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Biomedical subjects

S C Risch

Publications and source records attributed to S C Risch.

At least 127 records · Page 7Linked to original sources

beta-Endorphin hypersecretion in depression: possible cholinergic mechanisms.

Morning plasma concentrations of beta-endorphin immunoreactivity were significantly higher in a group of depressed patients meeting the Research Diagnostic Criteria for Major Depressive disorder or Schizo-affective disorder, depressed, than in age- and sex-matched groups of normal controls and psychiatric patients without affective disorders. Furthermore, physostigmine-stimulated release of beta-endorphin immunoreactivity was also significantly greater in the depressed patients. These results provide the first evidence for elevated plasma concentrations of beta-endorphin in depression and also represent further evidence for cholinergic supersensitivity in depression. These results suggest that elevated plasma concentrations of beta-endorphin and cholinergically stimulated hypothalamic-pituitary beta-endorphin release, might potentially represent biological state or trait markers for depression.

Adrenocorticotropic Hormone↗

Naloxone effects on beta-endorphin, cortisol, prolactin, growth hormone, HVA and MHPG in plasma of normal volunteers.

8 mg of naloxone were administered IV to 14 normal volunteers in a placebo-controlled, double-blind experiment. Plasma levels of beta-endorphin, cortisol, prolactin, growth hormone, HVA and MHPG were determined before and 45 min after administration. Naloxone elicited significant increases in cortisol and MHPG but did not change plasma levels of the other compounds. In an additional experiment on two subjects, 20 mg of naloxone caused elevations of beta-endorphin as well as of cortisol. This parallel increase indicates that the linkage between the secretion of beta-endorphin and ACTH/cortisol may be dose-dependent. The increase in MHPG is in agreement with the hypothesized association of noradrenergic hyperactivity and opiate withdrawal.

Adult↗

Physostigmine induction of depressive symptomatology in normal human subjects.

Nine normal volunteers, screened for the absence of a personal or family history of affective disorders and free of concurrent marijuana usage, received intravenous infusions of high dose physostigmine or saline in a randomized, double-blind, counterbalanced paradigm. Self-rating and observer ratings both demonstrated a statistically significant, physostigmine associated increase in depressive-type symptoms in the group as a whole, particularly pronounced in certain individuals. These results are the first report of physostigmine associated depressive symptomatology in normal subjects. While our findings are discrepant with two previous studies, our use of multiple self-ratings, and some differences in physostigmine dosage and infusion times might have contributed to this difference. These findings suggest that high dose physostigmine may represent a pharmacological model of depression in normal subjects, or alternatively may be diagnostic of vulnerability to affective disorder in certain subjects free of a previous history of affective disturbances.

Adolescent↗

Indications and guidelines for plasma tricyclic antidepressant concentration monitoring.

Some tricyclic antidepressants appear to have critical ranges of plasma tricyclic antidepressant concentrations necessary for optimal clinical efficacy. For any given dose of tricyclic medication, there are marked interindividual variations in steady-state tricyclic concentrations. Furthermore, plasma tricyclic concentrations may be influenced by factors such as weight, diet, smoking status, differences in bioequivalence among manufacturers, and the addition or withdrawal of concurrent medications. There has been considerable controversy in the literature about the clinical utility of plasma tricyclic level monitoring. These authors believe that, at present, routine plasma level monitoring probably is not warranted, but that there are a variety of instances where plasma tricyclic concentration determinations may be clinically useful. The authors review methodological issues in plasma tricyclic concentration determinations and suggest guidelines for when such determinations may be clinically appropriate.

Antidepressive Agents, Tricyclic↗

Use of dexamethasone suppression test in clinical psychiatry.

The dexamethasone suppression test (DST) has been used in clinical medicine to evaluate overactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Consistent evidence has linked a specific dysfunction of the HPA axis to depressive illness. This article will review the physiology of the HPA axis and the method of the DST. After a critical review of the studies using the DST in psychiatric patients, the authors conclude that the overnight low dose DST can be a useful tool for the practitioner involved in the diagnosis and treatment of psychiatric illness.

Depression↗

Neurochemical mechanisms in the affective disorders and neuroendocrine correlates.

This symposium offers the practicing clinician a general overview of ongoing research strategies exploring possible functional alterations in neurotransmitters, neuroreceptors, and regulatory neuropeptides in subjects with major affective disorders. Such alterations, if demonstrable, might provide new mechanistic insights into the pathophysiology of these illnesses and suggest novel therapeutic approaches to their pharmacological management. Rather than attempting to describe all neurobiological research strategies, we have selectively focused on strategies using specific pharmacological challenges attempting to perturb discrete central nervous system neurotransmitter pathways while recording the behavioral and neuroendocrine correlates of such manipulations. This introductory manuscript will describe the advantages as well as the limitations of such strategies and, in addition, will attempt to provide a general overview of neuroanatomical, neurochemical, and neuroendocrine mechanisms relevant to a conceptual understanding of the putative psychiatric relevance of such strategies.

Brain Chemistry↗

Cholinergic challenges in affective illness: behavioral and neuroendocrine correlates.

The cholinergic-adrenergic balance hypothesis of affective disorders suggests that, in the areas of the brain that regulate mood, depression may represent a relative predominance of central cholinergic tone over adrenergic tone and that mania may represent the converse. Currently, converging lines of investigation from a number of independent groups suggest that affective disorder patients may have a central cholinergic receptor hypersensitivity that induces a vulnerability to affective and neuroendocrine disturbances. This article reviews the evidence for cholinergic mechanisms in the regulation of affective state and describes current research strategies using centrally active cholinomimetic agents to explore disturbances in affective disorder subjects.

Clinical Trials as Topic↗

Involvement of the central serotonergic system in affective illness.

This paper reviews the neuroanatomy and neuropharmacology of the central serotonergic system. Clinical evidence implicating altered serotonergic function in patients with affective disorders is summarized, as are the attempts to uncover central serotonergic dysfunction in these patients using pharmacological challenges. The authors conclude that the function of the brain serotonergic system in patients with affective disorders is relatively unexplored and would be a fruitful area of study for both the clinician and researcher.

Brain↗

The dexamethasone suppression test as a measure of hypothalamic-pituitary feedback sensitivity and its relationship to behavioral arousal.

A nonhuman primate model was used to evaluate the value of the dexamethasone suppression test as an index of hypothalamic-pituitary-adrenal responsiveness to arousal. In 8 rhesus monkeys plasma cortisol was suppressed by dexamethasone in a dose-dependent fashion at doses between 0.75 and 33 microgram/kg. A replication study was performed 5 months later using a single dexamethasone dose (17 microgram/kg) known to produce maximal plasma cortisol suppression. This yielded highly correlated results (r = 0.91, p less than 0.005) suggesting that dexamethasone suppressibility may be a stable characteristic of individual animals. In 9 other animals whose arousal responses to a stressful procedure (nasogastric tube insertion) had been rated daily over a previous 3-month period, baseline plasma cortisol levels and the percent suppression of plasma cortisol by dexamethasone were evaluated. Baseline plasma cortisol levels did not significantly correlate with the degree of dexamethasone-suppression and the mean arousal ratings within animals. However, the postdexamethasone percent of baseline cortisol did correlate significantly (r = 0.75, p less than 0.025) with individual mean arousal ratings. These preliminary results suggest that assessment of the sensitivity of an individual's hypothalamic-pituitary glucocorticoid feedback system may be a better predictor than its baseline cortisol concentrations of its degree of behavioral arousal to stress.

Animals↗

Diurnal variation in cerebrospinal fluid prolactin concentration of the rhesus monkey.

PRL immunoreactivity in the cerebrospinal fluid (CSF) of the rhesus monkey was found found to undergo a diurnal variation. Hourly samples of CSF from four adult male rhesus monkeys showed a mean peak PRL immunoreactivity of 6.30 +/- 2.53 ng/ml at 0200 h and a mean minimum concentration at 1500 h of 3.15 +/- .68 ng/ml. To our knowledge, this is the first report of a significant diurnal variation in the concentration of an anterior pituitary peptide hormone in CSF.

Animals↗

Interfaces of psychopharmacology and cardiology--part one.

At least 10% of the American population medically use prescribed psychopharmacological medications; and such psychotropic medications account for approximately 20% of all prescriptions in this country. Furthermore, there is widespread illicit use of psychoactive drugs, including narcotics, psychostimulants, and central nervous system depressants. All of these agents have potent effects on the cardiovascular system and, in addition, may undergo numerous drug-drug interactions with cardiovascular medications. Given the high incidence of both cardiovascular disease and psychoactive drug use in the United States, it is likely that clinicians manage many patients with cardiovascular disease, possible receiving cardiovascular medications, and also needing psychopharmacological interventions. Consequently, the authors have reviewed the pharmacology of the major classes of psychoactive agents: (I & II) Antidepressants (tricyclic antidepressants and monoamine oxidase inhibitors); (III) Lithium Carbonate; (IV) Major Tranquilizers (phenothiazines, thioxanthines, butyrophenones, reserpine); and (V) Minor tranquilizers, Sedatives, and Hypnotics (benzodiazepines and barbiturates) with respect to their cardiotoxicity, cardiovascular side effects, and drug-drug interactions. Management of the cardiovascular complications of psychotropic overdose is discussed, as well as potential therapeutic uses of psychopharmacological medications in patients with cardiovascular pathology.

Analgesics, Opioid↗

Interfaces of psychopharmacology and cardiology--Part two.

At least 10% of the American population medically use prescribed psychopharmacological medications; and such psychotropic medications account for approximately 20% of all prescriptions in this country. Furthermore, there is widespread illicit use of psychoactive drugs, including narcotics, psychostimulants, and central nervous system depressants. All of these agents have potent effects on the cardiovascular system and, in addition, may undergo numerous drug-drug interactions with cardiovascular medications. Givaen the high incidence of both cardiovascular disease and psychoactive drug use in the United States, it is likely that clinicians manage many patients with cardiovascular disease, possibly receiving cardiovascular medications, and also needing psychopharmacological interventions. Consequently, the authors have reviewed the pharmacology of the major classes of psychoactive agents: (I & II) Antidepressants (tricyclic antidepressants and monoamine oxidase inhibitors); (III) Lithium Carbonate; (IV) Major Tranquilizers (phenothiazines, thioxanthenes, butryophenones, reserpine); and (V) Minor Tranquilizers, Sedatives, and Hypnotics (benzodiazepines and barbiturates) with respect to their cardiotoxicity, cardiovascular side effects, and drug-drug interactions. Management of the cardiovascular complications of psychotropic overdose is discussed, as well as potential therapeutic uses of psychopharmacological medications in patients with cardiovascular pathology.

Adrenergic alpha-Antagonists↗

Mood and behavioral effects of physostigmine on humans are accompanied by elevations in plasma beta-endorphin and cortisol.

Administration of physostigmine to normal volunteers produced significant elevations in plasma cortisol and beta-endorphin immunoreactivity as well as alterations in mood, cognition, and behavior. These observations might be explained by a cholinergically mediated stress syndrome. However, peak elevations in plasma beta-endorphin immunoreactivity (but not in plasma cortisol) were significantly correlated with physostigmine-induced increases in depression ratings. These results suggest that a cholinergically mediated beta-endorphin pathway may be involved in the observed affective changes.

Behavior↗