The relationship of plasma free MHPG to anxiety and psycho-physical pain in normal volunteers.
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Biomedical subjects
Publications and source records attributed to M S Buchsbaum.
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8 mg of naloxone were administered IV to 14 normal volunteers in a placebo-controlled, double-blind experiment. Plasma levels of beta-endorphin, cortisol, prolactin, growth hormone, HVA and MHPG were determined before and 45 min after administration. Naloxone elicited significant increases in cortisol and MHPG but did not change plasma levels of the other compounds. In an additional experiment on two subjects, 20 mg of naloxone caused elevations of beta-endorphin as well as of cortisol. This parallel increase indicates that the linkage between the secretion of beta-endorphin and ACTH/cortisol may be dose-dependent. The increase in MHPG is in agreement with the hypothesized association of noradrenergic hyperactivity and opiate withdrawal.
Somatosensory evoked potentials (SEPs) and body temperature were recorded in patients subjected to induced total hyperthermia for treatment of advanced neoplasms. Elevation of body temperature up to 42 degrees C for 2 h was achieved using a computer-controlled external heating system. SEPs were recorded continuously on-line during the treatment using finger shock stimulation. Evoked potential components later than 160 msec disappeared in the early part of the treatment, but reappeared quickly during cooling. P50 and P50-N70 amplitudes decreased regularly and significantly over the whole duration of the heating period. During the plateau period, no evoked potential peaks could be detected but short latency peaks reappeared as soon as cooling started. The disappearance of SEPs to finger stimulation during sustained hyperthermia at 42 degrees C confirms the findings obtained by EEG recording that a major neuronal dysfunction occurs under these circumstances which subsides quickly as temperature is dropped.
Six offspring of manic-depressive patients, whose parents were lithium responders, were selected on the basis of their incapacitating psychopathology for treatment with lithium. The children ranged in age from 6 to 12. A double-blind, crossover design was used over 16-18 weeks. Weekly ratings were done, and average evoked potentials (EPs) were measured at each crossover. Two children diagnosed as having a bipolar affective disorder had a clear-cut response to lithium and were strong augmenters on the EP. This, taken together with the similarity of the EP changes on lithium to those occurring in adult patients treated with lithium, supports a physiological parallel between bipolar affective illness in adults and children.
Gamma-hydroxybutyrate (GHB) was administered to seven chronic schizophrenic patients in the first double-blind, placebo-replacement trial of this compound. No significant drug effect in this group was obtained. Two patients became nonpsychotic during the drug trial, three got worse and two patients did not respond. The two patients who responded with improvement were augmenters, as measured by average evoked potential (EP), had low platelet MAO activity and high cerebrospinal fluid (CSF) homovanillic acid (HVA). A number of patients developed akathisia and dystonia during the trial, especially after receiving probenecid for lumbar puncture. Further study is warranted, possibly in a selected patient group.
The behavioral and cognitive effects of single doses of caffeine (3 and 10 mg/kg) were studied using a double blind placebo-controlled crossover design. Subjects were 19 prepubertal boys and 20 college age men. In general, children tended to show more objective effects of caffeine than did adults, with increased motor activity, increased speech rate, and decreased reaction time. Adults generally reported side effects following caffeine while children did not, and side effects were more prominent for adults with low habitual caffeine intake. Autonomic measures of arousal were similarly affected for both age groups. Caffeine had some effects that differed from those of amphetamine, indicating distinctive actions of the two stimulants.
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Stressful procedures are reported to increase urinary MHPG in both normal and depressed patients. Bipolar depressed patients are also shown to be especially pain tolerant in comparison to normals. In the present study, 12 depressed patients (6 bipolar and 6 unipolar patients) and 10 normal volunteers had average evoked potentials recorded for visual and painful electrical stimuli. MHPG urinary excretion was measured during this session and during an unstimulated resting session on the home ward. Male normal volunteers showed a significant increase in urinary MHPG under stress, while no MHPG increment was noted for the depressed group. Depth of depression, assessed by the Zung and Beck scales, was found to be correlated with the reduced urinary MHPG response to stress. Possible interpretations of the results are discussed.
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The authors collected clinical diagnostic, neurophysiological, electrophysiological, and biochemical data on 9 adolescents who had primary obsessive-compulsive disorder. The results indicate considerable descriptive validity of the syndrome in childhood and its independence from obsessional traits; however, all of the children had a history of major depressive disorder, and their sleep EEG measures resembled those of young adults with primary depressive disorder. The patients' families did not have a more consistent pattern of anxiety disorder or any other psychiatric disorder than do families of adult obsessive patients. Psycholinguistic test results showed a lack of normal laterality, which has been reported for other psychiatric illness.
A recent study demonstrated that dextroamphetamine has an effect in normal prepubertal boys similar to that seen in hyperactive children. The purpose of the present study was to see whether the effects of caffeine are similar to those of amphetamine in normal children. The authors observed 19 prepubertal boys following administration of a single dose of placebo, 3 mg/kg of caffeine, and 10 mg/kg of caffeine in a double-blind, crossover design. Caffeine produced increased vigilance and decreased reaction time, as does amphetamine. Unlike amphetamine, however, the higher dose of caffeine did not have a motor calming effect but increased motor activity. Separate biological systems, therefore, may be differentially affected by the two substances.
The effects of a single night of sleep deprivation on the amplitude and amplitude/stimulus intensity function of the visual evoked potential (EP) were studied in 16 patients with primary affective disorder and 20 normal controls. Visual EP amplitude and amplitude/intensity slopes tended to increase after sleep deprivation in the patient group, a direction found in other studies to be associated with a spontaneous mood improvement and changes with antidepressant medication. In contrast, normal volunteers who showed little or no mood elevation showed generally opposite EP effects. Taken together, the results suggest a similarity in the neurophysiological effect of sleep deprivation between patient and antidepressant medication in depressed patients.
College students in two separate studies had platelet monoamine oxidase (MAO) activity determinations and average evoked potential (AEP) measurements taken. On the basis of Minnesota Muliphasic Personality Inventory (MMPI) or Research Diagnostic Criteria (RDC) evaluations, psychopathology, particularly affective disorder, was found to be more prevalent among both persons with the combination of low MAO activity and AEP augmenting and those with high MAO activity and AEP reducing. The same pattern is apparent whether students were selected for extremely high or low MAO activity (study 1) or for elevated or normal MMPI scores (study 2). Some psychiatric patient groups also show this pattern. An interactive model of sensation-seeking and sensory inhibition is presented.
The effects of a single oral dose of dextroamphetamine sulfate on motor activity, vigilance, learning, and mood were compared for normal and hyperactive prepubertal boys and normal college-aged men using a double-blind crossover design. Both groups of boys and men showed decreased motor activity increased vigilance, and improvement on a learning task after taking the stimulant drug. The men reported euphoria, while the boys reported only feeling "tired# or "different# after taking the stimulant. It is not clear whether this difference in effect on mood between adults and children is due to differing experience with drugs, ability to report affect, or a true pharmacologic age-related effect. While there were some quantitative differences in drug effects on motor activity and vigilance between these different groups, stimulants appear to act similarly on normal and hyperactive children and adults.
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Deficient sustained attention is a symptom of hyperactivity that can be improved by stimulant medication. Recently, amphetamine has been shown to increase detections during a vigilance task in both normal and hyperactive boys. The present study applied signal detection analysis to the vigilance performance of 15 hyperactive and 14 normal boys dsivided into two age groups (6-9 and 10-12). A computerized continuous performance test was administered under amphetamine and placebo. Overall group comparisons indicated that perceptual sensitivity or d' was higher for the normal boys and the older groups, and analysis of drug treatments showed that amphetamine significantly increased d'. Interactions between drugs and age groups demonstrated that amphetamine affected the younger boys to a significantly greater degree than the older children for both d' and response bias or beta. It is notable that the results were essentially parallel for both normal and hyperactive children.
No differences in levels of type A monoamine oxidase (MAO) were observed in cultured human skin fibroblasts from nine patients with bipolar depressive illness as compared to 18 age-, sex-, and race-matched controls. All cells were biopsied and cultured under parallel conditions. Fibroblasts from monozygotic twins (three sets) had levels of MAO activity that were highly concordant, indicating that levels measured in fibroblasts are genetically determined. Together these findings suggest that an inherited predisposition to bipolar depressive illness does not involve inherited variations in levels of type A MAO activity. Using a larger control population, a positive correlation was observed between age of donor and level of MAO activity. This finding demonstrates the need for age-matched control and patient groups when comparing levels of type A MAO in fibroblasts.
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