Behavioral and electrophysiological effects of androstadienone, a human pheromone.

Androstadienone is the most prominent androstene present on male human axillary hair and on the male axillary skin surface. We have previously shown that this volatile steroid is able to stimulate [corrected] the human female vomeronasal organ in picogram (pg) quantities, resulting in changes in autonomic activity. These effects are gender-specific. The purpose of the present study was to ascertain whether androstadienone could be considered a human pheromone by altering behavior as well as autonomic function. Forty normal female subjects were randomized in a double-blind manner to receive either control or 100 pg of androstadienone directly to the vomeronasal organ. We report that administration of this steroid under these conditions results in a significant reduction of nervousness, tension and other negative feeling states. Concordant changes were observed in autonomic physiology.

Ultrastructure of the human vomeronasal organ.

Virtually all vertebrates have a vomeronasal system whose involvement in pheromone detection plays a crucial role in reproduction. In humans, the vomeronasal organ has been assumed to be vestigial or absent and without functional significance. In the present study involving over 400 subjects, vomeronasal pits were observed in all individuals except those with pathological conditions affecting the septum. Electron microscopy of the adult human vomeronasal organ indicates the presence of two potential receptor elements in the pseudostratified epithelial lining: microvillar cells, and unmyelinated, intraepithelial axons. In addition, unmyelinated axons are common in the lamina propria surrounding the organ. They appear to constitute the components essential for a functional chemosensory system, and may thus provide the basis for a pheromone detection system as in other animals.

Effect of putative pheromones on the electrical activity of the human vomeronasal organ and olfactory epithelium.

The summated receptor potential was recorded from the vomeronasal organ (VNO) and olfactory epithelium (OE) of 49 human subjects of both sexes (18 to 55 years old) using surface non-polarizable silver-silver chloride electrodes. 15-25 pg of human putative pheromones, clove oil and a diluent were administered to the VNO or the OE in 0.3-1 s pulses from a 0.05 mm dia cannula connected to a multichannel delivery system. Local stimulation of the VNO produces negative potentials of 1.8-11.6 mV showing adaptation. Responses are not obtained when the recording electrode is placed in the nasal respiratory mucosa. Pheromone ER-830 significantly stimulates the male VNO (P less than 0.01; n = 20), while ER-670 produces a significant effect on female subjects (P less than 0.001; n = 20). The other pheromones tested do not show significantly different effects in both male and female (P greater than 0.1). Similar quantities of odorant or diluent produce an insignificant effect on the VNO. Stimulation of the OE with clove oil produces depolarization of 12.3 +/- 3.9 mV, while pheromones do not show a significant effect. Our results show that the VNO is a functional organ in adult humans having receptor sites for human putative pheromones.

Fluoxetine, a selective serotonin uptake inhibitor, for the treatment of outpatients with major depression.

In a double-blind, placebo-controlled study the authors found that fluoxetine, a potent and selective inhibitor of serotonin reuptake, was an effective antidepressant in moderately depressed, ambulatory outpatients. Typical adverse effects reported by patients treated with fluoxetine included agitation, nausea, fatigue, and insomnia. Compared to imipramine, fluoxetine was associated with fewer complaints of dry mouth, constipation, and dizziness.

Decreased beta-adrenergic receptors in rat brain after chronic administration of the selective serotonin uptake inhibitor fluoxetine.

Fluoxetine, a novel antidepressant compound that potently and selectively inhibits serotonin uptake, was chronically administered to laboratory rats. Using in vitro receptor autoradiographic techniques, we found that the binding of [3H]-dihydroalprenolol [( 3H]-DHA) decreased significantly in frontal cortex layers. Analysis of saturation experiments indicated that the reduction was due to a change in number but not affinity of [3H]-DHA binding sites. The data support the hypothesis that the mechanism of action of most antidepressant compounds involves a change in beta-adrenergic receptor function.

Chronic administration of sertraline, a selective serotonin uptake inhibitor, decreased the density of beta-adrenergic receptors in rat frontoparietal cortex.

Sertraline, a potent and selective inhibitor of serotonin uptake, was chronically administered to laboratory rats. Using in vitro receptor autoradiographic techniques, we found that the binding of [3H]dihydroalprenolol ([3H]DHA) was reduced in cortex layers IV-VI. Results of a saturation experiment indicated that the reduction in cortex layer IV was due to a change in number but not affinity of beta-adrenergic receptors.

5-Hydroxytryptophan: a review of its antidepressant efficacy and adverse effects.

Alterations in serotonin metabolism may be an important factor in the etiology and treatment of depression. In this regard, 5-hydroxytryptophan (5-HTP), a serotonin precursor, has been given to patients with depression. Although a review of these studies suggests that 5-HTP possesses antidepressant properties, additional trials are clearly indicated. Following a discussion of the pharmacology of 5-HTP, the authors highlight adverse effects associated with its administration to depressed patients, neurologic subjects, and normal individuals. Relatively few adverse effects are associated with its use in the treatment of depressed patients.

Receptor alterations associated with serotonergic agents: an autoradiographic analysis.

Controversy exists concerning whether receptor down-regulation is involved in the efficacy of antidepressants. Many investigators believe that norepinephrine (NE) receptor down-regulation is more important than serotonin (5-HT) receptor down-regulation. The ability to accurately determine which receptor types or subtypes have been down-regulated has been impaired by the lack of sufficiently specific ligands for labeling these receptor subtypes. Studies that have attempted to examine 5-HT2 receptor down-regulation have used [3H]-ketanserin as the ligand of choice to label 5-HT2 receptors, but this ligand also labels a nondescript site. The binding of [3H]-ketanserin to sites other than 5-HT2 receptors can be examined and controlled for by autoradiographic techniques. The authors briefly review potential problems involved in analyzing receptor binding after antidepressant treatment and present new findings of receptor alterations in rat brain as examined by autoradiographic techniques following chronic exposure to fluoxetine (a selective 5-HT uptake inhibitor that has been shown to be an effective antidepressant). Laboratory animals injected with fluoxetine showed receptor down-regulation (reduced density) in the serotonergic system. A provocative and potentially important finding of this study is that this selective 5-HT uptake blocker also down-regulates beta-adrenergic receptors in the CNS.

Total artificial heart implantation.

This report details the implantation of a total artificial heart into a human being who survived for 112 days. Included are the criteria for candidate selection, the preoperative psychiatric evaluation, and the description of operative and postoperative complications in the context of the research subject's mental status over the period of his survival. Postmortem pathologic findings are reviewed. We summarize pertinent literature, including disordered behavior, postcardiotomy, and neuropsychiatric syndromes in hepatic, renal, and cardiac transplant patients.

Anorexia nervosa with hyperthyroidism: case report.

Clinical signs of hypometabolism in anorexia nervosa may result from the "low triiodothyronine syndrome," in which thyroxine (T4) and thyroid stimulating hormone are usually normal, but triiodothyronine (T3) is in a range compatible with hypothyroidism. A case in which anorexia nervosa presented with unsuspected hyperthyroidism is reported.

On betaH-Leu5-endorphin and schizophrenia.

A previously unknown peptide, betaH-Leu5-endorphin, has been reported in the dialysates of schizophrenic patients. Accordingly, hemofiltrates from two schizophrenic and two control patients were examined for the presence of betaH-Leu5-endorphin. The opioid peptides were detected by a radioreceptor assay after separation and identification by gel filtration and high-performance liquid chromatography. With a detection limit of 30 pmole/L of hemofiltrate, no betaH-Leu5-endorphin or Met5-endorphin was found in controls or in patients. Whatever the possible involvement of endorphins in schizophrenic behavior, they are not present at detectable levels in the hemofiltrates of two well-characterized schizophrenic patients, thereby casting doubt on a general relationship of Leu-endorphin and schizophrenia.

Dialysis/hemofiltration in schizophrenia: a journey by night and cloud.

Hypotheses for the etiology of schizophrenia are discussed and related to possible treatments utilizing artificial kidney systems. For hemofiltration particularly, a theoretical framework is presented for treatment planning. Emphasis is placed on the necessity of using rigid diagnostic criteria for patient selection. Results are reported on two "strict" schizophrenic patients after a series of hemofiltration treatments. One patient showed no clinical improvement after seventeen treatments and died subsequently in a mountaineering accident. Though clinical improvement was noted in the second patient (22 treatments in four months), it is unjustifiable to attribute this solely to hemofiltration. Increased family and medical staff attention towards the patient is sufficient explanation for all changes noted in the patient's symptomatology. Chemical analyses so far have failed to detect any endorphins, normal or abnormal, in the hemofiltrates of either the two patients or two normal controls (sensitivity 30 pmol/L).

Effect of lithium on neutrophil mass and production.

We measured the effect of lithium on the blood neutrophil mass and neutrophil production, using standard di-isopropylfluorophosphate (DF32P) methods. In 12 lithium-treated patients the total blood neutrophil pool was 105 (42 to 270) x 10(7) cells per kilogram (median and 95 per cent limits) as compared with 61 (27 to 138 x 10(7) in 71 controls (P less than 0.001). The neutrophil turnover rate, a measure of effective neutrophil production, was 230 (108 to 380) x 10(7) cells per kilogram per day in the lithium-treated group and 160 (62 to 400) x 10(7) in the controls (P less than 0.05). Neutrophil migration into skin lesions ranged from 34 to 469 x 10(5) cells per day in the lithium-treated patients, as compared with 1.7 to 68 x 10(5) in 10 controls. Lithium causes enlargement of the total circulating neutrophil mass and accelerates neutrophil production without impairing neutrophil migration into skin lesions.

Effect of steroid competition and time on the uptake of (3H)corticosterone in the rat brain; an autoradiographic study.

The localization of [3H]corticosterone in the brain and pituitary of the adrenalectomized rat was studied by autoradiography. Corticosterone was concentrated preferentially by neurons in the hippocampus, septum, amygdala, and neocortex, with the hippocampal and septal neurons having the greatest concentration. [3H]-Corticosterone localization was significantly greater in neurons from adrenalectomized animals. Administration of unlabeled corticosterone (3 mg) 30 min before injection with [3H]corticosterone significantly decreased cellular localization of the labeled corticosterone, whereas [3H]corticosterone localization was not affected by progesterone pretreatment. Animals were sacrificed 15, 30 and 120 min after the injection of [3H]corticosterone to study the distribution of the hormone over the cytoplasm and nuclei. Silver grains were localized primarily over the cytoplasm of the concentrating neurons 15 min after injection; however, by 30 min after injection they were evenly distributed over both nuclei and cytoplasm.