Smaller head of the hippocampus in Gulf War-related posttraumatic stress disorder
Introduction
The finding of smaller hippocampal volume in individuals with posttraumatic stress disorder (PTSD) has generated interest and controversy in the field of psychological trauma. PTSD as a result of combat-related trauma experiences during the Vietnam War has been associated with smaller right (Bremner et al., 1995) and left and right hippocampal volume (Gurvits et al., 1996, Hedges et al., 2003, Villarreal et al., 2002). Reduced hippocampal volume has also been reported in civilian survivors of sexual and/or physical abuse (Bremner et al., 1997, Bremner et al., 2003b, Stein et al., 1997), mixed trauma (Villarreal et al., 2002) with recent PTSD (Wignall et al., 2004), and policeman with PTSD (Lindauer et al., 2004). However, not all published studies found smaller hippocampal volume in subjects with PTSD (Bonne et al., 2001, De Bellis et al., 1999, De Bellis et al., 2001, Fennema-Notestine et al., 2002, Pederson et al., 2004, Schuff et al., 1997, Schuff et al., 2001, Winter and Irle, 2004).
Possible explanations for discrepant findings regarding hippocampal volume include differences in imaging methodology, differences in comparison groups, variability in intensity and duration of trauma exposure, chronicity of PTSD symptomatology, and presence of co-morbid psychiatric disorders associated with reduced hippocampal volume. It is also possible that discrepant findings in PTSD volumetric studies could, in part, be related to differences in the subregions of the hippocampus. Schizophrenia is associated with focal abnormalities in the head of the hippocampus in the absence of a generalized decrease in hippocampal volume (Csernansky et al., 2002). Focal abnormalities in the subiculum have also been recently reported in major depression (Posener et al., 2003). To date, morphometry of the subregions of the hippocampus has not been evaluated in subjects with PTSD or in veterans of the Gulf War.
There are several possible explanations for smaller hippocampal volume in PTSD (reviewed in Pitman, 2001). A pre-existing smaller hippocampal volume could predispose traumatized subjects to develop PTSD (Gilbertson et al., 2002). Alternatively, small hippocampal volume could be a result of comorbid conditions such as alcohol dependence (Agartz et al., 1999, Caetano et al., 2004) and major depression (Caetano et al., 2004, Sheline et al., 1999, Videbech and Ravnkilde, 2004); could be secondary to trauma exposure; or could be due to the chronic stress of PTSD. The aim of the present study was to measure the volume of the hippocampus and its subregions, including the head and body, in veterans of the Gulf War and to relate these findings to hippocampal mediated neuropsychological testing. Gulf War veterans with PTSD were compared with deployed veterans who did not develop PTSD and non-deployed reservists. History of early childhood abuse and presence of co-morbid major depression and/or substance abuse were assessed thoroughly, as these variables have previously been associated with reduced hippocampal volume (Agartz et al., 1999, Bremner et al., 1997, MacQueen et al., 2003, Sheline et al., 1999, Sheline et al., 1996, Stein et al., 1997, Vythilingam et al., 2002). Because the reservists had greater rates of major depressive disorder (MDD), alcohol abuse and childhood trauma than anticipated, healthy controls without military service and who did not meet criteria for any past or present psychiatric disorders were included as an additional control group. All groups were imaged using the same scanner and identical scan sequence.
We hypothesized that deployed Gulf War veterans with PTSD would have smaller volumes of the head, body and whole hippocampus and poorer hippocampal mediated memory function than deployed Gulf War veterans without PTSD, reservists and healthy civilians.
Section snippets
Subjects
Eighty-eight subjects were assigned to one of four groups based upon their deployment status and presence of combat-related PTSD. Fourteen subjects (8 men, 6 women; mean age 35 ± 9 years) had PTSD related to trauma [Gulf War (1990–1991)], 23 (15 men, 8 women; mean age 35 ± 7 years) had been deployed to the Gulf but did not develop PTSD and did not have a lifetime history of PTSD, 22 (9 men, 13 women; mean age 39 ± 7 years) were non-deployed reservists, and 29 (9 men, 20 women; mean age 34 ± 10 years)
Subject characteristics (Table 1)
Table 1 presents the sociodemographic and clinical characteristics of the subjects. PTSD subjects had significantly greater rates of current MDD than other subjects. PTSD, deployed non-PTSD, and reservists had rates of past MDD that were significantly greater than healthy civilians, but only PTSD and deployed non-PTSD subjects had greater rates of past alcohol abuse and dependence than healthy civilians.
As expected, subjects with PTSD had significantly greater scores on the Mississippi Scale
Discussion
In the present study, volume of the head of the hippocampus was smaller in subjects with Gulf War-related PTSD compared with healthy civilians. It is possible that hippocampal structural abnormalities in PTSD are restricted to subregions of the hippocampus, and measurement of the whole structure could miss the detection of subtle, but important, differences that have functional significance in PTSD. The head or the anterior part of the hippocampus has reciprocal connections with the prefrontal
Acknowledgments
The authors thank Martha Dillon, M.A., and Karen Partlow for assistance with data collection; Sara Norris, M.P.H., for assistance with statistical analysis; and Alex Noury, M.A., for help in preparing the manuscript. This study was supported in part by Department of Defense HURRAD log number a-7152.
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