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Hippocampal subregion volume changes associated with antipsychotic treatment in first-episode psychosis

Published online by Cambridge University Press:  14 February 2017

K. Rhindress ,
D. G. Robinson ,
J. A. Gallego ,
R. Wellington ,
A. K. Malhotra  and
P. R. Szeszko
K. Rhindress*
Affiliation:
Department of Psychiatry, New York University School of Medicine, New York, NY, USA
D. G. Robinson
Affiliation:
Department of Psychiatry, Hofstra Northwell School of Medicine, Hempstead, NY, USA Center for Psychiatric Neuroscience, The Feinstein Institute for Medical Research, Manhasset, NY, USA Division of Psychiatry Research, Zucker Hillside Hospital, North Shore-LIJ Health System, Glen Oaks, NY, USA
J. A. Gallego
Affiliation:
Department of Psychiatry, Weill Cornell Medical College, White Plains, NY, USA
R. Wellington
Affiliation:
Department of Psychology, St John's University, Queens, NY, USA
A. K. Malhotra
Affiliation:
Department of Psychiatry, Hofstra Northwell School of Medicine, Hempstead, NY, USA Center for Psychiatric Neuroscience, The Feinstein Institute for Medical Research, Manhasset, NY, USA Division of Psychiatry Research, Zucker Hillside Hospital, North Shore-LIJ Health System, Glen Oaks, NY, USA
P. R. Szeszko
Affiliation:
James J. Peters VA Medical Center, Bronx, NY, USA Icahn School of Medicine at Mount Sinai, New York, NY, USA
*
*Address for correspondence: K. Rhindress, Ph.D., Department of Psychiatry, Bellevue Hospital Center, 462 First Avenue, New York, NY 10016, USA. (Email: [email protected])
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Abstract

Background

Hippocampal dysfunction is considered central to many neurobiological models of schizophrenia, yet there are few longitudinal in vivo neuroimaging studies that have investigated the relationship between antipsychotic treatment and morphologic changes within specific hippocampal subregions among patients with psychosis.

Method

A total of 29 patients experiencing a first episode of psychosis with little or no prior antipsychotic exposure received structural neuroimaging examinations at illness onset and then following 12 weeks of treatment with either risperidone or aripiprazole in a double-blind randomized clinical trial. In addition, 29 healthy volunteers received structural neuroimaging examinations at baseline and 12-week time points. We manually delineated six hippocampal subregions [i.e. anterior cornu ammonis (CA) 1–3, posterior CA1–3, subiculum, dentate gyrus/CA4, entorhinal cortex, and fimbria] from 3T magnetic resonance images using an established method with high inter- and intra-rater reliability.

Results

Following antipsychotic treatment patients demonstrated significant reductions in dentate gyrus/CA4 volume and increases in subiculum volume. Healthy volunteers demonstrated non-significant volumetric changes in these subregions across the two time points. We observed a significant quadratic (i.e. inverted U) association between changes in dentate gyrus/CA4 volume and cumulative antipsychotic dosage between the scans.

Conclusions

This study provides the first evidence to our knowledge regarding longitudinal in vivo volumetric changes within specific hippocampal subregions in patients with psychosis following antipsychotic treatment. The finding of a non-linear relationship between changes in dentate gyrus/CA4 subregion volume and antipsychotic exposure may provide new avenues into understanding dosing strategies for therapeutic interventions relevant to neurobiological models of hippocampal dysfunction in psychosis.

Keywords

Antipsychotic treatmentdendate gyrushippocampuspsychosissubiculum
Type
Original Articles
Information
Psychological Medicine , Volume 47 , Issue 10 , July 2017 , pp. 1706 - 1718
Copyright
Copyright © Cambridge University Press 2017 

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