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    Chronic exposure to haloperidol and olanzapine leads to common and divergent shape changes in the rat hippocampus in the absence of grey-matter volume loss

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    Author
    Crum, WR; Danckaers, F; Huysmans, T; Cotel, M-C; Natesan, S; Modo, MM; Sijbers, J; Williams, SCR; Kapur, S; Vernon, AC
    Date
    2016-11-01
    Source Title
    Psychological Medicine
    Publisher
    CAMBRIDGE UNIV PRESS
    University of Melbourne Author/s
    Kapur, Shitij
    Affiliation
    Medicine Dentistry & Health Sciences
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Crum, W. R., Danckaers, F., Huysmans, T., Cotel, M. -C., Natesan, S., Modo, M. M., Sijbers, J., Williams, S. C. R., Kapur, S. & Vernon, A. C. (2016). Chronic exposure to haloperidol and olanzapine leads to common and divergent shape changes in the rat hippocampus in the absence of grey-matter volume loss. PSYCHOLOGICAL MEDICINE, 46 (15), pp.3081-3093. https://doi.org/10.1017/S0033291716001768.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/257806
    DOI
    10.1017/S0033291716001768
    Abstract
    BACKGROUND: One of the most consistently reported brain abnormalities in schizophrenia (SCZ) is decreased volume and shape deformation of the hippocampus. However, the potential contribution of chronic antipsychotic medication exposure to these phenomena remains unclear. METHOD: We examined the effect of chronic exposure (8 weeks) to clinically relevant doses of either haloperidol (HAL) or olanzapine (OLZ) on adult rat hippocampal volume and shape using ex vivo structural MRI with the brain retained inside the cranium to prevent distortions due to dissection, followed by tensor-based morphometry (TBM) and elastic surface-based shape deformation analysis. The volume of the hippocampus was also measured post-mortem from brain tissue sections in each group. RESULTS: Chronic exposure to either HAL or OLZ had no effect on the volume of the hippocampus, even at exploratory thresholds, which was confirmed post-mortem. In contrast, shape deformation analysis revealed that chronic HAL and OLZ exposure lead to both common and divergent shape deformations (q = 0.05, FDR-corrected) in the rat hippocampus. In particular, in the dorsal hippocampus, HAL exposure led to inward shape deformation, whereas OLZ exposure led to outward shape deformation. Interestingly, outward shape deformations that were common to both drugs occurred in the ventral hippocampus. These effects remained significant after controlling for hippocampal volume suggesting true shape changes. CONCLUSIONS: Chronic exposure to either HAL or OLZ leads to both common and divergent effects on rat hippocampal shape in the absence of volume change. The implications of these findings for the clinic are discussed.

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