Original articleReduced hippocampal volume and total white matter volume in posttraumatic stress disorder
Introduction
Previous magnetic resonance imaging (MRI) studies report reduced hippocampal volumes in adult patients with posttraumatic stress disorder (PTSD) related to combat exposure or childhood sexual abuse Bremner et al 1995, Bremner et al 1997, Gurvits et al 1996, Stein et al 1997. Two prospective studies have failed to document hippocampal changes in PTSD. A report in adults studied after traumatic events and at a 6-month follow-up found no hippocampal changes in subjects who developed PTSD (Bonne et al 2001). Pediatric subjects with PTSD did not show hippocampal changes at baseline or follow-up at least 2 years later (De Bellis et al 2001).
The cause of these volumetric changes is currently debated. Several explanations of reduced hippocampal volumes have been put forward and can be summarized as follows: 1) The smaller hippocampal size is a preexisting condition that predisposes individuals to experience events as traumatic or increases vulnerability to develop PTSD following trauma; 2) traumatic experiences and/or subsequent PTSD causes hippocampal damage; and 3) PTSD leads to complications (such as alcohol abuse) that damage the hippocampus (discussed in Pitman 2001). Findings from current prospective PTSD studies Bonne et al 2001, De Bellis et al 2001 do not support hippocampal damage or preexisting hippocampal abnormalities in PTSD; longer studies are needed.
Bremner (1999) has proposed that reduced hippocampal volumes are a result of neurotoxic effects related to traumatic events/PTSD, in a process similar to hippocampal damage in animal models of stress. Studies in nonhuman primates and rodents demonstrate specific hippocampal neuronal atrophy resulting from chronic psychosocial stress Magarinos et al 1996, McEwen and Magarinos 1997, Uno et al 1989. Mounting evidence indicates that hippocampal neuronal injury in these animal models of stress is due to an interaction of elevated glucocorticoids and excitatory neurotransmiters Armanini et al 1990, Magarinos et al 1996. This is considered a specific effect on the hippocampus, owing to its high concentration of glucocorticoid receptors (reviewed in McEwen and Magarinos 1997); however, there is some evidence of decreased hippocampal glucocorticoid receptors in primates (Sanchez et al 2000). Furthermore, there is also evidence of genetic variability in hippocampal volumes (Lyons et al 2001).
Volumetric studies in PTSD have typically measured control brain regions to test how specific hippocampal changes are, but they have not examined whole-brain volumes Bremner et al 1995, Bremner et al 1997, Stein et al 1997. Only one study assessed whole-brain volumes, but it had a small n of 7 subjects per group and no matched control subjects (Gurvits et al 1996). To our knowledge, no study has examined total volumes of white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) in PTSD. Furthermore, reports in pediatric PTSD failed to replicate changes in hippocampal volumes and instead found smaller brain volumes Carrion et al 2001, De Bellis et al 1999, enlarged ventricles, and decreased area of the corpus callosum (De Bellis et al 1999). These findings are consistent with impaired brain development or generalized atrophy in pediatric PTSD. It is therefore important to examine indices of brain atrophy in adult PTSD.
The aim of this study was to investigate the specificity of hippocampal volumetric changes in a sample of civilian PTSD patients by measuring hippocampal volumes and whole-brain GM, WM, and CSF volumes. Because hippocampal atrophy is thought to be a very specific effect, we hypothesized that 1) PTSD patients have smaller hippocampal volumes; and 2) PTSD patients do not have evidence of whole-brain atrophy.
Section snippets
Patients
This study was conducted at the Department of Psychiatry and the Clinical and Magnetic Resonance Research Center (CMRRC), University of New Mexico (UNM) Health Sciences Center. Subjects with PTSD were recruited form psychiatric outpatient clinics, referred by clinicians, or self-referred. After explaining study procedures, all participants signed an informed consent approved by the institutional review board.
Twelve subjects with PTSD (10 women) diagnosed with the Clinician-Administered PTSD
Results
The following comorbid diagnoses were present in the 12 PTSD patients: current secondary (beginning after PTSD) major depressive (MD) episode in 4 (33%), MD in remission in 6 (50%), MD in partial remission in 1 (8%), alcohol abuse in remission for 32 years in 1 (8%). Of the 12 patients, 8 (67%) were taking medications (see Table 1). See Table 2. for detailed information on clinical and demographic variables of both groups. Because we matched control subjects by lifetime history of alcohol
Discussion
Our findings of decreased absolute and normalized hippocampal volumes are consistent with previous reports Bremner et al 1995, Bremner et al 1997, Gurvits et al 1996, Stein et al 1997 and support our primary hypothesis of reduced hippocampal volume in PTSD. Hippocampal volumes in PTSD were also smaller after controlling for lifetime weeks of alcohol intoxication. This suggests that hippocampal volumetric changes are not explained by the effects of alcohol, which is associated with hippocampal
Acknowledgements
This project was supported in part by the dedicated funds of the University of New Mexico School of Medicine.
The authors thank Clifford Qualls, Ph.D., for his assistance with the statistical analysis.
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