Marked lability in urinary cortisol levels in subgroups of combat veterans with posttraumatic stress disorder during an intensive exposure treatment program.

OBJECTIVE: The objective of this study was to obtain longitudinal data on lability of cortisol levels in posttraumatic stress disorder (PTSD) because previous studies have largely been based on sampling at a single time point and have yielded varying results. METHODS: This study measured urinary cortisol levels at admission, midcourse, and discharge during a 90-day hospitalization period in male Vietnam combat veterans with PTSD (N = 51). RESULTS: Although there were no significant differences in the mean +/- SEM urinary cortisol levels between the admission (59.4 +/- 3.0 microg/d), midcourse (55.6 +/- 3.9 microg/d), and discharge (53.4 +/- 3.4 microg/d) values, marked lability of cortisol levels in individual patients was observed over time, with changes ranging from +93 to -58 microg/d from admission to midcourse. In addition, this hormonal lability defined discrete subgroups of patients on the basis of the longitudinal pattern of cortisol change during exposure treatment, and there were significant psychometric differences in the level of social functioning between these subgroups. CONCLUSIONS: The findings do not support the concept of either a static "hypocortisolism" or "hypercortisolism" in PTSD, but rather suggest a psychogenic basis for cortisol alterations in PTSD in relation to psychosocial stress and indicate a central regulatory dysfunction of the hypothalamic-pituitary-adrenal axis characterized by a dynamic tendency to overreact in both upward and downward directions. The longitudinal findings fit with recent observations that cortisol elevations occur when acutely superimposed stressful conditions emotionally engage patients and overwhelm the usually dominating disengaging coping mechanisms associated with suppression of cortisol levels in PTSD. The findings emphasize the importance of longitudinal data in studies of the hypothalamic-pituitary-adrenal axis in PTSD.

Low platelet-poor plasma concentrations of serotonin in patients with combat-related posttraumatic stress disorder.

BACKGROUND: Combat-related posttraumatic stress disorder (CR-PTSD) is associated with a dysregulation of various neurotransmitter systems. METHODS: We assessed levels of platelet-poor plasma (PPP) norepinephrine (NE), and serotonin (5-HT), and 24-hour urinary excretion of NE, dopamine (DA), and homovanillic acid (HVA) in 17 male outpatients with untreated chronic CR-PTSD (age, 33.1 +/- 7.4 years) and 10 normal control subjects (age, 35.8 +/- 2.7 years). RESULTS: Compared with the control subjects, the PTSD patients showed significantly lower PPP 5-HT levels, elevated PPP NE levels, and significantly higher mean 24-hour urinary excretion of all three catecholamines (NE, DA, and HVA). The 24-hour urinary HVA values of the CR-PTSD patients correlated significantly and positively with the total Impact of Event Scale scores and the avoidance symptoms cluster scores, and the PPP 5-HT levels correlated negatively with the Hamilton Anxiety Rating Scale scores. The PPP NE/5-HT ratio was significantly higher in the study group than in the control subjects. CONCLUSIONS: We believe this combined enhanced noradrenergic activity and diminished 5-HT activity may be relevant to the neurobiology of CR-PTSD.

Low urinary cortisol excretion in Holocaust survivors with posttraumatic stress disorder.

OBJECTIVE: The authors' objective was to compare the urinary cortisol excretion of Holocaust survivors with posttraumatic stress disorder (PTSD) (N = 22) to that of Holocaust survivors without PTSD (N = 25) and comparison subjects not exposed to the Holocaust (N = 15). METHOD: Twenty-four-hour urine samples were collected, and the following day, subjects were evaluated for the presence and severity of past and current PTSD and other psychiatric conditions. RESULTS: Holocaust survivors with PTSD showed significantly lower mean 24-hour urinary cortisol excretion than the two groups of subjects without PTSD. Multiple correlation analysis revealed a significant relationship between cortisol levels and severity of PTSD that was due to a substantial association with scores on the avoidance subscale. CONCLUSIONS: The present findings replicate the authors' previous observation of low urinary cortisol excretion in combat veterans with PTSD and extend these findings to a non-treatment-seeking civilian group. The results also demonstrate that low cortisol levels are associated with PTSD symptoms of a clinically significant nature, rather than occurring as a result of exposure to trauma per se, and that low cortisol levels may persist for decades following exposure to trauma among individuals with chronic PTSD.

Tribulin in post-traumatic stress disorder.

Tribulin (endogenous monoamine oxidase inhibitor/benzodiazepine receptor binding inhibitor) output was measured in the urine of 18 patients with post-traumatic stress disorder (PTSD) and 13 controls. The level of the two inhibitory activities was highly significantly correlated in the group as a whole. There was no difference between output of either inhibitor in patients and controls. However, when the PTSD group was subdivided according to various psychometric ratings, a pattern of output did emerge. Levels of both inhibitory activities were higher in agitated compared with non-agitated subjects, and lower in extroverts compared with introverts. This finding supports the view that tribulin output is raised in conditions of greater arousal.

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.