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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.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).Although there were no significant differences in the mean ± SEM urinary cortisol levels between the admission (59.4 ± 3.0 μg/d), midcourse (55.6 ± 3.9 μg/d), and discharge (53.4 ± 3.4 μg/d) values, marked lability of cortisol levels in individual patients was observed over time, with changes ranging from + 93 to −58 μg/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.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.