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Biomedical subjects

F K Goodwin

Publications and source records attributed to F K Goodwin.

At least 91 records · Page 5Linked to original sources
PubMed1986

Psychobiology and psychopharmacology: issues in clinical research training.

Although the scope of basic studies in psychopharmacology and psychobiology has been expanding steadily for about 30 years, relatively few clinical psychiatrists, psychologists, and psychopharmacologists now choose to become researchers or teachers in these disciplines. Such training is crucial to the future vitality of both academic and private-practice psychiatry, and in view of increasing constraints on training funds, student researchers may well be an endangered species. With these concerns in mind, at its 1984 meeting, the American College of Neuropsychopharmacology's Education and Training Committee organized a symposium of investigators, administrators, and former trainees to explore aspects of effective clinical research training in psychobiology and psychopharmacology. Aspects discussed included mentoring, settings and content of training, depth versus breadth of curriculum, and the effect of a critical mass of colleagues at various stages of professional development. Following a brief overview, selected panelists addressed the issues from their individual perspectives.

National Institute of Mental Health (U.S.)↗
PubMed1985

Sleep and circadian rhythms in affective patients isolated from external time cues.

Sleep electroencephalographic activity, circadian rhythms in motor activity and rectal temperature, and clinical state were monitored longitudinally in four affectively ill patients (two depressed, one manic, and one rapidly cycling between depression and mania) who lived in isolation from external time cues (zeitgebers) for 3 to 4 weeks. In these conditions it was possible to observe the intrinsic or free-running behavior of circadian pacemakers and thereby to test several hypotheses about the role of sleep and circadian rhythms in the pathogenesis of depression. No hypothesis was consistently supported by the results. We found that the intrinsic rhythm of a circadian pacemaker appeared to free-run with an abnormally fast frequency in one patient. No patient remained stably depressed during temporal isolation. Our experience suggests that this type of study can be carried out safely with appropriate precautions. Temporal isolation is a means to test decisively predictions of several chronobiological hypotheses about affective illness and should be applied to additional patients.

Adult↗
PubMed1985

Characterization of [3H]ouabain binding sites in human brain, platelet, and erythrocyte.

[3H]Ouabain binding was investigated in membranes prepared from human brain, erythrocyte, and platelet. Scatchard analysis of [3H]ouabain binding to human hypothalamic membranes revealed a single class of noninteracting binding sites with an apparent affinity constant (KD) of 21 nM. Though the number of [3H]ouabain binding sites was lower in human platelets than in erythrocytes, both tissues exhibited a single class of high-affinity binding sites with an apparent KD similar to that found in human brain. Specific [3H]ouabain binding in basal ganglia tissue from patients with Huntington's disease was more than 50% lower than in tissue from age- and sex-matched controls. These results, along with previous findings in rat brain, suggest that high-affinity [3H]ouabain binding labels the neuronal form of Na, K-ATPase in human brain, and may prove useful in quantitating this enzyme in postmortem brain samples.

Basal Ganglia↗
PubMed1985

Characterization of "high-affinity" [3H]ouabain binding in the rat central nervous system.

The characteristics of [3H]ouabain binding were examined in various areas of rat brain. In the striatum, Scatchard analysis revealed a single class of "high-affinity" binding sites with an apparent binding affinity (KD) of 10.4 +/- 0.9 nM and an estimated binding capacity (Bmax) of 7.6 +/- 1.9 pmol/mg protein. Similar monophasic Scatchard plots were found in the brainstem, cerebellum, hypothalamus, and frontal cerebral cortex. [3H]Ouabain binding to rat brain was sodium- and ATP-dependent and strongly inhibited by potassium. Proscillariden A was the most potent cardiac glycoside tested in inhibiting specific [3H]ouabain binding to brain membranes, and the rank order of inhibitory potencies for a series of cardiac glycosides was similar to that previously reported for inhibition of heart Na,K-ATPase. To assess whether the high-affinity binding sites for [3H]ouabain were localized to neuronal or nonneuronal membranes, the effect of discrete kainic acid lesions on striatal [3H]ouabain binding was examined. Kainic acid lesions of the striatum reduced [3H]ouabain binding to striatal homogenates by 79.6 +/- 1.6%. This suggests that the "high-affinity" [3H]ouabain binding sites measured in our experiments are localized to neuronal elements. Thus, the high-affinity binding of [3H]ouabain to brain membranes may selectively label a neuronal form or conformation of Na,K-ATPase.

Animals↗
PubMed1984

Seasonal affective disorder. A description of the syndrome and preliminary findings with light therapy.

Seasonal affective disorder (SAD) is a syndrome characterized by recurrent depressions that occur annually at the same time each year. We describe 29 patients with SAD; most of them had a bipolar affective disorder, especially bipolar II, and their depressions were generally characterized by hypersomnia, overeating, and carbohydrate craving and seemed to respond to changes in climate and latitude. Sleep recordings in nine depressed patients confirmed the presence of hypersomnia and showed increased sleep latency and reduced slow-wave (delta) sleep. Preliminary studies in 11 patients suggest that extending the photoperiod with bright artificial light has an antidepressant effect.

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

CSF 5-hydroxyindoleacetic acid levels in suicidal schizophrenic patients.

Concentrations of 5-hydroxyindoleacetic acid (5-HIAA) in the lumbar CSF were measured in a group of suicidal schizophrenic patients and in a matched group of nonsuicidal schizophrenic patients. The suicidal group had a significantly lower level. This finding is consistent with reports of low levels of CSF 5-HIAA in suicidal patients with other psychiatric diagnoses and suggests that low CSF 5-HIAA may be a generalized marker of aggressive behavior against the self and others.

Adult↗
PubMed1983

Low cerebrospinal fluid 5-hydroxyindoleacetic acid concentration differentiates impulsive from nonimpulsive violent behavior.

Relationships of impulsive and nonimpulsive violent behavior to cerebrospinal fluid (CSF) monoamines and their metabolic concentrations were studied in thirty-six violent offenders. A relatively low 5-hydroxyindoleacetic acid (5HIAA) concentration was found in the CSF of impulsive violent offenders. This was not true for the offenders who had premeditated their acts. Other CSF monoamine or metabolite concentrations were not significantly different between the two groups. Of the groups studied, impulsive violent offenders who had attempted suicide had the lowest 5HIAA levels. A low CSF 5HIAA concentration may be a marker of impulsivity rather than violence.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1983

Thyroid abnormalities associated with rapid-cycling bipolar illness.

Bipolar patients taking lithium carbonate were classified as rapid-cycling or non-rapid-cycling based on whether they had ever experienced four or more affective episodes in a 12-month period. Overt hypothyroidism was found in 12 (50.7%) of the 24 rapid-cycling patients and in none of the 19 non-rapid-cycling patients. Elevated thyroid-stimulating hormone levels were present in 92% of the rapid-cycling group v 32% of the non-rapid-cycling group. Abnormalities of the hypothalamic-pituitary-thyroid axis, some of which may become apparent only during treatment with lithium carbonate, appear to interact with a predisposition to bipolar illness to produce rapid-cycling. These overt and covert abnormalities may help explain the reported efficacy of thyroid in treating "periodic catatonia" and rapid-cycling.

Bipolar Disorder↗
PubMed1983

RBC membrane adenosine triphosphatase activities in patients with major affective disorders.

Red blood cell Na+, K+-, Mg2+-, and Ca2+-adenosine triphosphatase (ATPase) activities were studied longitudinally in eight patients with affective disorders and 12 healthy volunteers. The patients had a higher mean Ca2+-ATPase activity than the volunteers, and the fluctuations in all three ATPase activities were greater in the patients than in the volunteers. Even though the mean Ca2+-ATPase activity was higher during manias and euthymic periods than during depressions, mood and ATPase activities did not correlate with each other in all patients. Lithium carbonate treatment did not alter the ATPase activities, and the quantity of vanadium present in the membranes could not account for the variations in the enzyme activities observed. We suggest that either the RBCs of manic-depressive patients are very sensitive to fluctuations of a lipophilic ATPase activity--regulating factor present in plasma or the patients have at times high levels of such a factor. In some patients, the level of this hypothesized regulator may fluctuate in synchrony with mood changes.

Adenosine Triphosphatases↗
PubMed1983

5-hydroxytryptamine and depression: a model for the interaction of normal variance with pathology.

1 Theories linking 5-hydroxytryptamine (5-HT) with depression are briefly reviewed. The various experimental strategies adopted to investigate this relationship, examination of autopsy data, CSF metabolite data, 5-HT re-uptake patterns in human blood platelets and imipramine binding studies in human platelets, are discussed. 2 Recent studies of 5-hydroxyindole acetic acid (5-HIAA) levels in cerebrospinal fluid have revealed a linkage between low 5-HIAA levels and suicide, aggression and impulsivity. Decreases in the number of imipramine binding sites have also been found in brains of suicide victims. 3 The available data lead to the conclusion that decreased 5-hydroxytryptaminergic function may be associated with an increased risk of depression, suicide, and some types of aggression.

Aggression↗
PubMed1983

The dexamethasone suppression test: promises and problems of diagnostic laboratory tests in psychiatry.

Diagnostic tests in medicine must satisfy certain validity and accuracy criteria to be clinically useful. In psychiatry, the validity of a diagnostic procedure might be tested independently against clinical diagnosis, treatment response, and family history criteria; a strong relationship to any of the three would suggest clinical usefulness. Predictive value theory provides a model for such a test. The dexamethasone suppression test (DST) has a lower predictive value for major depressive disorder than most conventional laboratory tests used for diagnosis in medicine. In spite of promising early reports, the DST is not predictive of treatment response nor does it appear to identify genetic subtypes of depression. Although no diagnostic laboratory test is currently powerful enough for routine clinical use in psychiatry, laboratory tests may prove useful in predicting relapse and in continuing research on the psychobiology of mental disorders.

Circadian Rhythm↗
PubMed1983

The effect of lithium on the osmoregulation of arginine vasopressin secretion.

The effect of lithium on the plasma arginine vasopressin (AVP) response to the iv infusion of 5% saline was determined in six patients with primary effective disorder. Lithium did not significantly affect baseline weight, plasma osmolality, sodium, or AVP levels. However, lithium significantly increased the mean rate of change or the sensitivity of the plasma AVP response to the osmotic stimulus (from 0.42 +/- 0.17 to 1.08 to 0.24 pg/ml/mosmol/kg; P less than 0.025, by paired t test). This change was associated with a slight but significant increase in the precision of the response, as reflected in the correlation coefficient, but there was no difference in the calculated intercept or osmotic threshold for AVP secretion. This study indicates that patients on lithium do not, as previously suggested, show partial central diabetes insipidus. Rather, AVP secretion seems to be enhanced. Moreover, the mechanism of this enhancement is a specific increase in the sensitivity of the osmoreceptor rather than a lowering of the osmotic threshold for AVP secretion. The effect of lithium cannot be clearly accounted for by any of the physiological variables known to influence the sensitivity of the system and is probably due to an effect of the drug on the level or activity of neuromodulators which influence the function of hypothalamic osmoreceptors.

Adult↗
PubMed1983

Carbamazepine diminishes the sensitivity of the plasma arginine vasopressin response to osmotic stimulation.

Carbamazepine, a drug used to treat manic-depressive illness, has been reported to possess antidiuretic properties, but its effects on arginine vasopressin (AVP) secretion are controversial. Consequently, we examined plasma AVP secretion during hypertonic (5%) saline infusion in seven manic-depressive patients while on placebo and after 3-5 weeks of carbamazepine treatment. We also measured carbamazepine's effects on basal levels of the hormone in cerebrospinal fluid. Carbamazepine significantly reduced the sensitivity of the plasma AVP response to osmotic stimulation without affecting the osmotic threshold for AVP secretion. Moreover, carbamazepine did not affect baseline weight, plasma osmolality, plasma sodium, urine output, plasma AVP, or cerebrospinal fluid AVP. Although the functional significance of these findings remain to be fully determined, the fact that carbamazepine significantly reduced AVP secretion without inducing diuresis supports previous suggestions that carbamazepine enhances renal responsivity to available AVP. In addition, since carbamazepine failed to affect the osmotic threshold, the reported cases of carbamazepine-induced inappropriate AVP secretion and water intoxication must be very uncommon and probably represent idiosyncratic responses.

Arginine Vasopressin↗
PubMed1983

Cerebrospinal fluid probenecid studies: a reinterpretation.

Probenecid is used to block the transport of acid monoamine metabolites from cerebrospinal fluid (CSF), on the assumption that the resultant rise in CSF concentrations of the metabolites will reflect presynaptic "turnover" of the parent monoamine. However, CSF levels of probenecid correlate with CSF levels of the metabolite, suggesting that the blockade is incomplete at the probenecid levels obtained in human studies. This article reviews the literature on CSF probenecid-metabolite correlations and presents data demonstrating variations in the correlations across diagnostic groups. These cross-diagnostic variations may be due to group differences in membrane transport characteristics and and confound attempts to "correct for" CSF probenecid concentrations in studies of monoamine turnover.

Biological Transport↗