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Biomedical subjects

F K Goodwin

Publications and source records attributed to F K Goodwin.

At least 109 records · Page 6Linked to original sources
PubMed1982

Peptides in the cerebrospinal fluid of neuropsychiatric patients: an approach to central nervous system peptide function.

This review highlights that essentially all of the recently discovered putative central nervous system (CNS) peptides and other peptide substances are measurable in human cerebrospinal fluid (CSF). Preliminary evidence also suggests that peptides in CSF may have an active regulatory role in relation to CNS function and behavior. Even if this is not the case, CSF peptides may prove to be a useful indirect marker of CNS peptide function and metabolism. Alterations in peptides have been reported in neurological and psychiatric illness, pain symptoms and their treatment, symptoms such as anxiety, and following treatment with CNS active drugs such as carbamazepine. CSF methodologies provide a strategy for the study of the interaction of classical neurotransmitters and peptide substances and their relationship to neural function and behavior in man. Assessment of peptides in CSF may supplement post mortem studies of peptide levels and receptor distribution and help lead to new diagnostic and treatment approaches in neuropsychiatric disorders.

Adrenocorticotropic Hormone↗
PubMed1982

Characterization of adenosine receptors in brain using N6 cyclohexyl [3H]adenosine.

The presence of distinct binding sites for adenosine in both the CNS and PNS has been proposed in numerous studies. The recent availability of stable adenosine analogues such as cyclohexyladenosine, 2-chloroadenosine and diethylphenylxanthine has made the characterization of such a receptor feasible. In the present report the binding of N6 cyclohexyl [3H]adenosine ([3H]CHA) to rat brain synaptosomal membranes is characterized. [3H]CHA binding is saturable and exhibits a biphasic kinetic saturation profile characteristic of 2 binding sites. The high affinity site has a Kd of 0.7 nM and the low affinity site 2.4 nM. The respective Bmax values are 230 and 120 fmol/mg protein in fat forebrain. The highest density of binding sites is found in the hippocampus and subcellular distribution studies indicate that the [3H]CHA site is predominantly synaptosomal. [3H]CHA binding is highly dependent in the presence of adenosine deaminase since only 30% of the binding capacity is observed in synaptosomal membranes not treated with this enzyme. Of the many cations and anions tested only copper and zinc have effects on [3H]CHA binding. Both metals are potent inhibitors of binding with copper having an IC50 of 30 microM and zinc 150 microM. Sulfhydryl reducing and alkylating agents also inhibit binding indicating that the binding site is a sulfhydryl-dependent protein.

Adenosine↗
PubMed1982

Clorgyline. A new treatment for patients with refractory rapid-cycling disorder.

Five women with primary, major, bipolar affective disorder, characterized by rapid mood cycles and nonresponsiveness to conventional drug treatments, including lithium carbonate, were given low doses (2.5 to 10.0 mg/24 hr) of clorgyline, a selective inhibitor of monoamine oxidase type A. In four patients, clorgyline, along or in combination with lithium carbonate, prolonged the duration and lessened the severity of mood cycles. One patient experienced prolonged mania while receiving clorgyline therapy. Clorgyline-induced remissions have lasted from three to more than 12 months.

Adult↗
PubMed1982

48-hour sleep-wake cycles in manic-depressive illness: naturalistic observations and sleep deprivation experiments.

Wrist motor activity and sleep were monitored longitudinally in 15 rapidly cycling and 52 nonrapidly cycling manic-depressive patients. The majority of patients experienced one or more consecutive 48-hour sleep-wake cycles (alternate nights with no sleep) when they switched out of depression into mania of hypomania. During a depressive phase, nine rapidly cycling patients were asked to simulate a 48-hour sleep-wake cycle by remaining awake for 40 hours (one night's total sleep deprivation). Eight switched out of depression, and seven were rated as manic or hypomanic; indicating that sleep loss (such as occurs with spontaneous 48-hour sleep-wake cycles) may help to trigger switches from depression to mania. The 48-hour sleep-wake cycles in patients may depend on a mechanism that is normally present in all humans, since normal persons also spontaneously experience near-48 hour sleep-wake cycles in certain experimental conditions.

Adult↗
PubMed1982

Chronic clonazepam administration induces benzodiazepine receptor subsensitivity.

Clonazepam and chlordiazepoxide were administered chronically in increasing doses for three weeks in two different strains of mice. Forebrain [3H]diazepam binding was assayed in groups of mice sacrificed at 2, 26, 50 hr and 10 days following the last dose. Scatchard and single point analyses revealed a significant decrease in the number of [3H]diazepam binding sites [Bmax] which persisted for at least two days following chronic clonazepam treatment. The Bmax changes observed following chlordiazepoxide treatment were less pronounced than those elicited by clonazepam. No significant changes in receptor binding affinity (Kd) were detected with either drug. In the clonazepam-treated animals, Bmax values returned to normal by day 10 after drug treatment. Chronic benzodiazepine administration therefore induced a decrease in the apparent number of benzodiazepine binding sites in the mouse forebrain. The magnitude and duration of the observed subsensitivity appears to depend on the potency of the administered benzodiazepine.

Animals↗
PubMed1982

Fluctuating high urinary phenylethylamine excretion rates in some bipolar affective disorder patients.

Five women with primary major bipolar affective disorders had variable and at times very high urinary phenylethylamine (PEA) excretion rates. The clinical picture of these patients was characterized by periodic bizarre behaviors and short psychotic episodes. These patients were generally nonresponsive to the usual treatment modalities, and their symptoms were exacerbated by nonspecific monoamine oxidase inhibitors which further increased PEA excretion rates.

Adolescent↗
PubMed1982

High reverse T3 levels in manic an unipolar depressed women.

A relatively high percentage of patients with affective disorders have abnormalities of thyroid function, and over 60% of endogenously depressed and most manic patients show a blunted thyroid-stimulating hormone (TSH) response to thyroid-releasing hormone (TRH) injections. We now replicate earlier findings concerning relatively high 3,3',5'-triiodothyronine (reverse T3) levels in unipolar depressives and find similarly high levels in manic women. The significance of the present finding is unknown, but measurement of reverse T3 levels as a potential tool in differential diagnosis of affective disorders and in psychobiological research should be explored further.

Adult↗
PubMed1982

Active metabolites of imipramine and desipramine in man.

Active hydroxy metabolites of imipramine (IMI) and desipramine (DMI) have been quantified in plasma and cerebrospinal fluid (CSF) from patients at steady-state. In plasma of prepubescent boys and adults the concentration of unconjugated 2-hydroxyimipramine is only 15% to 25% that of IMI; 2-hydroxydesipramine (OH-DMI) concentration, however, is usually 50% that of DMI and in some cases OH-DMI is the predominant compound. In CSF from adult patients the ratio of concentrations of OH-DMI/DMI is higher than in plasma. Judging from the CSF/plasma ratio 12% of DMI exists in the free form at steady state, whereas 16% of OH-DMI is free (P less than 0.02). There is no evidence for saturation of hydroxylation within the therapeutic dose and concentration ranges investigated. On the basis of a steady-state OH-DMI/DMI ratio of less than 1/30 in plasma 5% of the population studied could be classified as deficient DMI hydroxylators. This in the same as the incidence of deficient debrisoquine hydroxylators reported in other populations.

Adolescent↗
PubMed1982

Potentiation of antidepressant effects by L-triiodothyronine in tricyclic nonresponders.

Six women and 6 men who were treated in double-blind fashion major depressive illness did not respond to imipramine or amitriptyline, 150-300 mg/day, during periods of 26-112 days. After the addition of 25 micrograms/day (10 patients) or 50 micrograms/day (2 patients) of L-triiodothyronine (T3), 9 patients showed statistically significant improvement in depression scores; in 8 patients the response was marked. Improvement generally began within 1-3 days and was noted in all aspects of the depressive syndrome; side effects were minimal. T3 did not change plasma levels of imipramine or desipramine or their ratio but did suppress serum thyroxine.

Adolescent↗
PubMed1982

Aggression, suicide, and serotonin: relationships to CSF amine metabolites.

In an earlier, separate study, the authors found that human aggression and suicide (a specific aggression-related behavior) were associated with lower levels of CSF 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite. That study focused on subjects with personality disorders without affective illness. In the present study they examine the life history of aggression and history of suicidal behavior in 12 subjects with borderline personality disorders without major affective disorder. Histories of aggressive behaviors and of suicide attempts were significantly associated with each other, and each was significantly associated with lower 5-HIAA levels. Altered serotonin metabolism may be a highly significant contributing factor to these behaviors in whatever diagnostic group they occur.

Adolescent↗
PubMed1982

Intellectual function in primary affective disorder.

The possible effects of clinical depression on intellectual function were investigated in unipolar and bipolar patients. Ninety-six hospitalized depressed patients completed the Wechsler Adult Intelligence Scale (WAIS) on admission and 34 were retested on remission. The high average full scale IQs found remained relatively stable throughout, consistent with earlier studies indicating a limited relationship between intellectual function and clinical severity of depression. No evidence was found for retarded psychomotor activity in bipolar groups or increased psychomotor activity in unipolar groups on three WAIS subtests of psychomotor function, but full scale IQ increased slightly in hypomania.

Affective Disorders, Psychotic↗
PubMed1982

Biological substrates of anxiety: benzodiazepine receptors and endogenous ligands.

Benzodiazepines have been shown to produce most, if not all, of their pharmacological effects by directly interacting with specific recognition or receptor sites within the CNS. The presence of benzodiazepine receptors has prompted many studies as to their possible physiological significance, including attempts at isolating an endogenous ligand. To data a number of substances including the purines inosine and hypoxanthine, nicotinamide, beta-carbolines, and an unidentified peptide factor have been isolated and postulated as being endogenous ligands. A number of these compounds have also been shown to either mimic or antagonize the behavioral effects of benzodiazepines, although it is still unclear whether these occur under physiological conditions. More recent biochemical studies have established a functional (and perhaps structural) relationship between te benzodiazepine receptor and the receptor for gamma amino butyric acid (GABA), the major inhibitory neurotransmitter in brain. It now appears that the benzodiazepine receptor actually exists as a "supramolecular complex" consisting of a GABA receptor and an associated chloride channel. A number of anxiolytic drugs including the barbiturates and pyrazolopyridines appear to act through these associated "regulatory" sites rather than directly on the benzodiazepine recognition site.

Animals↗