Biomedical subjects

A Winokur

Publications and source records attributed to A Winokur.

At least 55 records · Page 3Linked to original sources

PubMed1987

Multiple hormonal responses to insulin-induced hypoglycemia in depressed patients and normal volunteers.

Studies have shown that some depressed patients may demonstrate multiple hormonal response abnormalities after a neuroendocrine challenge test; this finding has suggested the strategy of measuring several hormones after an insulin tolerance test. The authors gave insulin tolerance tests to 72 depressed patients and 51 age- and sex-matched healthy volunteer control subjects and measured glucose, cortisol, prolactin, and human growth hormone (GH) responses. Although there were no differences between patients and control subjects in the mean decrease in glucose levels after the insulin tolerance test, depressed men demonstrated significantly lower prolactin and GH levels after the test.

Adult↗

PubMed1986

Hormonal and behavioral effects associated with intravenous L-tryptophan administration.

Doses of 5.0, 7.5 and 10.0 g L-tryptophan, the amino acid precursor of serotonin, or saline alone were administered by IV infusion to a group of 11 healthy male subjects, and both hormonal and behavioral responses were monitored. Significant increases were observed in plasma concentrations of growth hormone and prolactin after all three doses of L-tryptophan, but not after saline infusion. No alterations in cortisol or thryotropin were noted at any level. Examination of behavioral effects of L-tryptophan revealed a dose-dependent impairment in performance on the symbol copying test. In addition, L-tryptophan produced significant effects on mental and physical sedation, but did not alter subjective ratings of tranquilization. In agreement with some prior reports, these observations support the ability of L-tryptophan, when administered IV in high doses, to produce pronounced effects on the central nervous system in humans, and suggest the potential utility of this paradigm as a neuroendocrine challenge test.

Adult↗

PubMed1986

Serum antibodies to Epstein-Barr virus in patients with major depressive disorder.

To determine whether major depressive disorder might be associated with serologic evidence for a chronic active Epstein-Barr virus infection, viral-specific antibodies were measured in two separate groups of depressed patients (N=43) and in 46 appropriately matched healthy volunteers. No evidence that depression affects cellular immunity to the point that a persistent Epstein-Barr virus carrier state becomes activated was found. There was also no evidence that depression results from an unrecognized chronic active Epstein-Barr virus infection. The authors conclude that the routine clinical determination of expensive commercial Epstein-Barr virus antibody profiles is not indicated in most patients with major depressive disorder in the absence of other signs of chronic active Epstein-Barr viral infection.

Adult↗

PubMed1986

Insulin-induced hypoglycemia and panic attacks.

To investigate whether hypoglycemia might trigger panic attacks, the authors administered intravenous insulin to 10 patients with panic disorder. All subjects developed hypoglycemia but no panic anxiety. They reported symptoms of adrenergic hyperactivity but differentiated them from spontaneous panic attacks.

Adult↗

PubMed1986

The dexamethasone suppression test in generalised anxiety disorder.

The dexamethasone suppression test was performed on 79 patients with a diagnosis of generalised anxiety disorder. A non-suppression rate of 27% was obtained, comparable to that found in out-patient major depression but notably higher than previous reports in panic disorder. No good clinical predictors of non-suppression were discovered, nor was the co-occurrence of depression sufficient to account for the finding.

Anxiety Disorders↗

PubMed1986

Autoradiographic localization of thyrotropin releasing hormone receptors in human brain.

We used quantitative autoradiography to localize thyrotropin releasing hormone (TRH) receptors in human brain. Highest concentrations of TRH receptors were localized within the cortical, basal, and lateral nuclei of the amygdala and the molecular layer of the hippocampus. Low levels were found in the cortex, diencephalon, and basal ganglia. The radioligand bound with similar affinity and pharmacology to pituitary gland as to brain. These data suggest that authentic TRH receptors in the hippocampus and amygdala may mediate the putative effects of TRH on the human brain.

Aged↗

PubMed1986

Localization and quantification of beta-adrenergic receptors in human brain.

Little information is currently available on the localization of noradrenergic systems in the human CNS. We used quantitative autoradiography with [125I] iodopindolol to examine beta-adrenergic receptors in postmortem human brain. The concentration of beta-receptors was highest in all subfields of the hippocampus, followed by cerebellum, and then thalamic nuclei, basal ganglia, midbrain, and cerebral cortex. Low levels were found in white matter and hypothalamus. This distribution differed from the distribution of beta-receptors reported in membrane homogenates of human brain and also from the distribution of beta-receptors in rat brain determined by autoradiography. The similarities and differences between the distribution of beta-receptors in the human and rat brains may have implications regarding the role of norepinephrine in the CNS of these two species.

Aged↗

PubMed1986

Ascorbic acid increases the thyrotropin-releasing hormone content of hypothalamic cell cultures.

Thyrotropin-releasing hormone (TRH) is one of many COOH-terminal alpha-amidated neuropeptides. Recent work with the intermediate pituitary has indicated that ascorbate is a required cofactor for the COOH-terminal alpha-amidation of alpha-melanotropin. This is consistent with the ascorbate requirement of an enzyme found in pituitary and hypothalamus capable of converting peptides with a COOH-terminal glycine (-X-Gly) to alpha-amidated molecules (-H-NH2). Thus, it has been proposed that COOH-terminal glycine-extended TRH (TRH-Gly) may be the direct precursor to TRH. In the present study, primary hypothalamic cultures supplemented with ascorbate for 7 d contained two- to threefold more TRH immunoactivity (amide-specific) than cultures maintained without ascorbate. A dose-response experiment indicated that 20 microM ascorbate was capable of producing 50% of the maximum observable increase in culture TRH immunoactivity; this concentration is similar to the Km value for ascorbate uptake obtained in adrenal chromaffin and pituitary cells. A stereoisomer of ascorbate, D-isoascorbate, was also capable of producing an increase in TRH immunoactivity, but oxidized ascorbate was not. Recent studies have shown that the amidation enzyme from pituitary is capable of utilizing both L-ascorbate and D-isoascorbate but is incapable of utilizing oxidized ascorbate. The culture extracts were analyzed further by reversed-phase high-performance liquid chromatography; the increased TRH immunoactivity observed in extracts of cultures maintained in ascorbate comigrated with standard synthetic TRH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Patterns of melatonin rhythms in depression.

The nocturnal rise of melatonin in serum of humans is the result of endogenously released norepinephrine (NE) acting upon beta-adrenergic receptors of the pineal gland. As there is much interest in the possibility of there being changes in the function of beta-receptors in depressed patients, the nocturnal rise of melatonin was measured in depressives and healthy control subjects. In one study, multiple serum samples were taken between 4.30 p.m. to 7.30 a.m. in seven male depressed patients with melancholia and five healthy male control subjects. The melancholic patients had a significantly reduced nocturnal elevation of melatonin. In a separate study, serum samples were taken at 8 a.m. and 11 p.m. in melancholic depressives, non-melancholic depressives and healthy control subjects. The melancholic patients had a significantly lower concentration of melatonin at 11 p.m., but not at 9 a.m., than that measured in either the control subjects or the non-melancholic depressed patients. These results are similar to those found recently by several other groups of investigators. Further research is indicated to elucidate mechanism(s) responsible for this phenomenon.

Adult↗

PubMed1985

Ibotenic acid decreases thyrotropin-releasing hormone receptor binding in the rat amygdala.

Thyrotropin-releasing hormone (TRH) receptor densities in the amygdala were examined with quantitative autoradiography in rats treated with the cellular neurotoxin ibotenic acid (IBO). Microinjections of IBO (10 micrograms) into the right basolateral amygdaloid nucleus (BsA) reduced the concentration of TRH receptors in this nucleus by over 50%, when compared to the contralateral BsA and to vehicle-injected control rats. IBO lesions left amygdaloid terminals intact, as shown by normal levels of presynaptic choline uptake sites. Our results strongly suggest that TRH receptors in the amygdala are predominantly located on cell bodies.

Amygdala↗

PubMed1985

Thyrotropin-releasing hormone in lamprey central nervous system.

Thyrotropin-releasing hormone (TRH) levels were measured by radioimmunoassay in the CNS of larval and adult sea lampreys and adult river lampreys. In larval sea lampreys, the pituitary complex contained approx. 609 pg TRH/mg, brain contained 43.5 +/- 5.5 pg/mg (mean +/- S.E.M.) while the spinal cord contained 11.2 +/- 2.3 pg/mg. Corresponding levels in the adult sea and river lampreys were similar. Complete spinal transection did not significantly alter TRH levels below the lesion. Thus, the spinal cord contains TRH independent of supraspinal axonal projections.

Animals↗

PubMed1985

Detection of serum antibodies to Borna disease virus in patients with psychiatric disorders.

Borna disease virus causes a rare meningoencephalitis in horses and sheep and has been shown to produce behavioral effects in some species. The possibility that the Borna virus is associated with mental disorders in humans was evaluated by examining serum samples from 979 psychiatric patients and 200 normal volunteers for the presence of Borna virus-specific antibodies. Antibodies were detected by the indirect immunofluorescence focus assay. Antibodies to the virus were demonstrated in 16 of the patients but none of the normal volunteers. The patients with the positive serum samples were characterized by having histories of affective disorders, particularly of a cyclic nature. Further studies are needed to define the possible involvement of Borna virus in human psychiatric disturbances.

Adult↗

PubMed1985

Desipramine and 2-hydroxydesipramine plasma levels in endogenous depressed patients. Lack of correlation with therapeutic response.

Studies of the relationship between plasma concentrations of desipramine hydrochloride and clinical response have shown contradictory results, and only one prior study examined 2-hydroxydesipramine and its relationship to treatment. We therefore performed a study in a large, carefully diagnosed group of depressed patients taking fixed maintenance doses of desipramine to elucidate a potential relationship between clinical response and plasma concentrations of desipramine and 2-hydroxydesipramine. There was no significant correlation between clinical response and steady-state plasma levels of desipramine, 2-hydroxydesipramine, or the sum of desipramine plus 2-hydroxydesipramine. Although some commercial laboratories suggest a specific therapeutic plasma level "range" for desipramine, our data provide no support for such a range, nor for the routine measurement of plasma desipramine and 2-hydroxydesipramine concentrations in depressed patients.

Adolescent↗

PubMed1985

Borna disease virus. A possible etiologic factor in human affective disorders?

Borna disease virus is a unique neurotropic agent that appears to have a predilection for the limbic area of the brain. In some animal species, it can produce a behavioral syndrome characterized by aggressive and passive phases. This syndrome has suggested an analogy to certain human affective disorders. In this preliminary study, we examined the possible involvement of Borna disease virus in the etiology of human mood disorders by assaying for virus-specific antibodies in 265 patients with unipolar or bipolar depression and 105 normal, healthy volunteers. Twelve patients (4.5%) and none of the healthy controls demonstrated this antibody in their serum samples. It will be necessary to replicate and extend these intriguing preliminary results to determine if Borna disease virus is possibly involved in the pathogenesis of affective disorders in humans.

Adult↗

PubMed1985

Intraventricular 6-hydroxydopamine increases thyrotropin-releasing hormone (TRH) content in regions of rat brain.

Rats were given intraventricular (ivt) injections of various doses (50-400 micrograms, hydrobromide salt) of 6-hydroxydopamine (6-OHDA) and killed 1, 3 or 6 days later. Brains were removed, dissected into 11 regions, and the thyrotropin-releasing hormone (TRH) content of each region was measured by radioimmunoassay. 6-OHDA (400 micrograms) caused significant elevations in the TRH content of 6 regions: olfactory bulb, anterior cortex, brainstem, posterior cortex, hippocampus, and amygdala-piriform cortex. The magnitude of these increases ranged from 59% in olfactory bulb to 497% in hippocampus and was, in all cases, greatest at 3 days. These results suggest that the TRH content of certain brain regions may be regulated by catecholamine neurotransmitters.

Animals↗

PubMed1985

Intraventricular 5,7-dihydroxytryptamine increases thyrotropin-releasing hormone content in regions of rat brain.

Rats received intraventricular (i.v.t.) injections of 5,7-dihydroxytryptamine (5,7-DHT) (100-600 micrograms). Some animals also received intraperitoneal injections of the 5-hydroxytryptamine uptake blocker fluoxetine (FX) (20 mg/kg) or the norepinephrine uptake blocker desmethylimipramine (DMI) (48 mg/kg) 30-90 min prior to i.v.t. 5,7-DHT. Rats were killed between 2 and 35 days following i.v.t. 5,7-DHT, brains were dissected, and regions were assayed for thyrotropin-releasing hormone (TRH) by radioimmunoassay. Dose-dependent increases in TRH content following i.v.t. 5,7-DHT were noted in the brainstem and hippocampus. DMI pretreatment blocked the increase in hippocampal TRH, but not in brainstem TRH. FX pretreatment was ineffective in blocking any increases in TRH content. These results suggest differential regulation of regional TRH content by interactions with specific neurotransmitter systems.

5,7-Dihydroxytryptamine↗

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↗

PubMed1985

Autoradiographic localization of thyrotropin-releasing hormone receptors in amyotrophic lateral sclerosis spinal cord.

We used quantitative autoradiography to determine the density of thyrotropin-releasing hormone (TRH) receptors in discrete regions of spinal cord from four patients with amyotrophic lateral sclerosis (ALS). The density and distribution of [3H]-3-methyl-histidine-TRH binding to TRH receptors differed from reported values in normal individuals, with fewer TRH receptors in lamina II and lamina IX. The diminished concentration of TRH receptors in lamina IX may reflect the loss of motor neurons in ALS.

Amyotrophic Lateral Sclerosis↗