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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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Title: 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.
Authors: Crum, W. R., Williams, S. C. R., Danckaers, F., Huysmans, T., Sijbers, J., Cotel, M.-C., Natesan, S., Kapur, S., Vernon, A. C., Modo, M. M.
Source: Psychological Medicine. Nov2016, Vol. 46 Issue 15, p3081-3093. 13p.
Subjects: Animal experimentation, Hippocampus (Brain), Magnetic resonance imaging, Rats, Olanzapine, Haloperidol
Abstract: BackgroundOne 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.MethodWe 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.ResultsChronic 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.ConclusionsChronic 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. [ABSTRACT FROM PUBLISHER]
Copyright of Psychological Medicine is the property of Cambridge University Press and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: 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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  Data: <searchLink fieldCode="AR" term="%22Crum%2C+W%2E+R%2E%22">Crum, W. R.</searchLink><br /><searchLink fieldCode="AR" term="%22Williams%2C+S%2E+C%2E+R%2E%22">Williams, S. C. R.</searchLink><br /><searchLink fieldCode="AR" term="%22Danckaers%2C+F%2E%22">Danckaers, F.</searchLink><br /><searchLink fieldCode="AR" term="%22Huysmans%2C+T%2E%22">Huysmans, T.</searchLink><br /><searchLink fieldCode="AR" term="%22Sijbers%2C+J%2E%22">Sijbers, J.</searchLink><br /><searchLink fieldCode="AR" term="%22Cotel%2C+M%2E-C%2E%22">Cotel, M.-C.</searchLink><br /><searchLink fieldCode="AR" term="%22Natesan%2C+S%2E%22">Natesan, S.</searchLink><br /><searchLink fieldCode="AR" term="%22Kapur%2C+S%2E%22">Kapur, S.</searchLink><br /><searchLink fieldCode="AR" term="%22Vernon%2C+A%2E+C%2E%22">Vernon, A. C.</searchLink><br /><searchLink fieldCode="AR" term="%22Modo%2C+M%2E+M%2E%22">Modo, M. M.</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Psychological+Medicine%22">Psychological Medicine</searchLink>. Nov2016, Vol. 46 Issue 15, p3081-3093. 13p.
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  Data: <searchLink fieldCode="DE" term="%22Animal+experimentation%22">Animal experimentation</searchLink><br /><searchLink fieldCode="DE" term="%22Hippocampus+%28Brain%29%22">Hippocampus (Brain)</searchLink><br /><searchLink fieldCode="DE" term="%22Magnetic+resonance+imaging%22">Magnetic resonance imaging</searchLink><br /><searchLink fieldCode="DE" term="%22Rats%22">Rats</searchLink><br /><searchLink fieldCode="DE" term="%22Olanzapine%22">Olanzapine</searchLink><br /><searchLink fieldCode="DE" term="%22Haloperidol%22">Haloperidol</searchLink>
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  Label: Abstract
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  Data: BackgroundOne 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.MethodWe 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.ResultsChronic 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.ConclusionsChronic 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. [ABSTRACT FROM PUBLISHER]
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  Data: <i>Copyright of Psychological Medicine is the property of Cambridge University Press and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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