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Biomedical subjects

D E Sternberg

Publications and source records attributed to D E Sternberg.

At least 19 recordsLinked to original sources
PubMed1986

Does the cholecystokinin antagonist proglumide possess antipsychotic activity?

Cholecystokinin (CCK), a neuropeptide which fulfills almost all criteria for neurotransmitter status, has been co-localized with dopamine in midbrain mesolimbic and mesocortical neurons that have been implicated in the pathogenesis of schizophrenia. Preclinical research suggests that CCK may in part act to enhance central dopaminergic activity. In an attempt to evaluate the role of CCK relative to the dopamine hyperactivity hypothesis of schizophrenia, in the present investigation the putative CCK receptor antagonist, proglumide, was administered to four schizophrenic patients in a double-blind, placebo-controlled study. All patients were receiving concurrent neuroleptic medication, but were still significantly symptomatic. Proglumide was without effect on the patients' psychosis ratings. Potential reasons for this negative finding are discussed.

Adult↗
PubMed1986

Testing for physical illness in psychiatric patients.

The presence of causative, exacerbating, or coexisting medical illness is often missed by both psychiatric and nonpsychiatric physicians. Reasons for these misdiagnoses are examined, and it is suggested that the evaluation of psychiatric patients should include a detailed physical examination, thorough medical and psychiatric history, including the use of informants in addition to the patient, and laboratory testing. The willingness to consider nonobvious causes of psychiatric symptoms can help to avoid premature diagnostic closure and inappropriate treatment.

Clinical Laboratory Techniques↗
PubMed1985

Family concerns about hospitalizing a patient in a psychiatric research unit.

Family members involved in a patient's hospitalization on a psychiatric research unit have special concerns related to the choice of the unit and the conduct of the patient's treatment. Based on work with 350 families of patients on a research unit, the authors describe families' motivations for choosing the unit and the expectations and misconceptions they may develop during the patient's stay. Certain interventions are specifically directed to family members' concerns about research, including providing information and education, monitoring informed consent, and working through how the family's expectations of treatment match actual treatment outcome. Most families are able to conceptualize the research approach adequately and to use the supportive relationship with the unit's family advocate to deal with their ambivalence about the approach.

Adult↗
PubMed1984

Serotonin function and mechanism of action of antidepressant treatment. Effects of amitriptyline and desipramine.

The effects of amitriptyline hydrochloride and desipramine hydrochloride treatment on brain serotonin (5-HT) function were investigated in 21 patients. The ability of an intravenous infusion of the serotonin precursor tryptophan to raise serum prolactin (PRL) levels was determined in 13 depressed patients during placebo administration and after 28 to 35 days of treatment with either amitriptyline or desipramine. Both desipramine (N = 7) and amitriptyline (N = 6) significantly increased the PRL rise induced by tryptophan compared with a preceding placebo period. In contrast, following long-term amitriptyline and desipramine treatment, the ability of tryptophan to increase PRL was enhanced two weeks following abrupt cessation of amitriptyline therapy (N = 5), but not after discontinuation of desipramine therapy. The results of this investigation are consistent with electrophysiologic and behavioral studies in laboratory rats and suggest that desipramine- and amitriptyline-induced alterations in 5-HT function may be related to their antidepressant mechanism of action.

Aged↗
PubMed1984

Serotonergic function in depression. Prolactin response to intravenous tryptophan in depressed patients and healthy subjects.

There is considerable evidence that serotonergic function may be reduced in the brains of depressed patients. Serotonin is an effective stimulant of prolactin release, and intravenous (IV) tryptophan (the amino acid precursor of serotonin), when administered to healthy subjects, produces a reliable and robust increase in serum prolactin level. To evaluate serotonergic function in depressed patients, we gave 25 patients and 19 age- and sex-matched controls tryptophan, 7 g IV. There was a marked blunting of the maximal prolactin response to the tryptophan in both the male and female patients. The patient control differences could not be accounted for on the basis of age, sex, or time without medications. The data provide strong support for a possible serotonergic abnormality in depression.

Adult↗
PubMed1984

The effect of mianserin on alpha-2 adrenergic receptor function in depressed patients.

Recent clinical investigations have shown that long term treatment with the tricyclic antidepressants desipramine and amitriptyline reduces the sensitivity of the alpha-2 adrenergic autoreceptor. In order to determine whether the tetracyclic antidepressant mianserin also has this action, the effect of clonidine, an alpha-2 adrenergic receptor agonist, on plasma levels of the norepinephrine metabolite 3-methoxy-4- hydroxyphenlethyleneglycol (MHPG), blood pressure, and patient-rated sedation were measured in fifteen depressed patients before and during mianserin treatment. Postsynaptic alpha-2 adrenergic receptor function was assessed by measuring the growth hormone response to clonidine before and during treatment. Mianserin had little or no effect on the ability of clonidine to lower plasma MHPG and blood pressure, and to increase sedation and growth hormone secretion. The findings of this investigation indicates that long term mianserin treatment does not produce significant subsensitivity of the alpha-2 adrenergic receptor and suggests that a reduction in alpha-2 adrenergic autoreceptor sensitivity is not a necessary action for all effective antidepressant treatments.

Adult↗
PubMed1984

Biologic tests in psychiatry.

Neurobiologic research has discovered a number of abnormalities that might serve as biologic markers for specific psychiatric disorders. Tests for these markers could aid in differential diagnosis and in the choice and monitoring of treatment. Tests with potential clinical utility in affective illness (unipolar and bipolar depression and mania), panic disorder, and schizophrenia are discussed.

Anxiety Disorders↗
PubMed1983

Dopamine-beta-hydroxylase activity and homovanillic acid in spinal fluid of schizophrenics with brain atrophy.

Schizophrenic patients with high ventricle brain ratios and cortical brain atrophy, as shown by computerized tomography, had decreased spinal fluid concentrations of homovanillic acid and dopamine-beta-hydroxylase activity. These decreased cerebral spinal fluid concentrations in patients with brain atrophy support the proposal of disturbed noradrenaline and dopamine neurotransmission in a subgroup of schizophrenic patients.

Adolescent↗
PubMed1983

Plasma homovanillic acid as an index of brain dopamine metabolism: enhancement with debrisoquin.

Plasma levels of the dopamine (DA) metabolite homovanillic acid (HVA) may be a useful measure of brain HVA production by central DA systems. Even though there is a significant peripheral contribution to plasma HVA, experimental manipulations that alter brain HVA produce parallel changes in plasma HVA levels. This study was designed to assess whether the ability of plasma HVA to reflect haloperidol induced increases in brain HVA could be strengthened by reducing the contribution to plasma HVA from peripheral sources. Debrisoquin sulfate, a monoamine oxidase inhibitor that does not enter the brain, was given in a low dose schedule to rats and lowered the peripheral contribution to plasma HVA by between 42 and 68%, resulting in a situation where between 62 and 87% of plasma HVA derived from brain. Using this dose schedule, rats pretreated with debrisoquin displayed a significant increase in plasma HVA following a lower dose of haloperidol than that required in the vehicle pretreated rats. In the debrisoquin pretreated group, a 71% increase in brain HVA was accompanied by a significant 60% increase in plasma HVA, whereas the vehicle pretreated group required a 136% increase in brain HVA to display a significant 50% increase in plasma. These findings indicate that debrisoquin pretreatment improves the reliability of plasma HVA to reflect changes in brain DA metabolism. Plasma HVA samples obtained from humans following debrisoquin may provide a clinically applicable method for assessing brain DA systems in neurologic and psychiatric illness.

Animals↗
PubMed1983

CSF dopamine beta-hydroxylase in schizophrenia.

Dopamine beta-hydroxylase (DBH), the enzyme that converts dopamine to norepinephrine, was measured in the CSF of 30 schizophrenic patients and 27 normal controls. The CSF DBH activity in the patients was not significantly different from that in controls. Levels of CSF DBH activity in individual patients were highly constant over time and were not influenced by clinical state or neuroleptic treatment. Low levels of DBH in CSF did significantly relate to good social and sexual functioning, good prognosis, less symptoms between hospitalizations, and excellent clinical response to neuroleptic treatment. We speculate from these data that low brain DBH activity may produce a type of vulnerability to psychotic decompensation and thereby influence the clinical course, although it does not cause schizophrenia, in general. Low CSF DBH activity may delineate a "reactive" subgroup from the heterogenous population of patients with diagnoses of schizophrenia.

Adolescent↗
PubMed1983

Lithium carbonate augmentation of antidepressant treatment. An effective prescription for treatment-refractory depression.

To assess whether lithium carbonate augments antidepressant effects of long-term antidepressant treatment in non-responding patients, 15 treatment-refractory patients were studied using a placebo-controlled, double-blind design. After at least 21 days of antidepressant drug therapy, and while continuing to receive the same daily dose of antidepressant drug, eight patients received lithium carbonate and seven received placebo. In comparison with placebo, lithium carbonate produced a small but statistically significant improvement in the mean daily nursing ratings of depression during the first two days of treatment. The beneficial effects of lithium carbonate were more variable during the next four days, but by the seventh through 12th day of the trial, the drug produced a significant and clinically meaningful improvement. When the seven placebo-treated patients received active lithium carbonate on the 13th day of the study, their rate of improvement was similar to that of the eight patients who had received active lithium carbonate initially. This augmentation of the anti-depressant effect was seen in patients treated with desipramine hydrochloride, amitriptyline hydrochloride, or mianserin hydrochloride. Although in five of the 15 patients, the improvement appeared as early as 24 to 48 hours after the first lithium carbonate dose, the remaining patients did not show a clear improvement until approximately five to eight days later. We concluded that lithium carbonate does augment the antidepressant effect when added to the long-term antidepressant treatment of nonresponding patients.

Adult↗
PubMed1983

Lithium prevents adaptation of brain dopamine systems to haloperidol in schizophrenic patients.

To evaluate the effect of lithium treatment on haloperidol-induced changes of brain dopamine systems, cerebrospinal fluid homovanillic acid (HVA) was assessed in nine patients during a sequential treatment protocol with placebo, lithium, lithium plus acute haloperidol, and lithium plus chronic haloperidol. None of the patients developed tolerance to the rise in HVA during treatment with haloperidol and lithium. Concurrent treatment with lithium appears to prevent the development of tolerance in dopamine metabolism during chronic haloperidol treatment. These data provide the first evidence in man that lithium may prevent neuroleptic-induced functional supersensitivity of brain dopamine systems.

Adult↗
PubMed1983

Alpha-2 adrenergic receptor sensitivity and the mechanism of action of antidepressant therapy. The effect of long-term amitriptyline treatment.

It has been hypothesized that the mechanism of action of antidepressant treatments is related to their ability to decrease the sensitivity of the alpha-2 adrenergic autoreceptor. In order to assess alpha-adrenergic autoreceptor sensitivity, the effects of clonidine, the alpha-2 adrenergic receptor agonist, on plasma levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenethyleneglycol (MHPG), blood pressure (BP) and patient-rated sedation were measured in nine depressed patients before and during amitripytline treatment. Postsynaptic alpha-2 adrenergic receptor sensitivity was assessed by determining the growth hormone (GH) response to clonidine before and during treatment. Amitriptyline significantly attenuated the effects of clonidine on plasma MHPG, standing systolic BP, and sedation, indicating that alpha-2 adrenergic autoreceptors had become subsensitive. In addition, baseline plasma MHPG levels were significantly reduced. Amitriptyline had no effect on the GH response to clonidine.

Adolescent↗
PubMed1983

Effects of electroconvulsive therapy on mood, parkinsonism, and tardive dyskinesia in a depressed patient: ECT and dopamine systems.

A patient suffering from delusional depression, Parkinson's disease, and tardive dyskinesia (TD) exhibited a marked improvement in mood and parkinsonian symptoms following electroconvulsive therapy (ECT). In contrast, her TD symptoms worsened. The inverse relation between the intensity of TD symptoms on the one hand and the parkinsonian and depressive symptoms on the other is discussed with respect to ECT's effect on central dopaminergic systems.

Aged↗
PubMed1982

Schizophrenia: dopamine beta-hydroxylase activity and treatment response.

Cerebrospinal fluid levels of dopamine beta-hydroxylase, found to be relatively constant over time in individual patients, were significantly lower in schizophrenic patients who became nonpsychotic during neuroleptic treatment than in those who remained psychotic. Dopamine beta-hydroxylase activity may delineate a subgroup of patients who have a dopamine-sensitive brain disorder.

Antipsychotic Agents↗
PubMed1982

Assessment of alpha 2 adrenergic autoreceptor function in humans: effects of oral yohimbine.

Administration of three oral doses of yohimbine (10 mg, 15 mg, 20 mg) to eight healthy subjects resulted in significant increases in plasma free 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG). The 15 mg and 20 mg yohimbine doses induced modest increases in systolic blood pressure and autonomic symptoms such as piloerection and rhinorrhea. Marked behavioral effects such as anxiety were not observed. These results indicate that determination of the plasma MHPG response to yohimbine may be of value in assessing alpha 2 adrenergic autoreceptor function in humans.

Adult↗
PubMed1982

CSF levels of gamma-aminobutyric acid in schizophrenia. Low values in recently ill patients.

gamma-Aminobutyric acid (GABA) levels in CSF were not significantly different in 30 drug-free schizophrenic patients and in 39 normal control subjects, because the control subjects were significantly older. Schizophrenic women had significantly lower levels than age-matched normal control women (less than 30 years). The GABA levels increased with duration of illness, number of hospitalizations, and months of hospitalizations, as well as with age. They correlated nonsignificantly with psychosis levels. After short-term pimozide treatment, GABA levels in all patients were raised, albeit nonsignificantly. The date suggest that low GABA levels may be observed only in the early years of the illness, particularly in female schizophrenic patients, and that these levels increase with time and with long-term neuroleptic treatment.

Adult↗