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Original Research

Hippocampal Volume Change in Schizophrenia

P. Cédric M. P. Koolschijn, PhD; Neeltje E. M. van Haren, PhD;       Wiepke Cahn, MD, PhD; Hugo G. Schnack, PhD; Joost Janssen, PhD;       Floris Klumpers, MS; Hilleke E. Hulshoff Pol, PhD; and René S. Kahn, MD, PhD

Published: January 12, 2010

Article Abstract

Objective: Patients with schizophrenia show reductions in hippocampal volume. However, the time course of these changes is still unresolved. The aim of this study is to examine the extent to which hippocampal volume change in patients with schizophrenia is confounded by effects of age and/or antipsychotic medication.

Method: Between 1995 and 2003, two structural magnetic resonance imaging brain scans were acquired from 96 patients with DSM-IV-diagnosed schizophrenia and 113 healthy subjects within an interval of approximately 5 years. Hippocampal volume change was measured and related to age and cumulative medication intake during the scan interval.

Results: Patients with schizophrenia and healthy controls demonstrated significantly different age-related trajectories of hippocampal volume change. Before the age of 26 years, patients with schizophrenia showed increased volume loss relative to controls. In contrast, after the age of 40 years, controls showed larger volume loss than patients with schizophrenia. Higher exposure to atypical antipsychotic medication was related to a smaller decrease in hippocampal volume over time.

Conclusion: Our findings suggest progressive hippocampal volume loss in the early course of the illness in patients with schizophrenia but not in the more chronic stages of the illness. The relationship between larger exposure to atypical antipsychotic medication and smaller hippocampal volume loss during the interval may suggest neuroprotective effects of these agents on hippocampal volume.

J Clin Psychiatry 2010;71(6):737-744

Submitted: July 28, 2008; accepted January 30, 2009.

Online ahead of print: January 12, 2010 (doi:10.4088/JCP.08m04574yel).

Corresponding author: P. Cédric M. P. Koolschijn, PhD, Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, A.01.126, University Medical Center Utrecht, PO Box 85060, 3584 CX Utrecht, The Netherlands (

Volume: 71

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