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Biomedical subjects

C L Bowden

Publications and source records attributed to C L Bowden.

At least 91 records · Page 5Linked to original sources
PubMed1990

Response to treatment with antidepressants of patients with severe or moderate nonpsychotic depression and of patients with psychotic depression.

Hospitalized patients were divided into nonpsychotic severely depressed (N = 53), nonpsychotic moderately depressed (N = 54), and psychotic depressed (N = 25) groups and treated with either imipramine or amitriptyline, up to 250 mg/day, for 4 weeks. Good response occurred in 39% of the 38 severely depressed, 67% of the 49 moderately depressed, and 32% of the 19 psychotic depressed patients who completed treatment. The response of the patients with nonpsychotic severe depression did not differ significantly from the response of those with psychotic depression, and both groups fared worse than the group with nonpsychotic moderate depression.

Adult↗
PubMed1989

The effect of debrisoquin on MAO A and MAO B activities.

To examine the mode of action of debrisoquin (DEB), we studied the effect of this drug in vitro on MAO A and MAO B enzyme activities. DEB was shown to be a competitive inhibitor of highly purified human MAO A and MAO B enzyme activities. DEB inhibited placental MAO A with a Ki value of 0.5 microM and liver MAO B with a Ki value of 8.8 microM, 18-fold greater effect on the A form. Kynuramine was used as substrate for both enzymes. Additional studies using a dilution technique showed that DEB was a reversible inhibitor of both forms of the enzyme. The results of this study show that DEB is a potent competitive and reversible inhibitor of both MAO A and MAO B enzymes.

Biogenic Amines↗
PubMed1988

Calcium function in affective disorders and healthy controls.

Calcium metabolism has been reported to be disturbed in some forms of affective disorder. We studied concurrently a battery of calcium measures in 29 unipolar, 14 bipolar depressed, 11 manic, and 10 healthy control subjects. In addition to measures of extracellular calcium, we studied intracellular calcium concentration in platelets and measures that reflect cellular capability to maintain a low intracellular Ca++ concentration in red blood cells (RBCs) and platelets. Plasma calcium was lower in unipolar and manic patients than in control subjects. Platelet calcium concentration was lower in unipolar than bipolar depressed patients. RBC Ca++ adenosine triphosphatase (ATPase) was lower in unipolar and control subjects than in bipolar depressed and manic patients. Platelet Ca++ ATPase and Ca++ uptake were inversely correlated with severity of illness in unipolar patients. In bipolar depressed patients, RBC Ca++ ATPase and platelet Ca++ uptake were inversely correlated with severity. In addition to indicating abnormalities in calcium activity in affective disorders, the data suggest that unipolar and bipolar patients differ in several measures and may have different pathophysiological disturbances in calcium metabolism.

Adult↗
PubMed1988

Dopamine metabolism and disposition in schizophrenic patients. Studies using debrisoquin.

Debrisoquin sulfate, a monoamine oxidase inhibitor that does not enter the brain, was administered to 23 schizophrenic subjects. Plasma, cerebrospinal fluid (CSF), and urine samples were obtained before and during debrisoquin administration and were assayed for their content of norepinephrine and dopamine metabolites, ie, 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and dihydroxyphenylacetic acid. The severity of the patient's schizophrenic symptoms was also assessed with several types of rating scales. During debrisoquin administration there were significant reductions in plasma, urine, and CSF MHPG levels. Regression analyses suggested that the reduction in CSF MHPG level was probably due to the reduction in plasma MHPG level, which contributes to the CSF MHPG pool. Debrisoquin administration was not associated with changes in CSF HVA level, although it did produce marked reductions in plasma and urinary HVA and dihydroxyphenylacetic acid levels. Significant correlations between plasma and CSF concentrations of HVA were noted during, but not before, debrisoquin administration. Before debrisoquin administration there were trends toward positive relationships between symptom severity and plasma HVA concentrations, which became stronger and statistically significant during debrisoquin administration. These data suggest that debrisoquin may be used as a research tool to create a condition in which measures of HVA in peripheral body fluids reflect dopamine system function and metabolism within the central nervous system.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Cerebrospinal fluid and urinary biogenic amines in depressed patients and healthy controls.

The National Institute of Mental Health-Clinical Research Branch Collaborative Study investigated 132 drug-free, severely depressed patients and 80 healthy controls. Forty-five percent of the depressed patients excreted markedly elevated levels of urinary epinephrine (E) and metanephrine (MET), while only 5% of healthy controls did so. Using gaussian mixture distributions, we identified two subgroups of depressed patients: one excreting normal levels and the other excreting high levels of urinary E, MET, norepinephrine, and normetanephrine. Cerebrospinal fluid homovanillic acid levels were low in a subgroup of depressed patients. When analyzed by subgroup, the elevated E + MET group had markedly lower cerebrospinal fluid homovanillic acid levels than controls, whereas depressed patients with normal catecholamine levels did not. Since it has been postulated that there are two subgroups of depressed patients, those with low 3-methoxy-4-hydroxyphenylglycol (MHPG) levels and normal 5-hydroxyindoleacetic acid (5-HIAA) levels and those with normal MHPG levels and low 5-HIAA levels, several analyses were performed to see if such a group could be identified. Our analysis failed to find evidence of a subgroup of depressives with low MHPG and normal 5-HIAA levels or normal MHPG and low 5-HIAA levels.

Biogenic Amines↗
PubMed1987

Catecholamine metabolism and disposition in healthy and depressed subjects.

Depressed patients as a group have been found to excrete greater amounts of catecholamines (CAs) and metabolites than healthy control subjects, but these differences were not uniform for all metabolites. Patients may differ from controls in the metabolism and/or disposition of CAs. We analyzed the suggested metabolic-dispositional differences by determining 24-hour urine values for norepinephrine (NE), epinephrine (E), normetanephrine (NM), metanephrine (M), vanillylmandelic acid (VMA), and 3-methoxy-4-hydroxyphenylglycol (MHPG). For each subject, we calculated ratios of CAs or metabolites to an estimate of CA synthesis and determined ratios of CAs and metabolites to each other based on a precursor-product paradigm. The results indicate that as a group, patients have modestly but significantly greater CA synthesis rates than controls; patients excrete disproportionately more NE and E and disproportionately less MHPG relative to estimated CA synthesis, as well as other metabolites, than do controls; in contrast to NE, E, and MHPG, the increased NM, M, and VMA excretion rates by patients are proportional to each other as well as to the increase in CA synthesis; and the differences in NE, E, and metabolite excretion in the patients as a group are due principally to unipolar rather than bipolar depressives. The differences would be expected if patients, relative to controls, released more NE and E into the circulation. These data indicate the need to measure several CAs and metabolites when evaluating differences between groups since the significance of any given metabolite value needs to be examined in the context of total CA and metabolite production and excretion.

Adult↗
PubMed1987

Changes in urinary catecholamines and their metabolites in depressed patients treated with amitriptyline or imipramine.

The effects of treatment with amitriptyline (AMI) or imipramine (IMI) on changes in catecholamines and their metabolites in urine were studied in 95 unipolar and bipolar depressed patients. For the entire group, not separated by drug, substantial reduction in concentrations of all metabolites, but not catecholamines, occurred. Although catecholamine and metabolite change was similar for most substances assayed, there were some specific drug and diagnostic group differences. Vanillylmandelic acid (VMA) reduction was limited to bipolar patients; metanephrine (M) reduction to unipolar patients. Greater M and 3-methoxy-4-hydroxyphenylglycol (MHPG) reduction were associated with response in unipolar, but not bipolar patients. In bipolar, but not unipolar patients, norepinephrine (NE) rose in responders in contrast to reductions among nonresponding bipolar patients. The results suggest that effectiveness of blockade of reuptake of norepinephrine may be relatively more important for recovery in bipolar than in unipolar patients. Study of a battery of amine substances may contribute more information to our understanding of antidepressant drug effects on aminergic systems than analyses of MHPG alone.

Adult↗
PubMed1987

The timing, specificity and clinical prediction of tricyclic drug effects in depression.

This research was aimed at studying the rate of action of tricyclic drugs in depressive disorders, specifying the behavioural effects associated with recovery, and predicting clinical response. The research design involved comparison of a recovered group with a group treated for the equivalent four weeks, who showed minimal to no response. The findings indicated significant differences in baseline characteristics between responders and non-responders. Further, the drugs were found to act early in the responders, within the first week of treatment. Specific changes at one week which distinguished responder and non-responder groups occurred in the disturbed affects, and in cognitive functioning. Improvements also occurred in somatic symptoms, but these latter changes were general and not associated with later recovery. At 2 1/2 weeks, all facets of the depressed condition showed positive change in the responders. Implications of the results for assessing rate of tricyclic drug actions, their effects on the interaction of affect and neurochemistry, and the practical application of the results for the clinical situation, are discussed.

Adult↗
PubMed1986

Is there a metabolic basis for the fibrositis syndrome?

Patients with the fibrositis syndrome experience moderately severe musculoskeletal discomfort, mood changes associated with nonrestorative sleep, and tenderness to palpation at specific body sites. There is no characteristic abnormal laboratory finding in these patients to help identify the population. A report by Moldofsky and Warsh (Pain 1978; 5: 65-71) of low serum levels of free tryptophan in patients with severe fibrositis syndrome is intriguing but remains unexplained. Those data plus the observation by Hudson et al (Am J Psychiatry 1985; 142: 441-446; Biol Psychiatry 1984; 19: 1489-1493) that patients with fibrositis syndrome exhibit an increased prevalence of anxiety and depression suggest a number of possible avenues for further study. They include potential alterations in the homeostasis of catecholamines, corticosteroids, serotonin, aromatic amino acids, platelet membrane receptor levels, and the activity of platelet membrane monoamine oxidase. Among these possibilities, evidence is now available that suggests an increased production of catecholamines in fibrositis syndrome.

Animals↗
PubMed1986

Double-blind comparison of buspirone and clorazepate in anxious outpatients.

Buspirone, a new nonbenzodiazepine anxiolytic agent, was compared with clorazepate in a double-blind, multicenter trial conducted with 336 outpatients who had moderate to severe anxiety. The two treatments were equally effective for relief of symptoms, including anxiety with associated depression. Although both agents were generally well tolerated, the profile of side effects was dissimilar. Drowsiness and depression occurred significantly (p less than 0.055) more frequently with clorazepate, whereas nausea and headache occurred significantly (p less than 0.055) more frequently with buspirone. Clorazepate-treated patients were significantly (p less than 0.055) more likely to have had an adverse experience that was considered drug related or that interfered with the therapeutic effect. In this study, buspirone was shown to be an effective antianxiety agent, causing significantly less sedation than clorazepate.

Administration, Oral↗
PubMed1986

Path analysis of psychopharmacological data: catecholamine breakdown in man.

This article applies path analysis to the problem of characterizing metabolic alterations in catecholamine systems when only static or single measures of precursor and products are available. In this article, simulated data from kinetic models of norepinephrine metabolism were examined using path analysis. The method of path analysis, which is based on correlations between compartments and not actual flow, correctly identified operative and nonoperative metabolic pathways in simulated models. In addition, actual data from normal subjects as to the 24-hour urinary values for norepinephrine, normetanephrine, vanillylmandelic acid, and 3-methoxy-4-hydroxyphenylglycol were analyzed using path analysis. It was found that metabolic routes that are known to be incomplete did not fit these data, whereas the known metabolic pathways for norepinephrine were correctly identified using path analysis. These results suggest that path analysis may provide a useful tool in identifying normal and abnormal catecholamine metabolic pathways in experimental situations where only single values of precursor and products are available.

Humans↗