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Hippocampal volume in chronic posttraumatic stress disorder (PTSD): MRI study using two different evaluation methods

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Abstract

The hippocampus is discussed as one of the key regions in the pathogenesis of Posttraumatic Stress Disorder (PTSD). MRI results concerning the volume of the hippocampus are, however, inconsistent. This may be due to the heterogeneity of patients' traumata or postprocessing of the imaging data. To overcome these problems, the present study investigates volume changes in well-characterized chronic PTSD patients in comparison to controls using two different evaluation methods.

Material and Methods

15 patients with chronic PTSD, traumatized at the same air show plane crash in 1988 (Ramstein, Germany), and 15 matched healthy controls participated in this study. All patients suffered from significant impairment by the PTSD; none had a history of drug or alcohol abuse. Hippocampus volume changes were processed by a semi-automated standard procedure performed with BRAINS2 as well as the voxel based morphometry (VBM) using SPM2.

Results

No differences in total brain grey or white matter were detected between patients and controls. No differences in total hippocampal volume or in right and left parts were seen, even when hippocampal volumes were corrected by total brain volume or correlated with clinical data. Finally, no significant differences were detected between patients and controls in hippocampal regions using VBM.

Discussion

This is the first study examining long-term changes in hippocampal volumes in chronic PTSD patients compared to matched controls using two different evaluation methods. Neither conventional volumetry nor VBM could detect any differences in the volume and structure. This supports the hypothesis that previously described hippocampal volume reduction is not necessarily due to PTSD or at least that, after 15 years, volume changes have been restored or have not yet developed.

Introduction

One of the key players in the pathophysiology of posttraumatic stress disorder (PTSD) is the hippocampus-formation, which is involved in memory processing and therefore thought to be functionally important for the pathogenesis of the persistent reexperiencing symptoms in the context of trauma. Early structural findings in traumatized patients illustrated a reduction in hippocampal volume of 5–12% (Bremner et al., 1997, Stein et al., 1997). This led to the theory that during acute trauma and its aftermath, the hippocampus might be damaged by the release of neurotoxic agents such as high levels of cortisol (Sapolsky, 1996), whereas cortisol levels have been found lower in PTSD (Yehuda et al., 1995). However, these results could not be consistently replicated: while 11 cross-sectional studies (Bremner et al., 1995, Bremner et al., 1997, Bremner et al., 2003, Gurvits et al., 1996, Hedges et al., 2003, Lindauer et al., 2004, Schuff et al., 1997, Shin et al., 2004, Stein et al., 1997, Villarreal et al., 2002, Vythilingam et al., 2002) described smaller hippocampus volumes in PTSD compared to non-PTSD patients or controls, 9 studies (Bonne et al., 2001, Carrion et al., 2001, De Bellis et al., 2001, De Bellis et al., 1999, De Bellis et al., 2002, Fennema-Notestine et al., 2002, Neylan et al., 2004, Pederson et al., 2004, Winter and Irle, 2004) failed to show such a relationship. More importantly, the only two longitudinal studies in the literature (Bonne et al., 2001, De Bellis et al., 2001) did not identify structural alterations, which argues against the model of severe neurotoxicity in the hippocampus. Furthermore, Gilbertson et al. (2002) found evidence in monozygotic twins discordant for trauma exposure which suggest that smaller hippocampi may rather constitute a predisposing risk factor for the development of stress related psychopathology. Studies of dizygotic twins would be needed to clarify whether genetic or environmental risk factors are the basis of the results shown above.

In addition to biological reasons, the substantial differences found for volume changes in the literature across studies also point to methodological limitations. Bremner et al., 1995, Bremner et al., 1997, Bremner et al., 2003 for example traced only the middle portion, while other studies measured the entire hippocampus. Furthermore, there is a wide range of hippocampal sizes (2.1 up to 6.4 cm3) reported (Stein et al., 1997), revealing that manual techniques are highly rater dependent which limits the interpretation in psychiatric patients. Automatic procedures, however, are more dependent on the quality of MRI images and the capability to distinguish between grey and white matter compared to manual techniques.

The basic idea of the present study was to employ the two techniques upon the same subjects to compare and validate the findings in the hippocampus volume and structure in a well-defined sample of chronic PTSD patients.

Section snippets

Subjects

Our study sample consisted of 30 subjects: 15 patients (13 male, 2 female) suffering from chronic PTSD according to DSM IV after witnessing an air show crash (Ramstein, Germany, 1988) of an airplane crashing into the spectator crowd. None of the subjects had been taking psychoactive drugs on a regular basis three months prior to the study. Eight patients had taken antidepressive medications (serotonin reuptake inhibitors) for a short time in the past but not on a regular basis, seven had not. A

Results

All patients were significantly impaired by PTSD symptoms: CAPS (59 +/− 23), IES-R (70 +/− 19), PDS (24 +/− 14), BDI (22.8 +/− 17.8). Two patients had suffered burns from the crash incident, one of 60% and one of 20% of their body surface.

Discussion

To the best of our knowledge, this is the first study examining changes in hippocampal volumes in well characterized chronic PTSD subjects, all traumatized at the same event, compared to matched controls using two different evaluation methods. Both evaluation techniques showed the same results. Neither method detected any volume or structural differences in this region. Furthermore, no significant correlations between hippocampal volumes and clinical data have been found. Our results are in

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