Natural killer cell activity in adolescents with major depression.
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Biomedical subjects
Publications and source records attributed to Z Kronfol.
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To study the effects of electroconvulsive therapy (ECT) on hormone release, we measured circulating concentrations of adrenocorticotropic hormone (ACTH), prolactin (PRL), growth hormone (GH) and cortisol (CORT) immediately before and at 2 min, 5 min, 15 min, and 30 min following ECT. Compared to pre-ECT concentrations, there were significant increases in post-ECT plasma ACTH, PRL and CORT. GH did not change consistently. No significant difference between unilateral and bilateral ECT was observed. Compared to the first ECT, repeated treatments were associated with a significant decrease in the magnitude of hormone surge. These hormonal changes induced by ECT may reflect changes at the neurotransmitter level.
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The central nervous system and the immune system are closely related. Psychiatric illness is often associated with a dysregulation of the immune response. In an attempt to expand on previously reported immune abnormalities in patients with depressive illness, we compared several immune measures in a group of hospitalized depressed patients and healthy normal controls. Depressed patients had significantly higher percentages of circulating neutrophils, significantly lower percentages of circulating lymphocytes and significantly lower in vitro lymphocyte responses to mitogenic stimulation than normal controls. Basal plasma cortisol and circulating levels of the complement components C3 and C4 were also higher in the depressed group. We also found a significant association between cortisol values and the traffic of leukocytes on the one hand, and complement levels and the lymphocyte mitogenic activities on the other. These findings expand previously reported evidence of immune abnormalities in depressive illness and provide a partial explanation for some of these findings.
1. Fever and leukocytosis are occasionally observed in patients with psychiatric disorders. A thorough medical evaluation does not always reveal the origin of these abnormalities. 2. We report the case histories of three patients with bipolar affective disorder and an abnormal DST who had fever and leukocytosis during the acute phase of their illness. No organic etiology could be found. 3. All three patients responded to ECT with resolution of the depression, the fever, and the leukocytosis, and normalization of the DST. 4. We propose that fever and leukocytosis may be rare physical manifestations of bipolar affective disorder, particularly in patients with abnormal DST.
Psychiatric patients presenting with chronic psychogenic polydipsia are often difficult to treat with standard psychiatric interventions. Pharmacologic intervention was attempted in three patients and was successful in one. One patient had a significant and sustained reduction of water intake while on 160 mg of propranolol. One patient did not improve with either propranolol or captopril while a third patient showed no improvement of serum sodium with demeclocycline nor reduction of water intake with propranolol. The potential mechanisms by which these pharmacologic agents might alter thirst in patients with primary polydipsia are discussed.
An impairment in lymphocyte response to mitogen stimulation, a correlate of cell-mediated immunity, has been reported in patients with depressive illness. To investigate whether such impairment in lymphocyte function is related to excessive secretion of cortisol, an immunosuppressive hormone, we compared mitogen-induced lymphocyte proliferation in three groups of subjects: depressed patients with elevated 24-hour urinary free cortisol (UFC) excretion; depressed patients with normal UFC excretion; and normal controls. Depressed patients in both groups showed significant reductions in lymphocyte mitogenic activity, in comparison with the normal controls, but the two depressive groups did not significantly differ from each other in their lymphocytic responses to any of the mitogens used. Furthermore, no significant correlations were found, within depressed patients, between UFC excretion and lymphocyte mitogenic responses. Depression is therefore associated with an impairment in lymphocyte function that cannot be explained solely on the basis of increased cortisol secretion.
Total, differential, and absolute blood cell counts were compared in 66 untreated manics and 178 untreated schizophrenics. Mania was associated with significantly higher total leukocyte counts (p less than .001), accounted for by a significant increase (p less than .0001) in the number of neutrophils. There were no significant differences between the two groups in any other blood cell elements. Using normative values, manic patients had significantly higher frequencies of both leukocytosis (25.8% vs. 12.4%) and neutrophilia (34.8% vs. 12.4%) than the schizophrenic group. These data suggest a significant association between leukocytosis, neutrophilia, and mania.
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Depression is often associated with hypercortisolemia. Because high levels of cortisol influence the distribution of different types of leukocytes in the blood stream, we examined the percentages and absolute numbers of circulating neutrophils and lymphocytes in 29 depressed patients who were nonsuppressors on the Dexamethasone Suppression Test (DST), 28 depressed patients who were suppressors on the DST, and 52 schizophrenic controls. We found no significant differences in either RBC or WBC counts in the 3 groups. There were, however, significant differences in the percentages of both neutrophils and lymphocytes as well as the absolute number of lymphocytes among the groups. These differences were mostly due to significantly lower lymphocyte percentages and absolute counts in the depression-nonsuppressor group. We also found a significant negative association between post-dexamethasone plasma cortisol concentrations and blood lymphocyte counts. These data suggest a close interaction between cortisol metabolism and lymphocyte regulation in major depression.
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Several clinical and physiologic associations between depression and diabetes mellitus have been reported. In this study, a potential neuroendocrine association was studied by measuring hypothalamic-pituitary-adrenocortical (HPA) axis activity in patients with diabetes mellitus. Plasma cortisol levels and response to dexamethasone administration were determined in 54 diabetics. Twenty-three (55%) of forty-two 1-mg dexamethasone suppression tests (DSTs) performed in 34 subjects, with eight repeated tests, and two (10%) of twenty 2-mg DSTs demonstrated a blunting of normal suppression. None of a variety of potential demographic, physiologic, or mood factors predicted nonsuppression. This study replicates prior findings that HPA dysfunction occurs in association with diabetes, and invalidates the use of the 1-mg DST as a diagnostic marker for melancholia in patients with diabetes.
The distribution of leukocytes in the blood stream is affected by levels of circulatory glucocorticoids. Elevated concentrations of cortisol are usually associated with an increase in the number of neutrophils and a decrease in the number of lymphocytes. Since primary depressive illness is often associated with hypercortisolemia, we hypothesized that similar changes in the blood stream of depressive patients may occur. To test this hypothesis, we retrospectively compared leukocyte counts in 177 untreated depressive patients and 178 untreated schizophrenic controls. We found a significant increase in the absolute and relative numbers of neutrophils and a significant decrease in the absolute and relative numbers of lymphocytes in the depressive group. Furthermore, when compared to normative values from the general population, depressed patients showed higher frequencies of both neutrophilia and lymphopenia than the schizophrenic group. These results indicate differences in the regulation of leukocytes in depression and schizophrenia consistent with the effects of higher levels of plasma cortisol in the depressive group.
A case report of a 62-year-old patient is presented with apparent dose-dependent kinetics for nortriptyline following the administration of therapeutic doses of the drug. Twelve-hour measurements of total plasma nortriptyline following steady state administration of the drug at 10 mg every other day, 10 mg daily, and 25 mg daily were 38, 86, and 647 ng/ml and while free plasma nortriptyline concentrations were 0.37, 0.9, and 6.6 ng/ml, respectively. Half-lives calculated from samples collected at 12, 24, and 36 hours status after administration of steady state 10 mg every other day, 10 mg daily, and 25 mg daily maintenance doses were 30.4, 36.7, and 64 hours, respectively. Toxicity did not occur despite excessive total plasma tricyclic antidepressant concentrations as a result of abnormally increased plasma protein binding of nortriptyline. The case is contrasted to the usual pharmacokinetic characteristics for the tricyclic antidepressants.