of multiple studies on the association between antipsychotic use and structural brain changes in schizophrenia have been assessed only in qualitative literature reviews to date
A relatively low number of studies have addressed this issue, which is made more difficult by the complex task of harmonizing or balancing the effects of all the other possible variables, and by the crucial necessity of more homogeneous samples of patients, with respect to the variables related to the illness and individuals and to those related to antipsychotics
It seems clear that the idea of antipsychotics as potential agents contributing to the structural brain changes in schizophrenia should certainly be taken into account
Summary
The results of multiple studies on the association between antipsychotic use and structural brain changes in schizophrenia have been assessed only in qualitative literature reviews to date. With the advent of more sophisticated neuroimaging techniques such as magnetic resonance imaging (MRI), which allows in vivo studies of the brains of individuals with schizophrenia, structural brain changes in schizophrenia have been extensively characterized [8,9,10]. Some of these findings include smaller mean cerebral volumes and greater mean total ventricular volume in patients with schizophrenia, with significant decreases in both gray and white matter [11]. An interaction between these early brain insults and environmental factors delineating the brain maturation in adolescence would be necessary to trigger psychotic behavior [7,12,13,14,15,16,17]
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