Neopterin levels and dexamethasone suppression test in posttraumatic stress disorder

Neopterin has recently gained growing importance as an immunological marker in psychiatric disorders. In the present study, we aimed to evaluate whether the dexamethasone suppression test (DST) and neopterin were associated with posttraumatic stress disorder (PTSD). Fourteen patients with PTSD and 14 controls were enrolled in the study. A clinical evaluation and measurements of cortisol and neopterin levels before and after DST were performed. Additionally, all patients were assessed by Clinician Administered PTSD Scale (CAPS). There was a significantly higher DST nonsuppression in the patient group than control group. There were positive correlations between the duration of illness and CAPS, basal cortisol or postdexamethasone cortisol levels in the patient group. The mean neopterin levels for both before and after DST were significantly lower in the patient group than control group. In conclusion, our results suggest that not only the patients with PTSD have considerable DST nonsuppression but also PTSD may be associated with neopterin. Received: 13 February 2002 / Accepted: 13 June 2002     

The correlation of dexamethasone suppression test and thyrotropin-releasing hormone test results in different subtypes of depression

TSH response to I.V. TRH and suppression of cortisol secretion by dexamethasone were studied in 51 depressive inpatients. There was no significant relationship between the results on both tests, considering blunted TSH responses to TRH and nonsuppression on the DST. Both tests were not complementary in identifying various subgroups of depression as far as the predictive value of a positive result on either or both tests is concerned. Methodological and clinical issues regarding these markers are briefly discussed.     

The corticotropin-releasing hormone test in patients with posttraumatic stress disorder

To evaluate the hypothalamic-pituitary-adrenal (HPA) axis in patients with posttraumatic stress disorder (PTSD), we measured adrenocorticotropin hormone (ACTH) and cortisol responses following administration of corticotropin-releasing hormone (CRH) in 8 combat veterans with chronic PTSD. The PTSD patients had a significantly lower ACTH response to CRH compared to a control group of normal volunteers. Blunted ACTH responses occurred in patients with PTSD alone, as well as those PTSD patients who also had major depression. The cortisol response, although reduced, was not significantly different from normal. The blunted ACTH response to CRH in PTSD patients is similar to that seen in other psychiatric disorders, such as depression, panic disorder, and anorexia nervosa.     

Blunted ACTH response to dexamethasone suppression-CRH stimulation in posttraumatic stress disorder

Previous studies have suggested that patients with posttraumatic stress disorder (PTSD) have an enhanced negative feedback sensitivity of the hypothalamic-pituitary-adrenal (HPA) system and a blunted ACTH response to corticotropin releasing hormone (CRH). The effects of two dexamethasone dosages (0.75 and 1.5 mg) on the ACTH and cortisol concentrations after CRH stimulation (100 μg) were studied in eight patients with PTSD and matched healthy control subjects. Compared to healthy subjects, patients with PTSD have a blunted ACTH response to CRH. Cortisol concentrations were only significantly influenced by dexamethasone dosage. Our results give further evidence for a central role of the pituitary in reflecting changes of the negative feedback sensitivity of the HPA system in patients with PTSD.     

The dexamethasone suppression and thyrotropin-releasing hormone tests in depressed borderline patients

Borderline patients can be both a diagnostic and a therapeutic enigma. We investigated a group of 24 depressed women with borderline personality disorder or strong borderline features by DSM III criteria for the presence of either an abnormal dexamethasone suppression test (DST) or a blunted TSH response to TRH, abnormalities which have been reported in major depression. Thirteen of the 24 borderlines failed to suppress on the DST, compared with one of 14 normal women (p < 0.01). Nine of the 24 borderlines had a blunted TSH response to TRH, compared with one of 11 normal women. Neuroendocrine abnormalities were found in a total of 75% of the borderline women, independent of whether or not they met DSM III criteria for major depressive disorder. The results of this study support the notion that many borderline patients with depression have a genuine affective component to their illness, perhaps biologically similar to major depression in non-borderlines.     

The dexamethasone suppression test in panic disorder

The dexamethasone suppression test (DST) was performed in 35 patients with panic disorder and 21 normal control subjects. Non-suppression of plasma cortisol was determined as 4 micrograms/dl and using this figure 29% of panic patients and 9.5% of controls were non-suppressors. There was no significant difference in the number of suppressors and non-suppressors between patient and control groups (chi 2 = 1.81; P greater than 0.05). Both pre- and postdexamethasone cortisol concentrations were significantly different between the two groups possible indicating a cortisol hypersecretion in some panic patients.     

Cortisol suppression by dexamethasone reduces exaggerated fear responses in posttraumatic stress disorder

PTSD symptoms are associated with heightened fear responses in laboratory fear conditioning paradigms. This study examined the effects of dexamethasone administration on hypothalamic-pituitary-adrenal (HPA) function and fear-potentiated startle (FPS) in trauma-exposed individuals with and without PTSD. We used an established fear discrimination procedure, in which one visual stimulus (CS+, danger cue) was paired with aversive airblasts to the throat (unconditioned stimulus, US), and another stimulus (CS-, safety cue) was presented without airblasts. In addition to FPS, the dexamethasone suppression test (DST) was performed. The study sample (N=100) was recruited from a highly traumatized civilian population in Atlanta, GA. Half of the subjects (n=54, 16 PTSD, 38 controls) underwent conditioning at baseline and the other half (n=46, 17 PTSD, 29 controls) after DST, in a cross-sectional design. We found a significant interaction effect of diagnostic group and dexamethasone treatment. Under baseline conditions, subjects with PTSD showed more than twice as much fear-potentiated startle to the danger cue compared to traumatized controls, F(1,53)=8.08, p=0.006. However, there was no group difference in subjects tested after dexamethasone suppression. Furthermore, there was a significant treatment effect in PTSD subjects but not in controls, with dexamethasone reducing fear-potentiated startle to the CS+, F(1,32)=4.00, p=0.05. There was also a positive correlation between PTSD subjects' FPS and cortisol levels, r=0.46, p=0.01. These results suggest that transient suppression of HPA function via dexamethasone suppression may reduce exaggerated fear in patients with PTSD.     

The desipramine-induced growth hormone response and the dexamethasone suppression test in obsessive-compulsive disorder.

Ten patients with DSM-III-R obsessive-compulsive disorder (OCD) underwent the desipramine (DMI) growth hormone (GH) stimulation test as well as the dexamethasone suppression test (DST). The results were compared with the responses in a group of matched healthy controls. The GH response to DMI did not differ between patients and controls and 9 of 10 patients showed cortisol suppression in response to dexamethasone. The data suggest that neither alpha 2 adrenergic dysfunction nor DST non-suppression are features of primary OCD.     

Dexamethasone suppression test in borderline personality disorder--effects of posttraumatic stress disorder

BACKGROUND: Divergent findings of hypothalamic-pituitary-adrenal (HPA) axis functioning in borderline personality disorder (BPD) may be caused by a different degree of comorbid posttraumatic stress disorder (PTSD), in which alterations of the HPA axis are well known. Here we investigate alterations of the HPA axis in BPD patients with and without comorbid PTSD compared to healthy controls. Considering previous findings current major depression (MDD) was taken into account as a confounding variable. METHODS: Apart from clinical assessment the 0.5 mg dexamethasone suppression test (DST) was performed in 21 female borderline patients and 23 healthy controls. RESULTS: Twelve BPD patients suffered from comorbid PTSD. Relative suppression (%) did not differ between healthy controls and the total BPD group, but BPD patients with comorbid PTSD showed increased suppression compared to those without. Comorbid MDD was not associated with suppression. CONCLUSIONS: Our results do not indicate a dysfunction of the HPA axis in BPD. However, comorbid PTSD seems to be associated with a relative hypersuppression in the 0.5 mg DST.     

The dexamethasone suppression test in mixed bipolar disorder

The authors administered the dexamethasone suppression test to 10 patients who met DSM-III criteria for bipolar disorder. All 7 patients with bipolar disorder, mixed type, failed to suppress cortisol; however, the 3 patients with bipolar disorder, manic type, were normal suppressors.     

The thyrotropin-releasing hormone and dexamethasone suppression tests in the familial classification of depression

Eighty-eight depressed patients who had received a dexamethasone suppression test (DST) and thyrotropin-releasing hormone (TRH) test were divided into four subgroups based on family history of psychiatric illness. Nonsuppression on the DST was found in 46% of familial pure depressive disease (FPDD) patients, 38% of sporadic depressive disease (SDD) patients, 38% of depressive spectrum disease (DSD) patients, and 50% of mixed depressive disease patients (patients with both a first degree relative with alcoholism and one with depression). A blunted thyroid-stimulating hormone response to TRH was found in 50% of FPDD patients, 56% of SDD patients, 47% of DSD patients, and 56% of mixed depressive disease patients. Neither the DST nor TRH test was found to distinguish significantly among the four familial subgroups of depression.     

The TRH stimulation test and the dexamethasone suppression test in depression

The thyrotropin-releasing hormone (TRH) stimulation test and the dexamethasone suppression test (DST) were performed in 40 depressive patients. More endogenously depressed patients than nonendogenously depressed patients showed a blunted response to TRH. No difference was found in delta max thyroid-stimulating hormone (TSH) between patients who responded to dexamethasone administration with a normal suppression of cortisol and those who responded with nonsuppression.     

Increased adrenocorticotropin suppression following dexamethasone administration in sexually abused adolescents with posttraumatic stress disorder

Evidence suggests that individuals with posttraumatic stress disorder (PTSD) have an enhanced sensitization of the hypothalamic–pituitary–adrenocortical (HPA) axis. However, few studies in adolescents have been performed. Fourteen sexually abused adolescent inpatients with DSM-IV PTSD (12 female, two male; mean±SD age, 16.2±1.9 years) were compared with 14 adolescent hospitalized controls (11 female, three male; mean age, 15.7±2.0 years). All subjects underwent a standard dexamethasone suppression test (DST, 1 mg given orally at 2300 h) five days after admission. Baseline blood samples were obtained at 0800 h, and the following day, adrenocorticotropin (ACTH) and cortisol levels were measured at 0800, 1600, and 2300 h. Clinical assessment included the Impact of Event Scale, Stanford Acute Stress Reaction Questionnaire, Beck Depression Inventory, and Coping Inventory for Stressful Situations. Post-DST ACTH levels were significantly lower in PTSD than in control adolescents (at 0800 h: P<0.005; at 1600 h: P<0.001; at 2300 h: P<0.05). In patients, post-DST cortisol levels were reduced but not significantly. No correlations were found between ACTH and cortisol levels and time elapsed since trauma. These results demonstrate that sexually abused adolescents with PTSD show ACTH hypersuppression to DST suggesting enhanced glucocorticoid receptor sensitivity in the pituitary.     

The thyrotropin-releasing hormone stimulation test: a methodological study

The spontaneous and drug-induced remission of alcoholic organic brain syndrome was studied in a double-blind, placebo-controlled trial. Forty patients with alcoholic organic brain syndrome (OBS) were randomly assigned to a 6-week treatment with either placebo or piridoxilate, a reciprocal salt between two stereo-isomers of the glyoxylic acid-substituted piridoxine. Clinical, psychometric, and computer-assisted spectral analyses of the electroencephalogram (EEG) were carried out in weeks 0, 2, 4, and 6. Piridoxale-5-phosphate (PLP) blood level determination and laboratory investigations were performed before therapy and also in weeks 4 and 6. Both groups of patients demonstrated significant clinical improvement over 6 weeks of treatment, but the improvement in the piridoxilate-treated group was significantly greater than that in the placebo group. This conclusion was also confirmed by psychometric tests demonstrating a greater improvement in attention, concentration, attention variability, tapping, visual and numerical memory, and aftereffect (Archimedean spiral) in the piridoxilate than in the placebo group. Spectral analysis of the EEG showed an increase in alpha and a decrease in fast beta activities in both groups, while delta activity was attenuated only in the piridoxilate-treated group. The latter was found to be significantly correlated with the improvement in psychopathology. The present data confirm previous predictions about the encephalotropic and psychotropic properties of piridoxilate; these predictions were based on pharmaco-EEG trials in the elderly that suggested vigilance-improving qualities of piridoxilate. The reversible alcoholic OBS appears to be a suitable model for the assessment of therapeutic efficacy of nootropic drugs.     

Enhanced cortisol suppression in response to dexamethasone administration in traumatized veterans with and without posttraumatic stress disorder

BACKGROUND: While enhanced cortisol suppression in response to dexamethasone is one of the most consistent biological findings in posttraumatic stress disorder (PTSD), the relative contribution of trauma exposure to this finding remains unclear. METHODS: Assessment of diurnal salivary cortisol levels and 1600 h salivary cortisol before and after oral administration of 0.5mg dexamethasone in veterans with PTSD, veterans without PTSD (trauma controls) and healthy controls. Assessment of 1600 h plasma cortisol, ACTH and corticotrophin binding globulin (CBG) in response to dexamethasone in PTSD patients and trauma controls. RESULTS: Both PTSD patients and trauma controls demonstrated significantly more salivary cortisol suppression compared to healthy controls. Salivary cortisol, plasma cortisol and ACTH suppression as well as CBG levels did not differ between PTSD patients and trauma controls. PTSD patients showed a reduced awakening cortisol response (ACR) compared to healthy controls that correlated significantly with PTSD symptoms. No significant differences were observed in ACR between PTSD patients and trauma controls. CONCLUSIONS: These data suggest that enhanced cortisol suppression to dexamethasone is related to trauma exposure and not specifically to PTSD. The correlation between the ACR and PTSD severity suggests that a flattened ACR may be a result of clinical symptoms.     

The dexamethasone suppression test in panic disorder and major depressive episodes

Dexamethasone Suppression Tests (DST) were performed on 30 patients with panic disorder and on 30 patients treated for major depressive episodes in order to seek an answer to the question of whether or not the two disorders have a common biological background. The hypothesis was based on the results of family studies known from the literature and on the favorable therapeutic response obtained with tricyclic antidepressants. Normal suppressive (i.e., negative in our terminology) DSTs were found in 16.7% of the patients with panic disorder and in 56.7% of patients suffering from major depressive episodes. The anxiety indices of the two groups differed significantly from each other. The results do not suggest the possibility of a close genetic relationship between the two conditions.