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Biomedical subjects

B Lerer

Publications and source records attributed to B Lerer.

At least 181 records · Page 10Linked to original sources

Bereavement in combat.

Despite the obvious fact that loss and bereavement are an integral part of the war experience, surprisingly little has been written about bereavement and grief in combat. This article discusses reasons for the resistance to the concepts of loss and bereavement in military psychiatry, distinctive aspects of combat bereavement, factors that impede appropriate grieving in war, and, with the aid of case vignettes, the varieties of bereavement states seen in combat situations. The authors conclude that the clinical phenomena of grief run like a connecting thread through the various presentations of combat-related psychiatric syndromes, including post-traumatic stress disorders, and that more research in this area is called for.

Adult↗

Proactive and retroactive effects of repeated electroconvulsive shock on passive avoidance retention in rats.

In spite of technical modifications, the therapeutic administration of electroconvulsive shock (ECS) to humans is still associated with significant memory impairment. Studies aimed at elucidating the neurobiologic basis of this impairment and developing appropriate treatment approaches have been limited by the absence of an appropriate animal model. We report here that ECS administered daily for 1-7 days to male albino rats (ECS X 1-ECS X 7) cumulatively impaired retention of passive avoidance when animals were trained 24 hours after the last ECS and tested 24 hours after training. Retention was directly proportional to the interval between training and testing; animals trained 24 hours after ECS X 7 and tested 1 hour later showed no deficit while animals tested after 24 hours showed maximal impairment. Retention was significantly improved by 10 days following the last of ECS X 7 and intact by 21 days. These findings parallel the effects of ECS on memory function in humans. The retrograde effects of ECS also paralleled those demonstrated in humans; while retention of a passive avoidance task learned 24 hours before ECS X 7 was grossly impaired, retention was intact if learning took place 7 days before the ECS course. The application of these findings as an animal model of ECS-induced memory impairment in humans, is discussed.

Amnesia↗

Verbal and non-verbal recall by depressed and euthymic affective patients.

This study uses matched-tasks methodology in order to test memory function in depressed and euthymic patients with major affective disorder. Neither drug-free depressed patients nor lithium-treated euthymic patients show a differential deficit in verbal versus non-verbal recall. However, while euthymic patients show no memory impairment, drug-free depressives do show poor memory functioning. The results support the view that memory deficits observed in affective patients in the depressed state are transient, secondary manifestations of depression and are neither indicative of underlying organic pathology, nor of abnormal hemispheric laterality. This suggests that memory impairment in depression can be treated by treating depressive symptoms, both chemically and behaviourally. The results also support the view that prophylactic lithium treatment has no adverse effects on these memory tasks.

Adult↗

Electroconvulsive shock and cyclic AMP signal transduction: effects distal to the receptor.

Chronic electroconvulsive shock (ECS) induced a significant decrease in noradrenaline- and forskolin-stimulated cyclic AMP production in rat cortical slices, whereas a single ECS had a much smaller effect. In a cortical membrane preparation, adenylate cyclase activity in response to stimulation by forskolin, guanosine-5'-(beta,gamma-imido) triphosphate, and Mn2+ ions was significantly increased in membranes derived from rats that had received chronic ECS, but was either unchanged or reduced in membranes from rats that received a single treatment only. The results are interpreted in terms of changes occurring at components of the adenylate cyclase enzyme distal to the receptor.

Adenylyl Cyclases↗

Post-traumatic stress disorder following combat exposure: clinical features and psychopharmacological treatment.

Post-traumatic stress disorder may follow combat stress or civilian psychological traumata. In 25 retrospectively studied patients, symptoms were severe in terms of number of DSM-III items fulfilled, chronicity, and severity of psychosocial disability. Antidepressants had good or moderate results in 67% of cases treated, but major tranquilisers were much less effective; response to drug treatment was not clearly related to somatisation symptoms, significant depression, or panic attacks. Pharmacotherapy appeared to have had a positive impact on psychotherapy in 70% of cases.

Adult↗

Effect of chronic lithium on cholinergically mediated responses and [3H]QNB binding in rat brain.

Lithium (Li) has been previously reported to increase acetylcholine turnover and release in rat brain and to potentiate the neurotoxicity of cholinergic agents. We studied the effect of chronic Li administration, alone and in combination with the muscarinic antagonist, scopolamine, on two cholinergically-mediated responses and on muscarinic cholinergic receptor (MCR) binding in rat brain. Administered separately, Li and scopolamine enhanced the cataleptic and hypothermic responses to pilocarpine; combined administration resulted in an additive effect on both these measures. [3H]Quinuclidinyl benzilate ([3H]QNB) binding was increased by Li in the corpus striatum but not in the cortex, hippocampus and hypothalamus. Scopolamine increased [3H]QNB binding in the striatum, cortex and hippocampus; Li and scopolamine effects on striatal MCR were not additive. Contrary to a previous report, antagonist-induced MCR supersensitivity was not prevented by concurrent Li administration in any of the brain areas studied. The additive effect of Li and scopolamine on pilocarpine-induced catalepsy and a trend in this direction for pilocarpine-induced hypothermia suggest that the actions of the two agents to enhance cholinergically mediated responses may be achieved by different mechanisms. Supersensitive responses following scopolamine may be attributed to antagonist-induced up-regulation of postsynaptic muscarinic receptors as demonstrated in the binding studies. The effects of Li to enhance cholinergically-mediated catalepsy and hypothermia are interpreted as extending previous reports that Li stimulates brain cholinergic function by a presynaptic increase in acetylcholine turnover and release.

Animals↗

Studies on the role of brain cholinergic systems in the therapeutic mechanisms and adverse effects of ECT and lithium.

Brain cholinergic systems are thought to play an important role in memory function and mood regulation. Electroconvulsive therapy (ECT) and lithium (Li) have substantial therapeutic effects on abnormal mood and may adversely affect cognitive processes. The effects of chronic electroconvulsive shock (ECS) and Li administration on brain muscarinic cholinergic receptors (MCR), and on functional correlates of altered brain cholinergic activity, were therefore studied. ECS reduced MCR number in the cerebral cortex and diminished cataleptic responses to the muscarinic agonist, pilocarpine. MCR down-regulation may have therapeutic implications in depression which has been putatively linked to central cholinergic supersensitivity. Alternatively, ECS effects on brain cholinergic function may be involved in the pathogenesis of ECT-induced memory deficits. Both ECS-induced MCR subsensitivity and a clinically equivalent model of ECT-induced anterograde amnesia were not demonstrable after a single ECS, were cumulatively induced by repeated treatments, and may be reversible by administration concurrently with ECS of a muscarinic antagonist. Li increased MCR binding marginally in the cortex and hippocampus and significantly in the corpus striatum. Li substantially enhanced cataleptic and hypothermic responses to pilocarpine. Combined Li-scopolamine pretreatment had an additive effect on these cholinergically mediated responses. Effects of Li and scopolamine on MCR binding were not additive, a finding supporting the conclusion that Li enhances brain cholinergic function by its presynaptic effects on acetylcholine turnover and release. Possible implications for the therapeutic mechanisms and adverse effects of Li are considered.

Animals↗

Methylphenidate infusion in euthymic bipolars: effect of carbamazepine pretreatment.

A number of studies have reported attenuation by lithium (Li) pretreatment of the activating and euphoriant effects of psychostimulants. In view of increasing interest in the therapeutic potential of carbamazepine (CBZ) in bipolar disorder, we examined the effect of CBZ pretreatment on methylphenidate-induced behavioral activation and euphoria. Seven euthymic bipolar subjects received 2 weeks of pretreatment with CBZ or placebo in a double-blind crossover design. After each pretreatment period, the subjects received methylphenidate, 30 mg i.v.; mood and behavior changes were monitored for a period of 5 hours after each infusion. Methylphenidate induced a striking psychostimulant effect that was not attenuated by CBZ pretreatment. Possible implications of this finding for the antimanic efficacy of CBZ and for mechanisms of action are discussed.

Adult↗

Cortical cholinergic impairment and behavioral deficits produced by kainic acid lesions of rat magnocellular basal forebrain.

The magnocellular basal forebrain (MNBF) provides extensive cholinergic innervation to frontoparietal cortex. In the rat, the MNBF is homologous to the human nucleus basalis of Meynert, a structure implicated in the cholinergic hypothesis of cognitive impairment in Alzheimer's disease (AD). Kainic acid (KA) was used to make lesions in the MNBF of rats which were compared with unoperated controls, sham-operated controls, and control rats injected with KA in the cortical area directly above the MNBF. The MNBF lesions depleted choline acetyltransferase in cortex but not in striatum or hippocampus. Cortical dopamine levels were unchanged; serotonin levels were unchanged in hippocampus and parietal cortex but decreased in frontal cortex. The metabolite levels of these neurotransmitters were unchanged in all brain regions examined. Compared with controls, rats with MNBF lesions were impaired in 24-hr retention, but not acquisition, of a passive avoidance task with escapable footshock. There were no differences between groups in mean number of daily avoidances on a bar-press active avoidance task, although the data suggested a slower rate of learning in MNBF rats. In a serial spatial discrimination reversal test with a snout-poke response, the MNBF rats performed significantly worse than controls, although all groups learned the task. This rodent model is useful for studying the role of the cholinergic system in memory and possibly for developing treatment strategies to alleviate the cognitive dysfunction of AD.

Animals↗

Three cases of carbamazepine toxicity.

The growing number of psychiatrists who prescribe carbamazepine therapy should be alert to the drug's potential complications. The authors report three such cases: one of hepatitis, one of a fatality due to aplastic anemia, and one of a severe dermatological reaction.

Adult↗

Alternative therapies for bipolar disorder.

The success of lithium in the treatment of manic-depressive illness has highlighted the problems posed by the minority of bipolar patients who are lithium nonresponders or who suffer severe adverse effects. A number of possible alternative treatments have been proposed, and the evidence in support of their clinical efficacy is evaluated. At this time, only the anticonvulsant carbamazepine can be regarded as a clinically applicable potential alternative to lithium. Further controlled studies are needed before the antimanic and prophylactic efficacy of carbamazepine can be regarded as conclusively established. Other treatment approaches are of considerable theoretical interest and of potential value clinically but need to be more thoroughly evaluated.

Ascorbic Acid↗