John W. Mason

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.

Urinary free-cortisol levels in posttraumatic stress disorder patients.

Urinary free-cortisol levels (micrograms per day) were measured by radioimmunoassay at 2-week intervals during the course of hospitalization in the following patient groups: posttraumatic stress disorder (PTSD); major depressive disorder; bipolar I, manic; paranoid schizophrenia; and undifferentiated schizophrenia. The mean cortisol level during hospitalization was significantly lower in PTSD (33.3 ± 3.2) than in major depressive disorder (49.6 ± 5.9), bipolar I, manic (62.7 ± 6.7), and undifferentiated schizophrenia (50.1 ± 8.9), but was similar to that in paranoid schizophrenia (37.5 ± 3.9). The same differences across groups are evident in the first sample following hospital admission. This finding of low, stable cortisol levels in PTSD patients is especially noteworthy, first because of the overt signs of anxiety and depression, which would usually be expected to accompany cortisol elevations, and second because of the concomitant chronic increase in sympathetic nervous system activity shown in prior psychophysiological studies of PTSD and reflected in marked and sustained urinary catecholamine elevations previously reported in our own PTSD sample. The findings suggest a possible role of defensive organization as a basis for the low, constricted cortisol levels in PTSD and paranoid schizophrenic patients. The data also suggest the possible usefulness of hormonal criteria as an adjunct to the clinical diagnosis of PTSD.

Hypothalamic-pituitary-adrenal dysfunction in posttraumatic stress disorder.

Neuroendocrine studies examining the hypothalamic-pituitary-adrenal (HPA) axis under baseline conditions and in response to neuroendocrine challenges have supported the hypothesis of altered HPA functioning in posttraumatic stress disorder (PTSD). However, to date, there is much debate concerning the nature of HPA changes in PTSD. Furthermore, in studies showing parallel findings in PTSD and major depressive disorder there is controversy regarding whether the HPA alterations suggest a specific pathophysiology of PTSD, or, rather, reflect comorbid major depressive disorder. This review summarizes findings of HPA axis dysfunction in both PTSD and major depressive disorder, and shows distinct patterns of HPA changes, which are probably due to different mechanisms of action for cortisol and its regulatory factors.

Sustained urinary norepinephrine and epinephrine elevation in post-traumatic stress disorder

Urinary norepinephrine and epinephrine levels (microgram/day) were measured at two-week intervals during the course of hospitalization in the following patient groups: post-traumatic stress disorder (PTSD); major depressive disorder (MDD); bipolar I, manic (BP); paranoid schizophrenia (PS); and undifferentiated schizophrenia (US). The mean norepinephrine level during hospitalization was significantly higher in PTSD (76 +/- 10.4 micrograms/day) than in BP (60.6 +/- 8.4 micrograms/day), MDD (41.2 +/- 4.7 micrograms/day), PS (33.4 +/- 4.9 micrograms/day) and US (34.3 +/- 5.9 micrograms/day) groups, according to Duncans multiple range test, (F(4,39) = 6.94, p less than 0.0003). The norepinephrine elevations in the PTSD group were sustained throughout hospitalization. The only other group to show mean levels in this range was the BP group in the first sample after hospital admission. This finding supports prior psychophysiological studies indicating increased sympathetic nervous system activity in PTSD patients. The mean epinephrine level during hospitalization was also significantly higher in PTSD (22.7 +/- 2.4 micrograms/day) than in MDD (13.6 +/- 1.7 micrograms/day), PS (14.7 +/- 2.4 micrograms/day), and US (18.9 +/- 1.8 micrograms/day), but not higher than in BP (21.5 +/- 2.7 micrograms/day). The relationship of epinephrine levels among diagnostic groups was sustained throughout hospitalization. It appears likely that the main underlying mechanisms for elevations of both hormones are psychological, but further work will be required to establish the exact nature of these mechanisms.

Glucocorticoid receptor number and cortisol excretion in mood, anxiety, and psychotic disorders ☆

In the present study, we measured cytosolic lymphocyte glucocorticoid receptor and 24-hour urinary cortisol excretion in patients with major depressive disorder, bipolar mania, posttraumatic stress disorder, panic disorder, and schizophrenia. Patients with major depression had the smallest, and posttraumatic stress disordered patients the largest, mean number of glucocorticoid receptors per cell compared to patients in the other groups. Bipolar manic and panic patients did not differ from each other in regard to the number of lymphocyte glucocorticoid receptors. Bipolar manic and panic patients did have significantly more glucocorticoid receptors/cell than schizophrenic patients. The mean 24-hour urinary cortisol excretion was significantly higher in patients with major depression and bipolar mania than in those in the other diagnostic groups. Lymphocyte glucocorticoid receptor number and cortisol excretion tended to be inversely related, when the entire sample was considered as a whole, but this effect did not reach statistical significance. It is concluded that lymphocyte glucocorticoid receptors may be modulated by multiple influences, not just ambient cortisol levels. These preliminary data suggest that the assessment of lymphocyte glucocorticoid receptor number in tandem with cortisol levels may provide a more meaningful estimate of hypothalamic-pituitary-adrenal axis activity than is achieved using cortisol alone.

Elevation of urinary norepinephrine/cortisol ratio in posttraumatic stress disorder.

We have previously reported the unusual combination of low urinary free cortisol levels with high urinary norepinephrine excretion in posttraumatic stress disorder (PTSD) patients in comparison with four other patient groups: major depressive disorder, endogenous type; bipolar I, manic; paranoid schizophrenia; undifferentiated schizophrenia. Cortisol levels alone did not distinguish PTSD from paranoid schizophrenia patients and norepinephrine levels alone did not distinguish PTSD from bipolar I, manic, patients. In further consideration of these findings, we have found that combining the values for the two systems in a norepinephrine/cortisol (N/C) ratio provides a measure that significantly distinguishes PTSD from all the other patient groups throughout the hospitalization period. The N/C ratio was more than twice as high in the PTSD group than in all the other patient groups in the first sample following hospital admission, in the mean sample during hospitalization, and in the last sample before discharge. The mean N/C ratio for the PTSD group was 2.54, compared with a mean of .99 for the other four groups, which ranged from .81 to 1.18. The diagnostic sensitivity was 78% and the specificity was 94% for correct classification of PTSD in our sample. These preliminary findings yield further encouragement for exploring multivariate strategies, using hormonal ratios or profiles, in an effort to increase the diagnostic sensitivity of neuroendocrine criteria in the assessment of psychiatric patients.

Neurobiological aspects of PTSD: Review of clinical and preclinical studies

Although physiologic studies of post-traumatic stress disorder (PTSD) date to World War I, clinical neuroscience has only recently explored biological mechanisms involved in this disorder. This review will selectively consider clinical and preclinical studies pertaining to biological theories and pharmacological treatments for PTSD, highlighting the role of central noradrenergic systems in its pathophysiology.

Relationships between hormonal profile and novelty seeking in combat-related posttraumatic stress disorder

This study examines relationships between hormonal levels and novelty seeking in a group of 27 Vietnam veterans with combat-related posttraumatic stress disorder (PTSD). Novelty seeking in the veteran sample, measured by the Cloninger Tridimensional Personality Questionnaire (TPQ), was almost twice as high as previously published norms. A distinctive pattern of significant positive correlations was found between novelty seeking scores and serum total triiodothyronine (T3), free T3, the T3/free thyroxine (FT4) ratio, urinary norepinephrine and the norepinephrine/cortisol ratio, while a negative correlation was found between novelty seeking scores and urinary cortisol levels. The findings were confirmed by t test analyses of high vs low novelty seeking subgroups and do not appear to be related simply to the severity of PTSD. These preliminary findings indicate the need to include measures of characterological traits in psychoendocrine studies of PTSD and to investigate their possible usefulness in subtyping this disorder.

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.

RELATIONSHIP BETWEEN PSYCHOLOGICAL DEFENSES AND MEAN URINARY 17-HYDROXYCORTICOSTEROID EXCRETION RATES. II. METHODOLOGIC AND THEORETICAL CONSIDERATIONS.

&NA; The previous paper reported that it was possible to predict the mean urinary 17‐hydroxycorticosteroid (17‐OHCS) excretion rates of parents of fatally ill children on the basis of an evaluation of the effectiveness of their defenses. This report presents in detail the methods used to make predictions. The criteria of effective defense and the interviewing methods are described, and the process of predicting and the problems related to it are discussed. Using the described methods, a second independent interviewer was able to replicate the predictive success of the first interviewer. Three case reports are presented, each illustrating a theoretical point relating to the hypothesis that the more effectively a parent defends against the threat of loss, the lower will be his mean 17‐OHCS excretion rate. Each case also illustrates a problem relating to the method of evaluation of defenses on the basis of behavioral data.