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Biomedical subjects

D E Sternberg

Publications and source records attributed to D E Sternberg.

34 records · Page 2Linked to original sources
PubMed1982

Impaired presynaptic regulation of norepinephrine in schizophrenia. Effects of clonidine in schizophrenic patients and normal controls.

Recent studies have found elevated levels of norepinephrine (NE) in CSF and brain specimens from schizophrenic patients. Presynaptic inhibitory alpha 2-adrenergic receptors regulate NE release in the brain. The hypothesis that the functional sensitivity of this presynaptic regulation of NE is impaired in schizophrenia was tested by evaluating, in schizophrenic patients and age-matched normal controls, the ability of clonidine, an alpha 2 agonist, to lower plasma levels of the NE metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) and to lower blood pressure (BP). Clonidine produced a significant decrease in plasma MHPG levels in the normal control group, but did not lower plasma MHPG levels in the schizophrenic patients. Clonidine decreased BP equally in both groups. These results suggest that there is a functional subsensitivity of the inhibitory presynaptic alpha 2-adrenergic receptor in schizophrenia, which may relate to an impaired regulation of NE turnover.

Adult↗
PubMed1982

Adrenergic receptor sensitivity in depression. Effects of clonidine in depressed patients and healthy subjects.

Several recent investigations have raised the possibility that the sensitivity of alpha 2-adrenergic receptor may be of etiologic importance in depression. To assess whether abnormalities in presynaptic alpha 2-adrenergic receptor exist in depressed patients not taking drugs, the effects of an alpha 2 agonist, clonidine, on plasma 3-methoxy-4-hydroxyphenelethyleneglycol (MHPG) and on blood pressure (BP) were evaluated in 15 depressed patients and 12 healthy controls of similar age. The ability of clonidine to increase growth hormone (GH) secretion was also assessed. The effect of clonidine on plasma MHPG and BP was not different between the depressed patients and controls. However, the GH response to clonidine was blunted in the depressed patients. These results suggest that in depression (1) the sensitivity of the presynaptic alpha 2-adrenergic receptor is not abnormal, and (2) the sensitivity of postsynaptic adrenergic receptors may be decreased.

Adult↗
PubMed1982

Clonidine and naltrexone. A safe, effective, and rapid treatment of abrupt withdrawal from methadone therapy.

Clonidine hydrochloride and naltrexone hydrochloride, given in combination, were found to provide a safe, effective, and extremely rapid treatment of abrupt withdrawal from methadone hydrochloride therapy. Under controlled inpatient conditions established to assess dosage guidelines and to examine specific signs and symptoms of withdrawal, ten (91%) of 11 patients were able to withdraw completely from methadone therapy by the end of a six-day period. Six days of clonidine hydrochloride treatment, with a peak mean dose of 2.9 mg/day on treatment day 2, attenuated the withdrawal-inducing effects of naltrexone. Naltrexone hydrochloride was gradually increased from an initial 1-mg dose on treatment day 2 to 50-mg maintenance dose on treatment day 5 without an associated increase in withdrawal symptoms. Clonidine significantly decreased BP without producing clinical problems. The withdrawal symptoms of anxiety, restlessness, and muscular aching were most resistant to treatment, but at discharge most patients were completely asymptomatic.

Adult↗
PubMed1982

The effect of intravenous L-tryptophan on prolactin and growth hormone and mood in healthy subjects.

In order to assess the effects of increased central nervous system serotonergic function in humans on prolactin (PRL), growth hormone (GH) and mood, intravenous L-tryptophan (TRP) was administered to ten healthy subjects. The TRP infusion induced robust increases in PRL in all ten subjects. A significant increase in GH concentration was also observed, although the response was more variable. The subjects reported feeling significantly more high, mellow, and drowsy following the TRP infusion in comparison to placebo. These findings indicate an important role for serotonin in PRL and GH secretion, as well as in mood regulation. The intravenous TRP challenge may be of use in the study of serotonergic function in a variety of neurologic and psychiatric diseases.

5-Hydroxytryptophan↗
PubMed1982

The effect of IV L-tryptophan on prolactin, growth hormone, and mood in healthy subjects.

In order to assess the effects of increased CNS serotonergic function in humans on prolactin (PRL), growth hormone (GH), and mood, IV L-tryptophan (TRP) was administered to ten healthy subjects. The TRP infusion induced robust increases in PRL in all ten subjects. A significant increase in GH concentration was also observed, although the response was more variable. The subjects reported feeling significantly more 'high', 'mellow', and 'drowsy' following the TRP infusion in comparison to placebo. These findings indicate an important role for serotonin in PRL and GH secretion, as well as in mood regulation. The IV TRP challenge may be of use in the study of serotonergic function in a variety of neurologic and psychiatric diseases.

Adult↗
PubMed1982

Cerebrospinal fluid hydroxylase cofactor in schizophrenia.

Cerebrospinal fluid levels of pterin cofactor were measured in off-medication schizophrenic patients and normal control subjects as one aspect of monoamine physiology in schizophrenia. Pterin cofactor is essential for the hydroxylation of several substances including tyrosine, the rate-limiting step in the synthesis of dopamine and norepinephrine. No significant differences were found. Platelet monoamine oxidase activity correlated significantly with pterin levels in male schizophrenic and in female control subjects.

Adult↗
PubMed1982

Failure of chronic antidepressant treatment to alter growth hormone response to clonidine.

The effect of 4 to 6 weeks of treatment with the antidepressants, desmethylimipramine and amitriptyline, on the growth hormone response to clonidine was studied in 12 depressed patients. In contrast to the reported effects of clonidine in healthy subjects, clonidine did not significantly increase growth hormone secretion in the depressed patients before treatment. The antidepressant treatments did not alter the growth hormone response to clonidine in either treatment responders or nonresponders.

Amitriptyline↗
PubMed1982

Abrupt discontinuation of tricyclic antidepressant drugs: evidence for noradrenergic hyperactivity.

The effect of abrupt discontinuation of amitriptyline, desipramine, or imipramine) on norepinephrine turnover and specific symptoms in seven depressed patients was examined. Turnover, as determined by plasma and urinary 3 methoxy-4-hydroxy-phenylethylene glycol (MHPG), was increased to a peak during the second week following discontinuation. There were no changes in blood pressure or heart rate. Two of the seven patients experienced clear increases in anxiety. The implications for the role of noradrenergic function is discussed.

Adult↗
PubMed1981

The clinical use of clonidine in abrupt withdrawal from methadone. Effects on blood pressure and specific signs and symptoms.

Clonidine hydrochloride was found to be effective in the treatment of methadone hydrochloride withdrawal. Under controlled inpatient conditions established to assess dosage guidelines and to examine specific signs and symptoms of withdrawal, 20 of 25 (80%) patients were able to withdraw completely from methadone by the end of a two-week period. In most patients, ten to 11 days of clonidine administration, with a peak mean dose of 16 micro g /kg/day, resulted in a perceived reduction in symptoms compared with previous attempts to become opiate free. At these doses clonidine significantly reduced standing blood pressure without producing clinical problems. The withdrawal symptoms of anxiety, restlessness, insomnia, and muscular aching were most resistant to clonidine treatment and were reported by the majority of patients.

Adult↗
PubMed1981

Presynaptic adrenergic receptor sensitivity in depression. The effect of long-term desipramine treatment.

Stimulation of presynaptic alpha 2-adrenergic receptors located on norepinephrine (NE)-containing cells in the brain decreases the firing rate and turnover of NE in these neurons. To assess whether abnormalities in the regulation of the NE system during desipramine hydrochloride treatment may be present in depressed patients, the effects of an alpha 2-agonist, clonidine hydrochloride, on plasma levels of the NE metabolite 3-methoxy-4-hydroxy/phenethyleneglycol (MHPG) and on blood pressure (BP) were evaluated in ten depressed patients before and during long-term desipramine treatment. Long-term desipramine treatment significantly attenuated the effects of clonidine on plasma MHPG level and BP, indicating that during desipramine treatment alpha 2-adrenergic receptors had become subsensitive. In addition, plasma MHPG levels were significantly reduced during long-term desipramine treatment. These findings are discussed in relation to the hypothesized therapeutic mechanism of action of desipramine and the hypotheses relating noradrenergic function and depression.

Adult↗
PubMed1981

Plasma MHPG in depression: effects of acute and chronic desipramine treatment.

The effects of acute and chronic desmethylimipramine (DMI) administration on 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) in plasma and urine were examined in eight depressed inpatients. DMI treatment induced an immediate and continuous highly significant reduction in plasma MHPG throughout the 30-day treatment period. This effect was not related to treatment response. In contrast to plasma MHPG, there was no uniform effect of DMI treatment on urinary MHPG. Chronic DMI treatment increased or did not change urinary MHPG in the three treatment responders and decreased urinary MHPG in five nonresponders. The correlation between plasma and urinary MHPG during the placebo period was not significant, and the effect of DMI treatment on the two measures differed markedly.

Adult↗
PubMed1981

The effect of pimozide on CSF norepinephrine in schizophrenia.

The authors measured CSF norepinephrine concentrations in drug-free schizophrenic patients with and without probenecid administration and in drug-free normal control subjects. Schizophrenic patients had significantly higher baseline norepinephrine values. The dopamine metabolite homovanillic acid correlated significantly with norepinephrine. During chronic treatment with the neuroleptic pimozide, patients' norepinephrine levels were significantly decreased. The pimozide-induced decrease in norepinephrine, as well as the percent decrease, correlated significantly with the patients' decrease in global psychosis. These data are consistent with recent reports of elevated concentrations of norepinephrine in specific brain areas of schizophrenic patients, and they support a role for norepinephrine metabolism in the pharmacological effects of antipsychotic drugs.

Adolescent↗
PubMed1980

Schizophrenia: elevated cerebrospinal fluid norepinephrine.

Concentrations of norepinephrine in cerebrospinal fluid are higher in schizophrenic patients, particularly in those with paranoid features, than in normal volunteer subjects of the same age. This observation supports recent reports of elevated concentrations of norepinephrine in specific brain areas adjacent to the cerebral ventricles of paranoid schizophrenic patients. Overflow of the amine from periventricular regions into the cerebrospinal fluid may reflect abnormally high release or diminished enzymatic destruction of norepinephrine in patients with schizophrenia.

Adult↗
PubMed1976

Memory functions in depression.

In an attempt to elucidate the memory deficit in depression, short-term memory and long-term memory were examined by means of a memory test battery in 26 hospitalized depressed patients. Their performance was compared with a matched control group and with the performance of those 20 patients who improved after 26 days of treatment with antidepressants. Results indicate that depressed patients show marked impairment in short-term memory without an impairment in long-term memory. The greater the improvement of the clinical state, the greater the improvement in short-term memory, whereas long-term memory was not influenced by the therapeutic success.

Amitriptyline↗