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Biomedical subjects

P E Stokes

Publications and source records attributed to P E Stokes.

At least 55 records · Page 3Linked to original sources
PubMed1986

Adrenocortical function and suicidal behavior in depressive disorders.

In order to examine the hypothesis that abnormal adrenocortical function is associated with suicidal behavior, morning and afternoon plasma cortisols and 1-mg dexamethasone suppression tests (DSTs) were performed in 65 patients with primary major depressive disorder. Patients with recent suicide attempts (within 28 days before DST) were compared to patients who had made past attempts and those who had never made suicide attempts with respect to age, gender, severity of depression, and plasma cortisol levels. Plasma cortisol levels did not differ significantly among the three groups. Nonsuppression on the DST was associated with presence of delusions, increasing age, and global severity of depression, but not with suicide attempts.

Adrenal Cortex↗
PubMed1986

Relationship of platelet MAO activity to characteristics of major depressive illness.

Sixty-seven patients (greater than or equal to 55 years of age) with major depressive disorder had pretreatment assays of platelet monoamine oxidase (MAO) activity. As in previous studies, women had higher MAO activity than men, and MAO activity was positively correlated with age. Patients with melancholia (DSM-III) had significantly higher MAO activity than those without melancholia. This finding may reflect the higher MAO activity associated with the symptoms of anhedonia and mood autonomy. Anxiety also was correlated with higher MAO activity, as was a positive family history of depression. In addition, postdexamethasone cortisol levels were correlated with platelet MAO activity.

Age Factors↗
PubMed1986

Dexamethasone suppression in dementia, depression, and normal aging.

Dexamethasone suppression tests (DSTs) were performed for 18 moderately demented elderly patients, 66 depressed elderly outpatients, and 25 age- and sex-matched healthy elderly control subjects. Seventeen percent of the demented patients and 4% of the normal subjects were DST nonsuppressors, compared to 38% of the total depressed group. The postdexamethasone plasma cortisol levels of the dementia group fell between those of the normal and the depressed subjects. In addition, demented patients had postdexamethasone cortisol levels significantly lower than those of depressed patients with high Hamilton depression scores. Older subjects in all diagnostic categories, including normal subjects, had higher postdexamethasone plasma cortisol levels.

Aged↗
PubMed1986

Effects of lithium carbonate on associative productivity and idiosyncrasy in bipolar outpatients.

To determine the effect of lithium carbonate on the productivity and idiosyncrasy of written associations of euthymic outpatients with affective disorder, the authors assessed 22 patients at weekly intervals during lithium treatment, 2 consecutive weeks of placebo, and 2 consecutive weeks after lithium was resumed. Lithium discontinuation produced a significant increase in associational productivity and a demonstrable increase in associative idiosyncrasy, and restoration of lithium dose significantly reversed both effects. The results suggest that lithium may affect the underlying neuropsychological functions critical to the ability to generate associations and indicate the need for further study of lithium's effects on these and other functions that may relate to neuropsychological and creative processes.

Adult↗
PubMed1985

Reduced sensitivity of lymphocyte beta-adrenergic receptors in patients with endogenous depression and psychomotor agitation.

It has been suggested that there are altered levels of norepinephrine or other neurotransmitters at functionally important receptors in patients with depressive disorders. This hypothesis is difficult to study in the human central nervous system. However, noradrenergic function can be assessed indirectly with peripheral-blood lymphocytes used as a model of the beta-adrenergic receptor complex. We found that drug-free inpatients with endogenous depression had lower isoproterenol-stimulated cyclic AMP levels in intact lymphocytes than did healthy control subjects (3.9 +/- 0.5 vs. 7.4 +/- 1.0 pmol per 10(6) cells, P less than 0.01). The density and affinity of beta-adrenergic receptors were similar in controls and depressed subjects (beta-receptor number, 5.4 +/- 0.7 and 5.3 +/- 0.8 fmol per 10(6) cells; binding affinity, 106 +/- 7.6 vs. 99.2 +/- 11.4 pM, respectively). When the depressed patients were subdivided by psychomotor manifestations, binding characteristics were indistinguishable among the subgroups. However, a significant reduction in beta-adrenergic responsiveness was observed in patients with psychomotor agitation, as compared with controls (2.6 +/- 0.5 vs. 7.4 +/- 1.0 pmol per 10(6) cells, P less than 0.01), but not in patients with psychomotor retardation (5.8 +/- 1.1 pmol per 10(6) cells, P less than 0.05). Thus, the desensitization of beta-adrenergic receptors was correlated more closely with the severity of psychomotor agitation than with the overall severity of depression.

Cyclic AMP↗
PubMed1985

Depressive behavior and hyperactive adrenocortical function.

This study examined relationships between depressive subtypes, clinical-behavioral characteristics, and hypothalamic-pituitary-adrenocortical (HPA) function in 132 hospitalized depressed patients. There were significant positive correlations between several pre- and postdexamethasone plasma cortisol measures and anxiety, psychomotor disturbance, distressed expression, and sleep disturbance. Few significant relationships were seen between illness severity and HPA function. Virtually no endocrine differences were seen between endogenous and nonendogenous subtypes or between psychotic and nonpsychotic subtypes. These results and the previous literature suggest a profile of depressed patients with HPA overactivation; they are likely to be anxious, to have sleep and psychomotor disturbances, to have lost weight in the current episode, and to be older.

Adrenal Cortex↗
PubMed1985

Differences in nocturnal melatonin secretion between melancholic depressed patients and control subjects.

The authors took multiple serum samples for measurement of melatonin between 4:30 p.m. and 7:30 a.m. in seven male depressed patients with melancholia and five healthy male control subjects and found that melancholic patients had a significantly lower rise of melatonin. They also compared a second, separate group of 14 women and five men suffering from melancholic depression with seven healthy male control subjects and nine depressed women without melancholia. The melancholic patients had a significantly lower concentration of serum melatonin at 11:00 p.m. than either the control subjects or the nonmelancholic depressed patients. These findings support the possibility that the functioning of the pineal gland is altered in these patients.

Adult↗
PubMed1984

Pretreatment DST and hypothalamic-pituitary-adrenocortical function in depressed patients and comparison groups. A multicenter study.

Pretreatment measures of hypothalamic-pituitary-adrenocortical (HYPAC) function in depressed, manic, and healthy normal subjects showed that nonsuppression on the dexamethasone suppression test (DST) had less positive predictive value for major diagnostic category and was more frequent in normals (8/77) than recently reported, although it was yet more frequent in depressed patients (35/111). Nonsuppression was common in manics (8/16), was similar in unipolar and bipolar depressed patients (35% and 27%, respectively), and did not segregate with melancholic, endogenous, or psychotic depression subtypes. Patterns of post-DST plasma cortisol concentration other than simple escape or nonescape from suppression were common. Nonsuppression of 9 AM plasma cortisol levels on the DST had as good or better diagnostic specificity as nonsuppression of any of three post-DST samples. Nonsuppression was not completely synonymous with HYPAC hypersecretion. Means of pre-DST HYPAC measures (morning plasma cortisol, urine free cortisol, and CSF cortisol levels) were elevated in depressed patients compared with normals. There were significant differences in HYPAC measures of depressed patients studied at different centers. Age correlated positively and body weight negatively with plasma cortisol level.

Adult↗
PubMed1984

Plasma cortisol and appetitively motivated arousal in monkeys.

A disagreement exists in the literature as to whether plasma glucocorticoids are a sensitive index of emotional arousal. In order to provide further data on this subject, arousal in adult male rhesus monkeys was produced by classical appetitive conditioning done once every 48 hr. Monkeys showed significantly more aroused behavior during CS+ sessions than during CS- sessions. Concurrent with these behavioral changes, appetitive conditioning suppressed the increase in plasma cortisol that took place in control conditions. This dissociation between cortisol and arousal provides additional data for the conclusion that plasma glucocorticoids are an insensitive index of arousal. The fact that glucocorticoids decrease dramatically under similar experimental conditions in rats suggests that hormonal regulatory mechanisms for this rodent species may differ from that for primates.

Animals↗
PubMed1984

Pretreatment neurotransmitter metabolite levels and response to tricyclic antidepressant drugs.

Relationships between pretreatment neurotransmitter metabolite levels and response to imipramine and amitriptyline were studied in 104 depressed patients. Normal values for urinary norepinephrine and low values for urinary MHPG were associated with greater incidence of drug response in bipolar, but not unipolar, patients. For unipolar, but not bipolar, patients low CSF 5-HIAA and high urinary metanephrine values were associated with a greater incidence of drug response. These data indicate that the pretreatment functional state of catecholamine and serotonin systems is associated with type of response to drug treatment. The authors present hypotheses about the association of alterations in serotonin and norepinephrine systems and definable subtypes of depression.

Amitriptyline↗
PubMed1984

Dexamethasone suppression in major depression.

Overnight 1 mg dexamethasone suppression tests were performed on 37 hospitalized patients with unipolar major depression and 13 psychiatric controls: 62% of the depressives and 38% of controls failed to suppress below 6 micrograms/dl of plasma cortisol at least once on the day after dexamethasone. Specificity for depressive diagnosis was only 62% but rose to 100% when a plasma cortisol value of 10 micrograms/dl was used as the criterion for normal suppression. Depressed patients were significantly more likely to show normal suppression if they were under age 65 (56% vs. 24% in the geriatric sample). Other demographic and clinical variables examined in the depressed sample did not assort by suppressor status.

Adult↗
PubMed1984

Hypothalamic-pituitary-adrenocortical function in geriatric depression: diagnostic and treatment implications.

Extensive work in the field has indicated a state-dependent hyperactivity of the hypothalamic-pituitary-adrenocortical (HYPAC) functions and unresponsiveness to dexamethasone suppression in at least 50% of patients suffering from endogenous depression. In this study, elderly outpatients, 60-85 years of age, suffering from major depressive illness according to research diagnostic criteria (RDC) were studied with the dexamethasone suppression test (DST). Careful diagnostic evaluation included RDC, the Newcastle index, and clinical interviews focusing on "endogenomorphic features." The great majority (83.3%) of patients diagnosed as endogenous depressives were nonsuppressors (abnormal DST) as compared to 16.7% nonsuppressors amongst nonendogenous patients. In addition, DST tended to normalize the clinical recovery. The research and clinical implications of our findings in this population are further discussed.

Aged↗
PubMed1983

Ultradian rhythms in cognitive functions and their relationship to visceral processes.

Visceral and behavioral data were repeatedly sampled over time in 7 men performing tests of eye-hand coordination and of recall. Spectrum analysis of behavioral data showed peaks in the ultradian range which for the group were significantly different from white noise. Relations between visceral and behavioral data were not striking. However, relations between (a) epinephrine and indices of sympathetic tone (i.e., norepinephrine or heart rate) and (b) ongoing performance were positive and the highest of all tested.

Activity Cycles↗
PubMed1982

Characterization of the phosphorylation sites and the surrounding amino acid sequences of the p21 transforming proteins coded for by the Harvey and Kirsten strains of murine sarcoma viruses.

The transforming protein coded for by the onc gene (v-rasHa) of Harvey murine sarcoma virus (Ha-MuSV) is the 21,000-dalton protein (p21) which is the immediate agent responsible for the virus-induced malignant transformation of normal cells. The p21 proteins of Ha-MuSV and the closely related Kirsten murine sarcoma virus are heavily phosphorylated in vivo. In the partially purified Ha-MuSV p21, the protein shows a guanine nucleotide-binding activity and, in addition, a very unique autophosphorylating activity at a threonine residue using as phosphoryl donor GTP but not ATP. In the present study, we compared the tryptic peptide maps of the Ha-MuSV p21 phosphorylated in vivo and in vitro. The results show that the major phosphorylation site is identical. Since the GTP-specific phosphorylation is very unique and distinct from all other known protein kinases, the present observation suggests that the in vitro enzymatic activity is responsible for the p21 phosphorylation in vivo. We have analyzed the amino acid sequence surrounding the major phosphorylation site of the Ha-MuSV p21 by automated Edman degradations of the tryptic phosphopeptides. Threonine residue 59 from the initiator methionine residue 1 of the p21 protein is the phosphorylated amino acid residue, and the surrounding amino acid sequence is NH2...-Thr-Cys-Leu-Leu-Asp-Ile-Leu-Asp-Thr-Thr(P)-Gly-Gln-Glu-Glu-Tyr-...COOH. The p21 proteins of both the Ha-MuSV and the closely related Kirsten murine sarcoma virus share the same phosphopeptide. The amino acid sequence of the phosphorylation site is distinct from all other known protein kinases.

Amino Acid Sequence↗
PubMed1982

Lithium toxicology: effect of isotopic composition on lethality and behavior.

Naturally occurring lithium consists largely of the stable lithium-7 isotope but it contains 7.6% of a second stable isotope, lithium-6. Biological effects of these two isotopes were not identical. When administered in isotopically pure form, the chloride of lithium-6 was more toxic after acute intake than the chloride of pure lithium-7:its LD in Swiss-Webster mice was 13.2 mEq/kg as opposed to 15.9 mEq/kg for the salt of the heavier isotope and 14.9 mEq/kg for that of the natural mixture of the two isotopes. A single injection of one or the other pure isotope in a constant dose, 14.5 mEq/kg led to a 90% mortality in mice given lithium-6 but only 10% in mice given lithium-7. Side effects such as hypoactivity, ataxia, intense perspiration and diarrhea appeared within 10 min after administration of toxic doses of lithium-6 but more gradually after lithium-7. The differences between the isotopes in toxicity and rate of appearance of effects on spontaneous motor activity were significant at the p less than 1% level.

Animals↗
PubMed1982

Lithium ratio and maintenance treatment response.

Erythrocyte/plasma lithium ratios were determined in 41 polar manic depressive outpatients maintained on lithium for a mean of 64 months. Sixteen patients experienced affective episodes requiring additional pharmacologic intervention during periods when their plasma lithium averaged 0.7 meq/l or above for at least 3 preceding months and they were on no concurrent medication known to induce depression or mania. These patients considered to be a homogeneous group of non-responders to lithium, had a mean lithium ratio of 0.50 (range 0.15-1.16). Seven patients experienced affective symptoms at plasma levels below 0.7 meq/1 and/or while taking concurrent medication known to induce affective symptoms, and therefore could not be categorized clinically as lithium non-responders or responders. Eighteen remaining patients, who had no affective episodes during lithium maintenance, were found to have a mean erythrocyte/plasma ratio of 0.52 (range 0.19-1.05). This latter group of apparent responders should be considered heterogeneous in that it may include spontaneous remitters. The difference in mean ratios between the non-responder group and the apparent responder group was not statistically significant. These findings support the contention that the erythrocyte/plasma lithium ratio does not correlate with response of bipolar outpatients to maintenance lithium.

Bipolar Disorder↗