PubMed Health⌕ Search

Biomedical subjects

S C Dilsaver

Publications and source records attributed to S C Dilsaver.

At least 145 records · Page 8Linked to original sources
PubMed1986

Pathophysiology of "cholinoceptor supersensitivity" in affective disorders.

Phenomenological and physiological variables demonstrate supersensitive changes to cholinergic challenge in affective disorder subjects. Theorists generally assume the primary defect is the postsynaptic muscarinic receptor. However, in addition to defectiveness or up-regulation of this receptor, the appearance of postsynaptic "cholinoceptor supersensitivity" can result from abnormal presynaptic mechanisms, membrane "pathology," derangement of intrasystolic mechanisms that amplify effects of receptor-agonist coupling, or aberrant cholinergic-monoaminergic interaction. This article discusses abnormalities of the postsynaptic receptor, regulation of postsynaptic receptor density, the presynaptic muscarinic receptor, and other mechanisms regulating the release of acetylcholine, membrane dynamics, and "cascade" mechanisms-specifically the phosphatidylinositol (PI) cycle, Ca2+ mobilization, and cyclic guanosine monophosphate (GMP) generation-as causes of cholinergic system "supersensitivity." It is suggested that an approach to the topic emphasizing site of abnormality will encourage greater clarity of thought in the study of the cholinergic component of the pathophysiology of affective illness.

Affective Disorders, Psychotic↗
PubMed1986

Cholinergic mechanisms in depression.

Evidence supporting a cholinergic hypothesis of depression is presented. First, cholinergic overdrive produces behavioral, neuroendocrine, and polysomnographic features of melancholia, and melancholics exhibit state-independent supersensitivity to cholinergic overdrive. Drugs inducing up-regulation and supersensitivity of cholinergic systems produce behavioral, polysomnographic, and neuroendocrine effects of melancholia when withdrawn. These observations also implicate cholinergic system supersensitivity as a factor in the pathophysiology of certain affective disorders. Cholinergic and monoaminergic mechanisms reciprocally regulate drive-reduction, and substances of abuse either activate monoaminergic networks or antagonize cholinergic systems. These points are consistent with the hypothesis that dynamic interaction between cholinergic and monoaminergic systems is involved in the regulation of mood and affect. Finally, antimuscarinic agents have antidepressant effects. Thus, the hypothesis that supersensitivity of cholinergic systems is involved in the pathophysiology of affective disorders is supported by several lines of evidence. This evidence is reviewed; directions for future research and promising methods of investigation are discussed.

Brain Diseases↗
PubMed1986

Cholinergic-monoaminergic interaction in the pathophysiology of the affective disorders?

Cholinergic and monoaminergic hypotheses have dominated affective disorders research. The propriety of an hypothesis is determined by the point of a field in its development. Both categories of hypotheses have encouraged important research but their utility can be limited by the assumption that the pathophysiology of depression and mania is due to cholinergic or monoaminergic pathology. In actuality, neurotransmitter networks interact and are mutually regulating. The cholinergic-monoaminergic interaction theory (CMIT) is a dynamic account of the mutual inter- and intra-regulation of cholinergic, noradrenergic, dopaminergic and serotonergic systems in the pathophysiology of affective disorders. This model maintains that virtually every variable related to the neurobiology of bipolar disorder is regulated by mechanisms internal and external to those neurotransmitter systems involved in its pathophysiology. In principle, these variables include receptor density and sensitivity, membrane properties, cytosolic calcium, magnesium and sodium ion concentrations, activities of ATPases and calcium channel gating and cascade mechanisms. This array of variables stems from the assumption that the brain is a complex, unified dynanism. The CMIT posits homeostatic mechanisms preserving the direction of this dynanism. In this article, the theme of neurotransmitter-neurotransmitter system interaction is developed and the CMIT is offered as a paradigm useful in addressing the pathophysiology of affective disease from within the conceptual framework of a neurotransmitter system interaction theory.

Humans↗
PubMed1986

Covariation of depressive symptoms, parkinsonism, and post-dexamethasone plasma cortisol levels in a bipolar patient: simultaneous response to ECT and lithium carbonate.

A patient presented with concurrent mood congruent delusions, parkinsonism, and elevated post-dexamethasone plasma cortisol levels. This triad could result from simultaneous development of cholinergic-monoaminergic dysfunction within critical limbic and extrapyramidal loci. The magnitude of each abnormality decreased in concert during a course of electroconvulsive therapy (ECT). Remaining abnormalities disappeared during treatment with lithium. Actions of ECT and lithium on muscarinic systems are reviewed, and a strategy for testing the hypothesis that dysfunction of cholinergic-monoaminergic mechanisms develops in parallel in different neural networks is considered.

Bipolar Disorder↗
PubMed1986

Cholinergic mechanisms in affective disorders. Future directions for investigation.

Advances in clinical and basic research methodology combined with clearly articulated concepts create new opportunities for researching the roles of cholinergic mechanisms in the pathophysiology of affective disorders. Areas for study include: roles of cholinergic mechanisms in mediating effects of stress and cholinergic mechanisms linking the pathophysiologies of affective and panic disorders, use of pharmacologic agents to produce cholinergic system supersensitivity in modeling biologic aspects of affective illness, use of multigenerational intrapedigree studies of cholinergic markers associated with affective disease, research into the neurobiology of lithium and ECT as they pertain to muscarinic cholinergic mechanisms, study of the interrelationship of sodium, calcium and lithium ion metabolism and their relationship to cholinergic-monoaminergic interaction, the development of brain imaging strategies and techniques, e.g., positron emission tomography (PET), to measure changes in cholinergic receptor density and affinity as a function of clinical state, identification and validation of a peripheral model of the central muscarinic receptor, study of the pharmacology of abusable substances and its relationship to mechanisms regulating mood, affect, psychomotor function and other variables related to the affective disorders, and development of in vitro and in vivo models useful in studying the physiology and biochemistry of the interaction of cholinergic and monoaminergic neurons. These models may allow us to bridge the traditional cholinergic and monoamine hypotheses of affective disorders.

Antidepressive Agents, Tricyclic↗
PubMed1986

Affective disorders and associated psychopathology: a family history study.

A pedigree in which affective psychosis, obsessive-compulsive phenomena, panic attacks, and eating disorders cluster over three generations is presented. The index proband is a 17-year-old girl with schizoaffective disorder, depressed type, bulimia nervosa, panic attacks, and intraepisode obsessive-compulsive phenomena. She has two male siblings; one has bipolar II disorder and the other has had multiple episodes of major depression. Both have panic attacks and exhibit obsessive-compulsive phenomena while depressed. The phenomenologies of the siblings' illnesses incorporate features from both sides of the family. It is proposed that the association of affective disorders with other forms of psychopathology might best be demonstrated by studying families transgenerationally.

Adolescent↗
PubMed1986

Pharmacologic induction of cholinergic system up-regulation and supersensitivity in affective disorders research.

Phenomenological, physiological, biochemical, and receptor binding measures are useful as dependent variables in affective disorders research. Abnormalities of these measures can result from up-regulation and supersensitivity of cholinergic systems and disturbances of cholinergic-monoaminergic interaction. These deviations are safely and inexpensively produced by pharmacologic induction of up-regulation and supersensitivity of central muscarinic cholinergic systems. Techniques for inducing these changes in cholinergic systems are reviewed, and principles governing their application to specific problems are illustrated.

Animals↗
PubMed1985

Effects of antidepressant withdrawal on the dexamethasone suppression test.

Withdrawal of antidepressant medications may be a source of variance in dexamethasone suppression test (DST) results. We investigated this issue retrospectively through the serial analysis of postdexamethasone plasma cortisol concentrations and clinical severity in 15 patients and 9 control subjects before, during, and after antidepressant withdrawal. Postdexamethasone cortisol concentrations were significantly higher during the antidepressant withdrawal phase. Drug-withdrawal subjects also had an increased frequency of DST nonsuppression. Recent withdrawal of antidepressants requires further study as a possible source of variance for hypothalamic-pituitary-adrenal measures.

Adult↗
PubMed1984

Antidepressant withdrawal-induced activation (hypomania and mania): mechanism and theoretical significance.

Electrocortical and behavioral arousal are separate phenomena subserved by different neural substrata operating in parallel. A comprehensive theory of 'activation' must take into account the relationships between the electrical and behavioral activating systems. In pathological or experimentally induced states paradoxes, resolvable by a theory positing functional interaction between these systems, arise. EEG arousal is directly mediated, in both the waking and sleeping state, by cholinergic mechanisms. Antidepressant withdrawal precipitates cholinergic overdrive; this would account for the apparent disturbances of REM sleep occurring when antidepressants are stopped. Generally, cholinergic overdrive would produce behavioral inhibition but in particular instances it triggers marked psychomotor arousal by mobilizing a 'limbic activating system'. The existence of a monoaminergic 'limbic activating system', system 'A', with the properties attributed to it in this paper, is supported by both clinical and laboratory observations. System 'A' theory provides a parsimonious means of adequately explaining many phenomena. This theory also has in its favor explanatory power and scope. The Cholinergic-Monoaminergic Interaction Theory of antidepressant withdrawal induced activation and of rapidly-cycling manic-depressive illness maintains that system 'A' and a cholinergic inhibitory system interact dynamically, and that excessive monoaminergic function can precipitate excessive cholinergic function and a dearth of monoaminergic function (due to autoregulation) and hence depression. Likewise, excessive cholinergic function is posited to activate monoaminergic systems and hence to secondarily cause behavioral activation. Rapidly-cycling manic-depressive patients, according to the model, develop alternating cholinergic and monoaminergic overdrive states because the homeostatic mechanisms which should serve to maintain, within normal limits, the composite of cholinergic inhibitory and monoaminergic activating influences are defective. Consequently, rather than reaching a reasonable balance compatible with adaptive function there is oscillation between extremes. Each oscillatory movement is actually a move towards the 'golden mean' and is induced by deviation from this ideal but the defective homeostatic mechanisms promote ' perpetual ' overshooting. Lithium and ECT may be useful in the treatment of rapidly-cycling patients as both treatments may down-regulate muscarinic receptors, and otherwise modify cholinergic and monoaminergic systems in ways promoting homeostasis.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic Fibers↗
PubMed1984

Lithium's effects on muscarinic receptor binding parameters: a relationship to therapeutic efficacy?

Variables confounding efforts to interpret data on lithium's effects in laboratory animals in vivo and from in vitro muscarinic receptor binding studies are discussed. After accounting for the effects of these variables, the author concludes that it is of theoretical interest and heuristic value to hypothesize that lithium renders cholinergic systems more stable or less perturbable in the face of mono-aminergic overdrive. Thus lithium may diminish the propensity of cholinergic systems to undergo up-regulation and supersensitization consequent to exogenous and endogenous events apt to induce these changes. Lithium's antidepressant, antimanic, and anticycling efficacy may depend on its cholinotropic properties. The potential significance of lithium's cholinergic effects is highlighted by findings that seizures and verapamil induce similar cholinotropic effects. The author hypothesizes that with further investigation anticycling agents will come to be regarded as unique among psychotropics by virtue of their effects on cholinergic-monoaminergic interactions and mechanisms.

Affective Disorders, Psychotic↗
PubMed1984

Antidepressant withdrawal phenomena.

The authors review the antidepressant withdrawal literature. Withdrawal of tricyclic antidepressants may precipitate the development of discrete syndromes. The most common of these are general somatic or gastrointestinal distress with or without anxiety and agitation, sleep disturbance characterized by excessive and vivid dreaming and initial and middle insomnia, movement disorder, and psychic and behavioral activation extending on a continuum to frank mania. The etiology of these syndromes is discussed. The "cholinergic overdrive hypothesis" explains most antidepressant withdrawal phenomena, including infrequent manifestations. Some antidepressant withdrawal symptomatology may be due to an interaction between cholinergic overdrive and monoaminergic systems. A treatment program useful in ameliorating the distress of patients who develop antidepressant withdrawal symptoms and who cannot continue to take antidepressants is outlined. The theoretical significance of tricyclic withdrawal phenomena and the heuristic value of current hypotheses as to their pathophysiology are discussed.

Adult↗