Victor Wahby

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.

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.

Psychological correlates of growth hormone response to stress

&NA; 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.”

Serum Testosterone Levels in Post-Traumatic Stress Disorder Inpatients

In a longitudinal clinical psychoendocrine study, serum testosterone levels (ng/dl) were measured at 2-week intervals during the course of hospitalization in 34 male psychiatric inpatients in four diagnostic groups, including post-traumatic stress disorder (PTSD), major depressive disorder (endogenous type) (MDD-E), paranoid schizophrenia (PS), and bipolar I disorder- manic (BP), as well as in a group of normal male control subjects (CONT). A one-way analysis of variance revealed that the mean (± SE) testosterone levels were significantly higher (p<0.0002) in the PTSD (578±59), PS (571±49), and CONT (494±24) groups than in the MDD-E (331±47) and BP (351±31) groups. The same group differences were significant in the first sample (p<0.02), while in the last sample the values were significantly higher (p<0.0004) in the PTSD (623±66) and PS (566±72) groups than in the CONT (482±26), BP (353±61), and MDD-E (291±52) groups. These preliminary findings, then, indicate that in spite of considerable depressive symptomatology, PTSD patients do not show the relatively low testosterone levels seen in major depressive disorder patients, but instead align more closely with the schizophrenic patients with regard to the pituitary-gonadal system. There is also an indication that chronic basal testosterone levels in PTSD patients may be elevated in comparison with normal subjects. The possible link suggested by the psychoendocrine literature between testosterone levels and trait factors, particularly paranoid style, in these patient groups is considered, as is the potential application of these findings for multidimensional approaches to the development of improved biologic criteria for psychiatric diagnosis.

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.

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 ≤ 6 μU/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.

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.

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.

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.

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.