Progressive lateral ventricular enlargement in schizophrenia: A meta-analysis of longitudinal MRI studies
Introduction
The presence of structural brain abnormalities in schizophrenia is well established (Vita et al., 2006, Wright et al., 2000); however the concept of progressive change, which may indicate neurodegeneration, is controversial (DeLisi, 2008, Weinberger and McClure, 2002). A number of MRI studies have reported changes in brain structure over time in patients with schizophrenia, however the findings appear inconsistent and the regions studied frequently differ (DeLisi and Hoff, 2005, Kasai et al., 2003). To clarify these findings, we carried out a meta-analysis of lateral ventricular volume change in longitudinal MRI studies of patients with schizophrenia and control subjects. Although there have been a number of meta-analyses of cross-sectional MRI studies in schizophrenia (Steen et al., 2006, Vita et al., 2006, Wright et al., 2000), to our knowledge this is the first meta-analysis of longitudinal studies. We selected the lateral ventricles because cross-sectional meta-analyses have repeatedly reported large effect sizes for ventricular dilation (Vita et al., 2006, Wright et al., 2000), and this region has also been consistently measured in longitudinal studies. We hypothesised that patients with schizophrenia would show progressive dilation of the lateral ventricles over time compared to controls. In terms of moderating variables we predicted that studies with a longer interscan interval would show greater volume increases.
Section snippets
Study selection
Our strategy in the meta-analysis was to use broad inclusion criteria, and to examine the effect of more selective criteria in the sensitivity analysis. Thus the initial inclusion criteria for the meta-analysis were peer-reviewed studies which measured the lateral ventricles or entire ventricular system in the brain at a minimum of two time points using Magnetic Resonance Imaging (MRI) in a group of patients with schizophrenia and a control group. We also included studies which combined
Main meta-analysis
The meta-analysis comprised 13 studies with a total of 473 patients and 348 control subjects (see Table 2, Table 3). Patients with schizophrenia and psychotic disorders showed increased rates of lateral ventricle dilation over time compared to controls (13 studies, effect size g = 0.449, 95%CI 0.192–0.707, p = 0.0006), see Fig. 2. There was significant moderate to high between-study heterogeneity (I2 = 63%, Q = 37.3, p < 0.001) and no evidence of publication bias (p = 0.27).
First episode patients compared to chronic patients
When the meta-analysis was
Discussion
In this meta-analysis we have shown that lateral ventricular volume continues to increase in patients with schizophrenia after illness onset. The ratio of patient to control changes in volume, suggest that the increase observed in patients is approximately 3 to 4 times that observed in normal aging. In a sub-analysis, progression of ventricular volume was also found in chronic patients who had been ill for an average of 7.6 years. We did not find significant ventricular progression in patients
Role of funding source
The authors acknowledge the financial support from the National Institute for Health Research (NIHR) Specialist Biomedical Research Centre for Mental Health award to the South London and Maudsley NHS Foundation Trust and the Institute of Psychiatry, King's College London. M J Kempton was also supported by a Wellcome Trust Value in People Award. S C R Williams and the Centre for Neuroimaging Sciences are supported by the Wellcome Trust and EPSRC Medical Centre Initiative. The above funders had
Contributors
Matthew Kempton undertook the meta-analysis, literature review and wrote the first draft of the manuscript. Lynn DeLisi conceived the study and provided scientific supervision. Daniel Stahl provided statistical advice and Steve Williams provided the scientific supervision. All authors contributed and have approved the final manuscript.
Conflict of interest
None of the authors report competing interests.
Acknowledgements
We would like to thank Drs. T Saijo, Y Obubo, A James, B Ho, W Cahn, N van Haren and D Mathalon who sent us data and/or extra information regarding their studies.
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