Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A salient feature of depression is eating disorders (reduced appetite and caloric intake) and/or weight loss. In the present study, reduction in food intake in rats, resulting in moderate weight loss, markedly attenuated the ability of various antidepressant drugs to reverse depressive-like behaviors: escape deficits provoked by previous exposure to uncontrollable stress. Further data support the notion that hypofunctioning of central noradrenergic processes, perhaps linked to reduced thyroid hormone levels, might contribute to such an altered response to antidepressants. These findings suggest that current nutritional status, even with marginal weight loss, could be an intervening factor in the delayed therapeutic response to antidepressants and/or in drug-resistant depression.
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PMID:Attenuation of response to antidepressants in animals induced by reduction in food intake. 271 Aug 63

Decreased levels of serum cholesterol are a well-recognized finding in hyperthyroidism. Since the conversion to bile acids is an important pathway for the elimination of cholesterol, we studied primary bile acid kinetics in seven hyperthyroid patients before and after medical treatment. Pool sizes, fractional turnover and synthesis rates of cholic acid and chenodeoxycholic acid were determined after oral administration of 50 mg [13C]cholic acid and 50 mg [13C]chenodeoxycholic acid. 13C/12C isotope ratios in serum were measured by capillary gas chromatography/electron impact mass spectrometry. Compared with the euthyroid state, serum cholesterol levels were distinctly lower in hyperthyroidism (150 +/- 33 vs. 261 +/- 51 mg per dl, p less than 0.01). Thyroid hormone excess caused a 34% reduction in cholic acid synthesis (5.8 +/- 2.8 vs. 7.9 +/- 4.2 mu moles per kg per day, p less than 0.02), which was associated with a 47% decrease in cholic acid pool size (11.7 +/- 3.4 vs. 22.0 +/- 5.2 mu moles per kg, p less than 0.01). Chenodeoxycholic acid kinetics exhibited no apparent changes. Thus, total primary bile acid synthesis was diminished by 20% in hyperthyroidism. After normalization of thyroid function, the ratio of cholic acid/chenodeoxycholic acid pool size increased in all patients. This was paralleled by a rise in the ratio of concentrations of cholic acid/chenodeoxycholic acid in serum. The depression of cholic acid synthesis in the presence of unaltered subjects is compatible with an inhibition of hepatic 12 alpha-hydroxylation by thyroid hormone. Furthermore, evidence is provided that, in man, the low serum cholesterol levels found during hyperthyroidism are not caused by an increased conversion of cholesterol to bile acid.
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PMID:Bile acid metabolism in human hyperthyroidism. 271 35

After demonstrating that prenatal exogenous thyroid hormone administration to pregnant rats produces decreases in fetal lung antioxidant enzyme (AOE) development despite increases in surfactant development, we examined the role of endogenous thyroid hormones on the development of these two lung systems. We administered the antithyroid drug methimazole (or diluent) to pregnant rats for the final 3 days before premature or term delivery; in a second series of experiments, propylthiouracil was administered for the 10 days before delivery. Both antithyroid drugs, known to cross the placenta, produced significantly decreased thyroid hormone levels in the pregnant dams. Fetal offspring from methimazole-, and propylthiouracil-treated dams demonstrated significant increases in pulmonary superoxide dismutase activity at 20 and 21 days of gestation and in catalase and glutathione peroxidase activities at 21 days compared with control offspring. Surfactant, measured as lung tissue disaturated phosphatidylcholine, was not different between either experimental group and controls. These results suggest that thyroid blockade increases AOE because the influence of thyroid hormone on AOE development may be one of depression. The findings confirm that certain hormonal regulators may influence different developing fetal lung systems in different ways.
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PMID:Thyroid inhibition and developmental increases in fetal rat lung antioxidant enzymes. 276 20

One of the leading causes of mortality in diabetics is myocardial disease. In the past few years this subject has generated a significant amount of interest with the result that myocardial problems associated with diabetes are far better understood. Though originally thought to occur as a result of atherosclerosis, various studies have shown that heart disease can occur in the absence of atherosclerosis, suggesting a diabetic cardiomyopathy. Using diabetic animals, it has been possible to characterize diabetes-induced myocardial abnormalities. Diabetic rat hearts do not respond to conditions of high stress as well as controls. The functional depression is accompanied by altered cardiac enzyme systems. A decrease in myosin ATPase activity which appears to be a result of diabetes-induced hypothyroidism is seen. Also, a depression of sarcoplasmic reticular calcium ATPase, along with a depression of calcium uptake by the SR, is seen in diabetic rat hearts. Na+, K+ ATPase activity has also been shown to be depressed and the depression appears to correlate with depressed atrial contractility. High levels of circulating fats in diabetics may alter the integrity of membranes leading to altered enzyme activities. Insulin treatment has been relatively successful at reversing or preventing myocardial changes in the diabetic rat. Other treatments that have been studied include thyroid hormone treatment, since the depression of myosin ATPase can be corrected by such treatment; and carnitine treatment, as the elevation of long chain acyl carnitines (LCAC) and the resulting depression of calcium uptake in the SR can be so normalized. These treatments have not been successful at normalizing cardiac function. A combination of the two treatments normalized function only partially, suggesting that factors besides myosin ATPase and SR calcium uptake are involved. Other treatments that have been tried include vanadate, methyl palmoxirate, and choline and methionine. Vanadate treatment has proved to be encouraging in that it normalizes both function and hyperglycemia. Methyl palmoxirate, a fatty acid analog, normalized only the elevation of LCAC but did not affect function. Methionine and choline were only partially successful in preventing the functional alterations of diabetic rat hearts. The purpose of the present article is to review our understanding of diabetes-induced myocardial problems and their possible causes. Findings from our laboratory and others are described in which attempts have been made to normalize cardiac function.
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PMID:Diabetes-induced abnormalities in the myocardium. 293 41

The isolated perfused working heart was used to study hypertensive diabetes-induced alterations in cardiac function at 6 and 12 wk after diabetes was induced. At 6 wk after diabetes induction, cardiac performance was depressed in the diabetic animals. However, there was no difference in cardiac function between normotensive Wistar and spontaneously hypertensive (SHR) diabetic rats. Wistar-Kyoto (WKY) rats were also included as normotensive controls in our 12-wk study. Hearts from 12-wk SHR and Wistar diabetic animals exhibited a depressed left ventricular developed pressure and positive and negative dP/dt when compared with control animals. However, this depression was not seen in the WKY diabetic animals. In addition, quantitation of various parameters of heart function revealed highly significant differences between SHR diabetic animals and all other groups associated with an increased mortality. Serum lipids were elevated in SHR and Wistar and were unaffected in WKY diabetic rats. Furthermore, thyroid hormone levels were not depressed in WKY diabetic rats as seen in the other two diabetic groups. This normal lipid metabolism and thyroid status could, in part, explain the lack of cardiac dysfunction in these animals. The data provide further evidence that the combination of hypertension and diabetes mellitus produces greater myocardial dysfunction than with either disease alone and is associated with a significant mortality.
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PMID:Cardiac function in spontaneously hypertensive diabetic rats. 294 94

The beneficial effects of L-carnitine administration were studied in vivo in isolated perfused working hearts from control and diabetic rats. Control and streptozocin-induced diabetic (STZ-D) rats were treated daily for 6 wk with high-dose L-carnitine (3 g.kg-1.day-1 i.p.). STZ-D results in loss of body weight and hypoinsulinemia. These effects were not altered by L-carnitine treatment. Myocardial free-carnitine levels were decreased in the untreated diabetic rats. L-Carnitine treatment of the diabetic rats increased myocardial free-carnitine levels, which were comparable with those of control rats. Six weeks after STZ administration, hearts from untreated diabetic animals exhibited depressed left ventricular developed pressure, cardiac contractility, and ventricular relaxation rates compared with control animals. However, this depression was not seen in the L-carnitine-treated diabetic animals. L-Carnitine treatment of diabetic rats significantly reduced plasma glucose and lipid levels but had no effect on control rats. Furthermore, thyroid hormone levels were higher in the L-carnitine-treated diabetic rats than in the untreated diabetic group. The data suggest that high-dose L-carnitine treatment may reduce the severity of diabetes and result in improved cardiac performance.
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PMID:Effect of L-carnitine treatment on lipid metabolism and cardiac performance in chronically diabetic rats. 297 Sep 82

To characterize endogenous control mechanisms for human erythrocyte membrane Ca2+-ATPase ("calcium pump") activity, we studied the effect of changes in blood glucose concentration in vivo within the physiologic range on Ca2+-ATPase activity in red cells. Red cells obtained in the course of induced hyperglycemia were also studied to determine susceptibility of membrane Ca2+-ATPase to stimulation in vitro by thyroid hormone and calmodulin, both of which have been shown previously to enhance Ca2+-ATPase activity. Oral glucose administration (75 g) to eight healthy, adult subjects induced predictable increases in concentrations of blood glucose and immunoreactive insulin. Basal levels of activity of Ca2+-ATPase in red cells obtained after glucose ingestion fell 55% (P less than 0.025) by 30 min after glucose with recovery of enzyme activity to levels not significantly different from basal by 60 min. Activity of red cell Ca2+-ATPase at time zero was significantly stimulated in vitro by thyroxine (T4, 10(-10) M), triiodo-L-thyronine (T3, 10(-10) M), and calmodulin (100 ng/mg membrane protein). In vivo glucose administration led to depression of red cell enzyme responsiveness in vitro to T4 and T3; recovery from this effect did not occur by 120 min after oral administration of glucose. Calmodulin responsiveness of the enzyme in vitro was less significantly reduced in red cells obtained after glucose ingestion. Intravenous (i.v.) glucose administration (20 g) to five subjects also led to decreased basal enzyme activity (61% of fasting level at 20 min). A significant decrease in response of enzyme to T4 was achieved by 8 min after glucose administration (P less than 0.02), with recovery by 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of in vivo glucose administration on human erythrocyte Ca2+-ATPase activity and on enzyme responsiveness in vitro to thyroid hormone and calmodulin. 298 51

The authors administered 50-100 micrograms of thyroxine (T4) alone for 2 weeks to 20 patients with primary major depressive disorders, evaluated clinical changes, and compared the thyroid functions before and after the trial. The results showed a significant decrease in the Hamilton Rating Scale scores, and the efficacy of thyroid hormone alone was demonstrated against depression. It was also shown that this antidepressive effect varied widely from marked improvement to mild aggravation. The degree of clinical improvement had no significant relationship with sex, age, subtype of depression, and severity of symptoms before treatment. But it had significant positive correlations with the pre-trial T3, T4, T3 uptake, free T4 index and BMR. That is, patients with a higher pre-trial thyroid function showed a greater improvement. Thus, it was suggested that the antidepressive effects is closely associated with the mechanism which suppresses endogenous thyroid hormones.
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PMID:Thyroid function and therapeutic efficacy of thyroxine in depression. 307 7

In an evaluation of the possible role of dopamine on TRH test results, 21 depressed patients were given TRH before and after one week of treatment with a low dose of haloperidol. Haloperidol significantly increased serum prolactin (both basal and after TRH) and cortisol levels, decreased body temperature, and had no effect on serum TSH, growth hormone, or thyroid hormone levels. Five of six patients with initial TSH blunting were retested with TRH; in four patients the TSH response remained blunted. These data render it unlikely that dopamine exerts a major inhibitory input on TSH secretion in depression.
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PMID:The TRH test during dopamine receptor blockade in depressed patients. 309 92

Although relationships between hormones of the hypothalamic-pituitary-thyroid (HPT) axis and behavior have been suspected for more than two centuries, there existed no framework within which they could be understood. It now appears that disturbances in the HPT-axis have more to do with affective state than with any other aspect of mentation, save possibly cognition. First, depression is the most frequently observed psychiatric symptom in patients suffering from hypothyroidism. Second, approximately 30% of euthyroid patients with major depression show a blunted, i.e., attenuated TSH response after TRH administration. Third, it is now well established that a small dose of thyroid hormone will accelerate the antidepressant effect of tricyclic antidepressants (TCA) in women, and convert TCA non-responders into responders in both sexes. Fourth, administration of TRH may induce an increased sense of well-being and relaxation in some patients and healthy volunteers. However, little is known about the pathophysiologic mechanism whereby evocative emotional factors express their effect on the HPT axis, or whereby thyroid gland alterations express their behavioral effects. Longitudinal, prospective studies of both patients with thyroid disease and patients with depression (through close collaboration between endocrinology and psychiatry) are most likely to separate cause and effect in most instances.
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PMID:Hormones of the hypothalamic-pituitary-thyroid axis: a psychoneuroendocrine perspective. 309 18


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