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Biomedical subjects

R Yehuda

Publications and source records attributed to R Yehuda.

At least 73 records · Page 4Linked to original sources

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.

Age Factors↗

Elevation of serum free triiodothyronine, total triiodothyronine, thyroxine-binding globulin, and total thyroxine levels in combat-related posttraumatic stress disorder.

BACKGROUND: This study was designed to assess both central and peripheral aspects of thyroid function in combat-related posttraumatic stress disorder (PTSD), with the particular purpose of finding a mechanistic explanation for an imbalance between serum levels of free thyroxine (T4) and total T4 previously observed in pilot work. METHODS: A total of 96 male combat veterans with PTSD diagnosed by DSM-III-R (72 from the West Haven, Conn, Veterans Affairs Medical Center and 24 from the Menlo Park, Calif, Veterans Affairs Medical Center) were compared with 24 male control subjects. One or more serum samples were analyzed by radioimmunoassays for levels of total T4, free T4, total triiodothyronine (T3), free T3, T4-binding globulin, and thyrotropin. RESULTS: The pilot observation of moderately elevated total T4 levels with no elevation in free T4 levels in patients with PTSD was confirmed, suggesting the hypotheses that (1) there may be an increased peripheral conversion of free T4 by deiodination to T3 or (2) there may be an increased binding of T4 secondary to elevated T4-binding globulin levels. Our findings support both hypotheses. The PTSD groups all showed a marked and sustained elevation in levels of both total T3 and free T3, as well as elevated T3/T4 ratios, supporting the increased T3 conversion hypothesis. The PTSD groups also showed a marked and sustained increase in T4-binding globulin levels, supporting the increased binding hypothesis. Thyrotropin levels did not differ between PTSD and control groups. CONCLUSIONS: These findings demonstrate an unusual pattern of thyroid alterations, featuring substantial elevations in total T3, free T3, and T4-binding globulin levels, in combat-related PTSD that differs from established endocrinopathies, such as classic hyperthyroidism, T3 thyrotoxicosis, or chronic T4-binding globulin elevation.

Adult↗

Depressive features in Holocaust survivors with post-traumatic stress disorder.

The present study was designed to explore several aspects of depressive phenomenology, including current symptoms, dependency (anaclitic) and self-criticism (introjective) themes, and issues of self-efficacy, in Holocaust survivors with and without posttraumatic stress disorder (PTSD). The Depressive Subscale of the Symptom Checklist-90 (SCL-90) and the Depressive Experiences Questionnaire (DEQ) were administered to 23 Holocaust survivors and 18 demographically-matched controls. Holocaust survivors with PTSD scored significantly higher on the SCL-90 depression scale, and portrayed more self-criticism on the DEQ, than Holocaust survivors without PTSD and demographically-matched non-exposed subjects. The data suggest that depressive symptoms in individuals who have been severely traumatized are more severe when associated with a concurrent PTSD. Furthermore, groups suffering different types of trauma may show similarities in psychological dimensions of depression.

Aged↗

Criteria for rationally evaluating animal models of posttraumatic stress disorder.

Animal models of stress have the potential to provide information about the course and etiology of posttraumatic stress disorder (PTSD). To date, however, there have been no systematic approaches for evaluating the relevance of animal models of stress to PTSD. It has been established in the animal literature that different types of stress paradigms lead to different biobehavioral consequences and that many different factors contribute to differential responsivity to stress. It becomes important therefore to differentiate between factors that are essential to the induction of PTSD-like symptoms and those that influence their manifestations. In the present commentary, we present five criteria that must be fulfilled by animal models of stress for them to be useful to understanding the induction of PTSD. We then evaluate two potential animal models of stress--inescapable shock-learned helplessness and time-dependent sensitization--to illustrate how to more successfully pair animal models of stress with the specific clinical syndrome of PTSD.

Animals↗

Psychoneuroendocrine assessment of posttraumatic stress disorder: current progress and new directions.

1. Studies in our laboratory have used the psychoendocrine strategy to explore differences in basal hormone levels between patients with posttraumatic stress disorder (PTSD) and other groups. This approach has allowed us to explore the relationship between hormone levels and specific psychological and biological processes which appear to develop following exposure to extreme trauma. 2. The concurrent assessment of several hormonal systems provides an opportunity to explore differences in hormonal patterns in various psychiatric disorders. PTSD appears to be characterized by a specific profile of hormonal changes that is distinct from that of other diagnostic groups and normal controls. These findings raise the possibility that the psychoendocrine approach may be useful in further exploring the pathophysiology and diagnosis of PTSD. 3. This paper reviews psychoendocrine changes in PTSD and describes updated multivariate methods that further elucidate psychological and neurochemical correlates of hormonal alterations in this disorder.

Hormones↗

Enhanced suppression of cortisol following dexamethasone administration in posttraumatic stress disorder.

OBJECTIVE: The authors investigated the possibility of enhanced negative feedback sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis in posttraumatic stress disorder (PTSD) by using a low dose of dexamethasone. METHOD: Baseline blood samples were obtained at 8:00 a.m., and 0.5 mg of dexamethasone was administered to 21 male patients with PTSD and 12 normal age-comparable men at 11:00 p.m. Cortisol and dexamethasone levels were measured 9 and 17 hours after dexamethasone administration. RESULTS: After correction for differences in dexamethasone levels, the PTSD patients showed greater suppression of cortisol in response to dexamethasone than did the normal subjects. This was true even in patients meeting concurrent diagnostic criteria for major depression. CONCLUSIONS: The data support earlier studies showing that HPA abnormalities in PTSD are different from those seen in depression and suggest that the low-dose dexamethasone suppression test may be a potentially useful tool for differentiating the two syndromes and further exploring differences in their pathophysiology.

Adult↗

Childhood physical abuse and combat-related posttraumatic stress disorder in Vietnam veterans.

OBJECTIVE: Early trauma in the form of childhood physical or sexual abuse has been associated with adult psychopathology. The purpose of this study was to compare rates of childhood abuse in Vietnam veterans with and without combat-related posttraumatic stress disorder (PTSD). METHOD: Premilitary stressful and traumatic events including childhood abuse and other potential predisposing factors were assessed in Vietnam combat veterans who sought treatment for PTSD (N = 38) and Vietnam combat veterans without PTSD who sought treatment for medical disorders (N = 28). Stressful and traumatic events including childhood physical abuse were assessed with the Checklist of Stressful and Traumatic Events and a clinician-administered interview for the assessment of childhood abuse. Level of combat exposure was measured with the Combat Exposure Scale. RESULTS: Vietnam veterans with PTSD had higher rates of childhood physical abuse than Vietnam veterans without PTSD (26% versus 7%). The association between childhood abuse and PTSD persisted after controlling for the difference in level of combat exposure between the two groups. Patients with PTSD also had a significantly higher rate of total traumatic events before joining the military than patients without PTSD (mean = 4.6, SD = 4.5, versus mean = 2.8, SD = 2.9). CONCLUSIONS: These findings suggest that patients seeking treatment for combat-related PTSD have higher rates of childhood physical abuse than combat veterans without PTSD. Childhood physical abuse may be an antecedent to the development of combat-related PTSD in Vietnam combat veterans.

Causality↗

Personality disorders in treatment-seeking combat veterans with posttraumatic stress disorder.

OBJECTIVE: Many patients with posttraumatic stress disorder (PTSD) appear to have co-occurring symptoms of character pathology; however, to date there have been no empirical studies of comorbid clinician-rated axis II personality disorders in war veterans with chronic PTSD. The authors' objective was to assess DSM-III-R personality disorders in treatment-seeking combat veterans with PTSD. METHOD: They used the Personality Disorder Examination, a standardized diagnostic interview for DSM-III-R axis II disorders, to assess DSM-III-R personality disorders in 34 patients with PTSD; 18 of the subjects were inpatients and 16 were outpatients. RESULTS: A high rate of character pathology was observed in both inpatient and outpatient groups. The most frequent disorders for which criteria were met were borderline, obsessive-compulsive, avoidant, and paranoid personality disorders. Inpatients had a higher rate of nearly every personality disorder than did outpatients. Inpatients were significantly more likely to meet diagnostic criteria for paranoid, schizotypal, avoidant, and self-defeating personality disorders. CONCLUSIONS: War-related PTSD in treatment-seeking Vietnam veterans is often accompanied by diffuse, debilitating, and enduring impairments in character. Subtyping patients with PTSD on the basis of specific axis II profiles may aid in the selection of more specific and effective treatments.

Ambulatory Care↗

The interaction between pharmacotherapy and psychotherapy in the treatment of posttraumatic stress disorder.

For patients with PTSD, the effective initiation of additional therapeutic modalities to ongoing individual psychotherapy is challenging. When pharmacologic agents are added, the therapist must carefully consider and monitor the impact of medications on PTSD core symptoms and on adjunctive symptoms such as depression. Further considerations include issues of countertransference, the possible symbolic meaning of medications for both the patient and the therapist, and the appropriate staging of medications. When nonphysician treaters work together with a medical back-up, both parties should frequently communicate with one another in order to avoid unnecessary treatment distortions and disruptions.

Combined Modality Therapy↗

Urinary catecholamine excretion and severity of PTSD symptoms in Vietnam combat veterans.

In the present study, we replicated and extended our previous findings of increased 24-hour urinary catecholamine excretion in posttraumatic stress disorder (PTSD). Dopamine, norepinephrine, and epinephrine concentrations were measured in 22 male patients with PTSD (14 inpatients and eight outpatients) and in 16 nonpsychiatric normal males. The PTSD inpatients showed significantly higher excretion of all three catecholamines compared with both outpatients with PTSD and normal controls. Dopamine and norepinephrine, but not epinephrine, levels were significantly correlated with severity of PTSD symptoms in the PTSD group as a whole. In particular, these catecholamines seemed related to intrusive symptoms. None of the catecholamines were correlated with severity of depression. The findings support the hypothesis of an enhanced sympathetic nervous system activation in PTSD, and suggest that increased sympathetic arousal may be closely linked to severity of certain PTSD symptom clusters.

Ambulatory Care↗

Exposure to atrocities and severity of chronic posttraumatic stress disorder in Vietnam combat veterans.

OBJECTIVE: The authors' objective was to explore aspects of trauma associated with severity of posttraumatic stress disorder (PTSD) in Vietnam veterans. METHOD: Several ratings of stress exposure and symptom severity were administered to 40 patients with combat-related PTSD. RESULTS: A significant relationship was observed between exposure to atrocities and the impact of PTSD on veterans' lives, as measured by the Mississippi Scale for Combat-Related Posttraumatic Stress Disorder. Exposure to atrocities was also significantly correlated with current symptom severity. In contrast, combat exposure alone was not significantly associated with overall symptom severity. Both atrocity and combat exposure, however, were significantly related to reexperiencing symptoms. CONCLUSIONS: The data suggest that the enduring effect and severity of PTSD symptoms on an individual are associated more with exposure to brutal human death and suffering than the threat of death associated with combat.

Adult↗

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.

Adrenocorticotropic Hormone↗

Regional patterns of brain growth during the first three weeks following early adrenalectomy.

Day 11 adrenalectomized (ADX) and sham-operated control rats were compared with respect to overall and regional brain growth and DNA content at 1, 2, and 3 weeks postsurgery. Possible treatment effects on the rate of postnatal cell loss were also assessed by injecting the animals with 3H-thymidine on day 2 postnatal (9 days prior to surgery) and subsequently measuring the amount of radiolabelled DNA remaining in various brain regions at each time point. Adrenalectomy led to reliable increases in cerebral cortex and midbrain-diencephalon weights within 1 week postsurgery, whereas cerebellum, hippocampus, and overall brain weights were not significantly elevated until 1 or 2 weeks later. The effects of adrenalectomy on tissue DNA content were likewise regionally dependent. According to the 3H-thymidine results, there was no significant influence of adrenalectomy on the loss of previously labelled DNA. In conclusion, the timing of brain growth acceleration following adrenal removal is regionally specific, with the most rapid effects occurring in the cortex and midbrain-diencephalon. Furthermore, adrenalectomy-induced increases in brain cell number appear to depend primarily on increased cellular genesis (as previously demonstrated) rather than decreased cell death.

Adrenal Glands↗

Neuroendocrine responses in alcoholics to the presentation and consumption of a perceived alcoholic beverage.

Eight male alcoholic inpatients in their 2nd week of treatment were presented with, and instructed to consume, a beverage described at one session as containing alcohol and at another as not containing alcohol. The beverage on each occasion did not, in fact, contain alcohol. The results indicated that when subjects believed they had consumed alcohol, the change in insulin from baseline was significantly greater at 10, 20, and 30 min following consumption. The findings suggest that the insulin response of alcoholics following ingestion of a carbohydrate-containing beverage is enhanced by the anticipation of ethanol.

Alcohol Drinking↗

Characterization of depression in war-related posttraumatic stress disorder.

OBJECTIVE: Many patients with posttraumatic stress disorder (PTSD) have symptoms of depression, but operationalized psychological constructs related to depression have not been used extensively in characterizing affective symptoms of PTSD. The authors' objective is to better characterize the affective component of PTSD. METHOD: The subjects were 45 male psychiatric inpatients at a Veterans Administration medical center; 28 met DSM-III-R criteria for PTSD and 17 met Research Diagnostic Criteria (RDC) for major depressive disorder. All of the subjects with PTSD were Vietnam veterans. The 21-item Hamilton Rating Scale for Depression was used to assess state measures of symptom severity, and the Depressive Experiences Questionnaire was used to measure dimensions of dependency, self-criticism, and self-efficacy. RESULTS: The mean total Hamilton scale score of the patients with PTSD was nonsignificantly higher than that of the patients with major depressive disorder; patients with PTSD had higher scores on almost all individual Hamilton symptoms, particularly insomnia, somatic anxiety, and diurnal variation. Patients with PTSD had significantly higher scores on the self-criticism scale but not on the dependency and self-efficacy scales of the Depressive Experiences Questionnaire. The scores of patients with PTSD on the dependency and self-criticism scales were negatively correlated. No significant differences between patients with PTSD with and without concurrent major depressive disorder were observed. CONCLUSIONS: Characterization of such depressive dimensions of PTSD as dependency and self-criticism may have important clinical implications.

Adult↗

Lymphocyte glucocorticoid receptor number in posttraumatic stress disorder.

OBJECTIVE: The authors' objective was to investigate the possibility that glucocorticoid receptor changes may be involved in the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in posttraumatic stress disorder (PTSD). METHOD: They measured the number of lymphocyte cytosolic glucocorticoid receptors and plasma cortisol concentrations in 15 consecutively admitted male combat Vietnam veterans with PTSD and in a normal comparison group of 11 subjects. RESULTS: Both the patients and the normal comparison subjects showed a morning-to-afternoon decline in glucocorticoid receptor concentrations, paralleling the normal diurnal decline in cortisol levels. The number of glucocorticoid receptors was 63% greater in the morning and 26% greater in the afternoon in the patients with PTSD than in the normal subjects. No group differences in cortisol levels were observed, nor were glucocorticoid receptor number and cortisol levels correlated. The number of morning glucocorticoid receptors was positively correlated with symptoms of PTSD and anxiety. CONCLUSIONS: These results provide further evidence for a dysregulation of the HPA axis in PTSD. The finding that patients with PTSD had a substantially greater number of lymphocyte glucocorticoid receptors than normal comparison subjects is consistent with the authors' previous observations of low 24-hour urinary cortisol excretion in subjects with PTSD. Furthermore, the receptor changes observed are opposite of those reported in major depressive disorder. The present data, along with other findings of HPA abnormalities in PTSD, support the possibility of a greater negative feedback sensitivity at one or more levels of the HPA axis.

Adult↗

Platelet alpha 2-adrenergic receptor binding sites in major depressive disorder and borderline personality disorder.

Platelet alpha 2-adrenergic receptor binding sites were measured in a group of patients with major depressive disorder (MDD) (n = 23) and in normal controls (n = 25). When all depressed subjects were compared to controls, there were no differences in either Kd (affinity of the ligand) or total binding site (number/platelet), although a significant change in the ratio of high to low affinity states was observed in the depressed group. When the depressed patients were subdivided into those with and without a co-occurring borderline personality disorder (BPD), the BPD group had significantly fewer alpha 2 high affinity binding sites, while the group with depression alone had significantly more binding sites (both low and high affinity) than the control group. The results support the concept that assessment of comorbid diagnoses may be essential to biological studies of depression.

Aged↗