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C 2003)
Journal of Traumatic Stress, Vol. 16, No. 4, August 2003, pp. 319–323 (°
Hypothalamic–Pituitary–Adrenal Activity Among
Armenian Adolescents With PTSD Symptoms
Armen K. Goenjian,1,6 Robert S. Pynoos,1 Alan M. Steinberg,1 David Endres,2
Khachik Abraham,3 Mitchell E. Geffner,4 and Lynn A. Fairbanks5
This study evaluated basal levels and responsiveness to exercise of plasma adrenocorticotropic hormone (ACTH), and serum thyroid stimulating hormone (TSH), growth hormone (GH) and cortisol
among adolescents from two differentially exposed groups 61 /2 years after the 1988 earthquake in
Armenia. Severity of total PTSD and Category C and D symptoms were negatively correlated with
baseline cortisol. Preexercise ACTH was significantly lower, and preexercise TSH higher, among
adolescents with more exposure. Depressive symptoms were negatively correlated with baseline cortisol and positively with TSH. Mean GH, TSH, and cortisol levels in both groups fell within normal
limits. The pre- to postexercise increase in GH, TSH, and cortisol suggests that exercise challenge
may be useful in the field investigation of neurohormonal activity among traumatized individuals.
KEY WORDS: trauma; PTSD; cortisol; ACTH; growth hormone; TSH.
Most studies of hypothalamic–pituitary–adrenal
(HPA) related stress hormones among traumatized individuals have been conducted among adults. In regard to
cortisol, studies have found lower basal urinary, serum,
and salivary cortisol levels among adults (Boscarino,
1996; Mason, Giller, Kosten, Ostroff & Podd, 1986;
Yehuda et al., 1990, 1995) and adolescents (Goenjian
et al., 1996) with chronic posttraumatic stress disorder
(PTSD) compared with controls. However, a number of
other studies have found the opposite (Carrion et al., 2002;
De Bellis et al., 1999; Lemieux & Coe, 1995; Pitman &
Orr, 1990), while others have found no difference from
controls (Baker et al., 1999; Kosten, Wahby, Giller &
Mason, 1990). Studies have also documented a negative
correlation between PTSD symptoms and salivary
(Goenjian et al., 1996), serum (Baker et al., 1999), and urinary cortisol (Yehuda et al., 1995), and a positive correlation between PTSD symptoms and plasma cortisol (Smith
et al., 1989). With regard to adrenocorticotropic hormone
(ACTH), DeBellis et al. (1994) have reported lower basal
plasma ACTH among sexually abused prepubescent girls
with depression, whereas Smith et al. (1989) found a trend
toward lower ACTH among combat veterans with chronic
PTSD.
Both thyroid stimulating hormone (TSH) and growth
hormone (GH) are secreted by the anterior pituitary gland,
and both are implicated in the hormonal response to stress.
Three studies among war veterans with PTSD have found
no difference in baseline TSH in comparison with controls
(Kosten et al., 1990; Mason et al., 1994; Wang & Mason,
1999). Bauer, Priebe, Kurten, Graf, and Baumgartner
(1994) found lower serum TSH among East German
1 Department
of Psychiatry and Biobehavioral Sciences, UCLA/Duke
University National Center for Child Traumatic Stress, UCLA School
of Medicine Los Angles, California.
2 Department of Clinical Pathology, University of Southern California,
California.
3 Medical Science Center, Glendale, California.
4 Department of Pediatrics, Keck School of Medicine, University of
Southern California, Los Angeles, California.
5 Department of Psychiatry and Biobehavioral Sciences, UCLA School
of Medicine, Los Angeles, California.
6 To whom correspondence should be addressed at NCCTS, 11150
Olympic Boulevard, Suite 770, Los Angeles, California 90064; e-mail:
[email protected].
319
C 2003 International Society for Traumatic Stress Studies
0894-9867/03/0800-0319/1 °
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Goenjian, Pynoos, Steinberg, Endres, Abraham, Geffner, and Fairbanks
refugees exposed to prolonged stress compared with controls. With regard to GH, civilian adults exposed to the Persian Gulf War showed no alterations in GH with changes in
anxiety from pre-, mid- to postwar (Weizman et al., 1994).
Similarly, patients with a diagnosis of noncombat-related
PTSD showed no difference in GH compared with controls (Yatham, Sacamano & Kusumaker, 1996). Though
less responsive to stress than cortisol, normal serum GH
response to vigorous exercise has been used as a screening
test for GH deficiency (Underwood & Van Wyk, 1992).
The 1988 earthquake in Armenia, known as the Spitak
earthquake, registered 6.9 on the Richter scale, caused the
destruction of 4 cities and 350 villages, killing at least
25,000 people in an area inhabited by 500,000 people. The
adolescents in this study were from two cities, Spitak, the
city at the epicenter, and Yerevan, a city at the periphery of
the earthquake zone. Adolescents who had lived in Spitak,
which was 90% destroyed with approximately 17% of the
population killed, were classified as the high exposure
group. Adolescents who had lived in Yerevan were classified as having experienced low exposure to the earthquake.
Five years after the earthquake, adolescents with
chronic PTSD symptoms from Spitak, the city at the epicenter, manifested lower morning cortisol levels and hypersuppression of cortisol after dexamethasone (Goenjian
et al., 1996). PTSD B category symptoms were significantly negatively correlated with basal morning cortisol
levels, and with percent suppression by dexamethasone.
This study was designed to determine whether low cortisol
levels would be found among a different group of similarly highly exposed adolescents evaluated at 61/2 years
postearthquake. The study also evaluated other aspects
of HPA axis activity, including ACTH, TSH, and GH.
To expose potential functional deficits, the effect of exercise challenge on these hormones was measured. The
study also examined the interrelationship among these
hormones, and their relation to PTSD and depression.
We hypothesized that cortisol and ACTH levels would
be significantly lower among the most exposed group, and
that there would be a negative correlation between cortisol
level and PTSD symptom severity. In regard to the other
stress hormones investigated, this study was exploratory,
not hypothesis-driven. These additional hormones were
investigated because they are components of HPA-Axis
functioning, which has been shown to be altered in PTSD.
Methods
Participants
Eighth-grade students from two representative
schools, one in Spitak, a city at the epicenter, and one
in Yerevan at the periphery of the earthquake zone, were
recruited from their respective classrooms. This age group
was selected because these adolescents were (1) old
enough to have experienced and remember the earthquake,
(2) were capable of reliably responding to the study instruments, and (3) would be available for follow-up studies before graduating from public school. All of the adolescents
from Spitak were considered to have had severe exposure
to trauma, whereas those from Yerevan were classified to
have had low exposure to earthquake-related trauma. The
students from both groups were of the same ethnic and
religious background, and had resided in their respective
cities during and since the earthquake. None of these adolescents were taking medications at the time of the study.
All of the recruited 8th-grade students, except two from
Yerevan, participated in the study. After having the study
procedures explained, adolescents gave their assent, and
one parent or guardian of each adolescent signed an informed consent form.
Demographic characteristics were: Spitak (N = 33),
17 boys, 16 girls (mean age = 14, SD = 0.5; mean
height = 64 in., SD = 3.4 in.; mean weight = 117 lbs.,
SD = 18 lbs.); Yerevan (N = 31), 15 boys, 16 girls (mean
age = 14, SD = 0.3; mean height = 63 in., SD = 2.8 in.;
mean weight = 110 lbs., SD = 19 lbs.). None of these
variables was significantly different between the two
groups.
Measures
PTSD symptoms were rated using the self-report
Child Posttraumatic Stress Disorder Reaction Index
(CPTSD-RI), a widely used 20-item self-report inventory in which symptom frequency is rated using a 0–4
Likert frequency scale. Prior comparisons of CPTSD-RI
scores with a diagnosis of PTSD in clinical populations
have suggested the following guidelines: 0–11 = doubtful; 12–24 = mild; 25–39 = moderate; 40–59 = severe;
60–80 = very severe (Nader, Pynoos, Fairbanks, &
Frederick, 1990). Previous findings have indicated that
a score of 40 or above is highly associated with PTSD
diagnosis (Pynoos et al., 1993). Depressive symptoms
were rated using the Depression Self-Rating Scale (DSRS;
Asarnow & Carlson, 1985), a 24-item self-report instrument with item frequency rated 0 = never; 1 = sometimes;
2 = most of the time. A score of 17 or above is highly associated with a diagnosis of major depression, dysthymic
disorder, or adjustment disorder with depressed mood.
Translation procedures and psychometric properties for
both of these instruments as used in this population have
been previously described (Pynoos et al., 1993).
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321
used to assess interrelationships among the clinical and
biological variables.
Procedure
Participants were clinically evaluated on the day before drawing blood. After overnight fasting, 9 a.m. blood
was drawn. Subsequently, participants jogged for 15 min.
and then ran vigorously for 5 min. according to guidelines for evaluating GH response to exercise challenge
(Underwood & Van Wyk, 1992). A second needle stick
was performed to draw a second blood 20 min after exercise. Tubes were placed on ice, centrifuged within 30 min,
and shipped on dry ice for analysis.
Results
Table 1 shows the mean pre- and postexercise values
for neurohormonal variables for subjects in Spitak and
Yerevan.
Mean CPTSD-RI score was significantly higher in
Spitak (35.2, SD = 13.6), with scores falling in the upper moderate range, and scores in Yerevan (25.7, SD =
11.1) falling in the lower moderate range, t(61) = 3.1,
p < .01. Mean DSRS score did not differ significantly between groups: Spitak = 15.5, SD = 6.2; Yerevan = 13.2,
SD = 6.0; t(62) = 1.5, ns, with both groups falling a few
points below the clinical cutoff for depression. Preexercise cortisol levels were not significantly different between
the groups (Z = .58, N = 64, ns). Preexercise ACTH
level was significantly lower in Spitak (Z = 4.56, N =
64, p < .001), with the mean slightly below the normal
limit. Preexercise TSH level was significantly higher in
Spitak (Z = 2.90, N = 64, p < .01), though both groups
were within normal limits. There was a trend for preexercise GH level to be higher in Spitak compared to Yerevan
(Z = 1.85, N = 64, p = .06). Both preexercise means
fell in the normal range.
For all subjects combined, there was a significant preto postexercise increase in, cortisol (Z = −3.19, N = 64,
p < .01), TSH (Z = −3.54, N = 63, p < .001), and GH
(Z = −5.47, N = 64, p < .001), but not for ACTH (Z =
−1.22, N = 62, ns). Comparison of the change in pre- to
postexercise hormone levels between Spitak and Yerevan
revealed that there were no significant differences for all
hormones studied.
For the combined groups, CPTSD-RI score was positively correlated with DSRS score, r (63) = .56, p < .01,
and negatively correlated with baseline cortisol, r (63) =
−.33, p < .01. Baseline cortisol level was negatively correlated with PTSD Category C, r (63) = −.27, p < .05,
and Category D scores, r (63) = −.30, p < .05, and
marginally missed significance with category B scores,
r (63) = −.24, p = .06. DSRS score was negatively
Assays
EDTA plasma ACTH was measured by immunoradiometric assay (IRMA) for intact ACTH (Nichols Institute Diagnostics). The method has a limit of detection of
1 pg/ml and a normal range (7–10 a.m.) of 7–52 pg/ml.
The within- and between-assay coefficients of variation
are 3.0% at 35 pg/ml and 7.8% at 36 pg/ml, respectively.
Serum cortisol levels were measured using solid-phase
IRMA based on monoclonal and polyclonal antibodies
(Diagnostic Products Corp., Los Angeles, CA). Serum
TSH levels were measured using solid-phase IRMA based
on monoclonal and polyclonal antibodies (Diagnostic
Products Corp., Los Angeles, CA). Serum GH was measured by using IRMA for human GH (Tandem-R,
Hybritech). This method has a limit of detection of
0.2 ng/ml. The within- and between-assay coefficients of
variation are 3.8% at 5.1 ng/ml and 5.2% at 7.8 ng/ml,
respectively.
Statistical Analysis
Student’s t-tests were used to compare groups with
regard to demographic and clinical variables. Because of
the presence of outliers within some of the hormone categories, Mann–Whitney Z tests were performed to compare the groups in regard to hormone levels. Wilcoxon
Signed Ranks Tests were used to compare pre- to postexercise change in hormone levels. Spearman correlation was
Table 1. Pre- and Postexercise Neurohormonal Measurements Among Adolescents 61/2 Years After the Earthquake in Armenia
Spitak (N = 33)
Pre
Normal range
Growth Hormone (0–10 ng/ml)
TSH (0.3–5 µIU/ml)
ACTH (9–52 pg/ml)
Cortisol (5–25 µg/dl)
M
SD
3.1 4.5
2.1 0.7
8.6 15.0
13.8 5.4
Median range
1.3–18.4
2.0–3.2
4.0–73
12.1–24.5
Yerevan (N = 31)
Post
M
SD
6.8 5.6
2.2 0.8
7.5 11.6
16.5 6.0
Median range
6.6–26.5
2.1–3.5
4.0–53
15.3–26
Pre
M
SD
2.4 3.9
1.6 0.5
18.8 11.8
13.4 3.6
Median range
0.5–14.2
1.5–2.4
15.5–41
13.2–17.5
Post
M
SD
6.1 3.9
1.7 0.5
18.7 11.1
15.4 5.7
Median range
4.9–13.9
1.7–2.1
19.0–60.0
14.5–21.3
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correlated with baseline cortisol, r (64) = −.40, p < .001,
and positively with baseline TSH, r (64) = .28, p < .05.
Baseline cortisol and ACTH were positively correlated,
r (64) = .37, p < .01.
There were no significant effects of sex, and no sex
by city interactions, for any of the clinical or hormone variables, including change in hormone levels from
pre- to postexercise.
Discussion
The finding of a negative correlation of basal cortisol
among adolescents with PTSD symptoms supports one
of our hypotheses, and extends our previous finding of
lower baseline salivary cortisol levels among more symptomatic Armenian adolescents at 5-years postearthquake
(Goenjian et al., 1996). The present finding is also similar
to ones reported among adults (Baker et al., 1999; Yehuda
et al., 1995), and lends support to the hypothesis that individuals with PTSD have enhanced negative feedback inhibition resulting in lower cortisol levels (Yehuda, 2001).
Despite the negative correlation, there was no significant
difference in mean basal cortisol level between the two
differentially exposed groups. This finding did not confirm another of our hypotheses. However, the finding of
a negative correlation with no group difference is similar
to a finding reported by Baker et al. (1999) among veterans. Yehuda et al. (1995) reported lower urinary cortisol
excretion among Holocaust survivors with chronic PTSD
compared to survivors without PTSD, and suggested that
exposure to trauma per se may not be associated with lower
cortisol levels. The fact that other studies have found group
differences may be attributable to the variability across
studies in severity and chronicity of PTSD symptoms, and
severity of comorbid depression between groups.
The equal positive cortisol response to exercise challenge between groups suggests that adrenal function may
not be compromised among this group of adolescents with
higher levels of chronic PTSD symptoms. However, it remains possible that a group difference in basal cortisol
and cortisol response to exercise may have emerged if
the mean CPTSD-RI scores between the groups had been
greater.
The present findings with regard to correlations
between baseline cortisol and PTSD symptom category
scores are consonant with the Yehuda et al. (1995) finding among adults of a negative correlation of cortisol level
with C category symptoms. However, this study also found
a similar negative correlation with D category symptoms,
and a trend in this regard for B category symptoms. Baker
et al. (1999) reported a similar correlation with regard to
Categories B and D, and a trend for Category C. The variations in correlations of PTSD symptom category scores
with cortisol level may reflect the phasic course of PTSD
symptoms, and differences between study populations in
regard to type of trauma and time since trauma.
To our knowledge, this is the first report of ACTH
levels and ACTH response to exercise challenge among
adolescents after a disaster. The significantly lower basal
ACTH levels among adolescents in the most traumatized
group is consistent with the findings of De Bellis et al.
(1994) among sexually abused girls. However, this finding needs replication with a larger sample, along with
concomitant CRF and cortisol measurement. Findings of
no difference in cortisol levels between subjects and controls in the De Bellis et al.’s study, and no difference between differentially exposed groups in the present study,
against a background of low ACTH, is consistent with
the proposed hyperresponsivity of the pituitary to cortisol by increased glucocorticoid receptor number or responsiveness (Yehuda, 2001), accompanied by adrenal
hyperresponsivity.
Unlike the attenuated response of ACTH to CRH
challenge among sexually abused girls (DeBellis et al.,
1994), this did not demonstrate any ACTH response to exercise challenge among either the adolescents in Yerevan,
or among the highly exposed adolescents in Spitak. However, exercise may not have been an adequate challenge to
expose this phenomenon.
The present finding of significantly higher basal TSH
levels among the more highly exposed group is discordant
with findings among veterans with chronic PTSD (Mason
et al., 1994; Wang & Mason, 1999) who showed no difference from controls. However, in both the present and
these prior studies, TSH levels were well within the normal
clinical range. The higher TSH levels in Spitak may reflect
an age-related trauma sensitive vulnerability to alteration
in pituitary activity, or may be associated with comorbid
depression, as suggested by the significant positive correlation of TSH with depression, and not PTSD symptoms,
in this study. This latter finding compliments the finding of elevated nocturnal TSH secretion among depressed
adolescents (Kutcher, Malkin, & Silverberg, 1991) and elevated serum TSH levels among patients with endogenous
depression (Kirkegaard, Korner, & Faber, 1990). Longitudinal assessments of T3 and T4 levels along with TSH
would help to determine whether the source of an elevated
TSH is primary or secondary in origin.
The finding that both groups had normal GH levels
extends prior findings among traumatized adults (Yatham
et al., 1996). The normal levels among adolescents from
Spitak, coupled with their response to exercise challenge
in the absence of significant differences in height and
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HPA Activity in Traumatized Adolescents
weight between the groups, suggests that this aspect of
their pituitary function is intact.
As reported among normal adults (Bosco et al.,
1996), this study, combining all participants, demonstrated
the effect of exercise in increasing GH, TSH, and cortisol
among adolescents. The study indicates that this methodology can be applied in the field, and may be useful in
the investigation of neurohormonal function among traumatized individuals. The study demonstrates the advantage of child trauma experts working collaboratively with
pediatric endocrinologists.
References
Asarnow, J. R., & Carlson, G. A. (1985). Depression Self-Rating Scale:
Utility with child psychiatric inpatients. Journal of Consulting and
Clinical Psychology, 53, 491–499.
Baker, D. G., West, S. A., Nicholson, W. E., Ekhator, N. N., Kasckow,
J. W., Hill, K. K., et al. (1999). Serial CSF corticotropin-releasing
hormone levels and adrenocortical activity in combat veterans with
posttraumatic stress disorder. American Journal of Psychiatry, 156,
585–588.
Boscarino, J. A. (1996). PTSD, exposure to combat, and lower plasma
cortisol among Vietnam Veterans: Findings and clinical implications. Journal of Consulting and Clinical Psychology, 64, 191–201.
Bosco, C., Tihanyl, J., Rivalta, L., Parlato, G., Tranquilli, C., Pulvirenti,
G., et al. (1996). Hormonal responses in strenuous jumping effort.
Japanese Journal of Physiology, 46, 93–98.
Bauer, M., Priebe, S., Kurten, I., Graf, K. J., & Baumgartner A.
(1994). Psychological and endocrine abnormalities in refugees
from East Germany: Part 1. Prolonged stress, psychopathology, and
hypothalamic–pituitary thyroid axis activity. Psychiatry Research,
51, 61–73.
Carrion, V. G., Weems, C. F., Ray, R. D., Glaser, B., Hessl, D., & Reiss,
A. L. (2002). Diurnal salivary cortisol in pediatric posttraumatic
stress disorder. Biological Psychiatry, 51, 575–582.
De Bellis, M. D., Baum, A. S., Birmaher, B., Keshavan, M. S., Eccard,
C. H., Boring, A. M., et al. (1999). Developmental traumatology.
Part I: Biological stress systems. Biological Psychiatry, 45, 1235–
1236.
DeBellis, M. D., Chrousos, G. P., Dorn, L. D., Burke, L., Helmeres, K.,
Kling, M.A., et al. (1994). Hypothalamic–pituitary–adrenal axis
dysregulation in sexually abused girls. Journal of Clinical Endocronology and Metabolism, 78, 249–255.
Goenjian, A. K., Yehuda, R., Pynoos, R. S., Steinberg, A. M., Tashjian,
M., Yang, R. K., et al. (1996). Basal cortisol and dexamethasone
suppression of cortisol and MHPG among adolescents after the
1988 earthquake in Armenia. American Journal of Psychiatry, l53,
929–934.
Kirkegaard, C., Korner, A., & Faber, J. (1990). Increased production of
thyroxine and inappropriately elevated serum thyrotropin inx levels
in endogenous depression. Biological Psychiatry, 27, 472–476.
323
Kosten, R. T., Wahby, V., Giller, E. L., & Mason, J. (1990). The dexamethasone suppression test and thyrotropin-releasing hormone stimulation test in posttraumatic stress disorder. Biological Psychiatry,
28, 657–664.
Kutcher, S., Malkin, D., & Silverberg, J. (1991). Nocturnal cortisol, thyroid stimulating hormone, and growth hormone secretory profiles in
depressed adolescents. Journal of the American Academy of Child
and Adolescent Psyciatry, 27, 751–754.
Lemieux, A. M., & Coe, C. L. (1995). Abuse-related posttraumatic stress
disorder: Evidence for chronic neuroendocrine activation in women.
Psychosomatic Medicine, 57, 105–115.
Mason, J. W., Giller, E. L., Kosten, T. R., Ostroff, R. B., & Podd, L.
(1986). Urinary free-cortisol levels in posttraumatic stress disorder
patients. Journal of Nervous and Mental Disease, 174, 145–159.
Mason, J., Southwick, S., Yehuda, R., Wang, S., Riney, S., Bremner,
D., et al. (1994). Elevation of serum free triiodothyronine, total
triiodothyronine, thyroxine-binding globulin and total thyroxine
levels in combat-related posttraumatic stress disorder. Archives of
General Psychiatry, 51, 629–641.
Nader, K., Pynoos, R. S., Fairbanks, L., & Frederick, C. (1990). Children’s PTSD reactions one year after a sniper attack at their school.
American Journal of Psychiatry, 147, 1526–1530.
Pitman, R. K., & Orr, S. (1990). Twenty-four hour urinary cortisol and
cathecolamine excretion in combat-related PTSD. Biological Psychiatry, 27, 245–247.
Pynoos, R. S., Goenjian, A. K., Karakashian, M., Tashjian, M.,
Manjikian, R., Manoukian, G., et al. (1993). Posttraumatic stress
reactions in children after the 1988 Armenian earthquake. British
Journal of Psychiatry, 169, 239–247.
Smith, M. A., Davidson, J., Ritchie, J. C., Kudler, H., Lipper, S.,
Chappell, P., et al. (1989). The corticotropin-releasing hormone
test in patients with posttraumatic stress disorder. Biological Psychiatry, 26, 349–355.
Underwood, L. E., & Van Wyck, J. J. (1992). William’s textbook of
endocrinology. In J. D. Wilson & D.W. Foster (Eds.), Normal and
aberrant growth (p. 1120). Philadelphia: WB Saunders.
Wang, S., & Mason, J. (1999). Elevations of serum T3 level and their
association with symptoms in World War II veterans with combatrelated posttraumatic stress disorder: Replication of findings in
Vietnam combat veterans. Psychosomatic Medicine, 61, 131–138.
Weizman, R., Laor, N., Barber, Y., Selman, A., Schujovizky, A., Wolmer,
A., et al. (1994). Impact of the gulf war on the anxiety, cortisol, and
growth hormone levels of Israeli civilians. American Journal of
Psychiatry, 151, 71–75.
Yatham, L. N., Sacamano, J., & Kusumaker, V. (1996). Assessment of
noradrenergic functioning in patients with non-combat related posttraumatic stress disorder: A study with desmethylimipramine and
orthostatic challenges. Psychiatry Research, 63, 1–6.
Yehuda, R. (2001). Biology of posttraumatic stress disorder. Journal of
Clinical Psychiatry, 62(Suppl.), 41–46.
Yehuda, R., Kahana, B., Binder-Brynes, K., Southwick, S. M.,
Zemelman, S., Mason, J. W., et al. (1995). Low urinary cortisol
excretion in Holocaust survivors with posttraumatic stress disorder.
American Journal of Psychiatry, 152, 982–986.
Yehuda, R., Southwick, S. M., Nussbaum, G., Wahby, V., Giller, E. L.,
& Mason, J. W. (1990). Low urinary cortisol excretion in patients
with posttraumatic stress disorder. Journal of Nervous and Mental
Disease, 178, 366–369.