Voxel-based morphometry (VBM) studies in schizophrenia-can white matter changes be reliably detected with VBM?

Voxel-based morphometry (VBM) is a hypothesis-free, whole-brain, voxel-by-voxel analytic method that attempts to compare imaging data between populations. Schizophrenia studies have utilized this method to localize differences in diffusion tensor imaging (DTI) derived fractional anisotropy (FA), a measure of white matter integrity, between patients and healthy controls. The number of publications has grown, although it is unclear how reliable and reproducible this method is, given the subtle white matter abnormalities expected in schizophrenia. Here we analyze and combine results from 23 studies published to date that use VBM to study schizophrenia in order to evaluate the reproducibility of this method in DTI analysis. Coordinates of each region reported in DTI VBM studies published thus far in schizophrenia were plotted onto a Montreal Neurological Institute atlas, and their anatomical locations were recorded. Results indicated that the reductions of FA in patients with schizophrenia were scattered across the brain. Moreover, even the most consistently reported regions were reported independently in less than 35% of the articles studied. Other instances of reduced FA were replicated at an even lower rate. Our findings demonstrate striking inconsistency, with none of the regions reported in much more than a third of the published articles. This poor replication rate suggests that the application of VBM to DTI data may not be the optimal way for finding the subtle microstructural abnormalities suggested in schizophrenia.