BackgroundDiffusion tensor magnetic resonance imaging studies in schizophrenia to date have been largely inconsistent. This may reflect variation in methodology, and the use of small samples with differing illness duration and medication exposure.AimsTo determine the extent and location of white matter microstructural changes in schizophrenia, using optimised diffusion tensor imaging in a large patient sample, and to consider the effects of illness duration and medication exposure.MethodScans from 76 patients with schizophrenia and 76 matched controls were used to compare fractional anisotropy, a measure of white matter microstructural integrity, between the groups.ResultsWe found widespread clusters of reduced fractional anisotropy in patients, affecting most major white matter tracts. These reductions did not correlate with illness duration, and there was no difference between age-matched chronically and briefly medicated patients.ConclusionsThe finding of widespread fractional anisotropy reductions in our larger sample of patients with schizophrenia may explain some of the inconsistent findings of previous, smaller studies.