Sheila Wang

Neuropeptide-Y, cortisol, and subjective distress in humans exposed to acute stress: replication and extension of previous report

BACKGROUND We previously reported that stress-related release of cortisol and neuropeptide-Y (NPY) were significantly and positively associated in U.S. Army soldiers participating in survival training. Furthermore, greater levels of NPY were observed in individuals exhibiting fewer psychologic symptoms of dissociation during stress. This study tested whether these findings would be replicated in a sample of U.S. Navy personnel participating in survival school training. METHODS Psychologic as well as salivary and plasma hormone indices were assessed in 25 active duty personnel before, during, and 24 hours after exposure to U.S. Navy survival school stress. RESULTS Cortisol and NPY were significantly and positively associated during stress and 24 hours after stress; NPY and norepinephrine (NE) were significantly and positively related during and 24 hours after stress. There was a significant, negative relationship between psychologic distress and NPY release during stress. Finally, psychologic symptoms of dissociation reported at baseline predicted significantly less NPY release during stress. CONCLUSIONS These data replicate our previous studies demonstrating that acute stress elicits NPY release and that this release is positively associated with cortisol and NE release. These data also replicate our previous finding that greater levels of NPY release are associated with less psychologic distress suggesting that NPY confers anxiolytic activity.

Increased pituitary and adrenal reactivity in premenopausal women with posttraumatic stress disorder.

BACKGROUND Limited studies of hypothalamic-pituitary-adrenal axis regulation in posttraumatic stress disorder have been performed in premenopausal women. We therefore undertook a study of hypothalamic-pituitary-adrenal axis regulation in this population. METHODS Outpatient posttraumatic stress disorder subjects were compared with healthy, age- and weight-matched nontraumatized subjects. Subjects were free from psychotropic medications, alcohol and other illicit substances for at least 4 weeks before study. Menstrual cycle phase was determined by monitoring the LH surge and plasma progesterone levels. Corticotropin releasing factor and adrenocorticotropin stimulation tests, as well as 24-hour urinary-free cortisol measurements were performed. RESULTS Corticotropin releasing factor test: Baseline adrenocorticotropic hormone and cortisol levels did not differ between the 12 PTSD and 11 comparison subjects, but the posttraumatic stress disorder group had greater adrenocorticotropic hormone and cortisol responses to corticotropin releasing factor, as well as a later cortisol peak. Adrenocorticotropic hormone test: Baseline cortisol levels did not differ between the 10 posttraumatic stress disorder subjects and seven controls, but the posttraumatic stress disorder group showed greater cortisol responses to adrenocorticotropic hormone. Peak cortisol responses to corticotropin releasing factor and adrenocorticotropic hormone were correlated with each other and with 24-hour urinary-free cortisol excretion. CONCLUSIONS Pituitary and adrenal hyperreactivity to exogenous corticotropin releasing factor and adrenocorticotropic hormone is demonstrated in premenopausal women with chronic posttraumatic stress disorder. Cortisol hyperreactivity thus may play a role in the pathophysiology of posttraumatic stress disorder in women.

Relationship among plasma cortisol, catecholamines, neuropeptide Y, and human performance during exposure to uncontrollable stress.

Objective Although many people are exposed to trauma, only some individuals develop posttraumatic stress disorder; most do not. It is possible that humans differ in the degree to which stress induces neurobiological perturbations of their threat response systems, which may result in a differential capacity to cope with aversive experiences. This study explored the idea that differences in the neurobiological responses of individuals exposed to threat are significantly related to psychological and behavioral indices. Methods Individual differences in neurohormonal, psychological, and performance indices among 44 healthy subjects enrolled in US Army survival school were investigated. Subjects were examined before, during, and after exposure to uncontrollable stress. Results Stress-induced release of cortisol, neuropeptide Y, and norepinephrine were positively correlated; cortisol release during stress accounted for 42% of the variance in neuropeptide Y release during stress. Cortisol also accounted for 22% of the variance in psychological symptoms of dissociation and 31% of the variance in military performance during stress. Conclusions Because dissociation, abnormalities in the hypothalamic-pituitary-adrenocortical axis, and catecholamine functioning have all been implicated in the development of stress disorders such as posttraumatic stress disorder, these data suggest that some biological differences may exist before index trauma exposure and before the development of stress-related illness. The data also imply a relationship among specific neurobiological factors and psychological dissociation. In addition, the data provide clues about the way in which individuals’ psychobiological responses to threat differ from one another.

Psychogenic lowering of urinary cortisol levels linked to increased emotional numbing and a shame-depressive syndrome in combat-related posttraumatic stress disorder.

Objective The purpose of the study was to search for the intrapsychic correlates of individual differences in cortisol levels in male Vietnam combat veterans with posttraumatic stress disorder. Methods The study involved measurement of urinary cortisol levels and clinical assessment with a broad profile of psychometric tests during a single 48-hour period in 30 inpatients. Results The main finding by both correlation and t test analyses was a significant inverse relationship between urinary cortisol levels and a symptom complex composed of two closely interrelated clinical subgroupings, “disengagement” (principally involving emotional numbing) and “shame-laden depression.” Conclusions The findings support the concept that cortisol levels reflect the ongoing balance between the undifferentiated emotional arousal state of engagement (associated with higher cortisol levels) and opposing antiarousal disengagement defense mechanisms (associated with lower cortisol levels). It appears that the low cortisol levels often seen in patients with posttraumatic stress disorder are psychogenic and reflect a dominating effect of disengagement coping strategies, which represent secondary compensatory adaptations during the chronic course of this disorder to counteract primary arousal symptoms, especially those related to an intractable shame-laden depressive syndrome. The psychoendocrine findings suggest that the relatively inconspicuous clinical feature of shame resulting from both the primary and secondary traumatizations is a particularly powerful, preoccupying, and overwhelming source of emotional engagement. Shame may represent a “sleeper” that is worthy of greater attention in both research and clinical efforts to understand the pathogenesis and psychopathology of this devastating stress-related disorder.

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.

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 &mgr;g/d), midcourse (55.6 ± 3.9 &mgr;g/d), and discharge (53.4 ± 3.4 &mgr;g/d) values, marked lability of cortisol levels in individual patients was observed over time, with changes ranging from + 93 to −58 &mgr;g/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.

Elevations of serum T3 levels and their association with symptoms in World War II veterans with combat-related posttraumatic stress disorder: replication of findings in Vietnam combat veterans.

OBJECTIVE In previous serum thyroid studies, we reported an unusual thyroid profile, including elevated levels of total and free triiodothyronine (T3), total thyroxine (T4), and thyroxine-binding globulin (TBG) with no elevations in free T4 and thyrotropin (TSH) in Vietnam veterans with combat-related posttraumatic stress disorder (PTSD) compared to control subjects. In a subsample of Vietnam veterans, we found a significant positive correlation between total T3, free T3, and PTSD symptoms, specifically hyperarousal symptoms. In the present study, we explored the generalizability of our findings to World War II (WWII) veterans with PTSD. METHOD Clinical symptoms were assessed in and serum thyroid measures were obtained from 12 WWII veterans with PTSD and 18 WWII veterans without PTSD. RESULTS WWII veterans with combat-related PTSD showed elevations of serum total and free T3 with no elevations of free T4 and TSH compared to control subjects, replicating the results of our previous studies. A significant positive relationship between total and free T3 and PTSD symptoms, specifically hyperarousal symptoms, was also replicated in the total WWII group. Elevations of total T4 and TBG were not replicated in the WWII group with PTSD, which may indicate a shift with age in the free/bound dynamics of the thyroid alterations observed. CONCLUSIONS This study supports the observation that the thyroid system is altered in chronic combat-related PTSD. The observed alterations of thyroid function along with PTSD symptoms appear to be chronic, detectable 50 years after the war.

Stages of decompensation in combat-related posttraumatic stress disorder: A new conceptual model

This conceptual article presents a model of severe, chronic combat-related PTSD based on several years of longitudinal clinical observations of Vietnam veterans. The model describes a repeating cycle of decompensation that profoundly disrupts the veteran’s life. There appear to be “stages” of decompensation that can be described clinically and may be distinct physiologically. The stages describe a wide range of functioning, from adaptive to totally dysfunctional. PTSD core symptoms, as well as several other dimensions of clinical functioning, such as affect regulation, defenses, ego states, interactions with the environment, capacity for self-destruction/suicide and capacity for attachment and insight are described for each stage. Clinical and research implications are discussed.

Twenty-four-hour urine cortisol in combat veterans with PTSD and comorbid borderline personality disorder.

Studies examining mean 24-hour urine cortisol excretion in patients with posttraumatic stress disorder (PTSD) have yielded mixed results with seven reports showing significantly lower urine cortisol levels, three showing significantly higher cortisol levels, and two studies failing to demonstrate si

Serum triiodothyronine elevation in Israeli combat veterans with posttraumatic stress disorder : A cross-cultural study

This study examines the thyroid hormonal profile in Israeli combat veterans with posttraumatic stress disorder (PTSD) and compares it with the previously reported profile in American Vietnam combat veterans with PTSD. Eleven male combat veterans with PTSD were compared with 11 normal subjects. Thyroid function was evaluated by the measurement of serum total triiodothyronine (TT3), free triiodothyronine (FT3), total thyroxine (TT4), free thyroxine (FT4), thyroxine-binding globulin (TBG), and thyroid-stimulating hormone (TSH). The mean total T3 level in the Israeli PTSD patients (160.5 ng/dL) was significantly elevated (t = 2.53, p