1. ¹NMR Study Group, Max-Planck-Institute of Psychiatry, Munich, Germany
2. ²Behavioral Neuroendocrinology, Max-Planck-Institute of Psychiatry, Munich, Germany

Correspondence: Dr R Kalisch, Functional Imaging Laboratory (FIL), Wellcome Department of Imaging Neuroscience, University College London, 12 Queen Square, London WC1N 3BG, UK, Tel: +44 207 833 7479, Fax: +44 207 813 1420, E-mail: rkalisch@fil.ion.ucl.ac.uk

³Both these authors have contributed equally to this work.

Received 20 December 2004; Revised 5 July 2005; Accepted 24 August 2005; Published online 28 September 2005.

Abstract

In depressed patients as well as healthy controls, a positive relationship between hippocampal volume and trait anxiety has been reported. This study sought to explore the possible inter-relation between hippocampal volume and trait anxiety further. Magnetic resonance imaging at 7 T was used to measure hippocampal volumes in a rat model of extremes in trait anxiety (experiment 1) and in a Wistar population with normal anxiety-related behavior (experiment 2). In addition to anxiety-related behavior, potentially confounding factors (depression-like, exploratory, and locomotor behavior) were assessed. Experiment 1 globally supported the hypothesis of a positive relationship between hippocampus volume and trait anxiety but did not allow for ruling out possible confounds arising from cosegregation of other behavioral traits. Experiment 2 yielded strong evidence for a negative relationship which was specific for trait anxiety. Thus, the relationship between hippocampal volume and anxiety may be more complex than expected. Interestingly, anxiety-related behavior in experiment 2 had a stronger influence on hippocampal volume than depression-like behavior. In the light of hippocampal volume loss in anxiety disorder and frequent comorbidity of anxiety and depression, this finding suggests that further research into the relationship between anxiety and hippocampal volume may be critical for understanding hippocampal contributions to normal and pathological behavior.