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Biomedical subjects

F K Goodwin

Publications and source records attributed to F K Goodwin.

At least 235 records · Page 13Linked to original sources

Effects of sleep deprivation on mood and central amine metabolism in depressed patients.

Nineteen patients, each hospitalized with a major depressive episode, were deprived of sleep for one night. Ten patients responded with clear improvement in depressive symptoms; the substantial clinical change was transient, usually lasting one day. Those who responded had significantly higher initial depression ratings (P less than .01) and tended to be older than nonresponders who experienced mild increases in irritability, fatigue, and discomfort following sleep deprivation. Amine metabolites, 5-hydroxyindoleacetic acid (5HIAA), and homovanillic acid (HVA) were not substantially affected by sleep deprivation, although there was a significant interaction of clinical response and direction of 3-methoxy-4-hydroxyphenylglycol (MHPG) change. Sleep deprivation thus produces acute, but only transient improvement in a selected group of severely depressed patients; it appears to be an important tool in the study of the affective disorders.

Adult↗

Negative effects of melatonin on depression.

In order to test the efficacy of the pineal neurohumor melatonin on depression, the hormone was administered in varying doses to six moderately to severely depressed patients and two patients with Huntington's chorea in double-blind crossover study. Melatonin exacerbated symptoms of dysphoria in these patients, as well as causing a loss of sleep and weight and a drop in oral temperature. Melatonin increased cerebrospinal fluid 5-hydroxyindoleacetic acid and calcium in three of four patients studied. The authors discuss the implications of this finding.

Adult↗

NIH conference. Dopamine- -hydroxylase. Basic and clinical studies.

Dopamine-beta-hydroxylase, the enzyme responsible for conversion of dopamine to norepinephrine, is released along with catecholamines from the adrenal medulla and from sympathetic nerve endings. The properties and mechanisms of the enzyme's action are discussed and its distribution described. Dopamine-beta-hydroxylase is a valuable indicator of exocytosis as a mechanism for neurotransmitter release. The enzyme is present in plasma, but its levels vary widely between individuals. This variation seems to be related more to genetic factors than to sympathetic nerve activity. Abnormally high or low plasma levels are associated with several diseases. However, the relation of these levels to disease pathogenesis rather than to genetic determinants is unclear. Levels of the enzyme are elevated in patients with pheochromocytoma and decline after removal of the tumor. Dopamine-beta-hydroxylase levels seem to be normal in hypertensive patients. Inhibition of dopamine-beta-hydroxylase provides a useful pharmacologic approach to evaluating the role of norepinephrine in psychiatric disorders.

Adolescent↗

Heritable factors in the severity of affective illness.

A review of clinical experience with 163 patients with primary affective disorder indicates that patients with a history characterized by recurrent depression interspersed with periods of hypomania (bipolar II) may have clinical courses that are distinguishable from bipolar I (depression with histories of mania) or unipolar patients. A prior history of suicide attempt and suicide after discharge from the research unit were most frequent among bipolar II patients. The family histories of bipolar I and bipolar II patients revealed similarly increased morbid risks for bipolar illness, whereas no bipolar illness was found in the first-degree relatives of unipolar patients. The suggestion that patients classified as bipolar II be separately considered in future studies of affective disorder is discussed.

Adult↗

Urinary excretion of 3-methoxy-4-hydroxyphenylglycol in depressed patients: modifications by amphetamine and lithium.

The excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG), the urinary metabolite which may best reflect brain norepinephrine, was measured in eight depressed patients on a longitudinal basis during the administration of placebo, d- and 1-amphetamine (30 mg/day), lithium carbonate (0.9 - 2.1 g/day), and d- and 1-amphetamine together with lithium. d-Amphetamine significantly decreased MHPG excretion. No significant change in MHPG was observed during administration of 1-amphetamine or when d- or 1-amphetamine was given together with lithium carbonate. Six patients responded with behavioral activation and euphoria to d-amphetamine, and these patients tended to have lower base line MHPG values in comparison to the nonresponders. Reductions in MHPG excretion during amphetamine administration were greatest in the patients with minimal behavioral responses to the drug, while some of the patients demonstrating more marked stimulant effects had elevated levels of MHPG during the amphetamine administration period. Variable changes, including elevated levels of MHPG in the responders, might represent the contribution of amphetamine-related changes in clinical state, including increased physical activity and (in two of the responding patients) the development of hypomania.

Adult↗

Time-dependent effects of phenothiazines on dopamine turnover in psychiatric patients.

Psychiatric patients studied early during treatment with chlorpromazine and thioridazine demonstrated elevated probenecid-induced accumulations of homovanillic acid, a major dopamine metabolite, in cerebrospinal fluid. In those studied after longer periods of treatment with phenothiazines, homovanillic acid values were not elevated. This suggests that there are time-dependent effects of phenothiazines on dopamine turn-over that may be relevant to the time course of antipsychotic efficacy.

Bipolar Disorder↗

The effect of lithium on urinary MHPG in unipolar and bipolar depressed patients.

Twenty-four hour urinary excretion of 3-methoxy-4-hydroxphaeylglycol (MHPG), the metabolite thought best to reflect brain norepinephrine metabolism, was studied longitudinally in ten depressed patients before and during the acute and chronic phases of lithium treatment. Five of the patients were identified as bipolar I (prior history of mania), 3 as bipolar II (history of hypomania) and 2 as unipolar (history of depression). During acute lithium administration (first week) there was no consistent pattern of change in MHPG. Comparing the predrug period with the third and fourth week of treatment, all of the responders showed an increase in MHPG, while the non-responders showed no change or a decrease. It is concluded that the change in clinical state is the most important variable contributing to MHPG changes in these patients. There was a tendency for the pretreatment MHPG excretion to be low in the patients who went on to show a clear-cut antidepressant response to lithium compared to those who were unequivocal non-responders. The predrug MHPG for the bipolar patients (prior history of mania) was significantly lower than the unipolar patients, a difference which apparently contributes to the lower MHPG in the lithium responders, all of whom were in the bipolar group.

Adult↗

Antidepressant response to tricyclics and urinary MHPG in unipolar patients. Clinical response to imipramine or amitriptyline.

The urinary excretion of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) was measured in unipolar depressed patients before and during the fourth week of treatment with either imipramine hydrocloride or amitriptyline hydroxhloride. On the basis of strict rating criteria, 24 patients were selected as either unequivocal responders or nonresponders. In the imipramine group the mean pretreatment MHPG was significantly lower in the nine responders in the seven nonresponders; the converse was found with the amitriptyline patients. Of particular interest is that there was no overlap in individual values between the responders and nonresponders to either drug. Treatment with eigher imipramine or amitriptyline was associated with a significant decrease in MHPG excretion, which was independent of clinical response.

Adult↗

Cerebrospinal fluid amine metabolites in acute schizophrenia.

The metabolites of serotonin, dopamine, and norepinephrine, 5-hydroxyindoleacetic acid (5HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxy-phenylethylene glycol (MHPG), respectively, were studied in cerebrospinal fluid of patients with acute schizophrenia. Base line levels of these metabolites were not significantly different from those in normal, neurological, and affectively ill controls. Accumulations of 5HIAA and HVA following probenecid administration, which provide a measure of serotonin and dopamine turnover, were also not significantly different in patients with acute schizophrenia and affective illness. After patients had recovered from their acute schizophrenic illness, HVA accumulations were significantly reduced. We discuss results in relation to amine hypotheses of schizophrenia and the suggestion that altered dopamine metabolism may reflect a biological change predisposing to acute schizophrenia.

Acute Disease↗