Citation
Klaassens, E. R. (2010, November 30). Bouncing back : trauma and the HPA-axis in healthy adults. Retrieved from https://hdl.handle.net/1887/16190
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Effects of childhood trauma on HPA-axis reactivity in women free of lifetime
psychopathology
Progress in Neuro-Psychopharmacology & Biological Psychiatry 2009;33:889-894
Ellen R. Klaassens Martijn S. van Noorden Erik J. Giltay Johannes van Pelt Tineke van Veen
2
Abstract
Background
Exposure to childhood trauma may induce persistent changes in hypothalamic- pituitary-adrenal (HPA)-axis functioning even in the absence of current psychopathology. Because previous studies did not systematically exclude subjects with lifetime psychiatric morbidity, prevalent psychopathology may have confounded the association. In this study we investigated whether women exposed to childhood trauma, but without a history of psychiatric disorders, show alterations in HPA-axis functioning.
Method
We included 10 women exposed to significant childhood trauma and 12 non- exposed women. All women were between 29 and 64 years old, mentally and physically healthy, and without current or lifetime psychopathology. HPA-axis functioning was assessed as (1) basal activity with salivary cortisol patterns over 8 time points on two consecutive sampling days and (2) plasma cortisol and adrenocorticotropic hormone (ACTH) reactivity over 7 time points after the combined dexamethasone/corticotropin-releasing hormone (Dex/CRH) challenge test.
Results
Basal salivary cortisol output did not differ between trauma-exposed compared to non-exposed women. Significantly blunted plasma cortisol and ACTH responses in response to Dex/CRH administration were found in the trauma-exposed compared to the non-exposed women (F(1,20)=5.08, p=.04 and F(1,20)=5.23, p=.03 respectively). Adjusting for age, body mass index (BMI), oral contraceptive use, and menopausal status, somewhat weakened the associations for cortisol as well as ACTH (F(1,16)=3.30, p=.09) and F(1,16)=2.17, p=.16 respectively), but for cortisol absolute differences in point estimates were largely unaffected.
Conclusion
Although basal cortisol patterns were similar in the two groups, exposure to childhood trauma seemed to be related to a blunted HPA-axis reactivity in women who were free of current or lifetime psychopathology.
2 Introduction
Early traumatization is associated with alterations in hypothalamic-pituitary- adrenal (HPA)-axis functioning in women suffering from stress related disorders such as posttraumatic stress disorder (PTSD) or major depressive disorder (MDD) (for review see 1). Alterations in HPA-axis functioning have not only been found in early traumatized women with current PTSD or MDD, but more recently also in early traumatized subjects without current PTSD or MDD 2-8. Compared to healthy controls, Heim et al 2 found elevated plasma adrenocorticotropic hormone (ACTH) levels in response to a psychosocial stress challenge (Trier Social Stress Test, TSST) in women who were sexually abused during childhood but who were free of current MDD. Furthermore, elevated cortisol levels in response to a dexamethasone/corticotropin- releasing hormone (Dex/CRH) test in healthy subjects with early parental loss were reported 8. In contrast, both blunted cortisol 6;7 and a blunted ACTH response 6 to the TSST were observed in early traumatized subjects currently not fulfilling DSM-IV criteria for PTSD or MDD. Thus, trauma exposure during childhood was associated with measures of HPA-axis activity, even in the absence of psychopathology. However, none of these previous studies have systematically excluded subjects with a history of psychiatric disorders, and only two studies have taken into account the history of psychiatric disorders in their statistical analyses 6;8. Therefore, in most studies subjects may have been included who do have a history of psychopathology and thus an increased vulnerability for psychiatric disorders. Patients who recovered from prior psychiatric disorders may demonstrate subtle changes, due to so-called
‘scarring’ of HPA-axis functioning 9-12. Therefore, the hypothesis that exposure to childhood trauma leads to altered HPA-axis functioning in adulthood needs further research.
In this study, we aimed to find an answer to the following question: do adults exposed to childhood trauma, but without lifetime psychiatric disorders show alterations in HPA-axis functioning? Considering the existing evidence in preclinical and clinical studies, we hypothesized that childhood trauma per se is associated with a change in cortisol release in response to a neuroendocrine stressor. HPA-axis functioning was measured in two ways: (1) basal HPA- axis activity was assessed with saliva cortisol, collected on two consecutive days, and (2) HPA-axis reactivity was assessed using the combined Dex/CRH challenge test in 22 female subjects.
Method
Subjects
Mentally healthy women were recruited through advertisements asking for people free of lifetime psychopathology to respond. For the exposed group, subjects with a history of exposure to childhood trauma, and for the non- exposed group, an absence of such history was mandatory. Forty-eight people responded of whom 22 were included in our study. All 22 subjects, aged 29 to 64, were without current or lifetime DSM-IV axis I disorder. They were all physically healthy, and none were pregnant or lactating. Exclusion criteria were endocrine diseases and other chronic medical conditions.
Use of psychotropic or recreational drugs and substance abuse, as well as working night shifts, were additional exclusion criteria. Furthermore, the use of medication thought to affect HPA-axis functioning, e.g., corticosteroids, thyroid hormone, estrogens or progesterones, and herbal medication (e.g.
Valerian, St. Johns Wort), was not allowed, but oral contraceptives were.
Ten women with a history of significant exposure to childhood trauma were included in the trauma group (TR) (Figure 1). Significant exposure to childhood trauma was defined as a score of at least moderate to severe on one or more of the five subscales of the Dutch version of the Childhood Trauma Questionnaire-Short Form (CTQ-SF) 13. For the control group, 12 healthy women without exposure to childhood trauma were included (scores of none/minimal on the five subscales of the CTQ-SF). A complete physical examination and routine laboratory evaluation was performed. Written informed consent was obtained from all participants after a complete written and verbal description of the study. The study was approved by the Medical Ethics Committee of the Leiden University Medical Center (LUMC), the Netherlands. All participants received a financial compensation as well as a reimbursement of travel expenses.
Procedure
Data collection for each participant took place during one day at the LUMC and two consecutive non-working days at home. On the morning of the test day, a routine medical examination, including the measurement of height and weight to calculate body mass index (BMI), was performed and demographic variables, childhood trauma exposure and psychological variables were assessed.
2
Instruments
Exposure to childhood trauma was assessed with the self-report CTQ-SF 14 as well as with a structured trauma interview (Early Trauma Inventory – ETI) 15. The CTQ-SF is a 25-item self-report questionnaire that provides brief, reliable and valid screening for histories of abuse and neglect (test-retest reliability was 0.88, internal consistency ranged from α=0.80 to α=0.97 and criterion validity was found to be acceptable). The CTQ-SF yields five subscales: (1) emotional abuse, (2) emotional neglect, (3) physical abuse, (4) physical neglect and (5) sexual abuse. Cut-off scores of moderate to severe on one or more subscales were used as an inclusion criterion for the trauma group 13. We used the Dutch translation of the CTQ-SF 16.
The ETI is a 56-item structured interview designed to assess traumatic experiences before the age of 18, covering 4 domains: (1) physical abuse; (2) emotional abuse; (3) sexual abuse, and (4) general trauma. An overall ETI trauma score was calculated by summing the times a question was answered Figure 1. Flow chart of screening, exclusion, and inclusion of trauma-exposed subjects.
Excluded:
- men (n=6) - too old (n=1)
- working in nightshifts (n=3)
- current psychological complaints (n=4) - thyroid disease (n=5)
- other somatic disease (n=5)
- no or too limited traumatic experience (n=1) - unable to get in contact with (n=2)
Eligible for inclusion n=21
Withdrawn n=10
Included in analyses n=10
Incomplete Dex/CRH data and missing salivary cortisol data
n=1 Inclusion
n=11 Recruitment by
advertisement N=48
Figure 1. Flow chart of screening, exclusion, and inclusion of trauma-exposed subjects.
with ‘yes’. High test-retest reliability (r=0.91), internal consistency (α=0.95), and external validity (r=0.63) have been reported (Bremner et al., 2000). We used the Dutch translation of the ETI 17.
Current and lifetime Axis-I psychiatric disorders, according to the DSM-IV criteria, were assessed with the Mini International Neuropsychiatric Interview (M.I.N.I.) Plus 5.0.0.-R. The overall reliability of the M.I.N.I. was good (interrater reliability kappa values ranging from 0.79 for current mania to 1.00 for major depression) and test-retest kappa values ranging from 0.52 for lifetime simple phobia to 1.00 for bulimia. Concordance with the Structured Clinical Interview for DSM-III-R Patients (SCID-P) demonstrated good validity 18. In this study, the Dutch translation was used 19;20.
Current psychological distress was measured with the Brief Symptom Inventory (BSI), a 53-item self-report questionnaire 21. The total mean BSI-score (TOT) generates an overall measure of psychopathological symptom severity. A cut-off score of 0.70 on the TOT is used as an indicator of psychopathology. In this study, the Dutch translation of the BSI was used. Internal consistency for the total BSI is very satisfactory (α=0.96), while construct validity is sufficient 22.
Saliva sampling protocol
Subjects were instructed to collect saliva samples on two consecutive non- working days 23. Participants were free to wake up either spontaneously or with the use of an alarm clock, but no later than 8:00h. Saliva was collected with Salivette collection devices (Sarstedt, Neumbrecht, Germany) immediately upon awakening (T1) and 30, 45 and 60 min thereafter, to measure the cortisol awakening response (CAR). For the diurnal cortisol response, additional samples were taken at 11:00h, 15:00h, 19:00h and 23:00h. Participants were instructed to take the first sample while still in bed, and to refrain from eating, drinking, smoking and brushing their teeth during the first hour after awakening as well as 30 min prior to collection of the additional samples. Samples were stored at 7°C and returned to the clinic within one week after collection. At the laboratory, saliva samples were stored at -20°C. Salivary cortisol levels were determined with a competitive electrochemiluminescence immunoassay (ECLIA), using a Modular Analytics E170 immunoassay analyzer (Roche Diagnostics, Mannheim, Germany). The sample volume was 20 μL, with a detection limit of 0.5 nmol/l and the intra- and inter-assay variability coefficients were less than 10%.
Dex/CRH protocol
Subjects were pre-treated with 1.5 mg dexamethasone at 23:00h on the evening before the test. The next day, to check for ingestion of the dexamethasone,
2
saliva was collected at awakening using a Salivette (Sarstedt, Neumbrecht, Germany). At 13:00h, participants were instructed to rest semi-supine in a quiet room. An intravenous cannula was inserted at 13:45h and kept open with 50 ml/h of 0.9% NaCl. Baseline samples for plasma cortisol and ACTH were taken at 15:00h. At 15:02h, 100 μg of human CRH (Ferring BV, Hoofddorp, the Netherlands) was administered in the cannula over 30 seconds. Blood samples were drawn every 15 min from 15:30h until 16:45h. Venous blood was collected in EDTA tubes, kept on ice and directly transported to the laboratory. All plasma samples were stored at -20 0C until further analysis.
Cortisol levels were assessed with the cortisol assay described above. The determination of ACTH was performed with a solid-phase, two-site sequential chemiluminescence immunometric assay (Immulite 2500, DPC, Los Angeles, USA), with a detection limit of 0.5 ng/l. The intra- and inter assay variability coefficients were less than 10%. All samples were assayed after thawing at 4
oC. Salivary dexamethasone concentrations were measured by a home-made radioimmunoassay 24.
Statistical analyses
We used independent samples t-tests and χ2 statistics for comparisons between the two groups for demographic variables (i.e., age, education, marital status, smoking status, alcohol use, BMI, menopausal status, and use of oral contraceptives), psychological variables (i.e., BSI) and trauma scores (i.e., ETI and CTQ-SF). Using Spearman’s correlation coefficients, CTQ-SF and the ETI sum scores were strongly interrelated (r=.81, p<.001). Because of these comparable results on the interview and self-report questionnaire, the CTQ-SF cut-off scores were used to classify subjects into either the trauma-exposed and non-exposed groups.
The mean salivary cortisol concentrations for each time point over the two sampling days were calculated and used in the statistical analyses. Per sampling point, physiologically unlikely high values (i.e., >50 nmol/l) were excluded from further analyses (0.9% of the data, i.e., 3 out of 320 samples) 25 and were substituted with the values of the same time point from the other day. As a measure of total cortisol concentrations in the first hour after awakening, the area under the curve with respect to ground (AUCgCAR) was calculated, using the trapezoidal method 26. As a measure of the total cortisol secreted over the rest of the day, the AUCg diurnal was calculated.
For plasma cortisol as well as ACTH levels obtained with the Dex/CRH test, the AUCg’s were again used as the primary outcome measure. Because the AUCg’s of plasma cortisol and ACTH had positively skewed distributions, they
were subsequently logarithmically transformed. We used analysis of variance (ANOVA) to analyze group differences in salivary and plasma cortisol and plasma ACTH levels. With General Linear Model (GLM) for repeated measures, we examined whether cortisol and ACTH levels within our two groups showed the expected changes over time (effect of ‘time’), with log-transformed cortisol and ACTH levels as the within-subject factors (i.e., ‘time’), and ‘group’ the between-subject factor. In case of violation of sphericity, we used Greenhouse- Geisser corrections. We also examined whether the curve patterns (effect of
‘time*group’) and total output of cortisol and ACTH (effect of ‘group’) differed between the two groups. Age and oral contraceptive use have been shown to affect cortisol secretion 27. Although inconsistent, previous studies have shown that HPA-axis functioning is also disturbed in obesity, with elevated cortisol secretion in obese adults (for review see 28). In multivariate models, we therefore adjusted for the potential confounding effect of age, oral contraceptive use and BMI. All analyses were carried out using SPSS 14.0. All tests were two-tailed, p-values <.05 were considered statistically significant.
Results
Demographic, psychological and clinical data for the two groups are shown in Table 1. There were no differences between the exposed and the non- exposed women for age, marital status, education, menopausal status, oral contraceptive use, or BMI. Groups differed on current psychological distress, but scores remained below the cut-off (TOT =0.70) for psychopathology and are therefore of limited clinical relevance. By definition, women with a history of childhood trauma had higher scores on the CTQ-SF and ETI (Table 1). Based on the CTQ-SF cut-off scores for moderate to severe exposure on either one of the five subscales, we included 10 women in our trauma group. Sexual abuse was reported by eight women, physical abuse and emotional abuse were both reported by five women, whereas physical neglect and emotional neglect were both reported by six women. Twelve non-exposed women, who all scored none or minimal on the five CTQ-SF subscales, were included in our control group.
Neuroendocrine results
There was only one smoker in our sample (Table 1). We analyzed our data with and without this subject. Exclusion of this subject weakened the significance level somewhat, but the absolute mean difference between the two groups was not importantly affected (data not shown).
2
Basal saliva cortisol levels
Analysis with univariate ANOVA showed no differences on any of the salivary cortisol outcome measures, indicating that the trauma group and the control group did not differ in salivary cortisol output (Table 2). Likewise, the GLM repeated measures analysis showed no difference between the trauma and control group, neither for the pattern of the cortisol curves (i.e., time*group effect; F(2.2, 39.3)=0.26, p=.79), nor for the total cortisol output (i.e., group effect; F(1,18)=0.01, p=.94; Figure 2). Adjusting for the potential confounders (BMI, age and oral contraceptive use) did not alter the results, nor did additional adjustment for menopausal status. None of the potential confounders had a significant effect; all p-values >.20.
Table 1. Demographic, psychological and trauma characteristics of mentally healthy women with a history of exposure to childhood trauma and non-trauma-exposed healthy controls
BSI=Brief Symptom Inventory, M.I.N.I.= Mini International Neuropsychiatric Interview, CTQ- SF= Childhood Trauma Questionnaire Short Form, ETI=Early Trauma Inventory, Mdn=median.
Childhood trauma (n=10)
Non-trauma controls
(n=12)
Test P-value
Age, mean (SD) 47.8 (12.1) 47.4 (11.9 t(20.0)=.08 .94
Age, range 29-64 29-63
Marital status, n (%)
• living together 10 (100) 10 (83) 2(1) = 1.83 .18
Years of education, Mdn 12 15 t(20)=1.920 .07
Body Mass Index, mean (SD) 24.5 23.8 t(10.37)=1.03 .33 BSI total score, mean (SD) 0.22 0.08 t(10.58)=2.82 .02
Smokers, n (%) 1 (10) 0 (0) 2(1) = 1.26 .26
Oral contraceptives, n (%) 3 (30) 1 (8) 2(1) = 1.73 .19 MINI diagnosis:
• current none none
• past none none
CTQ-SF, mean (SD):
• total score 64.5 (15.7) 29.0 (2.6) t(7.08)=7.76 <.001 • sexual abuse 16.7 (7.3) 5.4 (0.5) t(9.13)=5.19 .001 • emotional abuse 12.6 (4.6) 5.4 (0.5) t(9.18)=4.86 .001 • emotional neglect 14.9 (5.3) 7.9 (2.5) t(20) =4.04 .001 • physical abuse 9.2 (4.2) 5.2 (0.4) t(9.13)=3.06 .010 • physical neglect 10.3 (4.5) 5.1 (0.3) t(9.06)=3.66 .005 ETI total score, mean (SD) 331 (222.0) 3.0 (5.0) t(9.01)=4.97 .001
Chapter 2
Plasma cortisol and ACTH during the Dex/CRH test
The analysis of dexamethasone in saliva confirmed that all subjects had ingested the dexamethasone according to the protocol. We found a significant difference between the two groups for AUCg of cortisol with a smaller cortisol response to CRH in the traumatized subjects as compared to controls (F(1,20)=5.30, p=.03). Similarly, we found a significant effect for AUCg of ACTH (F(1,20)=4.74, p=.04), with the trauma-exposed women showing a smaller ACTH response to CRH (Table 2). Adjusting for BMI, age and oral contraceptive use removed statistical significant differences for cortisol (F(1,17)=3.40, p=.08) and ACTH (F(1,17)=1.78, p=.20; Table 2). However, for cortisol, absolute differences in point estimates were unaffected by adjustment for these covariates (data not shown).
GLM repeated measures analysis showed a significant time effect for plasma cortisol and ACTH after CRH infusion (F(2.0, 40.5)=27.30, p<.001 and F(2.8, 56.3)=14.01, p<.001, respectively). Figure 3 shows the changes over time for plasma cortisol and ACTH. We observed a significant group effect in cortisol and ACTH output, (F(1,20)=5.08, p=.04 and F(1,20)= 5.23, p=.03, respectively), with lower cortisol and ACTH levels in the trauma-exposed group. Baseline (15h) cortisol and ACTH did not differ between the groups, F(1,20)=0.29, p=.60 and
Time(h)
Salivary cortisol (nmol/l)
0 5 10 15 20 25
Non-trauma controls (n=11) Childhood trauma (n=9)
Awakening 30
min 45 11:00 15:00 19:00 22:00
min 60 min
Figure 2. Saliva cortisol response over the day in 9 mentally healthy women with a history of exposure to childhood trauma and 11 non-trauma-exposed healthy controls.
Error bars represent standard errors.
Figure 2. Saliva cortisol response over the day in 9 mentally healthy women with a history of exposure to childhood trauma and 11 non-trauma-exposed healthy controls. Error bars represent standard errors.
2
F(1,20)=0.37, p=.55 respectively. No significant group*time interactions were found, neither for cortisol (F(2.0, 40.5)=1.99, p=.15) nor for ACTH (F(2.8, 56.3)=2.16, p=.11). Adjustment for BMI, age and oral contraceptive use, none of which had a significant effect (all p-values >.20), removed statistical significance (F(1,17)=3.50, p=.08 and F(1,17)=2.26, p=.15, respectively). For cortisol, nevertheless, absolute differences in point estimates were unaffected by adjustment for these covariates (data not shown). Additional adjustment for menopausal status did not alter these results (F(1,16)=3.30, p=.09 for cortisol and F(1,16)=2.17, p=.16 for ACTH).
Geometric mean values are shown for the unadjusted data, whereas statistics are calcu- lated on log transformed values for plasma cortisol and ACTH values. Estimated marginal geometric means are adjusted for age, body mass index and oral contraceptives. The 95%
confidence interval is given between brackets. AUCg= Area Under the Curve with respect to ground, CAR=cortisol awakening response, diurnal=diurnal decline
Table 2. Comparison of measures of basal saliva cortisol release and cortisol and ACTH response to the Dex/CRH test between mentally healthy women with a history of exposure to childhood trauma and non-trauma-exposed healthy controls
Childhood trauma (n=9 basal and
n=10 Dex/
CRH test)
Non-trauma controls (n=11 basal and n=12 Dex/CRH test)
Test P-
value
Basal salivary cortisol:
• awakening (t1) (nmol/l)
• Mean 16.5 (10.3-22.7) 17.1 (11.5-22.7) F(1,18)=0.03 .88 • Estimated
Marginal Mean* 17.7 (10.8-24.6) 16.1 (10.0-22.3) F(1,15)=0.11 .74 • AUCgCAR (nmol/l/h)
• Mean 16.2 (11.1-21.4) 16.5 (11.8-21.2) F(1,18)=0.01 .94 • Estimated
Marginal Mean* 17.3 (11.6-23.0) 15.6 (10.5-20.7) F(1,15)=0.21 .65 • AUCgdiurnal curve (nmol/l/h)
• Mean 6.4 (4.1-8.6) 6.1 (4.1-8.2) F(1,18)=0.03 .87 • Estimated
Marginal Mean* 6.8 (3.5-8.1) 5.8 (3.5-8.1) F(1,15)=0.33 .58 Dexamethasone/corticotropin-releasing hormone (Dex/CRH) challenge test:
• AUCgcortisol (nmol/l/h):
• Mean 118 (63-221) 302 (170-535) F(1,20)=5.30 .03 • Estimated
Marginal Mean* 120 (58-248) 297 (15-570) F(1,17)=3.40 .08 • AUCgACTH (ng/l/h):
• Mean 879 (585 -1322) 1462 (1008 -2121) F(1,20)=4.74 .04 • Estimated
Marginal Mean* 887 (564 -1396) 1452 (963 -2191) F(1,17)=1.78 .20
Chapter 2
Figure 3. Plasma cortisol (A) and ACTH (B) responses (on logarithmic scales) to the com- bined dexamethasone/corticotrophin releasing hormone (Dex/CRH) challenge test in mentally healthy women with a history of exposure to childhood trauma and non-trauma-exposed controls. Error bars represent standard errors. Global p-values for the group difference by general linear model for repeated measures were p=.04 (A) and p=.03 (B), respectively.
After adjustment for age, body mass index (BMI) and oral contraceptive use these values were p=.08 (A) and p=.15 (B), respectively.
Time (h)
Plasma ACTH (ng/l)
5 7 10 15 24
Time (h)
Plasma cortisol (nmol/l)
15 50 100 200 400
Childhood trauma (n=10) Non-trauma controls (n=12) 15:00 15:30 15:45 16:00 16:15 16:30 16:45
A
B
23:00
15:00 15:30 15:45 16:00 16:15 16:30 16:45 23:00
Oral 1.5 mg dexamethasone I.v. 100 µgram CRH
Childhood trauma (n=10) Non-trauma controls (n=12)
2 Discussion
This study showed a relationship between early trauma exposure and a blunted plasma cortisol response to Dex/CRH in women without current or lifetime psychopathology. Basal salivary cortisol curves were remarkably similar between the two groups. Our findings are consistent with the hypothesis that cortisol reactivity to Dex/CRH is blunted by trauma exposure early in life. On the reverse, subjects born with a less reactive CRH response of the HPA-axis may be less prone to psychopathology in case of severe trauma and blunted HPA-axis responsivity may be seen as a marker for biological resilience. Alternatively, unmeasured confounders or residual confounding might explain the differences in HPA-axis reactivity between the two groups.
To our knowledge, this is the first study using HPA-axis reactivity to a biological stressor in early exposed individuals free of current and lifetime psychopathology. In contrast, PTSD and MDD in subjects with a history of childhood trauma have been associated with differences in measures of HPA-axis cortisol release in several studies (for review see 1). Most, however, studied patients with current or remitted disorders. Consequently, these studies cannot disentangle the effects on HPA-axis functioning of being a survivor of childhood trauma per se from the effects of suffering from current or previous psychiatric illness (i.e.,‘scarring’ as a result of (prior) psychopathology). Our findings are largely consistent with studies by Meinlschmidt et al 5, Carpenter et al 6 and Elzinga et al 7 who reported blunted cortisol and ACTH responses to a standard psychological stress test (TSST) in the trauma-exposed group relative to the non-exposed controls.
In contrast, compared to non-exposed controls, Heim et al 2 found increased ACTH reactivity to CRH in the TSST in early traumatized women without current psychiatric disorder. No difference, however, was found in cortisol release following the TSST. In addition to HPA-axis reactivity, we also measured basal salivary cortisol patterns in addition to HPA-axis reactivity.
There are several explanations for our findings. First, childhood trauma may permanently alter the set point of HPA-axis reactivity. This may present itself as a blunted cortisol response following a biological stressor.
Second, trauma-exposed women included in this study might still develop a psychiatric disorder later in life, making the differences between our study group and those described in literature only a gradual one. Third, the decreased HPA-axis reactivity shown with the Dex/CRH test may be a symptom of reduced stress-reactivity in general, thus leading to a different vulnerability to stressful events. Our trauma-exposed women without lifetime
psychopathology may be resilient thanks to the blunted cortisol reactivity.
Our study has several limitations, including the small sample size, which urges us to be cautious while interpreting our results. Next, the cross- sectional design precludes causal inferences. Finally, we did not assess traumatic experiences after the age of 18 years. This study also has several strengths. First, we selected a group of trauma-exposed subjects without lifetime and current psychopathology, to exclude the influence of PTSD or MDD on HPA-axis functioning. Second, childhood trauma was assessed with a structured interview and self-report questionnaires. Third, measures of HPA-axis function were assessed both in basal as well as in challenged conditions. Fourth, saliva samples were collected on two consecutive non- working days to reduce day to day variation 23;29;30.
Conclusion
In this preliminary study, a blunted plasma cortisol following the Dex/CRH challenge test was found in women exposed to childhood trauma without current or lifetime psychopathology, according to the DSM-IV. No statistically significant effect on basal salivary cortisol levels was found. Future larger and prospective studies are necessary to confirm our findings.
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