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Biomedical subjects

D Pickar

Publications and source records attributed to D Pickar.

At least 199 records · Page 11Linked to original sources
PubMed1985

Hormonal effects of high dose naloxone in humans.

Utilizing a double-blind crossover design, the hormonal effects of high dose, 2 mg/kg, were compared to low dose, 0.4 mg (approx. 5 micrograms/kg), naloxone administration in physically healthy humans. A significant naloxone dose effect on plasma cortisol levels was found (p less than 0.001), but no significant effect on plasma or serum levels of prolactin, follicle stimulating hormone, luteinizing hormone, norepinephrine or epinephrine. These results confirm involvement of the endogenous opioid system (EOS) in the tonic regulation of the hypothalamicpituitary-adrenal axis, but fail to find evidence of EOS involvement in the regulation of adrenal medullary function or the gonadotrophic axis in man. The results are however consistent with a continuing action of naloxone as an EOS antagonist even at high doses in man.

Adult↗
PubMed1985

Life events in depression. Relationship to subtypes.

Life events that had occurred in the 6 months before the onset of depression were recorded in 40 depressed patients and 41 normal controls. The depressed patients had experienced significantly more life events and significantly more undesirable life events than the controls. The 20 patients with a DSM-III diagnosed major depressive episode (MDE) without melancholia had experienced significantly more life events in the 6 months before the onset of depression than the 20 patients with a major depressive episode with melancholia. The patients with MDE without melancholia, but not the MDE with melancholia patients, had also experienced significantly more life events than a group of age- and sex-matched normal controls.

Adult↗
PubMed1985

Dexamethasone increases plasma HVA but not MHPG in normal humans.

Several recent studies in animals and man indicate that corticosteroids may alter catecholaminergic activity in both the peripheral and central nervous systems. We administered 1 mg of the synthetic glucocorticoid, dexamethasone, to 12 drug-free healthy volunteers and measured plasma homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG). Dexamethasone was administered at 11 p.m. and blood was collected at 4 p.m. on the preceding and subsequent days. Dexamethasone administration resulted in a significant increase in plasma HVA but did not consistently affect MHPG. All subjects showed a suppression of serum cortisol to values less than 5 micrograms/dl while prolactin levels were unaltered. In an additional group of nine volunteers, we administered 2 mg of dexamethasone and observed a similar increase in plasma HVA without change in plasma MHPG, indicating a selective effect on dopamine metabolism. Implications of these findings for an understanding of the neurochemical and behavioral changes seen with steroid administration and in explaining previous results on plasma MHPG/HVA ratios in delusional depression are discussed.

Adult↗
PubMed1985

Cerebrospinal fluid monoamine and monoamine metabolite concentrations in melancholia.

Cerebrospinal fluid levels of norepinephrine and six monoamine metabolites were measured in 28 medication-free depressed patients. Patients with a major depressive episode with melancholia (n = 15) had significantly lower levels of the three dopamine metabolites: homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC), and conjugated dihydroxyphenylacetic (CONJDOPAC), when compared with a combined group of patients with a major depressive episode or dysthymic disorder (n = 13). In patients with major depressive episode with melancholia, levels of HVA and of the serotonin metabolite 5-hydroxyindoleacetic acid significantly correlated with the severity of depression. In the total group of 28 depressed patients, cerebrospinal fluid (CSF) levels of norepinephrine significantly correlated with symptoms of anxiety. In both patients with major depressive episode and major depressive episode with melancholia, those who were non-suppressors on the dexamethasone suppression test had significantly higher CSF levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol compared to those who were suppressors.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

CSF monoamine metabolites in chronic schizophrenic patients who attempt suicide.

The monoamine metabolites 5-hydroxindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) were measured in the lumbar cerebrospinal fluid (CSF) of 27 chronic schizophrenic patients who at some time had attempted suicide, and were compared with values from 27 chronic schizophrenic patients without a history of attempted suicide. There were no significant differences between either the violent or non-violent attempters and those without a history of attempted suicide in the mean lumbar CSF concentrations of the serotonin metabolite 5-HIAA, the dopamine metabolite HVA, or the norepinephrine metabolite MHPG. Significantly more of the suicide attempters had a previous major depressive episode, had received a course of ECT, and had significantly more psychiatric admissions than those who had never attempted suicide.

Adult↗
PubMed1985

The effects of cholecystokinin-like peptides in schizophrenics and normal human subjects.

Eight neuroleptic-resistant schizophrenic patients were treated with ceruletide, a cholecystokinin-like peptide, in a placebo-controlled, double-blind, crossover study. Ceruletide or placebo was administered intramuscularly twice a day for 4 consecutive days while patients were maintained on a constant dose of fluphenazine. There were no changes in either the positive or negative symptoms of schizophrenia between the periods of placebo and ceruletide administration. To further characterize ceruletide actions we also administered it to seven normal volunteers and evaluated its effects on cognition and mood. Volunteers were administered ceruletide (0.3 micrograms/kg or 0.6 micrograms/kg) or saline placebo intramuscularly. Ceruletide had no effects on recent or remote memory or attention, but the higher dose did cause a significant increase in fatigue. These results suggest that although CCK-like peptides lack antipsychotic or cognitive effects they do induce mild sedation. This sedation may be part of a "satiety-like" state induced by peripheral administration of CCK.

Adult↗
PubMed1985

Clinical correlates of decreased anteroposterior metabolic gradients in positron emission tomography (PET) of schizophrenic patients.

The finding in schizophrenic patients of a reversal of the normal frontal to posterior pattern of brain metabolic activity with positron emission tomography (PET) is of interest, but its relevance to psychopathology is unknown. Using PET, the authors studied 21 patients with chronic schizophrenia and 21 age- and sex-matched control subjects. Although eight of the 21 patients and only one of the control subjects showed a relatively lower anteroposterior metabolic gradient, no clinical correlates of this finding were noted. In addition, cerebral atrophy, as determined by CAT scan, was not associated with this aberrant metabolic pattern.

Adolescent↗
PubMed1985

Neuroendocrine and personality variables in dysthymic disorder.

In an attempt to characterize a subgroup of depressed patients diagnosed as having dysthymic disorder, the authors gave them two commonly used biological tests for depression and several personality inventories and compared the results with those from age- and sex-matched normal control subjects. There were no significant differences between the 11 early-onset dysthymic disorder patients and the 11 controls on the dexamethasone suppression test or the thyrotropin-releasing hormone test. The personality questionnaires, however, showed that the dysthymic disorder patients were significantly more neurotic, extrapunitive, and intrapunitive and had significantly lower self-esteem than the control subjects.

Adult↗
PubMed1985

Animal models of self-destructive behavior and suicide.

In this article we have addressed selected aspects of animal models that may have ramifications in our understanding of suicide and human self-destructive behavior. It should be kept in mind that these human behaviors have many determinants. In considering animal models, we do not propose that similar behaviors necessarily have the same causation nor that a particular experimental manipulation that produces a behavioral syndrome in one species will produce that response in another species. Even if environmental conditions or the resulting behaviors vary for different species, the biochemical intermediaries may be similar. The simplification inherent in the laboratory modeling of an aspect of human behavior should not mean that the complexity of the human syndrome be forgotten. However, if a simple explanation can account for the production of a particular behavioral syndrome in animals, it can help to structure our thoughts regarding the etiology of the behavior in humans. The ethologic observations discussed in this article may help to place human self-destructive behavior in a continuum with that of animals in the wild. Although care should be given to drawing direct parallels, the clear conclusion is that humans are not alone in exhibiting self-initiated behaviors that ultimately produce self-harm or death. Whereas laboratory models have been extensively used for modeling psychiatric illnesses or for producing specific pharmacologic manipulations of the CNS, surprisingly little attention has been given to the modeling of self-destructive behaviors themselves. Emphasis on self-destructive behaviors, as well as on their biologic and genetic underpinnings, represent an important future direction for work on animal models in psychiatry.

Altruism↗
PubMed1985

Neuropharmacological antagonism of the beta-carboline-induced "anxiety" response in rhesus monkeys.

A behavioral and physiological syndrome of stress-related responses was reported in primates following treatment with the benzodiazepine receptor antagonist, beta-carboline-3-carboxylic acid ethyl ester (beta-CCE). The behavioral and physiological effects of beta-CCE are similar to those observed during stressful or "anxiety"-related conditions characterized in rhesus monkeys under natural conditions. Pharmacological agents which are known to antagonize anxiety responses in other paradigms were tested for their ability to antagonize the actions of beta-CCE. Diazepam (1 mg/kg) completely blocked the effects of beta-CCE (200 micrograms/kg) on anxiety-related behaviors, heart rate and blood pressure, plasma catecholamines, cortisol, and adrenocorticotrophic hormone. A presynaptically active dose of the alpha-adrenoreceptor agonist, clonidine (10 micrograms/kg), significantly attenuated the effects of beta-CCE on all parameters, whereas the beta-adrenoreceptor agonist, propranolol (3 mg/kg), failed to alter the increases in plasma catecholamines, cortisol, or ACTH. In addition to these adrenergic agents, the serotonin antagonist, cyproheptadine (1 mg/kg), and the GABA-mimetic, 4,5,6,7-tetrahydroisoxazolo(5,4-C)pyrindin-3-ol (1 mg/kg), partially blocked the behavioral, physiological, and biochemical changes after beta-CCE. Manifestation of the complete "anxiety" syndrome evoked by beta-CCE in primates may require the functional activity of several neurotransmitter systems.

Adrenocorticotropic Hormone↗
PubMed1984

Neuroleptic-induced decrease in plasma homovanillic acid and antipsychotic activity in schizophrenic patients.

Plasma-free homovanillic acid, a major metabolite of dopamine, was measured in chronically ill schizophrenic patients both before and during treatment with the antipsychotic phenothiazine, fluphenazine. Neuroleptic treatment was associated with a significant time-dependent decrease in plasma homovanillic acid from pretreatment values, which were significantly elevated when compared with those of age- and sex-matched healthy control subjects. Further, both the absolute concentrations as well as the neuroleptic-induced reductions in plasma homovanillic acid determined over 5 weeks of neuroleptic treatment were statistically significantly correlated with ratings of psychosis and improvement in psychosis, respectively. These findings suggest that the delayed effects of neuroleptic agents on presynaptic dopamine activity may more closely parallel their therapeutic actions than do their immediate effects in blocking postsynaptic dopamine receptors and that a decrease in dopamine "turnover" may be responsible for their antipsychotic effects.

Adult↗
PubMed1984

Urinary 3-methoxy-4-hydroxyphenylglycol and major affective disorders. A replication and new findings.

We studied group and subgroup differences in urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) levels in patients with major affective disorder (66 depressed, 13 manic) and normal volunteers (27 subjects). Bipolar I depressed patients excreted less MHPG than unipolar depressed patients, manic patients, or normal volunteers. The mean (+/- SEM) MHPG excretion rate was 1.44 +/- 0.10 mg/day in 19 depressed bipolar I patients, 1.79 +/- 0.11 mg/day in 28 unipolar depressed patients, 2.11 +/- 0.19 mg/day in 13 manic patients, and 1.85 +/- 0.12 mg/day in 27 normal volunteers. Other sources of variance that affected urinary MHPG levels did not explain subgroup or state differences. There was only a trend for a low pretreatment MHPG level to be associated with positive response to imipramine hydrochloride or desipramine hydrochloride in the 19 patients treated with these drugs. The application of this biological test value for prediction of differential response to antidepressant drugs would therefore seem premature.

Adult↗
PubMed1984

The effects of ceruletide in schizophrenia.

Eight neuroleptic-resistant schizophrenic patients were treated with ceruletide diethylamine, a cholecystokininlike peptide, in a placebo-controlled, double-blind, cross-over study. Ceruletide or placebo was administered intramuscularly twice a day for four consecutive days while patients received a constant dose of fluphenazine hydrochloride. Cholecystokinin octapeptide was also administered to four different schizophrenic patients in a double-blind, cross-over study. Cholecystokinin or placebo was administered as a slow intravenous infusion daily for four days. There were no changes in either the positive or negative symptoms of schizophrenia between the periods of placebo, ceruletide, or cholecystokinin administration. Furthermore, there was no tendency for the patients' conditions to either improve or worsen during the course of ceruletide or cholecystokinin treatment. In contrast to previous reports from uncontrolled studies, cholecystokininlike peptides appear to be devoid of antipsychotic properties when administered parenterally.

Adult↗
PubMed1984

Endocrine effects of the cold pressor test: relationships to subjective pain appraisal and coping.

Blood was drawn from 14 normal volunteers twice before, immediately after a 1-minute immersion of the nondominant hand in ice water (cold pressor test), and twice during recovery. Serum levels of beta-endorphin, cortisol, prolactin, growth hormone, and opioid activity were determined, and measures of subjective pain appraisal and coping styles were obtained. Cortisol was the only variable to show a significant increase as a function of noxious stimulation. Correlational analysis yielded relationships between neuroendocrine variables and subjective pain appraisal as well as coping styles, suggesting complex interactions between neuroendocrine and psychological processes in human pain.

Adult↗