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Salivary cortisol and posttraumatic stress reactions: methodological and applied studies before and after trauma
Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Linköping University, Faculty of Health Sciences.
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The field of psychotraumatology has its roots in ancient history. During the past decades, the surveillance of the psychobiological background of reactions to and consequences of traumatic stress has made great progress and the complexity of the human stress response system stands out. The hypothalamic-pituitary-adrenocortical axis activity, modulated by various neuroimmunological substances, seems to play a major role in the stress response. However, there are still inconsistencies in explanations of relationships between biological and psychological changes following traumatic stress. Moreover, the matter of predictive factors for the development of posttraumatic morbidity is still in a speculative phase.

The aims of the present thesis were to further develop a commercial serum cortisol radioimmunoassay (RIA) for determination of cortisol in saliva and to test its reliability, specificity and sensitivity as a biochemical assay. The saliva sampling procedures and sample storage stability were also to be tested. Further issues were to investigate determinations of salivary cortisol and serum prolactin in relation to selfratings of posttraumatic psychological distress and general psychological health. Possible predictive and concurrent validity of salivary cortisol as a biochemical marker for posttraumatic psychological distress were to be tested.

Cortisol is present in saliva mainly in non-protein form, representing the free, biologically active fraction of the total plasma cortisol concentration. In a first phase of the present thesis, the commercial serum cortisol RIA was modified for determination of cortisol in saliva. The relation between salivary and serum cortisol concentrations was tested. Reference ranges at 8 AM and 10 PM for the salivary cortisol assay were established from 195 healthy subjects. Salivary cortisol concentrations were tested in relation to serum cortisol in estimating adrenocortical function during endocrine dynamic function tests in 37 patients and 13 healthy controls. In testing salivary cortisol as a marker for stress for fieldwork use, a screening study was performed on 66 male rescue workers. Salivary cortisol at 8 AM and 10 PM and serum prolactin were determined and general psychological health and posttraumatic psychological distress were estimated with the self-rating scales General Health Questionnaire, Impact of Event Scale and Posttraumatic Symptom Scale. These scales were used in the second phase of the thesis. Three applied follow-up studies were performed with sampling of salivary cortisol and self-ratings: (a) a study of 31 UN-soldiers five days, two and nine months after a mine accident; (b) a study of 145 UN-soldiers before, at return, and two and six month after a six month mission. (c) a study of 101 UN-soldiers six and twelve months after a six month mission with severe combat exposure.

The results from the present thesis indicate that the modified method of salivary cortisol determination possesses sufficient precision, accuracy, sample storage stability and procedural advantages for laboratory, clinical and field application. Moreover, it possesses moderate predictive information and moderate to high concurrent validity as a biochemical marker for posttraumatic psychological distress.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2002. , 106 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 705
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-25539Local ID: 9986ISBN: 91-7373-139-0 (print)OAI: oai:DiVA.org:liu-25539DiVA: diva2:245869
Public defence
2002-02-15, Berzeliussalen, Universitetssjukhuset, Linköping, 09:30 (Swedish)
Opponent
Supervisors
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2012-10-22Bibliographically approved
List of papers
1. Cortisol in Saliva: Reference Ranges and Relation to Cortisol in Serum
Open this publication in new window or tab >>Cortisol in Saliva: Reference Ranges and Relation to Cortisol in Serum
1995 (English)In: European Journal of Clinical Chemistry and Clinical Biochemistry, ISSN 0939-4974, Vol. 33, 927-932 p.Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to establish morning and evening reference ranges for cortisol in saliva. Another objective was to compare the concentrations of the mainly free cortisol in saliva to those of total cortisol in serum as determined with a commercial radioimmunoassay. The concentrations were determined in matched samples of saliva and serum collected at 8am and 10pm from 197 healthy volunteers. The saliva samples were stable for at least 7 days at room temperature and for 9 months at —20 °C. Reference ranges, the central 95%, were estimated to 3.5—27.0 nmol/1 at 8 am and < 6.0 nmol/1 at 10 pm. The intra-assay coefficient of variation (CV) was below 5% and total CV below 10%. The relation between the cortisol concentrations in serum and saliva was nonlinear with r = 0.86 for serum concentrations < 450 nmol/1 and r = 0.44 for serum concentrations ^ 450 nmol/1. In conclusion, the satisfactory precision of the analysis and the simple non-invasive sampling procedure suggest that saliva may be used for cortisol measurements in situations where blood sampling is difficult to perform.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-80129 (URN)10.1515/cclm.1995.33.12.927 (DOI)
Available from: 2012-08-21 Created: 2012-08-21 Last updated: 2012-08-21Bibliographically approved
2. Salivary cortisol: an alternative to serum cortisol determinations in dynamic function tests
Open this publication in new window or tab >>Salivary cortisol: an alternative to serum cortisol determinations in dynamic function tests
1998 (English)In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, Vol. 36, no 4, 215-222 p.Article in journal (Refereed) Published
Abstract [en]

Salivary cortisol was measured as an alternative to serum cortisol as a marker for adrenocortical function following insulin tolerance test, corticotropin-releasing-hormone stimulation and adreno-corticotrophic hormone stimulation. During insulin tolerance test and corticotropin-releasing-hormone stimulation adreno-corticotrophic hormone was also measured. The tests were performed on healthy control subjects as well as on patients under investigation for various disturbances in the hypothalamic-pituitary-adrenocortical axis (insulin tolerance test: 3 controls on two occasions and 14 patients; corticotropin-releasing-hormone stimulation: 4 controls and 18 patients; adreno-corticotrophic hormone stimulation: 6 controls and 10 patients). Five patients underwent both insulin tolerance test and corticotropin-releasing-hormone stimulation. Using criteria for adequate cortisol response in serum, the patients were classified as good or poor responders. In 42 of the 45 tests performed the same conclusion as to cortisol status was drawn when based on serum and salivary cortisol responses. In healthy subjects and good responders the mean cortisol relative increase was greater in saliva than in serum in all three tests (p < 0.05). Characteristic of the results for the insulin tolerance test was a significant initial mean decrease (p < 0.05), not found in serum, and the highest observed salivary cortisol value was delayed for at least 30 minutes compared to that in serum. Plasma adreno-corticotrophic hormone correlated significantly with the cortisol concentrations determined 15 minutes later in serum (r = 0.54–0.64) and in saliva (r = 0.76–0.85). The more pronounced cortisol response in saliva than in serum and its closer correlation with adreno-corticotrophic hormone offer advantages over serum cortisol, suggesting salivary cortisol measurement may be used as an alternative parameter in dynamic endocrine tets.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-80133 (URN)10.1515/CCLM.1998.037 (DOI)
Available from: 2012-08-21 Created: 2012-08-21 Last updated: 2012-10-24Bibliographically approved
3. Salivary cortisol and serum prolactin in relation to stress rating scales in a group of rescue workers
Open this publication in new window or tab >>Salivary cortisol and serum prolactin in relation to stress rating scales in a group of rescue workers
1999 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 46, no 6, 850-855 p.Article in journal (Refereed) Published
Abstract [en]

Background: Rescue service personnel are often exposed to traumatic events as part of their occupation, and higher prevalence rates of psychiatric illness have been found among this group.

Methods: In 65 rescue workers, salivary cortisol at 8 am and 10 pm and serum prolactin at 8 am were related to the psychiatric self-rating scale General Health Questionnaire (GHQ-28) measuring psychiatric health, and the Impact of Events Scale (IES) and Post Traumatic Symptom Scale (PTSS) measuring posttraumatic symptoms.

Results: Seventeen percent of the study population scored above the GHQ-28 cut-off limit but none scored beyond the cut-off limit in the IES and PTSS questionnaires. Salivary cortisol concentration at 10 pm correlated with statistical significance to anxiety (p < .005) and depressive symptoms (p < .01) measured with GHQ-28, as well as to posttraumatic symptoms, with avoidance behavior measured with IES (p < .01) and PTSS (p < .005). Two of the rescue workers were followed over time with the same sampling procedure after a major rescue commission.

Conclusions: The correlation between evening salivary cortisol and anxiety, depressiveness, and posttraumatic avoidance symptoms indicates that these parameters can be used in screening and follow-up after traumatic stress events.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-24816 (URN)10.1016/S0006-3223(98)00381-3 (DOI)9214 (Local ID)9214 (Archive number)9214 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2012-08-21Bibliographically approved
4. Salivary cortisol, posttraumatic stress symptoms, and general health in the acute phase and during 9-month follow-up
Open this publication in new window or tab >>Salivary cortisol, posttraumatic stress symptoms, and general health in the acute phase and during 9-month follow-up
2001 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 50, no 12, 986-993 p.Article in journal (Refereed) Published
Abstract [en]

Background: Because traumatic events are unpredictable, there are few studies of psychobiological states immediately following such events. Our study aimed to determine the relation of salivary cortisol to psychologic distress immediately after a traumatic event and then during follow-up.

Methods: Measurement of morning and evening salivary cortisol and ratings of psychologic distress (using the Impact of Events Scale [IES], the Post Traumatic Symptom Scale, and the General Health Questionnaire) were performed with 31 United Nations soldiers at three time points—5 days and 2 and 9 months—following a mine accident in Lebanon.

Results: Five days after the accident, 15 subjects reported substantial posttraumatic distress according to the IES, as well as significantly lower morning and higher evening cortisol levels compared with the low-impact group. Within 9 months, the posttraumatic distress of the high-impact group was reduced, accompanied by an increase in morning and a decrease in evening cortisol levels. There were significant relationships between evening cortisol and all rating scales at the first and third time points.

Conclusions: Subclinical posttraumatic stress following an adverse event can be measured biologically via salivary cortisol levels soon after the event.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-24817 (URN)10.1016/S0006-3223(01)01253-7 (DOI)9215 (Local ID)9215 (Archive number)9215 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2012-08-21Bibliographically approved
5. Pre-trauma Salivary Cortisol Levels and General Health Ratings in Relation to Post-trauma Changes in Cortisol and Psychological Distress after UN-service in Bosnia
Open this publication in new window or tab >>Pre-trauma Salivary Cortisol Levels and General Health Ratings in Relation to Post-trauma Changes in Cortisol and Psychological Distress after UN-service in Bosnia
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: The psychobiology of post-traumatic distress is known to some extent, however the pre-trauma psychobiology is not. The aims of the present study were to relate pre- and post-trauma salivary cortisol levels and general health to post-traumatic distress in a Swedish UN-battalion in Bosnia.

Methods: Salivary 8 AM and I 0 PM cortisol levels and "General Health Questionnaire" ratings were collected from 145 subjects before the six months' mission, at return and two and six months after mission. During follow-up, the ratings were extended by the "Impact of Events Scale" (IES) and "Post Traumatic Symptom Scale".

Results: Low pre-trauma morning and evening salivary cortisol levels were statistically significantly related to high scores in all rating scales six months after mission and to increasing IES scores during follow-up. Low morning and high evening post-trauma salivary cortisol levels were related to high ratings of psychological distress six months after mission

Conclusions: Pre-trauma salivary cortisol levels seem to be related to posttrauma psychological distress, however not to the extent that salivary cortisol levels in a simple way could be used for predictive screening.

Keyword
Saliva, cortisol, relation to, rating scales, traumatic stress, UN-soldiers
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-80134 (URN)
Available from: 2012-08-21 Created: 2012-08-21 Last updated: 2012-08-21Bibliographically approved
6. Twelve Months Follow-up of Salivary Cortisol in Relation to Psychological Distress and General Health in Swedish UN-personnel after Severe Combat Exposure during Six Months Mission in Bosnia
Open this publication in new window or tab >>Twelve Months Follow-up of Salivary Cortisol in Relation to Psychological Distress and General Health in Swedish UN-personnel after Severe Combat Exposure during Six Months Mission in Bosnia
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: Our group has presented evidence of relationships between salivary cortisol levels and psychological distress before, during and after trauma-related stress. The aim of the present study was to confirm the part of evidence of relationships between salivary cortisol and posttraumatic distress and their change over time.

Methods: Salivary cortisol levels at 8 AM and 10 PM and self-ratings were collected from 106 subjects six and twelve months after a six months UNmission in Bosnia. The rating instruments were the "Impact of Event Scale" (IES), the "Post Traumatic Symptom Scale" and the "General Health Questionnaire".

Results: Significant statistical interactions were found between changes in mean cortisol levels and IES scores over time. Decreasing evening cortisol levels over time were significantly related to decreasing IES scores and vice versa. Morning cortisol levels showed negative, and evening cortisol positive correlations with all rating scores.

Conclusions: The evidence from previous studies on trauma related stress, that salivary cortisol is related to the development of posttraumatic stress reactions, the morning cortisol in reverse (negative) direction to that (positive) of evening cortisol, were confirmed.

Keyword
Saliva, cortisol, follow-up, relation to, rating scales, traumatic stress, UN-soldiers
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-80136 (URN)
Available from: 2012-08-21 Created: 2012-08-21 Last updated: 2012-08-21Bibliographically approved

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