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

ABSTRACT: 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.To quantitatively examine the effect of antipsychotics as compared to illness related factors on progressive brain changes in schizophrenia.Electronic databases were searched until April 2012. All magnetic resonance imaging studies reporting progressive brain changes in schizophrenia subjects and antipsychotic exposure were retrieved.30 longitudinal MRI studies with antipsychotic administration in schizophrenia patients met the inclusion criteria.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.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.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.

SUBMITTER: Fusar-Poli P

PROVIDER: S-EPMC3964856 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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

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

Neuroscience and biobehavioral reviews 20130614 8

<h4>Context</h4>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.<h4>Objectives</h4>To quantitatively examine the effect of antipsychotics as compared to illness related factors on progressive brain changes in schizophrenia.<h4>Data sources</h4>Electronic databases were searched until April 2012. All magnetic resonance imagi ...[more]

PMID: 23769814

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Project description:Cortical gray matter deficits have been found in patients with schizophrenia, with evidence of progression over time. The aim of this study was to determine the extent of progressive cortical gray matter volume changes over time in schizophrenia, their site and time of occurrence, and the role of potential moderators of brain changes. English language articles published between 1 January 1983 and 31 March 2012 in the MEDLINE and EMBASE databases were searched. Longitudinal magnetic resonance imaging studies comparing changes in cortical gray matter volume over time between patients with schizophrenia and healthy controls were included. Hedges g was calculated for each study. Analyses were performed using fixed- and random-effects models. A subgroup analysis was run to explore the pattern of brain changes in patients with first-episode schizophrenia. A meta-regression statistic was adopted to investigate the role of potential moderators of the effect sizes (ESs). A total of 19 studies, analyzing 813 patients with schizophrenia and 718 healthy controls, were included. Over time, patients with schizophrenia showed a significantly higher volume loss of total cortical gray matter, left superior temporal gyrus (STG), left anterior STG, left Heschl gyrus, left planum temporale and posterior STG bilaterally. Meta-analysis of first-episode schizophrenic patients showed a more significant pattern of progressive loss of whole cerebral gray matter volume involving the frontal, temporal and parietal lobes, and left Heschl gyrus compared with healthy controls. Clinical, pharmacologic and neuroradiological variables were found to be significant moderators of brain volume changes in patients with schizophrenia. The meta-analysis demonstrates that progressive cortical gray matter changes in schizophrenia occur with regional and temporal specificity. The underlying pathological process appears to be especially active in the first stages of the disease, affects the left hemisphere and the superior temporal structures more and is at least partly moderated by the type of pharmacological treatment received.

Project description: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.

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

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

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