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Biomedical subjects

M H Ebert

Publications and source records attributed to M H Ebert.

At least 55 records · Page 3Linked to original sources
PubMed1984

Central nervous system catecholamine metabolism in Korsakoff's psychosis.

We attempted to replicate previous reports of impaired central noradrenergic activity in patients with Korsakoff's psychosis. No differences were demonstrated in lumbar cerebrospinal fluid concentrations of norepinephrine or its major metabolite, 3-methoxy-4-hydroxyphenyl glycol (MHPG), or in the contribution of plasma to cerebrospinal fluid free MHPG in 6 patients with clinically well characterized Korsakoff's psychosis and 8 age-matched healthy, normal volunteers. Likewise, cerebrospinal fluid concentrations of the major metabolites of dopamine (homovanillic acid) and serotonin (5-hydroxyindoleacetic acid) were the same in patients and controls.

Aged↗
PubMed1984

Hypersensitivity to d-amphetamine several years after early social deprivation in rhesus monkeys.

Social deprivation of rhesus monkeys in infancy results in increased sensitivity to psychotic-like behavioral effects of low doses of d-amphetamine given 2-3 years later. These behavioral effects are associated with increased levels of CSF norepinephrine. These data suggest that social developmental factors could be partially responsible for variation in neurochemical responses and long-lasting differential sensitivity of primates to the psychosis-inducing effects of d-amphetamine.

Analysis of Variance↗
PubMed1984

Catecholamine metabolism during clonidine withdrawal.

Abrupt cessation of clonidine treatment in hypertensive patients may precipitate a withdrawal syndrome. Since this drug is likely to be more widely prescribed to normotensive patients with neuropsychiatric diseases, we studied neurochemical, cardiovascular, and behavioral changes upon placebo substitution in seven patients receiving clonidine (6 micrograms/kg/day for 3 weeks) for treatment of alcohol amnestic disorder. Urinary excretion of all major catecholamine metabolites returned to pretreatment levels 3-5 days after discontinuing clonidine, without significant overshoot. The percentage increase during clonidine withdrawal of the norepinephrine metabolite normetanephrine was greater than were those of vanillylmandelic acid, 3-methoxy-4-hydroxyphenylglycol (MHPG), or the epinephrine metabolite metanephrine. Excretion of the dopamine metabolites homovanillic acid and 3-methoxytyramine did not change. Total plasma MHPG, heart rate, and mean arterial pressure were significantly elevated above pretreatment values 72 h after the last dose of clonidine. There was an enhancement of episodic memory compared to predrug values but no other behavioral changes were noted during clonidine withdrawal. These findings are consistent with augmented catecholamine release and central noradrenergic activation which may produce psychopathology in some psychiatric patients during clonidine withdrawal.

Aged↗
PubMed1984

Cerebrospinal fluid measures of neurotransmitter changes associated with pharmacological alteration of the despair response to social separation in rhesus monkeys.

Social separation is a risk factor for major depressions that can be modeled in nonhuman primates. Changes in central monoamine neurotransmission are also likely to be involved in major depression. This study examined the relationship between separation-induced depressive-like behavior and central monoamine neurotransmitter changes in rhesus monkeys. Measures of cerebrospinal fluid (CSF) norepinephrine (NE), 5-hydroxyindoleacetic acid (5HIAA), and homovanillic acid (HVA) were used to assess the neurobiological impact of social separation and drug treatments alone or in combination. alpha-Methyl-p-tyrosine exacerbated, and fusaric acid ameliorated, the depressive-like response to separation. Probenecid-induced accumulations of HVA and 5HIAA reflected changes in behavior, but were not consistently affected by drug treatment. In contrast, pretreatment CSF NE was comparatively stable across repeated sampling, and drug-induced changes in this measure were correlated with changes in behavior. Low CSF NE, whether drug-induced or naturally occurring, was associated with a more severe depressive-like response to separation.

Animals↗
PubMed1984

Cerebrospinal fluid homovanillic acid and 5-hydroxy-indoleacetic acid in adults with attention deficit disorder, residual type.

Following the hypothesis that attention deficit disorder in adults (attention deficit disorder, residual type; ADD, RT), as well as in children, is associated with decreased central dopaminergic activity, the authors measured lumbar cerebrospinal fluid monoamine metabolites in a group of adults with ADD, RT and matched control subjects. Patients were then entered into a double-blind, placebo-controlled trial of methylphenidate. It was predicted that the patients would have lower levels of homovanillic acid (HVA), the major dopamine metabolite in humans. Patients who had a significant response to methylphenidate showed a trend in this direction. Nonresponding patients had significantly higher levels of HVA than controls.

Adult↗
PubMed1984

Effects of clonidine on central and peripheral catecholamine metabolism.

Cerebrospinal fluid (CSF; n = 5) and plasma (n = 7) levels of norepinephrine (NE) and its major metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG) were examined in abstinent normotensive men with alcohol amnestic disorder during placebo and after 2 wk of clonidine treatment (6 or 12 micrograms/kg/day). Clonidine reduced concentrations of NE and both free and total MHPG in CSF and plasma. The CNS contribution to CSF free MHPG also decreased (as estimated from the differential reductions in CSF and plasma levels). Percent reductions in CSF and plasma NE were substantially greater than those for MHPG, suggesting diminished CNS and peripheral NE release and turnover. CSF levels of homovanillic acid (HVA), which is derived solely from CNS dopamine metabolism, rose in each patient, whereas the CSF serotonin metabolite, 5-hydroxyindoleacetic acid, did not change. Thus the increase in HVA cannot be attributed to inhibition of acid transport from brain to blood. Changes in central noradrenergic and dopaminergic activity correlated inversely; thus diminished NE release and enhanced dopamine metabolism may both contribute to the effects of clonidine in man.

Aged↗
PubMed1984

Disposition and metabolism of MHPG in humans: application to studies in depression.

MHPG is formed from norepinephrine metabolized throughout the body; its levels in plasma reflect total norepinephrine metabolism. Over half of the MHPG, is converted to VMA. Less than 20% of MHPG is derived from brain norepinephrine and urinary excretion of this metabolite cannot be used as a measure of brain norepinephrine metabolism. Because unconjugated MHPG is readily diffusable, there is a free exchange of this metabolite among plasma, cerebrospinal fluid, and nerve tissues (including brain and spinal cord). The CSF MHPG levels, after appropriately correction for the plasma contribution of the metabolite, reflect its rate of formation in the central nervous system.

Adrenal Gland Diseases↗
PubMed1984

Differences in brain serotonergic metabolism between nonbulimic and bulimic patients with anorexia nervosa.

CSF concentrations of serotonin and dopamine metabolites in 16 patients with anorexia nervosa were measured before and after probenecid administration, and the patients were studied before and at intervals after weight recovery. After probenecid administration, the weight-recovered nonbulimic anorexic patients had a higher concentration of the serotonin metabolite, 5-hydroxyindoleacetic acid, than the weight-recovered bulimic patients but no significant differences in CSF homovanillic acid. This finding is consistent with evidence that suggests a role for brain serotonin metabolism in carbohydrate and mood regulation.

Anorexia Nervosa↗
PubMed1984

Decreased 6-hydroxymelatonin excretion in Korsakoff's psychosis.

Mean (+/- SEM) urinary excretion rate of the major melatonin metabolite 6-hydroxymelatonin (micrograms/day) was lower in 7 (2.8 +/- 1.0) of 8 men with Korsakoff's psychosis (KP) than in 15 healthy men (11.4 +/- 1.4). Treatment with the alpha 2-noradrenergic agonist clonidine decreased daily 6-hydroxymelatonin excretion (p less than 0.02). Reduced daily excretion of 6-hydroxymelatonin in KP reflects decreased melatonin synthesis in the pineal gland, perhaps as a residual effect of lesions due to past thiamine deficiency (Wernicke's encephalopathy).

Aged↗
PubMed1984

Alpha-adrenergic receptors in orthostatic hypotension syndromes.

Alpha-adrenergic receptor function was measured in platelets from patients with orthostatic hypotension and normotensive controls. Patients with idiopathic orthostatic hypotension (IOH) or multiple system atrophy (MSA) had more alpha-receptors than controls. Patients with IOH, but not MSA, produced less prostaglandin E1 (PGE1)-stimulated cyclic AMP (cAMP) than controls. Patients with sympathotonic orthostatic hypotension (SOH) were similar to controls in receptor number and cAMP production. The percent norepinephrine (NE) inhibition of PGE1-stimulated cAMP production was similar in patients and controls. An increase in alpha-receptor number may result from decreased peripheral NE secretion in IOH and MSA. Increased alpha-receptor number and decreased cAMP production, which accompany essential hypertension, may contribute to the supine hypertension of IOH, and an increase in alpha-receptor number may contribute to the supine hypertension of MSA. SOH patients appear to have no abnormalities of alpha-receptor function.

Adolescent↗
PubMed1983

Distribution of free and conjugated dopamine in monkey brain, peripheral tissues and cerebrospinal fluid determined by high-performance liquid chromatography.

The occurrence of free and conjugated dopamine was determined by high-performance liquid chromatography with electrochemical detection in brain areas, peripheral tissues, and CSF from rhesus monkeys. Free norepinephrine, epinephrine, and 3,4-dihydroxyphenylacetic acid were also determined in some tissues. Conjugated dopamine was found to be widely, but not homogeneously, distributed in this species. In the brain, conjugated dopamine was found to account for greater than 10% of the total dopamine present in the frontal cortex (74%), cingulate gyrus (31%), cerebellum (16%), and occipital cortex (11%). Conjugated dopamine accounted for 21% of the total dopamine in the liver, and ranged from 10 to 20% of the total in testicle, kidney and heart. In CSF from both the lateral ventricle and lumbar thecal sac, free dopamine was not reliably detected, but conjugated dopamine was found in all samples tested.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1983

Clinical research in neuropsychiatry.

This paper presents the thesis that rapidly developing areas of knowledge in neuroscience will rekindle interest in neuropsychiatry, and increase scientific and clinical interaction between psychiatrists and neurologists in teaching hospitals. A neuropsychiatric clinical research unit at the National Institute of Mental Health is described. Examples of research conducted on the unit illustrate areas of biological science that are likely to increase the interface between psychiatry and neurology. Hopefully, the explosion of knowledge in the basic neurosciences in the last decade will be followed in this decade by clinical research of increasing specificity and sophistication of central nervous system disorders.

Brain↗
PubMed1983

Urinary catecholamine metabolites and effects of clonidine in patients with alcohol amnestic disorder.

Seven normotensive patients with alcohol amnestic disorder were treated with 2 micrograms/kg clonidine (C) three times daily for 1 wk. Four patients received 12 micrograms/kg/day during the subsequent week; three developed hypotensive symptoms at this dose and remained on 6 micrograms/kg/day. During a predrug placebo period and after 60 hr on each dose of C, urinary excretion rates of catecholamine metabolites were determined. C, 6 micrograms/kg/day, reduced the ratio of norepinephrine (NE) metabolites (mumol/24 hr) to normetanephrine (NM), vanillylmandelic acid (VMA), and 3-methoxy-4-hydroxyphenyl glycol (MHPG). The excretion of metanephrine (M) was not reduced significantly. The ratio M/NM and M/(VMA + MHPG) increased, indicating Cs effects are primarily noradrenergic. Reduction in NM/(VMA + MHPG) indicates disproportionate lowering of the O-methylated metabolite of NE compared to its deaminated metabolites, consistent with C inhibition of NE release. Patients with the highest predrug NM excretion had the greatest decrements with C. The dopamine metabolites 3-methoxytyramine and homovanillic acid were not decreased by C. C-induced reductions in the ratio NM/(VMA + MHPG), an index of NE release, correlated (n = 7) with reductions in supine systolic blood pressure, mean arterial pressure, and salivary flow rate.

Aged↗
PubMed1983

A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

A syndrome similar to idiopathic parkinsonism developed after intravenous self-administration of an illicit drug preparation in which N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (NMPTP) might have been responsible for the toxicity. In the present study we show that intravenous administration of NMPTP to the rhesus monkey produces a disorder like parkinsonism (akinesia, rigidity, postural tremor, flexed posture, eyelid closure, drooling) that is reversed by the administration of L-dopa. NMPTP treatment decreases the release of dopamine and dopamine accumulates in swollen, distorted axons in the nigrostriatal pathway just above the substantia nigra, followed by severe nerve cell loss in the pars compacta of the substantia nigra and a marked reduction in the dopamine content of the striatum. The pathological and biochemical changes produced by NMPTP are similar to the well-established changes in patients with parkinsonism. Thus, the NMPTP-treated monkey provides a model that can be used to examine mechanisms and explore therapies of parkinsonism.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1983

Psychological and behavioral characteristics of normal-weight bulimics and normal-weight controls.

This study compares psychological traits, physical traits, behavior, demographic data, incidence of family pathology, incidence of life stress, and scores on eating disorder scales in a sample of normal-weight female bulimics with a sample of normal-weight female controls. The groups, matched for age, socioeconomic status, and I.Q. were found to have comparable physical traits, family demographics, incidence of family pathology, and incidence of life stress. However, bulimics demonstrated significantly higher levels of psychological pathology and impulsive behavior. There were significantly more suicide attempts, psychiatric hospitalizations, episodes of stealing, use of drugs, and menstrual disturbances among the bulimics than the controls. The bulimics consistently rated themselves sicker than the controls on all psychometric scales. Most notable were the depression, anxiety, obsessive-compulsive, and interpersonal sensitivity factors on the Symptom Checklist 90, and the internal control score on the Nowicki-Strickland Locus of Control Scale. The discussion includes a brief description of weight set-point theory and its role in the maintenance of bulimia.

Adult↗
PubMed1983

Urinary catecholamine metabolites distinguish different types of sympathetic neuronal dysfunction in patients with orthostatic hypotension.

Urinary excretion rates of the major norepinephrine metabolites, 3-methoxy-4-hydroxymandelic acid, 3-methoxy-4-hydroxy-phenylglycol and normetanephrine, were determined in 12 normal subjects and 23 patients with neurogenic orthostatic hypotension due to either multiple system atrophy [Shy-Drager Dyndrome (MSA)] or idiopathic orthostatic hypotension (IOH). There were striking and parallel decreases in all catecholamine metabolites in IOH consistent with loss of peripheral sympathetic nerves. Patients with MSA excreted greater amounts of the deaminated metabolites than did the patients with IOH, but most excreted equally low amounts of normetanephrine. The disproportionate decrease in excretion of normetanephrine by patients with MSA is consistent with observations in experimental animals that O-methylation is the primary metabolic route for active released norepinephrine, whereas deamination is the predominant metabolic route for intraneuronal degradation of the catecholamine. The similar proportional decreases in all catecholamine metabolites in patients with IOH (who have no central nervous system deficit) indicates that brain norepinephrine is a source of only a small fraction of urinary norepinephrine metabolites, including 3-methoxy-4-hydroxy-phenylglycol.

Humans↗