Cerebrospinal fluid 3-methoxy-4-hydroxyphenylglycol and norepinephrine levels in alcohol withdrawal. Correlations with clinical signs.

Cerebrospinal fluid (CSF) and plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations were significantly elevated in patients during the alcohol withdrawal syndrome. When CSF MHPG was corrected using a formula proposed to determine CSF MHPG levels of central origin, these values were still significantly elevated when compared with control values. The MHPG concentrations in CSF also showed significant positive correlations with heart rate, systolic and diastolic blood pressures, tremor, anorexia, and sweating. The results of this study indicate increased presynaptic release of norepinephrine during alcohol withdrawal.

Alcohol and central serotonin metabolism in man.

Animal studies and some of thephenomena associated with alcoholism in humans suggest that some central effects of alcohol may involve serotonergic systems. The CSF metabolites of serotonin and dopamine, 5-hydroxyindoleacetic acid (5HIAA), and homovanillic acid (HVA) were studied in hospitalized alcoholics. There were no significant differences in HVA levels between groups. The level of 5HIAA of alcoholics in the abstinence phase, 28 to 63 days after their last drink, was significantly lower (21.8 +/- 1.9 ng/mL) than both a nonalcoholic comparison group (31.7 +/- 2.0 ng/mL) and alcoholics in the immediate postintoxication phase, within one to two days after their last drink (32.3 +/- 2.9 ng/mL).

Dopamine beta-hydroxylase in CSF. Relationship to personality measures.

Dopamine beta-hydroxylase (DBH), the enzyme that converts dopamine to norepinephrine, was measured in the CSF of 32 subjects. Those individuals with a low level of DBH in the CSF had significantly elevated profiles on the Minnesota Multiphasic Personality Inventory, suggesting a relationship between the central noradrenergic system and some aspects of personality in man.

Normal cerebral asymmetry in bipolar patients.

Reversal of normal cerebral asymmetry has been reported to be more frequent in children with higher cortical dysfunction and in schizophrenics, in whom it has clinical significance as well. As there are few studies of bipolar patients, we attempted to determine if significant reversal would be found in a clearly diagnosed sample of bipolar patients. As technical differences may account for varying results, we used two previously reported methods and a modified technique. Correlations of computed tomography (CT) findings with neuropsychological variables (Halstead Reitan Battery and WAIS subtests) were also studied. Bipolars and controls did not differ on any CT measure, nor were there meaningful correlations between asymmetry and neuropsychological variables. If if is confirmed that schizophrenics have increased reversed cerebral asymmetry but bipolars do not, it may point to an important difference, as all other CT abnormalities initially described in schizophrenics are now also noted in bipolar patients.

Dopamine-beta-hydroxylase in the cerebrospinal fluid: relationship to disulfiram-induced psychosis.

Cerebrospinal fluid (CSF) dopamine-beta-hydroxylase (DBH) activity in 32 male alcoholics was measured using a modification of the radioenzymatic method of Molinoff et al. In most, the CSF was obtained before treatment with disulfiram, while in others it was obtained while they were on the drug (250 or 500 mg). As expected, treatment with this reversible DBH inhibitor had no effect on the activity of the enzyme measured in our in vitro assay. However, low pretreatment DBH activity was found to correlate with adverse reactions to disulfiram. Mean DBH activity of four individuals who went on to become psychotic on disulfiram was 0.13 +/- 0.02 nmole/ml per hr (mean +/- SEM). An additional four individuals who developed dysphoric but nonpsychotic reactions had a mean DBH of 0.23 +/- 0.03. Both these values were significantly lower than the mean DBH activity of the remaining 24 individuals treated with disulfiram who had no adverse side effects, 0.53 +/- 0.06 p less than 0.02 and p less than 0.05, respectively, 2-tailed t-test.

Cerebrospinal fluid homovanillic acid in male alcoholics: effects of disulfiram.

It is well know that if an individual maintained on disulfiram (Antabuse) ingests alcohol, excess acetaldehyde is formed, resulting in a toxic reaction. In addition to this toxic interaction with alcohol (the basis of its use as a deterrent), there are both behavioral and biochemical observations to suggest that disulfiram alone has a direct effect on the CNS. The possibility that some of disulfiram's effects are related to alterations in biogenic amine metabolism led to the present study of cerebrospinal fluid amine metabolites in a group of male alcoholics. In this group, disulfiram treatment was associated with a significant reduction in homovanillic acid, the major metabolite of dopamine, while no change was noted in 5-hydroxyindoleacetic acid, the major metabolite of serotonin. Prior to disulfiram, patients with withdrawal symptoms had significantly lower homovanillic acid than those without such symptoms.

Dopamine-beta-hydroxylase in the cerebrospinal fluid of psychiatric patients.

The activity of dopamine-beta-hydroxylase (DBH) in cerebrospinal fluid (CSF) from 59 psychiatric patients has been analyzed by a highly sensitive radio-enzymatic assay. There was no sex difference in DBH, but there was a significant positive correlation with age. Probenecid administration had no effect on CSF DBH. DBH in CSF correlated positively (r = 0.60) with the plasma enzyme. Among patients hospitalized for major depressive disorder, unipolar or bipolar, schizo-affective disorder, schizophrenia, alcoholism, or personality disorders there were no significant between-group differences. Among the patients with bipolar affective disorder, DBH activity from manic patients was significantly lower than that from depressed or euthymic patients. The results are discussed with reference to the theory that the amount of DBH in CSF may serve as an indicator of central noradrenergic activity.

Central brain morphology in chronic schizophrenic patients: a controlled CT study.

A comprehensive quantitative computed tomography (CT) study of the diencephalic region of 23 chronic schizophrenic patients and 23 normal controls was done. The third ventricle width, the Sylvian fissure widths, and the densities of the head of the caudate nucleus, thalamic nucleus, and medial temporal lobe were measured. In the schizophrenic patients, there was a significant increase in third ventricle and Sylvian fissure widths and a significantly greater density of both periventricular nuclei. The several explanations for this atypical association of atrophy with greater density are discussed.

The quantitative measurement of depression and anxiety in male alcoholics.

Depression and anxiety have been reported to be commonly associated with alcoholism. Most attempts to clarify this relationship have suffered from a patient selection bias in that only those alcoholics who sought treatment were studied. The authors performed quantitative measurements of depression and anxiety in a group of 48 men referred for treatment solely on the basis of excessive drinking. The prevalence of depression and anxiety as measured by both the Zung and Hamilton scales was lower than that shown in previous studies. The results of this study indicate that problems in young, healthy male alcoholics.

The role of plasma amine oxidase, platelet monoamine oxidase, and red cell catechol-O-methyl transferase in severe behavioral reactions to disulfiram.

The authors assayed platelet monoamine oxidase (MAO), plasma amine oxidase (AO), and red cell catechol-O-methyl transferase (COMT) in 32 male alcoholics before they began disulfiram treatment. Seven subjects developed psychotic reactions to disulfiram; these 7 had significantly lower pretreatment MAO and AO levels and significantly higher COMT than the patients who had no adverse reactions to disulfiram, which suggests that severe behavioral reactions to disulfiram are associated with differences in enzyme activities.

Increased sympathetic nervous system activity in alcoholic patients treated with disulfiram.

The authors measured plasma levels of norepinephrine (NE) and dopamine beta-hydroxylase (DBH), pulse rates, and blood pressures of 81 hospitalized alcoholic patients. Treatment with 500 mg/day of disulfiram (but not 250 mg/day or placebo) resulted in small but significant increases in plasma NE and in blood pressure. The 500-mg dose did not appreciably inhibit DBH. Patients receiving high doses of disulfiram should have their blood pressure monitored and their dose decreased to 250 mg/day when possible.

CSF levels of norepinephrine during alcohol withdrawal.

Cerebrospinal fluid norepinephrine (NE) levels were determined by radioenzymatic assay in 21 patients with a variety of neurological diseases and 49 patients in acute alcohol withdrawal. A second determination was made in 19 patients who had recovered from the alcohol withdrawal syndrome. Cerebrospinal fluid NE concentration was higher in the patients during alcohol withdrawal (192.3 plus or minus 22.3 pg/mL) and decreased during recovery to 137.8 plus or minus 15.9 pg/mL. The CSF NE level was higher in both groups than in patients with other neurological disorders. This may help explain the adrenergic signs observed during alcohol withdrawal.

Dopamine-beta-hydroxylase in cerebrospinal fluid and plasma: effects of alpha-adrenergic agents.

Dopamine-beta-hydroxylase (DBH) and norepinephrine are both localized in noradrenergic storage vesicles. When noradrenergic nerves fire, both norepinephrine and DBH are released by exocytosis. DBH released from the peripheral nervous system and the adrenal medullae is found in blood, while DBH in cerebrospinal fluid (CSF) is presumably of central origin. This study was designed to: (1) investigate the effect of drugs which alter central noradrenergic activity on DBH activity in CSF; and (2) compare the effects of these drugs on DBH in CSF and plasma in cats. Phenoxybenzamine was given subcutaneously at 6 mg/kg and DBH was measured 8 h later. This treatment significantly increased DBH activity in CSF (n = 10,P less than 0.005). There were no consistent changes in plasma DBH, although there was a tendency for DBH to increase from low basal levels and to decrease from high basal levels. Clonidine was administered in 4 subcutaneous injections (100, 50, 50, 50 microgram/kg) over a 19-h period, and blood and CSF were taken 5 h after the last injection. This treatment caused a significant decrease in CSF DBH activity (P less than 0.05, n = 8). The effect of clonidine on plasma DBH was strongly dependent on the basal enzyme level. The 3 lowest DBH values increased and the 5 highest DBH values decreased on drug treatment. These results are discussed with respect to the theory that changes in CSF DBH may reflect central noradrenergic activity.

Differential effects of DL-propranolol on norepinephrine in cerebrospinal fluid and plasma.

Acute administration of DL-propranolol (5 mg/kg, subcutaneous) to cats caused a significant increase in cerebrospinal fluid (CSF) norepinephrine and a significant decrease in plasma norepinephrine. This increase in CSF norepinephrine is probably due to a reflex increase in central noradrenergic firing after beta blockade. The decrease in plasma norepinephrine reflects decreased sympathetic outflow. These results are consistent with the centrally mediated hypotensive effects of the drug.

Central noradrenergic adaptation to long-term treatment with imipramine in rhesus monkeys.

Rhesus monkeys were treated with the antidepressant drug imipramine; cerebrospinal fluid norepinephrine and dopamine-beta-hydroxylase were measured to assess central noradrenergic activity. Large changes occurred after short-term, but not long-term, treatment. Biochemical stabilization occurs at the time when therapeutic effects are seen in patients.

Electroconvulsive therapy in the 1980s.

Electroconvulsive therapy (ECT) has generated more controversy and strong feelings than any other psychiatric modality in use today. This review presents the facts upon which each reader can make a rational decision as to the advantages and disadvantages of ECT.

Aggression in humans correlates with cerebrospinal fluid amine metabolites.

Cerebrospinal fluid of the major central metabolites of serotonin (5HT), norepinephrine (NE), and dopamine (DA)--5-hydroxyindoleacetic acid (5HIAA), 3-methoxy-4-hydroxy=phenylglycol (MHPG), and homovanillic acid (HVA), respectively--were studied in a group of 26 age-similar military men with no history of major psychiatric illness, but with various personality disorders and difficulties adjusting to military life. Independently scored history of aggressive behavior showed a significant negative correlation with 5HIAA (r = -0.78) and a significant positive correlation with MHPG (r = 0.64).

Elevated cerebrospinal fluid histidine in alcohol withdrawal.

Cerebrospinal fluid (CSF) histidine concentration was significantly elevated in seven patients early in the alcohol withdrawal syndrome (206.3 +/- 74.4 (SEM) nanomols/ml CSF). When these same patients were restudied an average of six days later when alcohol withdrawal was clinically resolved, their mean CSF histidine concentration continued to be significantly elevated (164.7 +/- 24.7) when compared to normal (12.0 +/- 0.5 nanomols/ml CSF). Other amino acids (aspartic acid, serine, alanine, methionine, leucine, tyrosine, phenylalanine, lysine and arginine) showed no definite changes from normal, and no change during the course of alcohol withdrawal. Possible reasons for these high concentrations and the extreme variability (especially early in alcohol withdrawal) are discussed.

Human brain: aldehyde dehydrogenase activity and isozyme distribution in different areas.

Three human post-mortem brains were dissected into seventeen areas and assayed for aldehyde dehydrogenase (EC 1.2.1.3) activity employing two assay systems: one at 68 microM and another at 13.6 mM propionaldehyde. The levels of activity with 68 microM propionaldehyde were significantly higher in cerebellum and putamen. The same brain areas were also examined by isoelectric focusing. By this procedure two distinct bands of aldehyde dehydrogenase activity (the cytoplasmic E1 and mitochondrial E2) could be readily visualized in cerebellum and putamen while other brain areas contained mainly the mitochondrial E2 isozyme.

Trace element levels in human alcoholic brain.

Copper, magnesium, zinc and manganese levels in the temporal cortex of human alcoholic and control brains were measured by atomic absorption spectrophotometry using both the flame and graphite furnace. All of the 21 alcoholics were male with a mean age of 54.1 years; the 19 male controls had a mean age of 60.2 years. The only statistically significant change in ion levels was an increase in manganese concentration (expressed both as microgram/g wet weight and ng/mg protein) in the alcoholic group when compared to the control group. Five of the alcoholics had malignancies, while 16 of the controls had systemic malignancies. Covariance analysis showed there was no effect of age on the level of manganese in the temporal cortex.