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Biomedical subjects

B Lerer

Publications and source records attributed to B Lerer.

At least 19 recordsLinked to original sources
PubMed1992

Effect of clomipramine and lithium on fenfluramine-induced hormone release in major depression.

Prolactin (PRL) and cortisol responses to oral administration of d-1 fenfluramine hydrochloride (60 mg) and placebo were examined in patients with endogenous major depressive disorder on three separate occasions: prior to treatment with clomipramine (CMI), after 4 weeks of CMI administration (175-250) mg/day), and 3 weeks after addition of lithium (Li) carbonate (serum level 0.5-0.9 mmol) to the treatment regimen. CMI significantly increased baseline PRL levels which were further elevated following Li supplementation. PRL response to fenfluramine (minus elevated baseline PRL levels) but not to placebo, was significantly increased by CMI administration, reflected over the 6-hr time course examined and in peak minus baseline values. Following addition of Li, the degree of enhancement was diminished although the peak minus baseline value remained significant relative to the pretreatment response. Cortisol levels were not increased by fenfluramine and were not altered by CMI or CMI + Li administration. The effect of CMI extends previous observations regarding the action of antidepressant treatment on serotenergically mediated hormone release. Methodological considerations relevant to the effect of CMI + Li are discussed.

Adult↗
PubMed1992

Effect of fenfluramine on mood: a double-blind placebo-controlled trial.

Depressed patients (n = 10), schizophrenics (n = 6), and normal control subjects was (n = 9) were administered fenfluramine hydrochloride (FF) (60 mg/os) or placebo in the context of a randomized, double-blind crossover trial. No effect of FF on mood or activation was detected over a 6-hr period. A previous report claiming acute antidepressant effects of FF in depressed subjects was not confirmed.

Adult↗
PubMed1992

Platelet adenylate cyclase activity in depression and after clomipramine and lithium treatment: relation to serotonergic function.

Adenylate cyclase activity was measured in platelet membranes from 10 healthy controls, 12 depressed patients, and the same patients after treatment with clomipramine (CMI) followed by lithium carbonate (Li) supplementation, in an attempt to determine whether any evidence for an effect on the serotonergic system could be obtained in peripheral cells. There were no differences in basal, NaF-, PGE1-, or forskolin-stimulated activity either between the control subjects and depressed patients or between activities in the patients measured before treatment, after CMI, and after CMI+Li. The degree of inhibition of forskolin-stimulated adenylate cyclase by 5-HT, an effect putatively mediated by a 5-HT1A-like receptor, was not different in the depressed patients compared to controls or affected by CMI treatment, but was significantly reduced after Li supplementation.

Adenylyl Cyclases↗
PubMed1992

SPECT imaging in psychiatry. A review.

In the last two decades, brain imaging has become an integral part of clinical and research psychiatry. Single photon computed emission tomography (SPECT) is rapidly gaining acceptance as one of the major imaging techniques available, along with computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). Each of these techniques has its assets and drawbacks. This review concerns SPECT, a highly prevalent imaging technique whose potential value in brain imaging has not been appreciated until recently. Its purpose is to expose practicing clinicians and research psychiatrists alike to the attributes of this instrument, which is available in most nuclear medicine departments today. An effort is made to provide a comprehensive account of this technique, including a brief summary of the basic principles, the various methods of its application, and recent findings in most psychiatric disorders. Analogies to its "aristocratic cousin," PET, are presented to emphasize similarities and differences. Finally, directions for future development and implementation of SPECT are suggested.

Diagnosis, Differential↗
PubMed1992

Hormone responses to fenfluramine and placebo challenge in endogenous depression.

Plasma prolactin and cortisol levels after oral administration of d-l fenfluramine hydrochloride (60 mg) and placebo were examined in 24 endogenously depressed patients and 21 age- and sex-matched normal control subjects in a randomized, double-blind study. Prolactin levels were significantly increased by fenfluramine in both groups, but the response was significantly blunted in the depressed patients compared with the controls. This effect was partially dependent upon elevated baseline cortisol levels in the depressed group and was also influenced by a history of weight loss. Plasma cortisol levels were not increased by fenfluramine in either group. These findings confirm previous reports and suggest that patients with endogenous major depression are characterized by central serotonergic hyporesponsivity. The need to account for baseline effects on hormonal responses to putative serotonergic agents is supported by the findings; however, these effects appear to be less striking when endogenicity is a prominent clinical feature of the depressive syndrome. The apparently complex influence of weight loss on prolactin response to serotonergic challenge remains to be clarified as well as the role played by the bioavailability of the challenge drug and its metabolite.

Adult↗
PubMed1992

Enhanced serotonergic responsivity following electroconvulsive therapy in patients with major depression.

Prolactin release in response to fenfluramine hydrochloride (60 mg orally) and placebo was evaluated in 18 medication-free patients with RDC major depressive disorder, endogenous subtype, before and after a series of bilateral treatments with ECT. Before ECT, fenfluramine induced a twofold increase in plasma prolactin levels. This response was significantly enhanced after the ECT series, while baseline prolactin levels and response to the placebo challenge were not altered. There was no significant difference in plasma fenfluramine and norfenfluramine levels during the pre- and post-ECT challenges. These findings suggest that ECT enhances central serotonergic responsivity and extend to depressed patients pre-clinical observations regarding the effect of electroconvulsive shock on serotonergic function.

Depressive Disorder↗
PubMed1992

Regulation of 5-hydroxytryptamine1A receptor function in rat hippocampus by short- and long-term administration of 5-hydroxytryptamine1A agonist and antidepressants.

Single s.c. injections of the 5-hydroxytryptamine (5-HT)1A receptor agonists buspirone at 4 mg/kg, 8-hydroxy-2-(di-n-propylamino)tetralin at 1 or 4 mg/kg or ipsapirone at 10 mg/kg did not affect 5-HT inhibition of forskolin-stimulated adenylate cyclase activity in rat hippocampal membranes. However, a single injection of buspirone at 8 mg/kg, and daily injections of each of the agonists for 8 days, resulted in a reduction in the degree of enzyme inhibition by 5-HT. Chronic administration of the antidepressants fluoxetine, zimelidine and maprotiline by i.p. injections at 15 mg/kg for 3 weeks also resulted in a decreased degree of enzyme inhibition. Chronic iprindole at the same dose had no effect. It is concluded that the antidepressant-like properties of 5-HT1A receptor agonists may be mediated partly by a postsynaptic action at the level of serotonergic second messenger transduction in the hippocampus.

Adenylyl Cyclases↗
PubMed1991

Chloroamphetamine did not prevent the effects of chronic antidepressants on 5-hydroxytryptamine inhibition of forskolin-stimulated adenylate cyclase in rat hippocampus.

Administration of p-chloroamphetamine (PCA, 10 mg/kg i.p. on two occasions) to rats resulted in a severe depletion of [3H]paroxetine binding sites, a measure of presynaptic serotonergic terminals, in both cortex and hippocampus, but did not affect [3H]8-hydroxy-2-(di-n-propylamino)tetralin [( 3H]8-OH-DPAT) binding or 5-hydroxytryptamine (5-HT)-induced inhibition of forskolin-stimulated adenylate cyclase in hippocampal membranes. Administration of either imipramine (15 mg/kg i.p. for 2 weeks) or lithium (0.2% for 2 weeks) to PCA-treated rats did not affect [3H]8-OH-DPAT binding but reduced the degree of inhibition of forskolin-stimulated adenylate cyclase by 5-HT in hippocampal membranes. It is concluded that the effects of imipramine and Li+ on 5-HT1A receptor-mediated responses in the hippocampus are exerted postsynaptically, possibly at a level distal to the receptor.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1991

Phospholipase A2 activity in Epstein-Barr virus-transformed lymphoblast cells from schizophrenic patients.

We examined the activity of phospholipase A2 in Epstein-Barr virus-transformed lymphoblast cell lines established from ten schizophrenic patients and ten controls. A novel method for determination of enzyme activity in whole cells was employed, by measuring the hydrolysis of a fluorescent analogue of phosphatidylcholine. No significant difference in phospholipase A2 activity was found between the groups. These results suggest that the previously reported changes in phospholipase A2 activity in plasma and in fresh peripheral cells are indicative of environmental influences and not of "trait" characteristics intrinsic to schizophrenia.

Adult↗
PubMed1991

The 5-HT receptor--G-protein--effector system complex in depression. I. Effect of glucocorticoids.

Hormonal modulation of neurotransmission emerged as a concept from the recognition that adrenocortical steroids exert profound effects at the level of receptors, G-proteins and effector units. G-proteins, a family of guanine nucleotide binding regulatory components that couple neurotransmitter receptors to various types of intracellular effector systems, appear to be a key target of glucocorticoid (GC) action in the CNS. It is thought that Gs/Gi mediates stimulation/inhibition of adenylate cyclase (AC system), which forms cyclic AMP as second messenger, while receptors stimulating phospholipase C do so through Go to produce two second messengers, inositol 1,4,5-triphosphate and diacylglycerol (PI system). Recent evidence suggests that GC increase Gs alpha-and decrease Gi alpha-protein subunit expression without affecting Go alpha. Activation of central pre- and postsynaptic 5-HT1A receptors which are linked to the Gi-AC complex, induces hypothermia and ACTH/cortisol release in rodents and humans. Compared with controls, patients with a major depressive disorder exhibit increased basal cortisol secretion associated with decreased hypothermic and ACTH/cortisol responses. The attenuated neuroendocrine and thermoregulatory response to 5-HT1A receptor activation may reflect a GC-dependent feedback inhibition of the hypothalamic-pituitary-adrenal (HPA) system and subsensitivity of the presynaptic 5-HT1A-Gi-AC complex function. Differential regulation of 5-HT1A and 5-HT2 function leading to a relative 5-HT2-Go-PI complex supersensitivity may maintain HPA hyperactivity during the course of depression. These findings corroborate recent reports that GC, via GC-GC receptor (GR) complex activated promotion of gene transcription, modify the expression 5-HT1A-coupled Gi (but not 5-HT2-coupled Go) resulting in altered sensitivity of 5-HT1A-mediated signal transduction and further support the hypothesis of a differential regulation of 5-HT1A and 5-HT2 receptor function and a GC-GR/5-HT1A-G-protein--effector system-related abnormality in depression.

Adenylyl Cyclases↗
PubMed1991

Post-traumatic stress disorder: issues of co-morbidity.

There is considerable controversy over whether or not post-traumatic stress disorder (PTSD) should be considered as a separate diagnostic entity. The present study utilized the Symptom Checklist-90 (SCL-90) in order to examine the degree of overlap between PTSD and the related diagnoses of anxiety, depression and obsession-compulsion in a group of Israeli Lebanon War PTSD casualties. We found that the SCL-90 was able both to identify and discriminate between the clinical groups. Multiple discriminant analysis showed that although there is overlap between PTSD and obsessive-compulsive disorder, PTSD is, in fact, discriminated from all the other patient groups.

Adult↗
PubMed1991

Effects of lithium and desimipramine on second messenger responses in rat hippocampus: relation to G protein effects.

The effects of chronic administration of lithium, short-term administration of lithium, chronic administration of DMI and a combination of short-term administration of lithium and chronic administration of DMI on second messenger responses were studied in the hippocampus of the rat. Lithium reduced the ability of carbachol to inhibit forskolin-stimulated activity of adenylate cyclase in hippocampal membranes but had no effect on carbachol-stimulated formation of inositol phosphate in hippocampal slices. Lithium, however, reduced the degree of stimulation of formation of inositol phosphate, induced by noradrenaline. Desimipramine alone did not affect carbachol- or noradrenaline-mediated reactions and a combination of short-term administration of lithium and chronic administration of DMI did not potentiate the action of lithium on adenylate cyclase. Both lithium and DMI abolished the inhibition by 5-HT of carbachol-stimulated formation of inositol phosphate a 5-HT1A receptor-mediated response. It is concluded that the chronic effects of administration of lithium may be related to actions at the G protein level and that different modes of coupling of receptors to G proteins may be responsible for the variety of effects observed.

Adenylyl Cyclases↗
PubMed1991

Performance of long-stay schizophrenics on matched verbal and visuospatial recall tasks.

A verbal and a visuospatial recall task were compared for discriminating power, using the matched-tasks methodology. These tasks were administered to long-hospitalized schizophrenics. No evidence of a differential deficit, that is, better recall of either the verbal or the visuospatial materials, emerged in the patients. The results replicate a former finding showing no difference between verbal and visuospatial recall in schizophrenics, using memory tasks which were less sensitive as left- and right-hemisphere measures and a non-verbal task less affected by verbal mediation. This replication questions the assumption that the hemispheric differences observed in schizophrenics affect such memory tasks.

Adult↗
PubMed1991

Early and long-term effects of electroconvulsive therapy and depression on memory and other cognitive functions.

Twenty-seven medication-free, depressed patients (Research Diagnostic Criteria, endogenous subtype) were administered a comprehensive battery testing memory and other cognitive functions before and after a series of bilateral, brief-pulse electroconvulsive therapy (ECT) administered according to a dosage-titration procedure (8.9 +/- 1.981 treatments). A subset of patients (N = 14) were reexamined at 1 month and 6 months after the conclusion of the treatment. Anterograde (verbal and visuospatial tasks), as well as retrograde (famous and personal events), memory function was significantly impaired at the end of the ECT series. By 1 month follow-up, performance had improved to pre-ECT (depression) levels on both anterograde and retrograde tasks and exceeded these by 6 months. The memory deficits induced by ECT were not a consequence of generalized cognitive impairment. Furthermore, depression and ECT were shown to independently affect memory, and recovery from depression was not a consequence of the amnestic action of the treatment. The results generally confirm previous reports regarding the nature of ECT-induced memory impairment, in a different language and culture. They suggest that long-term effects of the treatment on memory are even less prominent than previously observed.

Adult↗
PubMed1991

Performance of long-stay schizophrenics after drug withdrawal on matched immediate and delayed recall tasks.

Both anticholinergic and neuroleptic drugs were withdrawn from eight long-stay hospitalized chronic schizophrenics. These patients and normal controls were then tested on Calev, Venables & Monk's (1983) immediate and delayed matched recall tasks to evaluate their rate of forgetting of verbal well-encoded materials. The results showed rapid forgetting in schizophrenics. This finding suggests that a post-encoding deficit characterizes long-stay schizophrenics after drug withdrawal. Cognitive and brain pathologies that may explain these results are discussed.

Adult↗