DNA methylation from germline cells in veterans with PTSD.

In this study we investigated genome-wide sperm DNA methylation patterns in trauma-exposed Vietnam veterans. At the genome-wide level, we identified 3 CpG sites associated with PTSD in sperm including two intergenic and one CpG within the CCDC88C gene. Of those associated with PTSD in sperm at a nominal level, 1868 CpGs were also associated with PTSD in peripheral blood (5.6% overlap) including the RORA, CRHR1 and DOCK2 genes that have been previously implicated in PTSD. A total of 10 CpG sites were significantly associated with a reported history of a diagnosed mental health condition in children and reached genome-wide significance. CpGs associated with a history of a reported mental health condition in children were also enriched (90% of tested genes) for genes previously reported to be resistant to demethylation, making them strong candidates for transgenerational inheritance. In conclusion, our findings identify a unique sperm-specific DNA methylation pattern that is associated with PTSD.

A Novel Animal Model Simulating the Beginning of Combat Exposure.

OBJECTIVE: Predator stress, social defeat stress, and fear conditioning animal models have been applied to investigate combat-related posttraumatic stress disorder (PTSD). However, no animal model psychopharmacological studies have investigated prevention of somatization of increased mental stress and fatigue at the beginning of combat exposure. This study utilized a novel animal model simulating the beginning of combat exposure that aided specification of a set of biomarkers. METHODS: Psychological stress was induced by both inescapable electric foot shock and noise stimuli. Physical fatigue was induced by sleep deprivation and forced exercise in a rotating cage. A new device reflecting simultaneous psychological stress and physical fatigue was constructed. The protocol simulating combat exposure was set as 3 rounds of 24-h exposure in a 2-week period, which was specified as intermittent unpredictable stress (IUS). RESULTS: Mice exposed to IUS (IUS mice) had significantly higher serum corticosterone levels (p < 0.05), excessive locomotive activity (p < 0.001), and anxiety-like behavior (p < 0.02) compared to control mice. IUS mice also had significantly higher IFN-γ (p < 0.001) and TNF-α (p < 0.05) levels in the supernatant of splenic T-cell culture compared to control mice. Brain-derived neurotropic factor levels were significantly decreased (p < 0.04) after IUS exposure. CONCLUSION: The proposed animal model of combat exposure reflected cognitive function impairment, behavior disturbance, and altered neuroimmune interactions without any apparent histopathological changes, and this animal model may be more applicable to protective research on war syndrome than combat-related PTSD after war because the hypothalamic-pituitary-adrenal axis has not been blunted.

The effects of captivity survival training on mood, dissociation, PTSD symptoms, cognitive performance and stress hormones.

In the Canadian Armed Forces (CAF), Conduct After Capture (CAC) training is a 4-day captivity survival course during which soldiers are exposed to increasing stress, and evaluated on their ability to accomplish military objectives. We hypothesized that: (a) compared to baseline, CAC training would cause significant, reversible perturbations in measures of psychological functioning and serum and salivary stress hormone levels relevant to models of stress hardiness and vulnerability; and (b) deviations from baseline would be maximal at the time point of most intense stress during training. CAF personnel were assessed at baseline, twice during training (immediately prior to a less challenging interrogation role-play scenario and again following another much more intense interrogation role-play scenario), and after completion of training. At each occasion, mood, fatigue, dissociation, PTSD symptoms, short-term and working memory, and salivary cortisol and dehydroepiandrosterone (DHEA) were assessed. As predicted, scores on all measures were degraded during CAC but recovered after completion of training, and almost all measures were most degraded at the more intense interrogation role-play scenario. Unexpectedly, memory performance was unaffected by training, suggesting that a short duration of intense stress might be insufficient for degrading it. Another unexpected finding was that mood assessed prior to training predicted successful completion of training, which bears important practical implications for increasing the success rate of training in similar environments. These results demonstrate that despite its relative brevity, CAC training nevertheless induces significant but reversible effects on psychological and physiological function-necessary preconditions for stress inoculation training.

Characterising intra- and inter-intrinsic network synchrony in combat-related post-traumatic stress disorder.

Soldiers with post-traumatic stress disorder (PTSD) exhibit elevated gamma-band synchrony in left fronto-temporal cortex, and connectivity measures in these regions correlate with comorbidities and PTSD severity, which suggests increased gamma synchrony is related to symptomology. However, little is known about the role of intrinsic, phase-synchronised networks in the disorder. Using magnetoencephalography (MEG), we characterised spectral connectivity in the default-mode, salience, visual, and attention networks during resting-state in a PTSD population and a trauma-exposed control group. Intrinsic network connectivity was examined in canonical frequency bands. We observed increased inter-network synchronisation in the PTSD group compared with controls in the gamma (30-80 Hz) and high-gamma range (80-150 Hz). Analyses of connectivity and symptomology revealed that PTSD severity was positively associated with beta synchrony in the ventral-attention-to-salience networks, and gamma synchrony within the salience network, but also negatively correlated with beta synchrony within the visual network. These novel results show that frequency-specific, network-level atypicalities may reflect trauma-related alterations of ongoing functional connectivity, and correlations of beta synchrony in attentional-to-salience and visual networks with PTSD severity suggest complicated network interactions mediate symptoms. These results contribute to accumulating evidence that PTSD is a complicated network-based disorder expressed as altered neural interactions.

Cytokine production as a putative biological mechanism underlying stress sensitization in high combat exposed soldiers.

OBJECTIVE: Combat stress exposed soldiers may respond to post-deployment stressful life events (SLE) with increases in symptoms of posttraumatic stress disorder (PTSD), consistent with a model of stress sensitization. Several lines of research point to sensitization as a model to describe the relations between exposure to traumatic events, subsequent SLE, and symptoms of PTSD. Based on previous findings we hypothesized that immune activation, measured as a high in vitro capacity of leukocytes to produce cytokines upon stimulation, underlies stress sensitization. METHODS: We assessed mitogen-induced cytokine production at 1 month, SLE at 1 year, and PTSD symptoms from 1 month up to 2 years post-deployment in soldiers returned from deployment to Afghanistan (N=693). Exploratory structural equation modeling as well as latent growth models were applied. RESULTS: The data demonstrated significant three-way interaction effects of combat stress exposure, cytokine production, and post-deployment SLE on linear change in PTSD symptoms over the first 2 years following return from deployment. In soldiers reporting high combat stress exposure, both high mitogen-stimulated T-cell cytokine production and high innate cytokine production were associated with increases in PTSD symptoms in response to post-deployment SLE. In low combat stress exposed soldiers as well as those with low cytokine production, post-deployment SLE were not associated with increases in PTSD symptoms. CONCLUSION: High stimulated T-cell and innate cytokine production may contribute to stress sensitization in recently deployed, high combat stress exposed soldiers. These findings suggest that detecting and eventually normalizing immune activation may potentially complement future strategies to prevent progression of PTSD symptoms following return from deployment.

Combat-related blast exposure and traumatic brain injury influence brain glucose metabolism during REM sleep in military veterans.

Traumatic brain injury (TBI), a signature wound of Operations Enduring and Iraqi Freedom, can result from blunt head trauma or exposure to a blast/explosion. While TBI affects sleep, the neurobiological underpinnings between TBI and sleep are largely unknown. To examine the neurobiological underpinnings of this relationship in military veterans, [(18)F]-fluorodeoxyglucose positron emission tomography (FDG PET) was used to compare mTBI-related changes in relative cerebral metabolic rate of glucose (rCMRglc) during wakefulness, Rapid Eye Movement (REM) sleep, and non-REM (NREM) sleep, after adjusting for the effects of posttraumatic stress (PTS). Fourteen veterans with a history of blast exposure and/or mTBI (B/mTBI) (age 27.5±3.9) and eleven veterans with no history (No B/mTBI) (age 28.1±4.3) completed FDG PET studies during wakefulness, REM sleep, and NREM sleep. Whole-brain analyses were conducted using Statistical Parametric Mapping (SPM8). Between group comparisons revealed that B/mTBI was associated with significantly lower rCMRglc during wakefulness and REM sleep in the amygdala, hippocampus, parahippocampal gyrus, thalamus, insula, uncus, culmen, visual association cortices, and midline medial frontal cortices. These results suggest that alterations in neurobiological networks during wakefulness and REM sleep subsequent to B/mTBI exposure may contribute to chronic sleep disturbances and differ in individuals with acute symptoms.

Mineralocorticoid receptor and heat shock protein expression levels in peripheral lymphocytes from war trauma-exposed men with and without PTSD.

Alterations in the number and functional status of mineralocorticoid (MR) and glucocorticoid receptors (GR) may contribute to vulnerability to posttraumatic stress disorder (PTSD). Corticosteroid receptors are chaperoned by heat shock proteins Hsp90 and Hsp70. We examined relations between corticosteroid receptor and heat shock protein expression levels, and related them with war trauma exposure, PTSD and resilience to PTSD. Relative levels of MR, Hsp90 and Hsp70 were determined by immunoblotting in lymphocytes from war trauma-exposed men with current PTSD (current PTSD group, n=113), with life-time PTSD (life-time PTSD group, n=61) and without PTSD (trauma control group, n=88), and from non-traumatized healthy controls (healthy control group, n=85). Between-group differences in MR, Hsp90 and Hsp70 levels and in MR/GR ratio were not observed. The level of MR was correlated with both Hsp90 and Hsp70 levels in trauma control and healthy control groups. On the other hand, GR level was correlated only with Hsp90 level, and this correlation was evident in current PTSD and trauma control groups. In conclusion, PTSD and exposure to trauma are not related to changes in lymphocyte MR, Hsp90 or Hsp70 levels, but may be associated with disturbances in corticosteroid receptors interaction with heat shock proteins.

The use of biomarkers in the military: from theory to practice.

This paper provides a summary of relevant issues covered in the conference, "The Use of Biomarkers in the Military: Theory to Practice" held at the New York Academy of Science on September 14, 2012. The conference covered the state of the science in identification of PTSD biomarkers, including, the definition of different classes of biomarkers pertaining to PTSD. The aim of the satellite conference was to bring together researchers who have been supported by the Department of Defense, Veterans Administration, National Institutes of Health, and other agencies around the world, who are interested in the identification of biomarkers for PTSD risk, diagnosis, symptom severity and treatment response, for a discussion of salient issues regarding biomarker development for PTSD, as well as special considerations for the use of biomarkers in the military.

NOS1AP is associated with increased severity of PTSD and depression in untreated combat veterans.

BACKGROUND: Posttraumatic stress disorder (PTSD) and depressive disorder are over represented in combat veterans. Veterans with both disorders have an increased risk of suicide. The nitric oxide synthase 1 adaptor protein (NOS1AP) gene, which modulates stress-evoked N-methyl-d-aspartate (NMDA) activity, was investigated in combat veterans. METHODS: A comprehensive genetic analysis of NOS1AP and its association with PTSD was investigated in Vietnam combat veterans with PTSD (n=121) and a group of healthy control individuals (n=237). PTSD patients were assessed for symptom severity and level of depression using the Mississippi Scale for Combat-Related PTSD and the Beck Depression Inventory-II (BDI). RESULTS: The G allele of NOS1AP SNP rs386231 was significantly associated with PTSD (p=0.002). Analysis of variance revealed significant differences in BDI-II and Mississippi scores between genotypes for rs386231 with the GG genotype associated with increased severity of depression (p=0.002 F=6.839) and higher Mississippi Scale for Combat-Related PTSD scores (p=0.033). Haplotype analysis revealed that the C/G haplotype (rs451275/rs386231) was significantly associated with PTSD (p=0.001). LIMITATIONS: The sample sizes in our study were not sufficient to detect SNP associations with very small effects. In addition the study was limited by its cross sectional design. CONCLUSIONS: This is the first study reporting that a variant of the NOS1AP gene is associated with PTSD. Our data also suggest that a genetic variant in NOS1AP may increase the susceptibility to severe depression in patients with PTSD and increased risk for suicide.

Glucocorticoid receptor pathway components predict posttraumatic stress disorder symptom development: a prospective study.

BACKGROUND: Biological correlates of posttraumatic stress disorder (PTSD) have mostly been studied using cross-sectional or posttrauma prospective designs. Therefore, it remains largely unknown whether previously observed biological correlates of PTSD precede trauma exposure. We investigated whether glucocorticoid receptor (GR) pathway components assessed in leukocytes before military deployment represent preexisting vulnerability factors for development of PTSD symptoms. METHODS: Four hundred forty-eight male soldiers were assessed before and 6 months after deployment to a combat zone. Participants were assigned to the PTSD or comparison group based on Self-Rating Inventory for PTSD scores after deployment. Logistic regression analysis was applied to predict development of a high level of PTSD symptoms based on predeployment GR number, messenger (m)RNA expression of GR target genes FKBP5, GILZ, and SGK1, plasma cortisol, and childhood trauma. We also investigated whether predeployment GR number and FKBP5 mRNA expression were associated with single nucleotide polymorphisms in the GR and FKBP5 genes, either alone or in interaction with childhood trauma. RESULTS: Several GR pathway components predicted subsequent development of a high level of PTSD symptoms: predeployment high GR number, low FKBP5 mRNA expression, and high GILZ mRNA expression were independently associated with increased risk for a high level of PTSD symptoms. Childhood trauma also independently predicted development of a high level of PTSD symptoms. Additionally, we observed a significant interaction effect of GR haplotype BclI and childhood trauma on GR number. CONCLUSIONS: Collectively, our results indicate that predeployment GR pathway components are vulnerability factors for subsequent development of a high level of PTSD symptoms.

Posttraumatic stress disorder and metabolic syndrome: retrospective study of repatriated prisoners of war.

OBJECTIVE: We conducted a retrospective study of metabolic data for Vietnam-era repatriated prisoners of war (RPWs) and a comparison group to determine if metabolic syndrome (MbS) was more common in those individuals with clinically diagnosed, current or lifetime posttraumatic stress disorder (PTSD) as suggested in a recent report. METHODS: The metabolic data of our patients nearest the time of psychiatric evaluation (1998-2004) for PTSD were analyzed using both an analysis of variance and logistic regression. RESULTS: Although we found elevated triglyceride levels (40 mg/dl higher) in RPWs with PTSD who met MbS criteria, overall the prevalence of MbS was the same in RPWs with and without PTSD and comparison group. Moreover, current PTSD symptom severity did not increase the likelihood of MbS. CONCLUSIONS: Our results from these repatriates who actively participate in a 37-year medical follow up program do not support the conclusion that MbS occurs more commonly in individuals with current PTSD.

Decreased nocturnal growth hormone secretion and sleep fragmentation in combat-related posttraumatic stress disorder; potential predictors of impaired memory consolidation.

BACKGROUND: Healthy sleep facilitates the consolidation of newly acquired memories. Although patients with posttraumatic stress disorder (PTSD) often complain of sleep disturbances and memory deficits, the interrelatedness of these symptoms is not well understood. Sleep may be disturbed in PTSD by increased awakenings during sleep, which has been associated with decreased growth hormone (GH) secretion. We conducted a controlled study in which we assessed sleep fragmentation, nocturnal secretion of GH, and memory consolidation in patients with PTSD. METHODS: While sleep EEG was being monitored, 13 veterans with PTSD, 15 trauma controls (TC) and 15 healthy controls (HC) slept with an iv catheter, through which blood was collected every 20 min from 23:00 h to 08:00 h. Declarative memory encoding was assessed with the 15 word task before sleep, and consolidation was assessed the next morning by a free recall. RESULTS: Sleep was more fragmented in patients with PTSD, with more awakenings in the first half of the night (p<0.05). Plasma levels of GH during the night were significantly decreased in PTSD compared with HC (p<0.05). Furthermore, GH secretion and awakenings were independent predictors for delayed recall, which was lower in PTSD compared to HC (p<0.05). CONCLUSIONS: These data show that PTSD is associated with increased awakenings during sleep and decreased nocturnal GH secretion. Furthermore, decreased GH secretion may be related to sleep fragmentation and both variables may exert a negative effect on sleep dependent memory consolidation.

Repeated assessments of endocrine- and immune-related changes in posttraumatic stress disorder.

OBJECTIVE: It is assumed that stress-related changes in the endocrine and immune systems are key mediators involved in the development of diseases associated with posttraumatic stress disorder (PTSD). Evidence suggests that those changes might be related to the duration of PTSD. The aim of our study was to investigate the differences in selected endocrine- and immune-related variables between PTSD patients and control subjects, and whether these differences persist over time. METHODS: We assessed 39 Croatian war veterans with PTSD and 25 healthy volunteers (civilians without traumatic experience), all men, at two time points separated by 5.6 years (median; interquartile range: 5.4-6.3). Cortisol and prolactin levels were measured by radioimmunoassays while interleukin-6 and tumor necrosis factor-α were determined by enzyme-linked immunosorbent assays. Immune function was assessed by in vitro natural killer cell cytotoxicity (NKCC). Lymphocyte counts, immunophenotype and intracellular glucocorticoid receptor expression in various lymphocyte subsets were determined by three-color flow cytometry. RESULTS: At the first assessment, moderate to large effect size estimates of differences between patients and controls were observed for most of the measured variables. Only prolactin levels and lymphocyte counts remained significantly elevated in PTSD patients at the second assessment with low to moderate effect size estimates of differences between patients and controls in other variables. CONCLUSION: Observed endocrine- and immune-related changes in PTSD over time may depend on the duration of the allostatic load posed by the disorder and its impact on interactions between the endocrine and immune systems involved in stress response.

Psychostimulant treatment of combat-related posttraumatic stress disorder.

The objective of this paper is to describe three cases of combat-related posttraumatic stress disorder (PTSD), largely refractory to standard medication treatment who responded well to psychostimulant treatment. Symptoms of PTSD potentially result from chronic, stress-induced dopaminergic dysfunction in the prefrontal cortex/basal ganglia system. Psychostimulants, by their relative propensity to enhance dopamine (DA) activity within these brain regions, may have particular value in targeting this dysfunction. Evidence of dopaminergic dysfunction following chronic stress is reviewed and possible mechanism of action of psychostimulants is explored. Psychostimulants appeared to be well tolerated and beneficial in the treatment of the cases of combat-related PTSD reported. General applicability of the use of psychostimulants in combat- and non-combat-related PTSD awaits further study. The potential implications of these findings in further delineating pathophysiology and treatment in PTSD deserve further exploration.

Natural killer cell cytotoxicity and lymphocyte perforin expression in veterans with posttraumatic stress disorder.

OBJECTIVE: To examine the effect of posttraumatic stress disorder (PTSD) on the measures of immune function and the hypothalamic-pituitary-adrenal axis components, and to determine whether additional life stressors affect measured variables. METHODS: We simultaneously examined the natural killer cell cytotoxicity (NKCC), perforin and glucocorticoid receptor (GCR) expression in natural killer (NK) and cytotoxic T (CD8) cells, as well as serum cortisol concentration in a group of Croatian war veterans with chronic, combat-related PTSD (n=29) and a group of healthy, age-matched men (n=13). PTSD patients were divided into two subgroups: compensation-seeking (n=15) and retired or compensation non-seeking (n=14) subjects. The former includes those involved in the process of getting disability-based army retirement as an additional life stressor. RESULTS: NKCC was decreased in both PTSD groups when compared to controls. Impairment of NKCC could not be attributed to the perforin expression as perforin was not decreased in comparison to controls. Moreover, the increased level of perforin was recorded in NK cells of retired PTSD subjects. Both PTSD groups shared an increased relative quantity of GCR in lymphocytes, whereas no difference between the groups in the baseline levels of serum cortisol was observed. CONCLUSIONS: Diminished NKCC was not accompanied by perforin insufficiency in PTSD subjects, and other causes should be examined. An additional life stressor does not contribute considerably to either immune or endocrine system related changes.

Resting metabolic activity in the cingulate cortex and vulnerability to posttraumatic stress disorder.

CONTEXT: Recent neuroimaging research has revealed functional abnormalities in the anterior cingulate cortex, amygdala, and hippocampus in individuals with posttraumatic stress disorder (PTSD). OBJECTIVE: To determine whether resting functional abnormalities found in PTSD are acquired characteristics or familial risk factors. DESIGN: Cross-sectional design including identical twins discordant for trauma exposure. SETTING: Academic medical center. PARTICIPANTS: Combat-exposed veterans with PTSD (n = 14) and their identical co-twins not exposed to combat (n = 14) as well as combat-exposed veterans without PTSD (n = 19) and their identical co-twins not exposed to combat (n = 19). MAIN OUTCOME MEASURES: We used positron emission tomography and fluorodeoxyglucose 18 to examine resting regional cerebral metabolic rate for glucose (rCMRglu). RESULTS: Veterans with PTSD and their co-twins had significantly higher resting rCMRglu in the dorsal anterior cingulate cortex/midcingulate cortex (dACC/MCC) compared with veterans without PTSD and their co-twins. Resting rCMRglu in the dACC/MCC in unexposed co-twins was positively correlated with combat exposure severity, PTSD symptom severity, and alcohol use in their exposed twins. CONCLUSIONS: Enhanced resting metabolic activity in the dACC/MCC appears to represent a familial risk factor for developing PTSD after exposure to psychological trauma.

Changes in relative glucose metabolic rate following cortisol administration in aging veterans with posttraumatic stress disorder: an FDG-PET neuroimaging study.

The authors aimed to examine central glucocorticoids effects by measuring relative glucose metabolic rate (rGMR) in the hippocampus, amygdala, and anterior cingulate cortex (ACC) and the relationship between amygdala and ACC activity. The participants were male combat veterans with and without PTSD, 52 to 81 years old. The authors utilized randomized, double-blind, placebo-controlled examinations of the rGMR response to 17.5 mg hydrocortisone (HCORT) using 2-Deoxy-2-[(18)F]fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) neuroimaging. Group differences in hemispheric laterality of rGMR were observed following placebo administration, reflecting lower rGMR in the right hippocampus and ventral amygdala, and higher rGMR in the left ventral amygdala in the PTSD+ group compared to the PTSD- group. HCORT reduced these group differences in laterality. The net effect of HCORT was to restore a normal inverse association between the ACC and amygdala in the PTSD+ group, but disrupt this neural network in the PTSD- group. The magnitude of improvement in working memory correlated with greater hemispheric laterality in the dorsal amygdala following HCORT in both groups. The restorative effects of HCORT on metabolism and working memory provide a rationale for examining the therapeutic benefits of glucocorticoid manipulation in aging PTSD patients.

Central type benzodiazepine receptors in Gulf War veterans with posttraumatic stress disorder.

BACKGROUND: A previous single photon emission computed tomography study showed decreased central type benzodiazepine receptors in the prefrontal cortex in Vietnam War veterans with posttraumatic stress disorder. To assess the generalizability of this finding to patients with more recent history, we studied central type benzodiazepine receptors in Gulf War veterans with posttraumatic stress disorder. METHODS: Nineteen Gulf War veterans with posttraumatic stress disorder and 19 age-matched, healthy, nondeployed veterans participated in a single photon emission computed tomography study using [(123)I]iomazenil. Regional total distribution volume (V(T)') was compared between two groups using Statistical Parametric Mapping 99 (Wellcome Department of Imaging Neuroscience, London, United Kingdom) and volumes of interest analysis. RESULTS: Benzodiazepine receptor levels did not show regional differences between the two groups, either with or without global normalization. Average difference in V(T)' was 2% across brain areas; however, by applying global normalization, V(T)' in the patient group showed significant negative correlation with childhood trauma scores in the right superior temporal gyrus. CONCLUSIONS: Less severe symptoms and shorter duration of the illness in the current group than the prior one may be the source of the difference in the results of the two studies.

The cortisol and glucocorticoid receptor response to low dose dexamethasone administration in aging combat veterans and holocaust survivors with and without posttraumatic stress disorder.

BACKGROUND: Because alterations in cortisol negative feedback inhibition associated with aging are generally opposite of those observed in posttraumatic stress disorder (PTSD), we examined the cortisol and glucocorticoid receptor (GR) response to dexamethasone (DEX) in older trauma survivors. METHODS: Twenty-three Holocaust survivors (9 men, 14 women), 27 combat veterans (all male), and 10 comparison subjects (7 men, 3 women) provided samples for plasma or salivary cortisol and glucocorticoid receptor determination in mononuclear leukocytes at 8:00 AM on the day of, and following, 0.5 mg of DEX at 11:00 PM. RESULTS: Greater percent suppression of cortisol and lymphocyte GR was observed in older trauma survivors with PTSD compared to survivors without PTSD and comparison subjects. There was a significant main effect of depression in the direction of reduced suppression following DEX, consistent with the effects of DEX in major depressive disorder patients. Responses to DEX were uncorrelated with PTSD symptom severity, but cortisol suppression was associated with years elapsed since the most recent, but not focal, traumatic event. CONCLUSIONS: The response to DEX is generally similar in older and younger trauma survivors, but the findings suggest that age, symptom severity, and lifetime trauma exposure characteristics may influence this response.

Salivary cortisol, posttraumatic stress symptoms, and general health in the acute phase and during 9-month follow-up.

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.