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Biomedical subjects

F K Goodwin

Publications and source records attributed to F K Goodwin.

At least 199 records · Page 11Linked to original sources
PubMed1979

Prediction of antidepressant responses to imipramine.

45 patients hospitalized for depression who had received double-blind trials with imipramine were examined for possible associations between pretreatment responses to the Minnesota Multiphasic Personality Inventory (MMPI) and their behaviorally-rated responses to this drug. Each patient was randomly assigned to one of two groups with the restriction that the number of responders and nonresponders be balanced for sex. Results from the group A patients suggest that responders and nonresponders to imipramine were best identified by using two sex-specific, empirically-derived, MMPI scales. In contrast, 12 of 13 regular validity and clinical scales and all 49 of the selected special scales of the MMPI failed to separate responders from nonresponders. In the cross-validation study with the group B patients, we were able to predict female and male responders from nonresponders by the new imipramine response scale with accuracy rates of 93 and 100%, respectively. The implications of these results are discussed.

Depression↗
PubMed1979

The existence and neurobiological significance of neuronal and glial forms of the glycolytic enzyme enolase.

The isoenzymes of the glycolytic enzyme enolase have been separated and purified. The structural and functional properties of two brain enolases are described. Immunocytochemical techniques have established that one brain enolase is restricted to neuronal cells (neuron-specific enolase, NSE) while the other is localized in glial cells (nonneuronal enolase, NNE). The brain enolases, therefore, represent the first example of functional markers for neuronal and glial cell types in brain. The two enzymes are structurally distinct with the evidence establishing that they are products of separate genes. Functionally, the neuronal enolase has been demonstrated to be uniquely stable to concentrations of chloride salts that rapidly inactivate the glial enzyme. NSE may therefore represent an adaptation of this enzyme that is specifically suited to the neuronal milieu. A specific radioimmunoassay is described for NNE and NSE with the studies reported indicating that neuronal enzyme levels vary considerably when different brain areas are compared, suggesting a relationship between functional activity and levels of NSE. In addition to being a marker for neuronal cells, NSE has also been found to be present in various glands. The cells of the APUD series (amine precursor uptake and decarboxylation cells) in the pituitary, adrenal medulla, pineal, thyroid, and pancreas have been shown to contain NSE. NSE is, therefore, also a marker for these neuronlike endocrine cells since they are the only cells other than neurons that contain this protein.

Adrenal Glands↗
PubMed1979

CSF calcium: clinical correlates in affective illness and schizophrenia.

In a study of electrolytes in lumbar cerebrospinal fluid (csf) from psychiatric patients, the authors found a positive correlation between calcium concentration and symptom severity in hospitalized depressed patients. CSF calcium levels tended to decrease as patients improved. In four rapidly cycling patients, CSF calcium was higher during depression than during mania. Mean CSF calcium for the depressed patients as a group was not significantly different from neurological controls or other psychiatric patients. Symptom remission from acute psychosis in schizophrenic patients was accompanied by a significant increase in CSF calcium concentration. These findings are discussed in relationship to calcium-induced alterations in neuronal and physiological excitability.

Bipolar Disorder↗
PubMed1979

The impact of normal volunteers on a psychiatric research unit.

Normal subjects were admitted to a psychiatric unit devoted to the study and treatment of affective illness. Initially the authors were concerned about the difficulties volunteers might have living with psychiatric patients. However, the volunteers adjusted with relative ease, while the patients' depressive symptoms were exacerbated. Their confrontation with the volunteers "normality" triggered an acute awareness of their underlying sense of failure. This response is analogous to depressed patients' reactions before discharge, when they struggle not only with their special vulnerability to separation and loss but with inevitable challenges to their fragile self-esteem during reintegration into the outside world. The presence of normal volunteers highlighted these issues and led to increased therapeutic work and considerable resolution.

Academies and Institutes↗
PubMed1979

Dopamine-beta-hydroxylase in the cerebrospinal fluid: relationship to disulfiram-induced psychosis.

Cerebrospinal fluid (CSF) dopamine-beta-hydroxylase (DBH) activity in 32 male alcoholics was measured using a modification of the radioenzymatic method of Molinoff et al. In most, the CSF was obtained before treatment with disulfiram, while in others it was obtained while they were on the drug (250 or 500 mg). As expected, treatment with this reversible DBH inhibitor had no effect on the activity of the enzyme measured in our in vitro assay. However, low pretreatment DBH activity was found to correlate with adverse reactions to disulfiram. Mean DBH activity of four individuals who went on to become psychotic on disulfiram was 0.13 +/- 0.02 nmole/ml per hr (mean +/- SEM). An additional four individuals who developed dysphoric but nonpsychotic reactions had a mean DBH of 0.23 +/- 0.03. Both these values were significantly lower than the mean DBH activity of the remaining 24 individuals treated with disulfiram who had no adverse side effects, 0.53 +/- 0.06 p less than 0.02 and p less than 0.05, respectively, 2-tailed t-test.

Adolescent↗
PubMed1979

Hydroxylated metabolites of tricyclic antidepressants: preclinical assessment of activity.

Studies investigating a possible relationship between the plasma concentration of tricyclic antidepressants and clinical response have measured only the tertiary and secondary amine forms of these drugs. The present study shows that the hydroxy metabolites of tricyclic antidepressants might also be active. Hydroxylated imipramine, desipramine, chlorimipramine, and nortriptyline inhibit the uptake of norepinephrine and serotonin into synaptosomes to the same extent as do their parent compounds. Hydroxylated nortriptyline and imipramine reverse or prevent reserpine-induced motor retardation and ptosis. Following chronic imipramine, significant steady-state concentrations of unconjugated hydroxylated metabolites are present in rat tissues including the cerebrospinal fluid. Accounting for steady-state concentrations of hydroxylated metabolites of tricyclic antidepressants in man may help to clarify whether there is a relationship between active drug concentration and clinical effect.

Animals↗
PubMed1978

Neuronal, non-neuronal and hybrid forms of enolase in brain: structural, immunological and functional comparisons.

Three forms of the glycolytic enzyme, enolase [2-phospho-D-glycerate hydrolase (E.C. No. 4.2.1.11)] have been prepared from rat whole brain extract. The most acidic enolase form is neuron specific enolase (NSE) which had previously been designated neuron specific protein (NSP). The least acidic form designated non-neuronal enolase (NNE) has been purified and compared structurally, immunologically and functionally to NSE. NNE is a dimer of 86,500 M.W. consistint of two very similar subunits. The data establish that NNE is larger than NSE which has been shown to be composed of two apparently identical 39,000 molecular weight subunits (78,000). NNE is less acidic than NSE having a pI of 5.9 compared to the value of 4.7 for NSE. Structural and immunological analysis establishes that the NNE subunit is distinct from the NSE subunit, and are therfore products of two separate genes. The structural designation of NSE is (gammagamma) and that of NNE (alpha' alpha'). NSE is strictly localized in neurons indicating that the gene coding for the gamma subunit is only expressed in neuronal cells. The intermediate brain enolase form has been partially purified; structural and immunological evidence indicate that it is a hybrid molecule consisting of one NNE subunit and one NSE subunit (alpha'gamma).

Amino Acid Sequence↗
PubMed1978

Vasopressin in affective illness.

Animal studies have revealed two important aspects of vasopressin function which make this peptide a suitable candidate for involvement in complex behavioural syndromes: (1) vasopressin deficiency produces deficits of behaviour which are reversed by vasopressin; (2) well-developed systems exist for the distribution of vasopressin throughout the central nervous system (C.N.S.) via either peptidergic neurons or the cerebrospinal fluid (C.S.F.) and provide the means by which vasopressin may regulate cells controlling behavioural or physiological processes. Among the processes which vasopressin can influence are several of significance in the symptom-complex of affective illness, including alterations in memory, changes in pain sensitivity, synchronisation of biological rhythms, the timing and quality of R.E.M. sleep, and the regulation of fluid and electrolyte balance. In addition, vasopressin is functionally linked to monoamine neurotransmitter systems and, like them, is altered by pharmacological agents which affect mood. Some of the pharmacological and clinical data suggest that vasopressin function is diminished in depression and augmented in mania; sometimes, however, alterations in vasopressin function may be detectable only during crucial periods of the manic-depressive cycle. The hypothesis that vasopressin plays a role in disorders of human behaviour, particularly manic-depressive illness, can now be directly tested by radioimmunoassays of vasopressin in C.S.F. and plasma and by the administration of specific vasopressin analogues and inhibitors.

Affective Symptoms↗
PubMed1978

Neuron specific protein (NSP) in neuroblastoma cells: relation to differentiation.

The spectrum of enolase enzyme forms has been examined in several lines of neuroblastoma cells and compared to those present in whole brain. The neuron specific enolase (NSP) is greatly decreased in the cultured cells as judged by activity profiles and radioimmunoassay. The synthesis of neuronal enolase appears to be extensively depressed in these cells while the total enolase activity is not affected. The non-neuron form of enolase (NNE) apparently compensates for the lack of the neuronal forms in the cultured cells. The preponderance of NNE in cultured neurons suggests that this enzyme is present in immature neurons, and that neuroblastoma cells are not fully differentiated with respect to the enolase function. Dibutyryl cyclic adenosine monophosphate treatment does increase NSP levels in mouse neuroblastoma cells, but not to the levels expected for fully differentiated neurons. The results indicate that NSP is a molecular correlate of fully differentiated neurons.

Animals↗
PubMed1978

Brain endolases as specific markers of neuronal and glial cells.

There are three distinct enolase isoenzymes in brain; neuron-specific enolase (NSE), formerly referred to as neuron-specific protein, which is specifically localized in neurons, a nonneuronal enolase (NNE), and a third hybrid form. Light microscopy with immunocytochemical techniques has permitted localization of non-neuronal enolase. The NNE is located in glial cells with no staining of endothelial cells or neurons. Thus, NSE and NNE can be used as specific metabolic markers for neurons and glial cells, respectively.

Animals↗
PubMed1978

Effects of a dopamine agonist piribedil in depressed patients: relationship of pretreatment homovanillic acid to antidepressant response.

Piribedil, a compound that stimulates dopamine receptors in a relatively specific fashion, was administered to 11 hospitalized depressed patients. The dopamine agonist significantly decreased rapid eye movement (REM) sleep and percent REM sleep and increased REM latency. Piribedil decreased the probenecid-induced accumulation of the dopamine metabolite homovanillic acid (HVA) in CSF. A range of mild to moderate antidepressant effects was noted; one patient worsened and one developed recurrent manic episodes. The degree of improvement in depression was negatively correlated with pretreatment values of HVA in CSF (r = -.66, P less than .05). These data suggest that the heterogeneity of clinical response may be related to biological differences in depressed patients and that those with low initial dopaminergic function respond best to increased dopamine receptor stimulation.

Adult↗
PubMed1978

Imipramine and desipramine in plasma and spinal fluid: relationship to clinical response and serotonin metabolism.

In a double-blind study of depressed patients treated with imipramine hydrochloride, levels of imipramine and desipramine were measured in plasma and in CSF. Levels of both drugs in CSF were approximately 10% of plasma levels, but the levels in the two body fluids were highly correlated. The levels of both drugs were approximately equal in plasma, but desipramine predominated in CSF (imipramine/desipramine ratio of 0.8). The imipramine-induced alteration in CSF levels of the serotonin metabolite (5-hydroxy-indoleacetic acid [5HIAA]) correlated with imipramine levels but not with desipramine. For the group of patients showing a clear antidepressant response, the mean drug levels were nearly double those of the nonresponder group, a difference that did not quite reach statistical significance in this relatively small sample. The desipramine levels showed no responder-nonresponder difference, while the ratio of imipramine/desipramine was significantly higher among the responders. On the average this particular patient group had relatively low pretreatment levels of 5HIAA in CSF, an observation that may partially account for the relatively low overall response rate to imipramine.

Adult↗