Age and treatment related local hippocampal changes in schizophrenia explained by a novel shape analysis method

Abstract

Volume reduction of the hippocampus observed with MRI is one of the most consistently described structural abnormalities in patients with schizophrenia. However, the timing, the association with treatment, and an intuitive explanation of morphologic changes in terms of shape differences are not known. This study analyzed subtle changes of the hippocampal structure in schizophrenics as compared to matched controls. The effect of age, duration of illness and treatment effects to local shape changes was studied with a new shape representation technique and an exploratory statistical analysis. Shape representation was based on a sampled medial model (M-rep) describing each shape by an 8 by 3 mesh with local position and width at each node. This model allows an independent analysis of shape deformation and of local atrophy. The exploratory statistical model was a repeated measures ANOVA, cast as a general linear multivariate model. The new procedure overcomes the problem of testing a very large number of correlated observations, which is a significant limitation of many other shape discrimination schemes. As a novel contribution not shown before, it models shape in combination with patient variables to answer important clinical questions in regard to drug response and longitudinal change in order to assess developmental and degenerative processes. The exploratory nature of the analysis means that our results must be replicated in a hypothesis driven independent patient study in order to provide full confidence in the conclusions.