PubMed Health⌕ Search

Biomedical subjects

D C Jimerson

Publications and source records attributed to D C Jimerson.

At least 91 records · Page 5Linked to original sources
PubMed1984

Neurotransmitter hypotheses of depression. Research update.

Recent research on the amine neurotransmitter hypotheses of depression has moved toward comparative analysis of presynaptic neurotransmitter release and postsynaptic receptor function. Although no single pathognomonic defect has been identified in major depression, alterations in these systems have been identified in subgroups of depressed patients. Therapeutic effects of antidepressant drugs may be linked to adaptive changes in brain neurotransmitter release and receptor function.

Acetylcholine↗
PubMed1983

Measurement of 3-methoxy-4-hydroxyphenylglycol in human plasma with high-performance liquid chromatography using electrochemical detection.

A new method utilizing high-performance liquid chromatography with electrochemical detection for the determination of unconjugated 3-methoxy-4-hydroxyphenylglycol, a major metabolite of norepinephrine, in human plasma is described. A novel internal standard, 3-ethoxy-4-hydroxyphenylglycol, was used to correct for variations in extraction efficiency and detector sensitivity. Separation of sample components was achieved isocratically in 20 min per sample in a reversed-phase system. Column temperature had to be carefully regulated. The sensitivity of the assay is suitable for clinical studies, with a limit of detection of 2 pmol/ml. Intra- and interassay precision was good, with observed coefficients of variation of 7.5 and 8.8%, respectively. Accuracy was tested by comparing the results of the present HPLC method to those found with a specific gas chromatographic-mass spectrometric assay. A satisfactory correlation of 0.96 was obtained, with no significant bias between the two methods.

Chromatography, High Pressure Liquid↗
PubMed1983

Relation between plasma and cerebrospinal fluid levels of 3-methoxy-4-hydroxyphenylglycol.

Concentrations of free 3-methoxy-4-hydroxyphenylglycol in the plasma and cerebrospinal fluid are highly correlated, but concentrations in the cerebrospinal fluid are always higher than those in plasma, even when large amounts of the catecholamine metabolite are derived from a tumor of the adrenal medulla. This is explained by considering the plasma and cerebrospinal fluid as a two-compartment system in which the rate constants for entry into and exit from the cerebrospinal fluid compartment are similar. 3-Methoxy-4-hydroxyphenylglycol that is synthesized, but not catabolized, in the central nervous system maintains cerebrospinal fluid levels at an increment over those in plasma. This increment can be used to provide the best available index of formation of 3-methoxy-4-hydroxyphenylglycol in the central nervous system.

Adrenal Gland Neoplasms↗
PubMed1983

Increased plasma MHPG in dexamethasone-resistant depressed patients.

Severely depressed patients frequently show inadequate suppression of serum cortisol levels by dexamethasone. In a study of 15 depressed patients, we found a robust correlation between plasma levels of cortisol and 3-methoxy-4-hydroxy-phenylglycol after dexamethasone administration. These results suggest that dexamethasone resistance and adrenergic activation reflect parallel responses to illness-related stress in some depressed patients.

Adult↗
PubMed1983

Behavioral, physiological, and neuroendocrine responses to arecoline in normal twins and "well state" bipolar patients.

Cholinergic supersensitivity has been postulated to be an etiologic factor in affective disorder. After several pilot dose-response studies, we administered 8 mg of the cholinergic agonist arecoline subcutaneously to eight pairs of normal volunteer identical twins and eight bipolar patients currently euthymic and unmedicated. During the hour following arecoline administration, the Profile of Mood States (POMS) showed an increase in total mood disturbance in both patient and control groups. Mean systolic blood pressure, pulse, plasma cortisol, prolactin, and growth hormone also increased. Anger and elation scores on the POMS showed significant concordance in identical twins, as did change in prolactin, implying that these are the components of drug response possibly influenced by genetic factors. None of these responses differentiated well state patients from controls. Thus, mood, behavioral, and neurochemical responses to arecoline, which appears to have nonspecific neurochemical effects at the dose employed, are not markers of vulnerability to affective illness.

Arecoline↗
PubMed1983

Clinical studies of monoamine receptors in the affective disorders and receptor changes with antidepressant treatment.

Pre-clinical and clinical studies suggest that the responsiveness of monoamine and cholinergic receptors may be altered in the affective disorders and that antidepressants may modify the sensitivity of these receptors. The growth hormone response to clonidine is reduced in depressed patients compared to controls according to several independent studies, suggesting that post-synaptic alpha 2-adrenergic receptors may be less responsive in depressed patients. The cortisol response to clonidine is enhanced in depressed patients compared to controls in our study raising the possibility that cortisol hypersecretion in depressed patients may be related to noradrenergic dysfunction. The hypotensive response to clonidine is blunted in patients on chronic antidepressant treatment with either clorgyline or desipramine suggesting that pre-synaptic alpha 2-adrenergic receptors may subsensitize with chronic antidepressant treatment. The prolactin increase in response to fenfluramine is less in depressed patients compared to controls suggesting decreased functional activity of the serotonergic system in depression. Platelet alpha 2-adrenergic receptor number as measured by tritiated dihydroergocriptine (3H-DHE) binding is increased in depressed patients compared to controls, while cyclic 3'-5' adenosine monophosphate (cAMP) production in response to prostaglandin E1 (PGE1) and norepinephrine (NE) inhibition of PGE1-stimulated cAMP production are reduced in the platelets of depressed patients. Thus, it is not clear that increased 3H-DHE binding reflects increased functional responsiveness and might in fact be compensatory to decreases in functional responses of alpha 2-adrenergic receptors.

Clonidine↗
PubMed1983

Growth hormone response to clonidine in obsessive-compulsive patients.

We have observed a lesser growth hormone response to intravenous clonidine administration in nine obsessive-compulsive disorder patients meeting research diagnostic criteria than in nine matched controls. The obsessive-compulsive disorder patients had higher plasma free 3-methoxy-4-hydroxyphenylglycol and plasma norepinephrine levels before clonidine than the controls. As blunted growth hormone responses to clonidine are also characteristic of affective disorder patients, these results support other observations of a psychobiologic affinity between these two groups and are also compatible with an association between increased presynaptic noradrenergic activity and decreased post-synaptic receptor responsiveness.

Adolescent↗
PubMed1983

A risk factor strategy for investigating affective illness.

A "risk factor" approach to affective illness is outlined. Characteristics which are correlated with vulnerability to depression (or mania) should be sought and attempts made to either modify them or elucidate a pathophysiologic link between the characteristic and the illness. Genetic factors, biochemical factors, life events, demographic variables, and behavioral factors may be examined under the assumption that affective illness is multifactorially determined. Identification of these risk factors by a prospective epidemiologic study in a geographically delimited area is discussed; the risk factor model is compared with the high-risk model.

Bipolar Disorder↗
PubMed1982

Growth hormone response to clonidine as a probe of noradrenergic receptor responsiveness in affective disorder patients and controls.

The growth hormone (GH) response to the alpha-adrenergic agonist clinidine was blunted in 19 depressed patients compared to 20 controls. The difference remained significant when age- and sex-matches pairs of patients and controls were compared from this sample, either including or excluding subjects with elevated GH baseline levels. Plasma levels of free 3-methoxy-4-hydroxyphenyl-glycol (MHPG) were assayed in blood samples drawn just before the clonidine infusion. A modest negative correlation was found between the plasma MHPG values and the magnitude of the GH responses to clonidine, although baseline plasma MHPG levels were not significantly different between patients and controls. The diminished GH response to clonidine observed suggests that many depressed patients may have decreased alpha-adrenoreceptor responsiveness. Decreased responsiveness may in some cases be associated with relatively increased indices of presynaptic noradrenergic availability. Such a model might have implications for understanding the functional status of the noradrenergic neurotransmitter system in depressed patients and the possible subtyping of affective disorder patients.

Clonidine↗
PubMed1982

Behavioral, biochemical and neuroendocrine responses to amphetamine in normal twins and 'well-state' bipolar patients.

An i.v. injection of dextroamphetamine (0.3 mgm/kg) was given to 13 pairs of normal monozygotic twins, three pairs of normal dizygotic twins and 11 patients with bipolar affective disorder in remission and off medications. Behavioral excitation in response to amphetamine was highly correlated in monozygotic twins; it was predicted by the baseline variables of high plasma MHPG, low serum prolactin and low pulse; it correlated with a rise in cortisol; and it was not correlated with plasma amphetamine level. Pre-infusion baseline MHPG and growth hormone and prolactin responses to amphetamine also were concordant in twins. Plasma amphetamine level, pulse and blood pressure and cortisol responses were not concordant, suggesting significant environmental influences. Haloperidol pretreatment in one pair of twins abolished the excitation response but did not reduce increases in cortisol and growth hormone. This suggests a role for dopamine in the excitation response but predominant serotonergic and noradrenergic mediation of the hormonal responses. None of the responses or baseline measures distinguished patients from controls. Thus, no consistently altered sensitivity to monoaminergic stimulation by amphetamine in bipolar affective disorder was demonstrated in this study. This is one of the first reports of familial (possibly genetic) variation in a psychostimulant drug response in man. The responses identified as concordant may be useful in characterizing other pathologic conditions.

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

Red cell ouabain-sensitive Na+-K+-adenosine triphosphatase: a state marker in affective disorder inversely related to plasma cortisol.

Ouabain-sensitive Na+-K+-stimulated ATPase was measured in red cell membranes using a spectrophotometric assay. The mean enzyme level in patients in the depressed state (1.2 nM/mg protein per min +/- 0.18 SEM) was lower lower than that in well-state patients (2.0 +/- 0.26) and hypomanic patients (2.4 +/- 0.31). Lithium treatment itself did not alter ATPase levels. Levels in patients in the well state were not significantly different from controls and thus ATPase does not constitute a "trait" marker for affective illness. Plasma cortisol level was higher in well-state patients (15.9 micrograms/dl +/- 1.46) than in controls (11.5 +/- 0.75). There were no significant differences in cortisol in these single morning samples during different mood states. Cortisol level correlated negatively with ATPase level in the total group of patients (r = 0.42, p less than 0.005), especially in those who were euthymic. These data indicate a relationship between cortisol and ATPase levels in affectively ill patients. Ouabain-sensitive NaK ATPase may be useful as an indicator of state in affective illness; plasma cortisol may be continuously elevated in some individuals with affective disorder.

Adult↗