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.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: Department of Neuroimaging,King's College London,Institute of Psychiatry,Psychology and Neuroscience,Centre for Neuroimaging Sciences,De Crespigny Park,London,UK.
authors: W R
authors: WR
authors: Crum
authors: Department of Physics,iMinds-Vision Laboratory,University of Antwerp,Antwerp,Belgium.
authors: F
authors: F
authors: Danckaers
authors: Department of Physics,iMinds-Vision Laboratory,University of Antwerp,Antwerp,Belgium.
authors: T
authors: T
authors: Huysmans
authors: Department of Psychosis Studies,King's College London,Institute of Psychiatry,Psychology and Neuroscience,De Crespigny Park,London,UK.
authors: M-C
authors: MC
authors: Cotel
authors: Department of Psychosis Studies,King's College London,Institute of Psychiatry,Psychology and Neuroscience,De Crespigny Park,London,UK.
authors: S
authors: S
authors: Natesan
authors: Department of Basic and Clinical Neuroscience,King's College London,Institute of Psychiatry,Psychology and Neuroscience,Maurice Wohl Institute for Clinical Neuroscience,London,UK.
authors: M M
authors: MM
authors: Modo
authors: Department of Physics,iMinds-Vision Laboratory,University of Antwerp,Antwerp,Belgium.
authors: J
authors: J
authors: Sijbers
authors: Department of Neuroimaging,King's College London,Institute of Psychiatry,Psychology and Neuroscience,Centre for Neuroimaging Sciences,De Crespigny Park,London,UK.
authors: S C R
authors: SC
authors: Williams
authors: Department of Psychosis Studies,King's College London,Institute of Psychiatry,Psychology and Neuroscience,De Crespigny Park,London,UK.
authors: S
authors: S
authors: Kapur
authors: Department of Psychosis Studies,King's College London,Institute of Psychiatry,Psychology and Neuroscience,De Crespigny Park,London,UK.
authors: A C
authors: AC
authors: Vernon
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D006220:Haloperidol / Q000494:pharmacology*; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D000077152:Olanzapine; D009929:Organ Size; D051381:Rats
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D006220:Haloperidol; D000077152:Olanzapine
keywords: antipsychotic; hippocampus; magnetic resonance imaging; schizophrenia; shape; volume