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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study examined dichotic listening performance in three subtypes of developmental dyslexia and in children with left temporal lobe brain tumors (clinical contrast group). Each child was administered a free-recall CV syllable dichotic paradigm (30 pairs). Analysis of variance and Tukey-HSD pairwise follow-up comparison indicated that the dichotic listening performance of the left temporal lobe brain tumor contrast group (strong LEA/right ear suppression) was significantly different from those of the visual-spatial/dyseidetic (strong REA/left ear depression) and mixed (moderate REA/bilateral ear suppression) dyslexic subtypes. The language disorder/dysphonetic dyslexic subtype demonstrated a REA with right ear depression. Closer inspection of the individual performances of the language disorder/dysphonetic dyslexic subtype revealed a bimodal distribution with 12 subjects demonstrating a strong LEA/right ear suppression and 8 subjects exhibiting a strong REA/left ear depression. These results lend support for the contention that the dyslexic population is heterogeneous in nature with each subgroup exhibiting (1) a distinct neuropsychological test profile and reading pattern and (2) a pattern of performance on the dichotic listening task which is consistent with what would be expected based upon the pattern of dysfunction exhibited on neuropsychological evaluation.
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PMID:Dichotic listening performance in subtypes of developmental dyslexia and a left temporal lobe brain tumor contrast group. 154 Aug 24

Experiments were conducted with rats and swine to determine the potential of dietary alfalfa as a treatment for zearalenone (Z) toxicosis. Ninety-six female weanling Wistar rats were fed a casein-based semipurified diet containing 0, 15 or 25% alfalfa and 0 or 250 micrograms Z/g feed. Exposure to Z for 14 d resulted in reduced growth, feed consumption and feed efficiency as well as kidney and liver enlargement and reduced activity of 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD). Z had no effect on uterine weight. Including alfalfa in these diets reduced the inhibitory effects of Z on growth and feed consumption, minimized Z-induced liver enlargement and increased hepatic 3 alpha-HSD activity. Dietary alfalfa also reduced concentrations of residual Z and zearalenols (Zl) in liver. In a second experiment, 108 Yorkshire gilts weighing 8 to 11 kg were fed diets containing 0, 15 or 25% alfalfa and 0, 10, 20 or 40 micrograms Z/g feed for 4 wk. Z caused uterine enlargement when fed as low as 10 micrograms/g feed, although no effects were seen in growth rate, feed consumption or feed efficiency. Alfalfa decreased uterine enlargement (P less than .05), but caused a depression in feed efficiency (P less than .05). Hepatic 3 alpha-HSD activity was five times lower in swine than in rats, although activity still tended to decrease with Z and increase with alfalfa feeding. Residues of Z and Zl in pig liver indicated species differences in the metabolism of Z. These studies show that dietary alfalfa promotes Z metabolism in rats and that this feedstuff may also be useful for treating Z toxicosis in livestock.
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PMID:Effect of dietary alfalfa on zearalenone toxicity and metabolism in rats and swine. 621 39

Facially disfigured people can experience significant psychological problems, commonly relating to difficulties in social interaction. The effect of social interaction skills workshops on the psychological well-being of 64 facially disfigured participants is described. Participants completed the Hospital Anxiety and Depression Scale (HAD), the Social Avoidance and Distress Scale (SAD) and an open-ended questionnaire, before a workshop and at 6 weeks and 6 months follow-up. The high levels of anxiety evident prior to the workshop fell significantly 6 weeks post-workshop (HSD = 1.297, P < 0.01) and remained significantly lower at 6 month follow-up (HSD = 1.563, P < 0.01). Similarly, SAD scores fell significantly at 6 weeks (HSD = 1.89, P < 0.05) and again at 6 month follow-up (HSD = 2.26, P < 0.01). 6 weeks post-workshop, participants reported feeling more confident in the company of strangers (HSD = -1.266, P < 0.01) and about meeting new people (HSD = -1.159, P < 0.01). This increase in confidence was maintained at 6 months (HSD = -1.068 and -1.042 respectively, P < 0.01 for both). 61% of those who experienced problems before the workshop reported a positive change in these situations. The potential of these workshops as an addition to surgical intervention is discussed.
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PMID:An evaluation of the impact of social interaction skills training for facially disfigured people. 877 41

Two breeds of rats, Charles River Wistar [Crl(Wi)Br.] and HSD Wistar [Wistar per LATI (Budapest) Br.], with remarkable difference in learning performance were selected. The rats were trained in the shuttle box with 100 trials per day and the number of conditioned avoidance responses (CARs), the escape failures (EFs) to the unconditioned stimulus and the intersignal reactions (IRs) were counted and evaluated by multi-way analysis of variance (ANOVA). Rats of the Crl (Wi) breed proved to be the 'low performing' (LP) animals and rats of the Wistar per LATI (Budapest) breed the 'high performing' (HP) ones. The HP rats produced higher number of CARs (p<0.001), lower number of EFs (P<0.05) and higher number of IRs (P<0.01) than their LP peers. Significantly higher amounts of noradrenaline from the locus coeruleus and serotonin from the raphe were released in the HP than in the LP rats (p<0.01). There was no difference between HP and LP rats in the amount of dopamine released from the striatum, the substantia nigra and the tuberculum olfactorium. The catecholaminergic activity enhancer (CAE) substance, 1-phenyl-2-propylaminopentane HCl, [(-)PPAP], which enhances action potential-transmitter release coupling in the catecholaminergic neurons, fully antagonized in a dose of 1 mg/kg, tetrabenazine-induced learning depression in HP rats and this dose was ineffective in LP rats. The findings were regarded as further support for the view that endogenous CAE substances regulate catecholaminergic activity in the brain and (-)PPAP acts via this regulation.
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PMID:High performing rats are more sensitive toward catecholaminergic activity enhancer (CAE) compounds than their low performing peers. 878

The enzyme 11-beta-hydroxysteroid dehydrogenase (11-beta-HSD) regulates glucocorticoid activity by converting cortisol into cortisone and vice versa. Frequent signs of major depression are elevated concentrations of circulating cortisol and ACTH. However, no information is available about the activity of 11-beta-HSD in this disorder. Therefore, we compared diurnal plasma concentrations of cortisol and cortisone and their ratios, reflecting 11-beta-HSD activity, in 25 severely depressed patients (Hamilton Depression Scale, 29 +/- 6; 14 men, 11 women, age 22-77 yr; mean, 47 +/- 16) and 30 control persons (20 men, 10 women age 23-85 yr; mean, 51 +/- 19). Cortisol and cortisone were measured at 0900 h, 1100 h, 1300 h, 2000 h, 2200 h, 0100 h, 0300 h, and 0700 h with specific RIAs after extraction. Both cortisol and cortisone concentrations were significantly increased in patients compared with controls (cortisol, 251.7 +/- 113.1 vs. 160 +/- 96.6 nmol/L; cortisone, 32.8 +/- 10.9 vs. 21.9 +/- 10.9 nmol/L). The calculated ratios of cortisol to cortisone were similar in controls and patients. Similar to cortisol, the circadian variation of cortisone was flattened in patients with the ratio of maximal cortisone to minimal cortisone being 1.9-fold higher in controls than in patients. There was no gender-specific difference in cortisone values neither in patients nor in controls. We conclude that in major depression increased cortisol is not due, at least partly, to an altered 11-beta-HSD activity or to a decrease in cortisone.
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PMID:Increased diurnal plasma concentrations of cortisone in depressed patients. 1072 51

During hypoxia in the CA1 region of the rat hippocampus, spreading-depression-like depolarization (hypoxic spreading depression or HSD) is accompanied by both a negative shift of the extracellular DC potential (DeltaV(o)), and a sharp decrease in light transmittance (intrinsic optical signal or IOS). To investigate alterations in mitochondrial function during HSD and normoxic spreading depression (SD), we simultaneously imaged mitochondrial depolarization, using rhodamine-123 (R123) fluorescence, and IOS while monitoring extracellular voltage. Three major phases of the R123 signal were observed during hypoxia: a gradual, diffuse fluorescence increase, a sharp increase in fluorescence coincident with the HSD-related DeltaV(o), primarily in the CA1 region, and a plateau-like phase if reoxygenation is delayed after HSD onset, persisting until reoxygenation occurs. Two phases occurred following re-oxygenation: an abrupt and then slow decrease in fluorescence to near baseline and a slow secondary increase to slightly above baseline and a late recovery. Parallel phases of the IOS response during hypoxia were also observed though delayed compared with the R123 responses: an initial increase, a large decrease coincident with the HSD-related DeltaV(o), and a trough following HSD. After reoxygenation, there occurred a delayed increase in transmittance and then a slow decrease, returning to near baseline. When Ca(2+) was removed from the external medium, resulting in complete synaptic blockade, the mitochondrial response to hypoxia did not significantly differ from control (normal Ca(2+)) conditions. In slices maintained in low-chloride (2.4 mM) medium, a dramatic reversal in the direction of the IOS signal associated with HSD occurred, and the R123 signal during HSD was severely attenuated. Normoxic SD induced by micro-injection of KCl was also associated with a decrease in light transmittance and a sharp increase in R123 fluorescence but both responses were less pronounced than during HSD. Our results show two mitochondrial responses to hypoxia: an initial depolarization that appears to be caused by depressed electron transport due to lack of oxygen and a later, sudden, sharp depolarization linked to HSD. The depression of the second, sharp depolarization and the inversion of the IOS in low-chloride media suggest a role of Cl(-)-dependent mitochondrial swelling. Lack of effect of Ca(2+)-free medium on the R123 and IOS responses suggests that the protection against hypoxic damage by low Ca(2+) is not due to the prevention of mitochondrial depolarization.
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PMID:Mitochondrial and intrinsic optical signals imaged during hypoxia and spreading depression in rat hippocampal slices. 1089 6

Sex steroid hormones exert important influences on neuroendocrine and behavioural brain function. As neuroactive steroids they are able to modify neuronal excitability. Unbalanced synthesis may thus be implicated in pathophysiological conditions, such as epilepsy, migraine, depression and anxiety. In sex steroid metabolism, 17beta-hydroxisteroid dehydrogenases (17beta-HSDs) play a crucial role in catalyzing the final steps of androgen and estrogen biosynthesis. The hippocampus appears to be a major target area of neurosteroidal action. The expression of 17beta-HSD isozymes has not yet been studied in human hippocampus. Therefore, we investigated the expression of 17beta-HSD 1, 2, 3 and 4 mRNAs in hippocampal tissue specimens obtained at neurosurgery from 42 patients with pharmacoresistant temporal lobe epilepsy. A competitive RT-PCR assay was used to quantify the mRNA transcript level. 17beta-HSD 1 mRNA concentrations were 10000 fold lower in the hippocampus compared to placental tissue, whereas 17beta-HSD 3 mRNA concentrations were 50 fold lower than in testis and 17beta-HSD 4 concentrations were in the same order of magnitude as in liver. 17beta-HSD 2 mRNA was not expressed. 17beta-HSD 1, 3 and 4 mRNA concentrations in the hippocampus showed no significant differences between men and women and there were no significant differences in expression levels of these enzymes between patients with Ammon's horn sclerosis (AHS) and those with histopathologically normal hippocampus associated with extrahippocampal lesions. No significant correlation could be detected between duration of epilepsy, individual seizure frequency and expression levels of 17beta-HSDs. In conclusion, the present study is the first to demonstrate mRNA expression of 17beta-HSD 1, 3 and 4 in the epileptic human hippocampus. Together with data on 5alpha-reductase 1, 3alpha-hydroxisteroid oxidoreductase 2 and cytochrome P450scc, previously shown to be expressed in the human hippocampus also, our data provide further evidence for the existence of sex steroid formation and metabolism in this specific brain area.
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PMID:Expression of mRNAs encoding for 17beta-hydroxisteroid dehydrogenase isozymes 1, 2, 3 and 4 in epileptic human hippocampus. 1092 71

Allopregnanolone (3alpha,5alpha-TH PROG) and 5alpha-dihydroprogesterone (5alpha-DH PROG), the two most important neuroactive steroids synthesized in the brain, potently modulate neuronal activity by allosterically regulating GABA action at GABA(A) receptors or by changing specific GABA(A) receptor subunit gene expression, respectively. We recently reported [Proc. Natl. Acad. Sci. USA 95 (1998) 3239] that in patients with severe depression there is a decrease in the CSF levels of 3alpha,5alpha-TH PROG, which is normalized by treatment with drugs (i.e. fluoxetine) that improve psychopathology. The mechanism by which fluoxetine and other selective serotonin reuptake inhibitors normalize 3alpha,5alpha-TH PROG CSF levels appears to involve a direct stimulation of 3alpha-hydroxysteroidoxidoreductase (3alpha-HSD), an enzyme that catalyses the reduction of 5alpha-DH PROG into 3alpha,5alpha-TH PROG. Here, we propose the use of socially-isolated mice that have a downregulation of 3alpha,5alpha-TH PROG and of 5alpha-DH PROG expression to establish a model to study the behavioral consequences of this deficiency. After 4-6 weeks of isolation, these mice exhibit increased anxiety and aggressive behavior and also a decreased response to the administration of GABA-mimetic drugs. In these mice, the decrease in 3alpha,5alpha-TH PROG is selectively normalized by the use of fluoxetine in doses that reduce behavioral abnormalities. In addition, the expression of 5alpha-reductase Type I mRNA and protein was lower in socially-isolated mice than that in group-housed mice whereas 3alpha-HSD mRNA expression remained unchanged. The results of these studies may enable us to design drugs that specifically affect neurosteroidogenic enzymatic activities and may provide an efficacious treatment for the psychopathologies associated with psychiatric disorders.
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PMID:The socially-isolated mouse: a model to study the putative role of allopregnanolone and 5alpha-dihydroprogesterone in psychiatric disorders. 1174 79

In neuroendocrinology, it is believed that steroid hormones are synthesized in the gonads and/or adrenal glands, and reach the brain via the blood circulation. In contrast to this view, we are in progress of demonstrating that estrogens and androgens are also synthesized locally by cytochrome P450s in the hippocampus, and that these steroids act rapidly to modulate neuronal synaptic plasticity. We demonstrated that estrogens were locally synthesized in the adult hippocampal neurons. In the pathway of steroidogenesis, cholesterol is converted to pregnenolone (by P450scc), dehydroepiandrosterone [by P450(17alpha)], androstenediol (by 17beta-hydroxysteroid dehydrogenase, 17beta-HSD), testosterone (by 3beta-HSD) and finally to estradiol (by P450arom) and dihydrotestosterone (by 5alpha-reductase). The basal concentration of estradiol in the hippocampus was approximately 1 nM, which was greater than that in blood plasma. Significant expression of mRNA for P450scc, P450(17alpha), P450arom, 17beta-HSD, 3beta-HSD and 5alpha-reductase was demonstrated by RT-PCR. Their mRNA levels in the hippocampus were 1/200-1/5,000 of those in the endocrine organs. Localization of P450(17alpha) and P450arom was observed in synapses in addition to endoplasmic reticulum of principal neurons using immunoelectron microscopy. Different from slow action of gonadal estradiol which reaches the brain via the blood circulation, hippocampal neuron-derived estradiol may act locally and rapidly within the neurons. For example, 1 nM 17beta-estradiol rapidly enhanced the long-term depression (LTD) not only in CA1 but also in CA3 and dentate gyrus. The density of thin spines was selectively increased within 2 h upon application of 1 nM estradiol in CA1 pyramidal neurons. Only ERalpha agonist propyl-pyrazole-trinyl-phenol induced the same enhancing effect as estradiol on both LTD and spinogenesis in the CA1. ERbeta agonist hydroxyphenyl-propionitrile suppressed LTD and did not affect spinogenesis. Localization of estrogen receptor ERalpha in spines in addition to nuclei of principal neurons implies that synaptic ERalpha can drive rapid modulation of synaptic plasticity by endogenous estradiol.
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PMID:Local neurosteroid production in the hippocampus: influence on synaptic plasticity of memory. 1714 99

Changes in neuro(active)steroid levels are involved in depressive states and mood disorders. For instance, dehydroepiandrosterone or pregnenolone sulfate showed anti-stress and antidepressant activity in rodents and regulation of allopregnanolone levels appeared to be one of the consequence of an effective antidepressant therapy in patients. 4alpha,5-Epoxy-17beta-hydroxy-3-oxo-5alpha-androstane-2alpha-carbonitrile (trilostane) inhibits the activity of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) that, in particular, converts pregnenolone into progesterone. We examined whether systemic administration of trilostane affects the response to stress and depression. An acute treatment with trilostane (6.3-50mg/kg SC injected twice -16 and -2h before the measure) increased 3beta-HSD mRNA levels in the hippocampus and adrenals, but had little effect on protein levels. The trilostane treatment failed to affect open-field, locomotor or exploratory behaviors, but significantly reduced the immobility duration in the forced swimming test, measuring antidepressant-like activity, and increased the time spent in open arm in the elevated plus-maze, measuring anxiety response. The antidepressant-like effect of trilostane was effective after a repeated treatment (2.5-20mg/kgSC twice-a-day during 7 days) or in mice submitted to a restraint stress during 21 days and showing several behavioral and physiological parameters of depression (decreased body weight, increased adrenal glands weight and anhaedonia). Trilostane also reduced stress-induced increase in plasma corticosterone and ACTH levels, showing direct effect on HPA axis activity. These observations suggest that the 3beta-HSD inhibitor trilostane present antidepressant-like activity, putatively by regulating brain and peripheral levels of neuroactive steroids.
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PMID:The 3beta-hydroxysteroid dehydrogenase inhibitor trilostane shows antidepressant properties in mice. 1911 88


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