evidence of resilience: neuroimaging in former prisoners of war
TRANSCRIPT
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Psychiatry Research: Neuroim
Evidence of resilience: Neuroimaging in former prisoners of war
Thomas Freeman a,b,c,h,*, Tim Kimbrell a,b,c,h, Leroy Booe a,h, Michael Myers a,h,
David Cardwell b,c,h, Diana M. Lindquist b,d,h, John Hart d,f,g,h,
Richard A. Komoroski b,c,d,e,f,h
a Mental Health Service, Central Arkansas Veterans Healthcare System (CAVHS), Little Rock, AR, USAb South Central MIRECC, CAVHS, Little Rock, AR, USA
c Department of Psychiatry, University of Arkansas Medical Sciences, Little Rock, AR, USAd Department of Radiology, University of Arkansas Medical Sciences, Little Rock, AR, USAe Department of Pathology, University of Arkansas Medical Sciences, Little Rock, AR, USA
f Department of Biochemistry, University of Arkansas Medical Sciences, Little Rock, AR, USAg GRECC, Central Arkansas Veterans Healthcare System, Little Rock, AR, USA
h Department of Geriatrics, University of Arkansas Medical Sciences, Little Rock, AR, USA
Received 10 May 2005; received in revised form 11 July 2005; accepted 15 July 2005
Abstract
In this study, single voxel proton magnetic resonance spectroscopic imaging (1H-MRS) and volumetric analysis of hippocampal
magnetic resonance imaging (MRI) images were used to determine if any differences in hippocampal biochemistry or volume were
present between former prisoners of war (POWs) with and without posttraumatic stress disorder (PTSD) and control subjects
matched for age and education. This study did not find lower hippocampal concentrations of N-acetylaspartate (NAA), smaller
hippocampal volumes, or more impaired memory function in older veterans with PTSD compared with a group matched for
traumatic experience or a nontraumatized control group.
Published by Elsevier Ireland Ltd.
Keywords: Posttraumatic stress disorder; Hippocampus; Magnetic resonance spectroscopy; N-acetylaspartate
1. Introduction
Posttraumatic stress disorder (PTSD) has been a
focus of attention for neuroimaging research over the
last decade. During that time, a number of human
research studies have implicated various brain regions
in this condition, including portions of the frontal lobe,
0925-4927/$ - see front matter. Published by Elsevier Ireland Ltd.
doi:10.1016/j.pscychresns.2005.07.007
* Corresponding author. CAVHS Psychiatry Services, Little Rock
VAMC, Mail Code: 116T/LR, 4300 West 7th Street, Little Rock AR
72205-5484, USA. Tel.: +1 501 257 3092; fax: +1 501 257 6602.
E-mail address: [email protected]
(T. Freeman).
the amygdala, and the hippocampus (Villarreal and
King, 2001). This last structure has received the most
attention in structural imaging studies, due to the rela-
tionships between stress and hippocampal atrophy dem-
onstrated in several animal studies (Sapolsky, 1996). To
date, most studies of PTSD subjects using magnetic
resonance imaging (MRI) have shown that these sub-
jects have smaller hippocampal volumes than matched
controls. Studies using proton magnetic resonance
spectroscopy (1H-MRS) have typically also revealed
abnormalities in hippocampal biochemistry in PTSD
subjects, commonly showing lower levels of hippocam-
pal N-acetylaspartate (NAA), an excitatory neurotrans-
aging 146 (2006) 59–64
T. Freeman et al. / Psychiatry Research: Neuroimaging 146 (2006) 59–6460
mitter associated with neuronal integrity, in PTSD sub-
jects relative to controls (Villarreal et al., 2002).
Considerable debate continues regarding the mean-
ing of these findings in PTSD subjects. Smaller hippo-
campal volumes or altered hippocampal biochemistry
could either precede a traumatic event and predispose
individuals to PTSD or follow the traumatic event as a
consequence of neurobiological changes associated
with extreme stress. Evidence for both arguments has
been put forward (Gilbertson et al., 2002; Bremner et
al., 1995). Given the widespread prevalence of PTSD in
the population, another very practical focus for inves-
tigation is the study of possible ongoing negative neu-
robiological and cognitive consequences associated
with chronic PTSD. Most neuroimaging studies that
have shown significant differences in hippocampal bio-
chemistry or structure among PTSD subjects have been
completed in individuals who have had the disorder for
decades. Studies of children or more recent victims of
trauma typically do not reveal similar differences in
hippocampal biochemistry or structure (Bonne et al.,
2001; De Bellis et al., 2001), though there are excep-
tions (Wignall et al., 2004). This suggests that if the
smaller hippocampal volumes and altered neurochem-
istry associated with PTSD are not purely premorbid to
the index traumatic event, the processes leading to these
deleterious outcomes may continue to act over the
affected individual’s lifetime.
To investigate the possibility of accelerated neurobi-
ological decline in subjects with chronic PTSD, inves-
tigators might need to construct longitudinal studies
that last for decades, since longitudinal neuroimaging
studies that have examined PTSD subjects over time
frames of 6 months to 2 years have not shown signif-
icant changes in hippocampal structure during that time
(Bonne et al., 2001; De Bellis et al., 2001). An alter-
native strategy that would not necessitate the logistical
problems associated with longitudinal studies lasting
decades would be to examine older subjects who
have been exposed to significant, documented traumas
earlier in life and who have met criteria for PTSD for
the majority of their lives. Examining hippocampal
morphometry and biochemistry in these subjects
could shed light on the chronic neurobiological con-
sequences of lifelong PTSD.
Former prisoners of war (POWs) have frequently
been the focus of research efforts into the relationship
of severe early adult trauma to psychopathology and
cognitive functioning, though few neuroimaging stud-
ies have examined this population. Former POWs have
been shown to have a high prevalence of PTSD. A
number of studies suggest that 30% to 70% of former
POWs meet lifetime criteria for PTSD (Sutker et al.,
1993; Engdahl et al., 1997). In addition to experiencing
a high rate of PTSD, former POWs have demonstrated
a direct relationship between their weight loss during
captivity and their current PTSD symptoms. We have
found that the documented percentage weight loss dur-
ing POW internment is strongly correlated with PTSD
symptom severity six decades after the original trauma
(Myers et al., 2005). Despite a clear research interest in
this subject group, investigations of former POWs have
tended to focus on issues of cognitive function (Sutker
et al., 1990; Sulway et al., 1996) and reports of psy-
chopathology (Sutker et al., 1993; Engdahl et al.,
1997), with little attention paid to neuroimaging,
though one early study did examine the relationship
of sleep disturbances to the ventricle/brain ratio as
determined by computed tomographic imaging (Peters
et al., 1990) in former Japanese held POWs, and one
more recent study (Brown et al., 2003) examined dif-
ferences in medial temporal lobe (MTL) biochemistry
between former POWs with and without PTSD using
magnetic resonance spectroscopy (MRS).
Our goals in this study were to expand on our
previous work by examining the 1H-MRS measures
of hippocampal biochemistry, hippocampal volumes,
and neuropsychological findings in three groups of
subjects: former POW subjects with PTSD, former
POW subjects without PTSD, and control subjects
matched for age and education. Our intent was to
determine if the presence of chronic PTSD would be
associated with decreased hippocampal N-acetylaspar-
tate/creatine ratios (NAA/Cr) and smaller hippocampal
volumes in subjects exposed to similar severe and
well-documented traumatic experiences compared
with a matched control group. Our previous work
had shown a significant correlation between reported
reexperiencing symptoms in PTSD subjects and me-
dial temporal lobe (MTL) NAA/Cr ratios but had
shown no significant differences in MRS-determined
MTL NAA/Cr or choline/creatine ratios (CHO/Cr)
between POWs divergent for PTSD diagnosis
(Brown et al., 2003); however, this earlier study had
not compared POW subjects with a matched control
group and had not examined hippocampal volumes
between POW groups.
2. Methods
A total of 26 male veteran subjects (20 former
POWs and 6 control subjects) participated in the
study. The Human Use Committee of the University
of Arkansas for Medical Sciences approved the research
T. Freeman et al. / Psychiatry Research: Neuroimaging 146 (2006) 59–64 61
protocol, and written informed consent was obtained
from all subjects. All POW subjects had combat expe-
rience and had been held captive during either World
War II (WW2) or the Korean War (KW). Eight of the
ten former POWs with PTSD were former German
POWs, and two were former Japanese POWs. Seven
of the ten former POWs without PTSD were former
German POWs, two were former Japanese POWs, and
one was a former Korean POW. Five POW subjects (4
POWs with PTSD and 1 POW without PTSD) were
also participants in our earlier study (Brown et al.,
2003). Average length of imprisonment is noted in
Table 1 for both POW groups. All study subjects
were carefully selected using stringent exclusion and
inclusion criteria. All subjects were Caucasian males,
were right-handed by Edinburgh criteria (Oldfield,
1971), had no history of traumatic brain injury with
loss of consciousness, had no history of neurological
impairment or degenerative neurological illness, did not
meet criteria for either current or lifetime alcohol de-
pendence, and had Mini Mental Status Examination
scores (MMSE) of 26 or higher. All research subjects
completed the study without compensation of any kind.
POW subjects were recruited through a POW out-
reach program initiated by the Central Arkansas
Veterans’ Healthcare System (CAVHS), and control
subjects were recruited through primary care clinics
within the CAVHS. Only four study subjects had a
Table 1
Comparison of POW subjects with and without PTSD and control subjects
Variable POW subjects with
PTSD (N =10)
Patient age (years) 79.6F3.2
Duration of imprisonment (months) 18.0F14.1
Years of education 14.1F2.6
Years of employment (including military service) 43.8F5.5
CAPS total 53.3F13.9
Combat Exposure Scale score 15.3F8.3
Dissociative Experiences Scale score 12.9F5.7
Beck Depression Inventory score 11.2F4.4
Davidson Trauma Scale total score 45.8F23.1
Right hippocampal NAA/Cr 1.57F0.63
Right hippocampal volume (mm3) 2746.0F677.9
Left hippocampal NAA/Cr 1.49F0.36
Left hippocampal volume (mm3) 2640.7F433.1
Right hippocampal CHO/Cr 1.35F0.26
Left hippocampal CHO/Cr 1.43F0.64
Rey Auditory Verbal Learning Test—5th trial 8.7F2.2
Rey Auditory Verbal Learning Test—total 33.3F6.9
Logical Memory—thematic score 8.9F3.3
Logical Memory—recall score 11.2F4.0
Recognition Memory (faces) 38.8F5.7
* One-way analysis of variance.
** Two-tailed t-test.
history of any previous psychiatric treatment; all four
were POWs with PTSD. No study subject had a
history of psychiatric hospitalization, alcohol or sub-
stance abuse treatment, or suicide attempt. The pres-
ence or absence of PTSD was ascertained with the
use of the Clinician Administered PTSD Scale
(CAPS-2) in all subjects (Weathers et al., 2001).
CAPS-2 scores were tallied for all subjects in terms
of both total score and symptom cluster scores (reex-
periencing, avoidance, and arousal). In using the
CAPS-2, we chose the more conservative brule of
4Q (Fleming and Difede, 1999)—i.e. the frequency
and severity scores needed to meet symptom criteria
had to add to a minimum of four. The Structured
Clinical Interview for DSM-IV (First et al., 1995) was
also administered to determine current and lifetime
psychiatric diagnoses. Former POW subjects who met
lifetime, but not current, diagnostic criteria for PTSD
were not included in the study. Subjects were initially
interviewed by a board-certified psychiatrist (TWF or
TK), their medical histories were reviewed (LB), and
they were then scheduled for neuroimaging if they
qualified and consented. All subjects were inter-
viewed for PTSD symptom severity, lifetime stressors,
lifetime alcohol use, and lifetime medical and psychi-
atric treatment. Subjects also completed the Edinburgh
Handedness Inventory (Oldfield, 1971), the Beck De-
pression Inventory (BDI), the Davidson Trauma Scale
POW subjects without
PTSD (N =10)
Control subjects
(N =6)
Significance
79.8F2.8 80.8F3.5 NS*
23.5F19.9 – NS**
15.7F3.9 12.5F2.6 NS*
46.1F12.3 43.0F6.4 NS*
14.2F11.3 3.5F4.2 F =67.4, P b0.001
8.7F7.3 7.6F16.3 NS*
11.5F9.9 5.4F6.1 NS*
8.4F4.3 6.8F3.6 F =3.3, P=0.05
9.4F6.3 10.9F14.3 F =18.4, P b0.001
1.50F0.50 1.29F0.18 NS*
2841.9F273.5 2955.1F531.1 NS*
1.41F0.28 1.18F0.23 NS*
2715.9F296.9 2866.4F351.2 NS*
1.21F0.29 1.26F0.32 NS*
1.32F0.28 1.02F0.21 NS*
8.6F2.5 8.7F2.3 NS*
34.1F10.1 34.5F8.9 NS*
8.6F3.9 8.7F4.5 NS*
9.0F3.7 9.5F4.3 NS*
41.2F2.9 38.7F2.4 NS*
T. Freeman et al. / Psychiatry Research: Neuroimaging 146 (2006) 59–6462
(DTS) (Davidson et al., 2002), and the seven-item
Combat Exposure Scale (CES) (Keane and Caddell,
1989). Memory was tested using the Rey Auditory
Verbal Learning Test, Logical Memory (Wechsler,
1987), and the Recognition Memory Test for Faces
(Warrington, 1984). All testing and self-reports were
completed on the day of scanning.
Neuroimaging investigations were performed on a
1.5-T General Electric Signa MRI system with a
standard head coil using the automated PROBE/SV
routine with minor modifications. A set of spin-echo
localizer MRI scans in three orthogonal planes was
first acquired with the following parameters: repetition
time (TR)=500 ms, echo time (TE)=8 ms, field of
view (FOV)=24 cm, and slice thickness=3 mm.
After localization of the hippocampi, an oblique loca-
lizer scan parallel to the hippocampal axis was ac-
quired with TR=500 ms, TE=10 ms, FOV=24 cm,
and slice thickness=1.5 mm. Voxel locations were
chosen in the oblique plane in the right and left
medial temporal lobes by an individual blind to the
diagnostic status of the subject. After localization of
an approximately 1�1�4 cm3 voxel within the hip-
pocampus, magnetic field homogeneity and water
suppression were optimized automatically. A set of
water reference scans and a water-suppressed, point-
resolved spectroscopy (PRESS) spectrum were ac-
quired with TE=144 ms, TR=2 s, 128 transients,
and spectral width=2500 Hz in 2048 points. The
data were transferred to an off-line SPARC (Sun
Microsystems) workstation and processed automatical-
ly to correct spectral phase, the effects of residual
eddy currents, and baseline. An automated Marquardt-
fitting routine yielded the ratios of the peak intensities
of NAA and CHO to Cr. When the automated routine
failed, the fitting routine was directed to the peaks of
interest to insure a fit. Spectra were rejected if the
resolution between the CHO and Cr peaks was not at
least 50% of the distance from peak maximum to
apparent baseline, or if obvious artifacts interfered.
Additional details have been given previously (Free-
man et al., 1998).
Determinations of hippocampal volumes were made
using 1.5-mm contiguous coronal slices collected with
a T1-weighted gradient echo 3D sequence with TR=24
ms, TE=5 ms, and flip angle=458. Using the technique
of Watson et al. (1992), two raters with good interrater
reliability (a=0.92) and who were blind to the subject’s
diagnostic status performed volumetric analyses on all
subjects after head rotation was corrected and slices
were created perpendicular to the long axis of the
hippocampi.
3. Results
The three subject groups did not differ in age or
years of education (Table 1). Former POW groups did
not differ in combat exposure, duration of imprison-
ment, or years of employment. In the former POW
group with PTSD, four (40%) of the subjects met
lifetime criteria for major depression, three (30%) met
lifetime or current criteria for panic disorder, and none
met lifetime criteria for either alcohol dependence or
abuse. Six (60%) of the ten POW subjects with PTSD
did not meet SCID criteria for any psychiatric illness
other than PTSD, current or lifetime. None of the POW
subjects with PTSD reported a history of psychiatric
hospitalization, and only four reported any history of
psychiatric treatment at all. In the former POW group
without PTSD, three subjects (30%) met lifetime crite-
ria for major depression and none met lifetime or
current criteria for panic disorder or alcohol dependence
or abuse. Seven (70%) of the former POW group
without PTSD did not meet criteria for any Axis 1
disorder. Two control subjects (33%) met criteria for
lifetime, but not current, alcohol abuse. The three
groups did differ significantly in reported psychopa-
thology with POWs with PTSD expressing significant-
ly higher CAPS-2 subscale and total scores, and higher
DTS and BDI scores than the other two groups. Within
the POW group as a whole, CAPS-2 total scores cor-
related strongly with DTS scores (r =0.723, P b0.001),
but not with BDI scores.
The three subject groups did not differ in hippocam-
pal NAA/Cr or CHO/Cr ratios. Likewise, no differences
found in hippocampal volumes, total brain volumes, or
hippocampal/total brain ratios between groups. When
the POW group as a whole was compared with the
control group, no differences were found in hippocam-
pal NAA/Cr or CHO/Cr ratios. Unlike our previous
study (Brown et al., 2003), we found no correlation
among the POW group with PTSD between reexper-
iencing symptoms and hippocampal NAA ratios. Nei-
ther CAPS total symptom scores nor DTS scores
correlated with hippocampal NAA ratios in POWs
with PTSD. As noted in Table 1, neuropsychological
testing showed no significant differences between
groups.
4. Discussion
Overall, we found no differences in MRS-deter-
mined hippocampal NAA/Cr or CHO/Cr ratios, brain
volumetric measures, or memory measures between the
subject groups. This negative study replicates our ear-
T. Freeman et al. / Psychiatry Research: Neuroimaging 146 (2006) 59–64 63
lier finding (Brown et al., 2003), and adds to that
finding in that no significant differences in hippocam-
pal biochemistry or hippocampal volumes were found
between either POW group or an age- and education-
matched control group. This study is unusual among
neuroimaging studies of PTSD subjects in that the
majority of our PTSD sample did not meet criteria for
any psychiatric disorder other than PTSD. In addition to
the unusual opportunity to study a PTSD population
with minimal comorbid psychiatric illness, this study
also offered the opportunity to compare a group of
former POWs with PTSD with a group of former
POWs with documented, similar traumatic experiences
(but without a history of PTSD) using two different
neuroimaging techniques.
Our findings potentially support two possible and
rather broad conclusions. First, these findings support
a lack of observable hippocampal pathology associat-
ed with chronic PTSD. However, this conclusion runs
counter to the bulk of neuroimaging studies in PTSD
subjects—both those suggesting that PTSD-related
hippocampal pathology is primarily a predisposing
factor for the acquisition of PTSD and those suggest-
ing that hippocampal pathology is a direct conse-
quence of deleterious neurobiological processes
associated with traumatic experience. A second possi-
ble conclusion also supported by our findings is more
complex, and is related to evidence suggesting exces-
sive medical morbidity and mortality in veterans ex-
posed to war trauma. There are numerous studies that
suggest that individuals with PTSD are prone to ex-
cessive levels of medical morbidity (Boscarino, 2004);
other studies suggest that simply being exposed to
combat in youth is associated with early mortality
(Lee et al., 1995). More recent work has suggested
that stress may be tied to accelerated aging (Epel et
al., 2004), and a recent longitudinal follow-up study of
Vietnam veterans with PTSD revealed a remarkably
high mortality rate over a 6-year period (Johnson et
al., 2004). A study of former Vietnam POWs (Guest
and Venn, 1992) showed an elevated mortality rate
immediately after the war. These findings support
another conclusion—namely that former POWs who
were more affected by the traumatic experiences of
their youth were unavailable to us as subjects due to
attrition, leaving a healthier and less affected group for
study. The subjects available for this study were re-
markably healthy and vital, and longer-lived than
average. It should also be noted that the majority
(60%) of former POW subjects with PTSD did not
meet SCID criteria for any Axis 1 disorder other than
PTSD, and the majority (70%) of former POW sub-
jects without PTSD did not meet SCID criteria for any
Axis 1 psychiatric illness at all. Our PTSD subjects
exhibited remarkably low levels of psychiatric morbid-
ity and expressed far lower levels of PTSD symptom
severity than our Vietnam veteran study populations.
This latter conclusion would also explain the report of
Golier et al. (2001), who found no difference in hip-
pocampal volume in elderly Holocaust survivors with
PTSD.
Our clinical impression of the vitality and relative
lack of severe psychopathology found in these elderly
former POW groups is entirely consistent with their
lack of tested neuropsychological impairment or cere-
bral pathology. This is not the clinical impression we
typically perceive when we examine younger veteran
populations with chronic PTSD. The comparative lack
of psychiatric comorbidity in these former POW
groups, together with the lack of differences in MRS
and MRI volumes between groups, suggests that the
frequent comorbid psychiatric and medical illnesses
found in Vietnam veteran populations with PTSD
may be coupled to neuroimaging findings in veteran
PTSD populations to date. This would suggest that
studies of elderly PTSD populations–especially those
composed of very old subjects–might reveal a less
impaired group than studies of younger PTSD popula-
tions, with the presumption that older populations have
already been subject to the attrition of more impaired
individuals.
Research using former POWs offers opportunities to
study a remarkably resilient group of individuals with
histories of unquestionably severe, well-documented
early adulthood traumatic experience, but who are re-
markably free of much of the comorbid psychiatric
illness that often accompanies neuroimaging research
into PTSD. It may be that not only are there groups of
individuals that are especially vulnerable to traumatic
experience, there may be populations that are especially
resilient to the effects of severe trauma. As has been
suggested recently (Charney, 2004), research using re-
silient populations may offer unique insights into the
psychobiological effects of extreme stress and healthy
aging.
References
Bonne, O., Brandes, D., Gilboa, A., Gomori, J.M., Shenton, M.E.,
Pitman, R.K., Shalev, A.Y., 2001. Longitudinal MRI study of
hippocampal volume in trauma survivors with PTSD. American
Journal of Psychiatry 158 (8), 1248–1251.
Boscarino, J.A., 2004. Posttraumatic stress disorder and physical
illness: results from clinical and epidemiologic studies. Annals
of the New York Academy of Sciences 1032, 141–153.
T. Freeman et al. / Psychiatry Research: Neuroimaging 146 (2006) 59–6464
Bremner, J.D., Randall, P., Scott, T.M., Bronen, R.A., Seibyl, J.P.,
Southwick, S.M., Delaney, R.C., McCarthy, G., Charney, D.S.,
Innis, R.B., 1995. MRI-based measurement of hippocampal vol-
ume in patients with combat-related posttraumatic stress disorder.
American Journal of Psychiatry 152 (7), 973–981.
Brown, S., Freeman, T., Kimbrell, T., Cardwell, D., Komoroski, R.,
2003. In vivo proton magnetic resonance spectroscopy of the
medial temporal lobes of former prisoners of war with and without
posttraumatic stress disorder. Journal of Neuropsychiatry and
Clinical Neuroscience 15, 367–370.
Charney, D.S., 2004. Psychobiological mechanisms of resilience and
vulnerability: implications for successful adaptation to extreme
stress. American Journal of Psychiatry 161, 195–216.
Davidson, J., Tharwani, H., Connor, K., 2002. Davidson Trauma
Scale (DTS): normative scores in the general population and effect
sizes in placebo-controlled SSRI trials. Depression and Anxiety
15, 75–78.
De Bellis, M.D., Hall, J., Boring, A.M., Frustaci, K., Moritz, G.,
2001. A pilot longitudinal study of hippocampal volumes in
pediatric maltreatment-related posttraumatic stress disorder. Bio-
logical Psychiatry 50, 305–309.
Engdahl, B., Dikel, T.N., Eberly, R., Blank Jr., A., 1997. Posttrau-
matic stress disorder in a community group of former prisoners of
war: a normative response to severe trauma. American Journal of
Psychiatry 154, 1576–1581.
Epel, E.S., Blackburn, E.H., Lin, J., Dhabhar, F.S., Adler, N.E.,
Morrow, J.D., Cawthon, R.M., 2004. Accelerated telomere short-
ening in response to life stress. Proceedings of the National
Academy of Sciences of the United States of America 101,
17312–17315.
First, M.B., Spitzer, R.L., Gibbon, M., Williams, J.B.W., 1995.
Structured Clinical Interview for DSM-IV Axis I Disorders
(SCID). Biometrics Research, New York State Psychiatric Insti-
tute, New York.
Fleming, M., Difede, J., 1999. Effects of varying scoring rules of the
Clinician Administered PTSD Scale (CAPS) for the diagnosis of
PTSD after acute burn injury. Journal of Traumatic Stress 12,
535–542.
Freeman, T.W., Cardwell, D., Karson, C.N., Komoroski, R., 1998. In
vivo proton magnetic resonance spectroscopy of the medial tem-
poral lobes of subjects with combat-related posttraumatic stress
disorder. Magnetic Resonance in Medicine 40, 66–71.
Gilbertson, M.W., Shenton, M.E., Ciszewski, A., Kasai, K., Lasko,
N.B., Orr, S.P., Pitman, R.K., 2002. Smaller hippocampal volume
predicts pathologic vulnerability to psychological trauma. Nature
Neuroscience 5, 1242–1247.
Golier, J., Yehuda, R., De Santi, S., Convit, A., de Leon, M., 2001.
Hippocampal Volume and Memory Performance in Holocaust
Survivors With PTSD. Abstract, Society for Biological Psychiatry.
Guest, C.S., Venn, A.J., 1992. Mortality of former prisoners of war
and other Australian veterans. Medical Journal of Australia 157,
132–135.
Johnson, D.R., Fontana, A., Lubin, H., Corn, B., Rosenheck, R.,
2004. Long-term course of treatment-seeking Vietnam veterans
with posttraumatic stress disorder: mortality, clinical condition,
and life satisfaction. Journal of Nervous and Mental Disease 192,
35–41.
Keane, T., Caddell, J., 1989. Clinical evaluation of a measure to
assess combat exposure. Psychological Assessment 1, 53–55.
Lee, K.A., Vaillant, G.E., Torrey, W.C., Elder, G.H., 1995. A 50-year
prospective study of the psychological sequellae of World War II
combat. American Journal of Psychiatry 152, 516–522.
Myers, M., Kimbrell, T., Booe, L., Freeman, T., 2005. Weight loss
and PTSD symptom severity in former POWs. Journal of Nervous
and Mental Disease 193, 278–280.
Oldfield, R., 1971. The assessment and analysis of handedness: the
Edinburgh Inventory. Neuropsychologia 9, 97–113.
Peters, J., van Kammen, D.P., van Kammen, W.B., Neylan, T., 1990.
Sleep disturbance and computerized scan findings in former pris-
oners of war. Comprehensive Psychiatry 31, 535–539.
Sapolsky, R.M., 1996. Why stress is bad for your brain. Science 273
(5276), 749–750.
Sulway, M.R., Broe, G.A., Creasey, H., Dent, O.F., Jorm, A.F., Kos,
S.C., Tennant, C.C., 1996. Are malnutrition and stress risk factors
for accelerated cognitive decline? A prisoner of war study. Neu-
rology 46, 650–655.
Sutker, P.B., Allain, A.N., Winstead, D.K., 1993. Psychopathology
and psychiatric diagnoses of World War II Pacific theater prisoner
of war survivors and combat veterans. American Journal of
Psychiatry 150, 240–245.
Sutker, P.B., Galina, Z.H., West, J.A., Allain, A.N., 1990. Trauma
induced weight loss and cognitive deficits among former prison-
ers of war. Journal of Consulting and Clinical Psychology 58,
323–328.
Villarreal, G., King, C.Y., 2001. Brain imaging in posttraumatic stress
disorder. Seminars in Clinical Neuropsychiatry 6, 131–145.
Villarreal, G., Petropoulos, H., Hamilton, D.A., Rowland, L.M.,
Horan, W.P., Griego, J.A., Moreshead, M., Hart, B.L., Brooks,
W.M., 2002. Proton magnetic resonance spectroscopy of the
hippocampus and occipital white matter in PTSD: preliminary
results. Canadian Journal of Psychiatry 47, 666–670.
Warrington, E.K., 1984. Recognition Memory Test. NFER-Nelson,
Windsor, U.K.
Watson, C., Andermann, F., Gloor, P., Jones-Gotman, M., Peters, T.,
Evans, A., 1992. Anatomic basis of amygdaloid and hippocampal
volume measurement by magnetic resonance imaging. Neurology
42, 1743–1750.
Weathers, F., Keane, T., Davidson, J.R., 2001. Clinician-administered
PTSD scale: a review of the first 10 years of research. Depression
and Anxiety 13, 132–156.
Wechsler, D., 1987. Wechsler Memory Scale-Revised Manual. The
Psychological Corporation, San Antonio, TX.
Wignall, E.L., Dickson, J.M., Vaughan, P., Farrow, T.F., Wilkinson,
I.D., Hunter, M.D., Woodruff, P.W., 2004. Smaller hippocampal
volume in patients with recent-onset posttraumatic stress disorder.
Biological Psychiatry 56, 832–836.