[The dexamethasone suppression test and TRH stimulation test in endogenous depressives, schizophrenics, and normal volunteers].
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Biomedical subjects
Publications and source records attributed to R B Lu.
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Glucocorticoids are known to play a role in the maturation of the exocrine pancreas. The exact mechanism of glucocorticoid action in pancreatic ontogeny is, however, not clear. The present study characterized and quantitated the binding of [3H]dexamethasone to cytosol fractions from pancreata of rats at various ages. Trunk blood samples from these rats were also checked for levels of free and bound corticosterone. Specific and saturable bindings for dexamethasone were found in pancreatic cytosol fractions from newborn suckling and adult rats. Competition studies showed a preference for steroids with glucocorticoid activity. Specific binding was relatively low in pancreatic cytosol from newly born and 1-day old pups. A significant rise was seen after day 15. Cytosolic binding capacities were greatest from pancreata obtained from pups at weaning (3rd to 5th weeks). Values then declined toward the adult level. Scatchard analysis revealed a single class of binding sites with a dissociation constant (Kd) of 7.3 (+/- 1.1) X 10(-8) M and number of binding sites equalled to 1.29 (+/- 0.18) X 10(-13) mole/mg of cytosolic protein in adult rat pancreas. Pancreata from 25- and 15-day old rats had Kds of 3.4 (+/- 0.8) X 10(-8) M and 2.7 (+/- 0.7) X 10(-8) M with the number of binding sites equal to 1.77 (+/- 0.21) X 10(-13) mole/mg protein and 1.31 (+/- 0.16) X 10(-13) mole/mg protein respectively. Total plasma corticosterone concentration was low before day 10. It rose significantly by day 15, peaked at day 25, and then declined after weaning. About 5-15% of corticosterone during weaning and about 20-30% before and after weaning were in the free form. The peak level of dexamethasone binding corresponded to an increase in the plasma corticosterone level during weaning. This suggests a close relationship between plasma corticosterone levels and pancreatic glucocorticoid receptors. Both may, therefore, play a role in pancreatic development in the rat.
The rate of abnormal dexamethasone suppression test (AbDST, post-dexamethasone cortisol greater than 5.0 micrograms/dl) was analyzed in different psychiatric samples, diagnostic categories and different time points of blood sampling. Differences in the AbDST rate in different samples were largely due to different composition of diagnostic categories and time points of samplings. By standard DST protocol (using 4 PM and 11 PM as sampling time points), melancholics had the highest AbDST rate (58.5%) among all diagnostic groups. DST was not a practical technique for differential diagnosis in psychiatric practice because of low prevalence of melancholia in the total patient population. However, it could be a promising variable for psychopathological study. The rate of AbDST was higher at the sampling time of 4 PM than any others. For one time point sampling, the 4 PM one was suggested. 8 AM and 4 PM sampling times were suggested as a practical 2-time-point sampling for DST. The rate of AbDST in different diagnostic groups had a positive relation with the severity of depressive psychopathology in a global sense. There was not any single item or any cluster of depressive symptomatology consistently related to AbDST among all diagnostic categories. Each diagnostic category had its own specific depressive symptoms in relation to AbDST, either positively or negatively. The severity of hypothalamic-pituitary-adrenal axis dysfunction, as shown in persistent AbDST and a high level of post-dexamethasone cortisol level, showed heterogeneous relation with depressive psychopathology. The relation was positive in schizophrenia and mania, was nill in melancholia, and probably reversed U relation in other psychotics and neurotics. Multiple psychopathological and pathophysiological mechanisms responsible for AbDST were suggested.
Serum prolactin and blood levels of haloperidol were assessed in schizophrenic patients after single acute oral doses of haloperidol and during fixed dose treatment with this medication. Although significant intrapatient correlations between prolactin responses to different doses of haloperidol were found, no statistically significant interpatient relationship between haloperidol dose and prolactin response emerged. There were statistically significant relationships between steady-state plasma and red cell haloperidol levels (measured by radioreceptor or gas liquid chromatographic techniques) and serum prolactin response, but not between blood levels after the acute haloperidol dose and prolactin response.
Quantitative and qualitative measures of brain morphology were derived through CT scans using computer-assisted methodology in patients with schizophrenia or schizo-affective psychosis and headache controls. Schizophrenics had significantly higher density of white matter, together with greater right vs. left asymmetry in density of white matter than controls. Schizophrenics tended to have larger widths of cortical sulci than headache patients. In our sample of schizophrenics, however, no significant differences were found on measures of lateral ventricle (LV) width, LV area, VBR, or other measures of ventricular size compared to headache controls. There were no differences between CT scan measures taken in patients with schizophrenia vs. schizo-affective psychosis.
As part of a plan to develop a rice-based oral rehydration solution containing short polymers of glucose instead of glucose, we determined the concentration of amylase that would yield the largest amount of short chain polymers. Thai rice (25 g) was boiled with 500 ml of distilled water for 30 min. Of 200 ml supernatant rice water obtained, 100 ml were digested with different amounts of amylase after cooling to 50 degrees C for 60 min, boiled for 5 min, and centrifuged (10,000 g, 25 degrees C) for 60 min. The resulting supernatant (80 ml) was freeze-dried; 1.75 g of the powder obtained were dissolved in 3.5 ml of water, passed through a Bio-Gel P2 column to separate short chain polymers (2-9 molecules of glucose) and long chain polymers (> 9 molecules of glucose), which were identified by spectrophotometry (lambda = 190 nm) or by high performance liquid chromatography. Ten mg of amylase (equivalent to 12,000 modified Wohlgemath units) per 100 ml of rice water was optimal for the production of short polymers of glucose from rice.
Nineteen endogenous depressive in-patients (13 with major depression and 6 with bipolar disorder-depressed) and 10 other patients with dysthymic disorder serving as the control group were given the dexamethasone suppression test (DST, 1 mg/subject). The results showed that the DST sensitivity in endogenous depressives was 73.7% and the specificity was 90%. After the patients were treated daily for 6 weeks with 150-200 mg imipramine, 88.9% of those endogenous depressive patients who previously had a positive DST response exhibited a negative response. Moreover, a significantly negative correlation was found between the CSF norepinephrine level and the pre-dexamethasone 4 p.m. plasma cortisol level in those endogenous depressed patients who had a positive DST response. Pre-treatment data also showed that the 4 p.m. plasma cortisol had a significant negative correlation with CSF dopamine. These findings suggest that endogenous depression with positive DST could be related not only to a lower norepinephrine level, but also to a lower dopamine level.
BACKGROUND: It has been suggested that platelet serotonin (5-HT) content may reflect aspects of the presynaptic reuptake of 5-HT, while plasma 3-methoxy-4-hydroxy-phenylglycol (MHPG) levels may provide an index of central noradrenergic function. METHODS: In order to determine if there is a biological distinction in 5-HT or noradrenergic function within bipolar I and bipolar II depressions, we measured levels of platelet 5-HT and plasma MHPG in 12 patients with bipolar I depression, 12 patients with bipolar II depression, and 20 normal healthy controls. All subjects were medication free for at least 4 weeks prior to the study. RESULTS: There was a trend towards higher platelet 5-HT in bipolar I or II depressions when compared to normal controls, whereas there was no difference in platelet 5-HT levels between bipolar I and II depressed patients. When bipolar I and II patients were pooled, there was a significant increase in platelet 5-HT levels in bipolar depressives compared to normal controls, and there was a trend towards a weak positive correlation between platelet 5-HT and 21-item HAMD scores in the patient group. In contrast, there was no difference in plasma MHPG levels between the three groups. LIMITATIONS: This study was limited to a small sample size, single point sampling and did not match seasons. CONCLUSIONS: Our findings did not provide supportive evidence for a distinctive 5-HT or noradrenergic function within bipolar I and bipolar II depressions. However, the finding of increased platelet 5-HT levels in bipolar depressed patients compared to normal controls is consistent with the results of previous studies, and may suggest an increase in presynaptic 5-HT reuptake, presumably resulting from diminished synaptic 5-HT availability in this condition.