The dexamethasone suppression test and thyrotropin-releasing hormone stimulation test in posttraumatic stress disorder.

Male veterans with posttraumatic stress disorder (PTSD) (n = 11), including 6 with concurrent major depressive disorder (MDD), were compared to veterans with MDD alone (n = 18) and to 28 controls in their response to the dexamethasone suppression test (DST) and thyrotropin-releasing hormone (TRH) stimulation tests. We found higher levels of 4 PM serum cortisol and lower peak thyroid-stimulating hormone (TSH) response to TRH in the MDD patients than in either the PTSD patients or controls, in spite of equivalent levels of depression for MDD and PTSD. DST suppression (cortisol less than 5 mg/dl) occurred in 90% of control, 90% of PTSD, and 78% of MDD subjects, whereas TRH blunting (dTSHmax less than 7 microU/ml) occurred in 28% of control, 27% of PTSD, and 67% of MDD subjects. Rather than blunting, four PTSD patients (36%) and only 10% of the control and MDD subjects had high TSH responses (13-24 microU/ml), which may be linked to high noradrenergic activity, since subclinical hypothyroidism seemed unlikely.

Prolactin response to thyrotropin-releasing hormone in schizoaffective depressed compared to depressed and schizophrenic men and healthy controls.

Biological tests may help clarify the relationship of schizoaffective disorder to major depressive disorder (MDD) and schizophrenia (SCZ). Thyrotropin-releasing hormone (TRH), 500 micrograms, was administered intravenously to eight schizoaffective depressed (SD), ten SCZ, 23 MDD patients and 43 healthy controls (HC), all males, ages 20-66 years and drug-free. Research Diagnostic Criteria (RDC) were utilized for establishing diagnoses, Hamilton Rating Scale for Depression (HRSD) total scores were used for assessing depressive symptoms. There were no differences in dmax PRL (post-TRH prolactin peak minus baseline, mean +/- SD) amongst SD, SCZ and HC groups (27.3 +/- 5.2, 28.8 +/- 5.4 and 31.5 +/- 5.6 ng/ml respectively). Mean dmax PRL in MDD was significantly lower than each of the other three groups (17.1 +/- 2.2 ng/ml, P less than 0.05 for all). The essentially normal PRL response to TRH in SD, significantly different from MDD but similar to SCZ parallels our previous observations on the pattern of thyrotropin (TSH) response to TRH in the same diagnostic groups. These biological findings may be taken to indicate that schizoaffective disorder, depressed subtype, is closer to schizophrenia than to major depressive disorder. However, they cannot be considered definitive evidence to that effect since schizoaffective disorders are known to be quite heterogeneous, and since the utilized biological tests lack specificity.

Low urinary cortisol excretion in patients with posttraumatic stress disorder.

In the present study, we replicated and extended our previous findings of low urinary free-cortisol levels in PTSD. Cortisol was measured in 16 male patients (nine inpatients, seven outpatients) with posttraumatic stress disorder (PTSD) and in 16 nonpsychiatric control subjects. The mean cortisol level in the PTSD group was significantly lower, and the range narrower, than that observed in control subjects. Low cortisol in PTSD did not seem to be related to the presence or absence of major depressive disorder or to overall psychiatric symptomatology as assessed by the sum Brief Psychiatric Rating Scale score. In the outpatient group, there was a relationship between PTSD symptomatology and cortisol levels. The findings suggests a physiological adaptation of the hypothalamic-pituitary-adrenal axis to chronic stress.

The dexamethasone suppression test in a group of research diagnostic criteria schizoaffective depressed men.

A dexamethasone suppression test (DST) was performed on 8 schizoaffective depressed men. Cross-sectional comparisons were made with three groups: schizophrenics (n = 10), unipolar major depressives (n = 23) and healthy controls (n = 43). All were drug-free and similar in age and body weight. Evaluations utilized the Research Diagnostic Criteria (RDC) for diagnosis, and the Hamilton Rating Scale for Depression for depressive symptom rating. DST nonsuppression, defined as a blood cortisol level of greater than or equal to 5.0 micrograms/dl at 16.00 h postdexamethasone, was observed in 43.5% of the major depressive disorder patients. This was different from the other three groups: 12.5% in schizoaffective depressed, 10.0% in schizophrenics and 9.3% in healthy controls (p less than 0.01, p less than 0.01, and p less than 0.001 respectively). Although schizoaffective depressed patients were significantly different from major depressive disorder patients in their DST responses, both groups were similar in their total HRSD scores and different from the schizophrenics (p less than 0.01 for each). These results, together with others previously reported by us on the thyrotropin-releasing hormone challenge in the same diagnostic groups, may be taken to mean that schizoaffective disorder, depressed type, is biologically distinct from major depressive disorder but not schizophrenia. On the other hand, until further corroborated, they should probably be considered a reflection of the heterogeneity of the schizoaffective syndrome and the nonspecificity of the DST.

Serum concentrations of circulating thyroid hormones in a group of depressed men.

Levels of circulating total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine TT3 and thyrotropin (TSH) were determined in 27 men with unipolar major depressive disorder ages 24-50, mean +/- SEM 36.9 +/- 2.9 years, and 38 healthy controls (HC) ages 20-50, mean +/- SEM 34.2 +/- 3.1 years. No significant differences were observed between HC and depressed men with regard to TT4 and FT4. Mean TT3 levels were lower, and mean TSH levels higher in depressed patients than in HC, p less than 0.05 for both, compatible with possible subclinical primary hypothyroidism in depressed patients. Consistent with this, an inverse correlation between basal TSH values and TT3 (r = -0.38, p less than 0.05) was noted in depressed but not in HC subjects.

Pharmacologic provocation and dexamethasone suppression test sensitivity.

In expectation of improving sensitivity, the standard 1-mg dexamethasone suppression test (DST) was given to 10 depressed inpatients and repeated with theophylline or caffeine and again following 3 days of lorazepam with abrupt discontinuation. Two patients showed nonsuppression on the standard DST; 2 suppressors changed to nonsuppression after lorazepam discontinuation, and 1 also changed after theophylline. This increase from 20 to 40% sensitivity remains significantly less than a desirable minimum 80% sensitivity (p less than 0.001), which suggests that a consistent DST sensitivity of 80% in melancholia is unlikely to be attained.

Relationship of age to TSH response to TRH in depressed men.

The relationship between age and TSH response to TRH was studied in 40 men with unipolar major depressive disorder (range 24-65 years, mean 44.7 years) and 36 healthy male volunteers of similar ages. Both groups were subdivided into younger and older than 40 years of age. "Blunted" TSH response to TRH was observed in 58% of depressed men and in 28% of controls, using a dTSH maximum of less than or equal to 6 microU/ml as a cut-off criterion. Older healthy men had a higher blunting rate (40%) than the younger group (19%). In depressed patients, by contrast, the blunting rate was 50% in the older group and 65% in the younger group. Higher mean maximum dTSH, higher basal TSH and lower mean circulating FT4 levels were also noted in older depressed men, suggestive of a subtle thyroid subsensitivity to TSH stimulation and subclinical primary hypothyroidism that may have contributed to the depression. Age is known to be a confounder of TRH test results. There may be a subset of depressed patients over 40 where the confounding effect of age is associated with an exaggerated, rather than decreased TSH response to TRH.

Thyrotropin response to thyrotropin-releasing hormone in RDC schizodepressed men.

Biological tests may help clarify the relationships of schizoaffective disorder to both major depressive disorder and schizophrenia. Thyrotropin-releasing hormone (TRH), 500 micrograms i.v., was administered to 14 schizodepressed, 23 schizophrenics, 41 unipolar major depressives (all by RDC) and 45 healthy controls, all males 20-67 years old with no significant differences in age, body height or weight. Results showed no differences in maximal delta TSH (dTSH max) amongst schizoaffective depressed, schizophrenia and healthy control groups (10.1 +/- 1.3, 9.2 +/- 1.1, 9.7 +/- 0.8 microU/ml, means +/- SEM respectively). Mean major depressives' dTSH max was lower than in each of the other three groups (6.2 +/- 0.4 microU/ml, P less than 0.01 for all). Utilizing a less than or equal to 5.0 microU/ml cut-off criterion for blunting, the schizodepressed had 36%, schizophrenics 44%, healthy controls 22% and major depressed 59% blunters (P less than 0.05 from other three groups). Schizodepressed patients appeared significantly different from major depressed but closer to schizophrenics (and healthy controls) on the TRH test.

Urinary free cortisol and separation anxiety early in the course of bereavement and threatened loss.

Among 56 persons who were acutely bereaved or threatened with a loss, a group with worsening separation anxiety over a period of a month early after the event had higher urinary free cortisol output than a group experiencing improvement in grief. Although not tested in this study, both these psychological and physiological measures may have potential for serving as early predictors of poor outcome in bereavement for the 15%-20% of exposed persons who are at risk for unresolved grief or persistent depressive syndromes.

Ethanol influence on calcium uptake and insulin release by rat islets.

Effect of acute ethanol treatment on simultaneous 45Ca++ uptake and insulin response to glucose was measured in isolated rat pancreatic islets. Ethanol, given ip 1 gm/Kg 1 h prior to sacrifice of the animal, decreased significantly 45Ca++ uptake and insulin response to 8.3 and 16.7 mM glucose. Addition of ethanol to the incubation media inhibited 45Ca++ uptake and insulin release in a dose-related matter. Ionophore A23187, which is known to enhance 45Ca++ efflux, decreased 45Ca++ uptake without affecting insulin release. Inhibitory effects of ethanol and ionophore A23187 were not additive when islets were exposed to both test substances simultaneously. Forskolin, an activator of the adenylate cyclase system potentiated the glucose mediated insulin response in rat islets. However, ethanol decreased the insulin response of islets exposed to glucose and forskolin. The data show that ethanol inhibits 45Ca++ uptake response to glucose and that ethanol influence on insulin release may involve a site beyond the formation of cyclic AMP in the process of excitation-secretion coupling.

Sex differences in prolactin change during mourning.

Fourteen men and 12 women were interviewed eight weeks after conjugal bereavement to discuss the events prior to the spouse's death and the subsequent bereavement period. Prolactin (PRL) was measured at the beginning and end of the interview. Descriptions of the deceased spouse were obtained during the interview and rated for Developmental Level of Object Representation (DLOR), a measure of the cognitive complexity of the description. There were significant correlations between DLOR and PRL change for both men and women but the correlation for women was positive and the correlation for men was negative. These findings extend the literature on the psychological correlates of PRL change and suggest that the physiological changes associated with mourning are different for men and women.

Characterization of the pituitary response in the TRH test by kinetic modeling.

Applying the principles of chemical kinetics to the time course of TSH concentrations after TRH infusion, individual values for total TSH release from the pituitary, TSH elimination and release rates, and latency for TSH release were found for 40 patients. Justification for using the observed peak TSH elevation as a consistent reflection of the total TSH release was provided by the high correlation between these two (r = 0.97, P less than 0.001). Kinetic modeling indicated that the most consistent reflection of total pituitary TSH response is the TSH elevation over baseline 35 min after TRH (with the peak expected 30 min post-TRH), rather than the area under the curve.

Psychological distress, depression and prolactin response in stressed persons.

We examined the relationship of psychological distress to serum prolactin response in 54 persons who had lost a spouse or were threatened with a loss. We found that our two measures of psychological distress, both separation anxiety and depression, were directly correlated with prolactin response during a stressful interview (p less than .05). When we stratified the sample first by depression score and then by separation anxiety, we found a positive correlation between separation anxiety and prolactin response only in the highly depressed half of the sample (r = .32) and a positive correlation between depression and prolactin response only in the highest quartile of intensity for separation anxiety (r = .49, p less than .05). This suggested that both depression and separation anxiety, each in conjunction with high levels of the other but not independently, rendered the individual under stress more physiologically sensitive to distressing challenges such as a stressful interview. Alternatively, it was global distress above a certain threshold that was associated with degree of physiological response.

Bereavement and catecholamines.

Urinary catecholamine output was studied in 59 middle-aged and elderly persons who were either acutely bereaved (n = 39) or threatened with the loss of a spouse (n = 20). The study was done with the hypothesis that urinary catecholamine output would be elevated among the bereaved subjects both in comparison to norms in the literature for non-stressed controls and to the group of subjects who were threatened with a loss. It was also expected that individually high measures of psychological distress would be associated with high urinary catecholamines. Twenty-four hour urinary output of norepinephrine and epinephrine was observed to be higher than normal during acute bereavement but was not associated with depression scores. No differences were found between those who had experienced an actual loss two months earlier and those who were threatened with a loss. Expected relationships between indices of psychological distress and catecholamine output were not observed. Finally, an association was found between increasing age and higher levels of urinary norepinephrine and epinephrine output among acutely bereaved subjects, suggesting that the adaptation of the sympathetic-adrenal medullary system to stress among older persons is slower.

Psychological correlates of growth hormone response to stress.

A stressful interview was conducted in 52 older people to determine whether a stress provoked change in growth hormone (GH) is correlated with anxiety and "defensiveness." The interview was referred to events surrounding the potential loss of a spouse hospitalized two months previously: in 29 instances, the spouse had died before this interview. GH was measured before and, in 23 subjects, during the interview. After the interview, in addition to GH, anxiety was measured using the Taylor Manifest Anxiety Scale (MAS), and defensiveness using the Crowne Marlowe Social Desirability Scale (SD). An elevation of at least 2.0 ng/ml in GH was used to classify subjects as GH responders (Rs) and nonresponders (NRs). Although the Rs and NRs had similar mean scores on defensiveness (SD), the Rs scored higher on anxiety (MAS) (14.9 vs. 10.2, p less than 0.05). Using a median cutoff with anxiety (MAS) alone, only 59% of the Rs were correctly classified as Rs. However, combining both scales in a discriminant function analysis (DFA) improved the ability of either scale alone to distinguish the Rs from the NRs. Using the DFA, 73% of the 29 NRs were correctly classified and 70% of the 23 Rs were correctly classified (p less than 0.005). With higher levels of defensiveness (SD), relatively low levels of anxiety were needed to provoke a GH response. This finding supports previous studies of GH response to stress and provides a multivariate model for the interaction of anxiety and "defensiveness."