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Biomedical subjects

R Yehuda

Publications and source records attributed to R Yehuda.

87 records · Page 5Linked to original sources

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.

Adult↗

Altered platelet alpha 2-adrenergic receptor binding sites in borderline personality disorder.

The authors found significantly fewer total platelet alpha 2-adrenergic receptor binding sites in 13 nonmedicated patients with borderline personality disorder than in 11 patients with borderline personality disorder who were receiving low doses of benzodiazepines and 18 nonpsychiatric control subjects. The two patient groups showed comparable degrees of depression as assessed by the Hamilton Rating Scale for Depression. However, nonmedicated borderline patients were considerably more anxious than medicated patients, raising the possibility that lower alpha 2-adrenergic receptor binding in borderline personality disorder is related to anxiety.

Anxiety Disorders↗

Low platelet monoamine oxidase activity in borderline personality disorder.

Platelet monoamine oxidase (MAO) activity was significantly lower in nonpsychotic, nonorganic, unmedicated male inpatients with DSM-III-R borderline personality disorder (BPD) than in nonpsychiatric controls. Patients with BPD who also met DSM-III-R criteria for antisocial personality disorder had significantly lower MAO activity than those with BPD alone. Low MAO activity in this sample did not appear to be related to the comorbid presence of major depressive disorder or a history of substance abuse.

Adolescent↗

Enhanced brain cell proliferation following early adrenalectomy in rats.

We have previously demonstrated an increase in adult brain DNA content in rats adrenalectomized on postnatal day 11. The present studies examined cell proliferation in cerebral cortex, cerebellum, hippocampus, and midbrain-diencephalon following adrenalectomy at this age. Compared to sham-operated controls, adrenalectomized animals showed increased [3H]thymidine incorporation into DNA (measured at 1 h following a pulse injection) in all brain regions at 7 and 14 days postsurgery. In some areas, the effect was already present as early as 2 days following adrenalectomy. Chronic replacement with corticosterone prevented this increase in DNA labelling in a dose-dependent manner. When cell proliferation in the cerebral cortex and cerebellum was independently assessed by measuring changes in thymidine kinase activity, enzyme activity was significantly elevated in both areas at 7 and 14 days postsurgery. Finally, histological examination of the cerebellar cortex suggested a delayed disappearance of the external granular layer in several cerebellar lobules of adrenalectomized animals. Overall, these findings indicate that day-11 adrenalectomy leads to a prolonged stimulation of mitotic activity in areas where cell formation at this time is exclusively glial (i.e., cerebral cortex and mid-brain-diencephalon) as well as in areas where postnatal neurogenesis is also occurring (cerebellum and hippocampus). It is hypothesized that this stimulation results from the removal of a tonic inhibitory effect exerted by circulating glucocorticoids in the normal intact animal.

Adrenalectomy↗

Maze-learning behavior in early adrenalectomized rats.

Rats adrenalectomized (ADX) on day 11 of life display enhanced brain growth due, at least in part, to a stimulation of cell proliferation and myelinogenesis. The present study investigated some functional consequences of this treatment. Rats were ADX or sham-operated (SHAM) on postnatal day 11 and then tested in adulthood for their problem-solving ability in a Hebb-Williams maze. The mean number of errors committed by ADX rats was lower than that of the SHAM controls on every test problem of the maze. ADX subjects also left the start box more quickly and ran the maze faster than the controls. When a subset of these same subjects was tested for running wheel activity, the ADX animals showed greater baseline running behavior and also learned more readily to respond to a fixed-interval schedule of reinforcement. The remaining animals were subjected to carcass analysis, which revealed that ADX rats under the food-restricted conditions necessary for maze testing had a lower percentage of body fat and a higher relative water content than SHAMs. Although there may be some relationship between enhanced maze-learning performance and altered activity or motivation in the ADX animals, the overall results suggest that the performance of these subjects reflects a real difference in learning ability. The neural mechanisms underlying this difference remain to be elucidated.

Adrenal Glands↗

Neuroendocrine aspects of suicidal behavior.

To assess biologic risk factors in suicidal behavior accurately, it is necessary to distinguish prospective from retrospective design. The former studies are more likely to elicit information concerning possible risk factors in suicide, whereas the latter may be better indicators of biologic traits. In both types of investigations, measures taken close to the suicide attempt are more likely to reflect the biologic state of the individual at the time of the behavior. Although the abnormalities present in suicidal individuals are not entirely clear, most evidence to date suggests an overactivity of the hypothalamic-pituitary-adrenal axis and a dysregulation of both serotonin and adrenergic metabolism. These systems are interrelated. Both animal and human studies have established that a multivariate biologic approach is necessary to the understanding of the pathophysiology of suicide.

Dexamethasone↗

Neuroendocrine aspects of suicidal behavior.

To assess biologic risk factors in suicidal behavior accurately, it is necessary to distinguish prospective from retrospective designs. The former studies are more likely to elicit information concerning possible risk factors in suicide, whereas the latter may be better indicators of biologic traits. In both types of investigations, measures taken close to the suicide attempt are more likely to reflect the biologic state of the individual at the time of the behavior. Although the abnormalities present in suicidal individuals are not entirely clear, most evidence to date suggests an overactivity of the hypothalamic-pituitary-adrenal axis and a dysregulation of both serotonin and adrenergic metabolism. These systems are interrelated. Both animal and human studies have established that a multivariate biologic approach is necessary to the understanding of the pathophysiology of suicide.

Adrenal Cortex Hormones↗

Platelet MAO activity and psychosis proneness in college students.

A population of individuals potentially at risk for psychiatric disorders was identified by screening 633 college students using the Wisconsin Scales for psychosis proneness. Platelet monoamine oxidase (MAO) activity was measured in high-scoring individuals and controls using 14C-benzylamine. Males with deviant scores on the Perceptual Aberration-Magical Ideation Scale showed a bimodal distribution of platelet MAO activity. Kinetic analysis of platelets from probands with the highest and lowest levels of MAO activity in this group revealed differences in Vmax but not in Km. Since abnormal platelet MAO activity has been linked to psychiatric vulnerability, the results provide further support for the validity of the Wisconsin Scales as predictors of psychopathology.

Adolescent↗

Serotonergic stimulation of pituitary-adrenocortical activity in rats: evidence for multiple sites of action.

5-Hydroxytryptophan (5-HTP) elevated serum corticosterone concentrations when administered either intraperitoneally (i.p.) or intraventricularly. Inhibition of aromatic L-amino acid decarboxylase outside of the blood-brain barrier antagonized the corticosterone response, but only when the 5-HTP was given i.p. Stimulation of the pituitary-adrenocortical system by fenfluramine was not affected by 5,7-dihydroxytryptamine pretreatment, whereas the stimulation produced by quipazine administration was blocked by lesions of the basomedial hypothalamus. These results suggest that serotonergic drugs can act at multiple sites (i.e., both central and peripheral) to evoke a pituitary-adrenocortical response.

5-Hydroxytryptophan↗

A role for serotonin in the hypothalamic-pituitary-adrenal response to insulin stress.

Controversy exists concerning the possible involvement of serotonin (5-HT) in the pituitary-adrenocortical response to stress. In the present research, a variety of pharmacological and physiological manipulations were used in male rats to study the role of this neurotransmitter in the adrenocortical response to insulin-induced hypoglycemia. We first examined the effect of insulin stress on hypothalamic 5-HT metabolism and found increased turnover as determined by an enhanced accumulation of 5-HT following monoamine oxidase inhibition. Brain 5-HT depletion by intraventricular injection of 5,7-dihydroxytryptamine significantly attenuated the corticosterone response to insulin, while treatment with the 5-HT receptor blocker methysergide tended to have the same effects. The corticosterone response to insulin was potentiated by prior administration of L-tryptophan, and blocked by pretreatment with valine, an amino acid that competes with tryptophan for transport across the blood-brain barrier. It therefore appears that the pituitary-adrenal response to insulin is mediated at least in part by 5-HT, and may be dependent on increased uptake of tryptophan by the brain.

Animals↗

Sustained attention in combat-related posttraumatic stress disorder.

There is substantial evidence that PTSD patients have information processing abnormalities for stimuli that are highly relevant to the traumas they have endured. The goal of the present study was to examine whether this extends to neutral stimuli as well. Twenty-four male Vietnam combat veterans with PTSD were compared to fifteen normal male comparison subjects on their performance on a sensitive measure of sustained attention, the Continuous Performance Test-Identical Pairs version (CPT-IP). PTSD subjects did not differ from controls in their ability to discriminate target stimuli from background noise on the CPT. Additionally they performed as well as controls, even in the presence of external distraction. Thus, this study did not find a generalized deficit in attention associated with PTSD on the CPT-IP. Nevertheless, further clarification of the nature of the information processing disturbance in PTSD is warranted.

Adult↗

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.

Adult↗

Relationship of parental trauma exposure and PTSD to PTSD, depressive and anxiety disorders in offspring.

This study examined the relationship of parental trauma exposure and PTSD to the development of posttraumatic stress disorder (PTSD), depressive and anxiety disorders in the adult offspring of Holocaust survivors. One hundred and thirty-five subjects (55 men and 80 women) were divided into three groups according to parental trauma exposure and PTSD: 60 subjects were offspring of Holocaust survivors who endorsed having at least one parent with PTSD, 33 were offspring of Holocaust survivors who reported having no parent with PTSD, and 42 were demographically similar subjects with no parental Holocaust exposure. All subjects underwent a comprehensive psychiatric interview in which information about lifetime psychiatric diagnoses and exposure to traumatic events was obtained. Subjects also completed a checklist based on the 17 DSM-IV symptoms of PTSD, to estimate the symptom severity of PTSD in their parents. A presumptive diagnosis of parental PTSD was assigned according to DSM-IV criteria. Forward and forced entry stepwise logistic regression analyses were used to determine the effects of parental exposure, parental PTSD, and the subject's own history of trauma in the development of PTSD, depressive, and anxiety disorders in the offspring. The findings demonstrate a specific association between parental PTSD and the occurrence of PTSD in offspring. Additionally, parental trauma exposure, more than parental PTSD, was found to be significantly associated with lifetime depressive disorder. The identification of parental PTSD as a risk factor for PTSD in offspring of Holocaust survivors defines a sample in which the biological and psychological correlates of risk for PTSD can be further examined.

Adult↗

Long-lasting hormonal alterations to extreme stress in humans: normative or maladaptive?

The biological consequences of stress have been studied for over half a decade, however, little is known about persistent biological alterations after extreme stress in humans. Posttraumatic stress disorder (PTSD) is a syndrome that occurs in some individuals after exposure to extreme stress. In this review, we summarize some of our studies of hypothalamic-pituitary-adrenal axis alterations in PTSD and compare and contrast these findings with knowledge concerning biological changes following stress.

Adaptation, Psychological↗

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.

Adult↗