Original Research ARTICLE

Front. Psychiatry, 12 November 2012 | http://dx.doi.org/10.3389/fpsyt.2012.00096

Hippocampal shape and volume changes with antipsychotics in early stage psychotic illness

Daniel Mamah1*, Michael P. Harms1, Deanna Barch1,2,3, Martin Styner4, Jeffrey A. Lieberman5 and Lei Wang6
  • 1Department of Psychiatry, Washington University, St. Louis, MO, USA
  • 2Department of Psychology, Washington University, St. Louis, MO, USA
  • 3Department of Anatomy and Neurobiology, Washington University, St. Louis, MO, USA
  • 4Neurodevelopmental Disorders Research Center, University of North Carolina, Chapel Hill, NC, USA
  • 5Department of Psychiatry, Columbia University Medical Center, New York, NY, USA
  • 6Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

Progression of hippocampal shape and volume abnormalities has been described in psychotic disorders such as schizophrenia. However it is unclear how specific antipsychotic medications influence the development of hippocampal structure. We conducted a longitudinal, randomized, controlled, multisite, double-blind study involving 14 academic medical centers (United States 11, Canada 1, Netherlands 1, and England 1). One hundred thirty-four first-episode psychosis patients (receiving either haloperidol [HAL] or olanzapine [OLZ]) and 51 healthy controls were followed for up to 104 weeks using magnetic resonance imaging and large-deformation high-dimensional brain mapping of the hippocampus. Changes in hippocampal volume and shape metrics (i.e., percentage of negative surface vertex slopes, and surface deformation) were evaluated. Mixed-models analysis did not show a significant group-by-time interaction for hippocampal volume. However, the cumulative distribution function of hippocampal surface vertex slopes showed a notable left shift with HAL treatment compared to OLZ treatment and to controls. OLZ treatment was associated with a significantly lower percentage of “large magnitude” negative surface vertex slopes compared to HAL treatment (p = 0.004). Surface deformation maps however did not localize any hippocampal regions that differentially contracted over time with OLZ treatment, after FDR correction. These results indicate that surface analysis provides supplementary information to volumetry in detecting differential treatment effects of the hippocampus. Our results suggest that OLZ is associated with less longitudinal hippocampal surface deformation than HAL, however the hippocampal regions affected appear to be variable across patients.

Keywords: schizophrenia, psychosis, hippocampus, olanzapine, haloperidol, MRI

Citation: Mamah D, Harms MP, Barch D, Styner M, Lieberman JA and Wang L (2012) Hippocampal shape and volume changes with antipsychotics in early stage psychotic illness. Front. Psychiatry 3:96. doi: 10.3389/fpsyt.2012.00096

Received: 05 July 2012; Accepted: 24 October 2012;
Published online: 12 November 2012.

Edited by:

Jun Soo Kwon, Seoul National University College of Medicine, Korea

Reviewed by:

Susannah Tye, Deakin University, Australia
Jun Soo Kwon, Seoul National University College of Medicine, Korea

Copyright: © 2012 Mamah, Harms, Barch, Styner, Lieberman and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

*Correspondence: Daniel Mamah, Department of Psychiatry, Washington University School of Medicine, (Box 8134), 660 South, Euclid Avenue, St. Louis, MO 63110, USA. e-mail: mamahd@psychiatry.wustl.edu