Bernard Lerer

A controlled trial of phenelzine in posttraumatic stress disorder

Thirteen patients meeting DSM-III criteria for posttraumatic stress disorder participated in a random-assignment, double-blind crossover trial comparing phenelzine (45-75 mg/day) and placebo. Ten patients completed at least 4 weeks of each treatment phase. Clinical response to phenelzine did not differ from placebo, and overall improvement by the end of the study could not be attributed to the active drug. The findings are discussed in the light of preliminary reports suggesting that phenelzine may be an effective treatment for posttraumatic stress disorder.

Cognitive functioning in post-traumatic stress disorder

Twelve Post-Traumatic Stress Disorder (PTSD) patients, 12 psychiatric patients matched for severity of psychopathology, and 12 normal controls were assessed for cognitive functioning by means of a comprehensive test battery. Both patient groups felt subjectively more impaired than normals. Performance on measures of intelligence, organicity, verbal fluency, memory, and attention was significantly poorer in patients than in normals. The performance of the PTSD patients and that of the psychiatric controls was, however, very similar. The premorbid intelligence of both the PTSD patients and the psychiatric controls was average and had deteriorated significantly by the time of current testing. These cognitive problems were not secondary to alcohol, drug abuse, or head injury. The results suggest a cognitive impairment in post-traumatic patients.

Chronic electroconvulsive shock and desimipramine reduce the degree of inhibition by 5-HT and carbachol of forskolin-stimulated adenylate cyclase in rat hippocampal membranes

The degree of inhibition of forskolin-stimulated adenylate cyclase activity by 5-HT and by carbachol in hippocampal membranes was significantly reduced after administration of either chronic ECS (10 days) or desimipramine (10 mg/kg i.p. for 3 weeks). A single ECS had no effect on the 5-HT response and slightly augmented the carbachol response. These results parallel previous observations on the effects of ECS and antidepressants on behavioral responses to 5-HT1a agonists and on muscarinic receptor number, and indicate the possible involvement of these receptors in the mechanism of action of antidepressant drugs.

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.

Neuroendocrine responses in chronic schizophrenia: Evidence for serotonergic dysfunction

Neuroendocrine and mood responses to a 60 mg oral dose of the serotonin-releasing agent, fenfluramine, were assessed in ten neuroleptic-free, chronic schizophrenic patients and in age- and sex-matched normal control subjects. The prolactin (PRL) response to fenfluramine was significantly blunted in the schizophrenic subjects. Growth hormone and cortisol levels were not differentially affected by the challenge. There was no significant effect of fenfluramine on mood in either group. The blunted PRL response in the schizophrenic group suggests serotonergic dysfunction; possible mechanisms of this finding and implications for treatment are considered.

Subsensitivity of human β-adrenergic adenylate cyclase after salbutamol treatment of depression

Although numerous studies have suggested that depression may be associated with a reduction in synaptic noradrenaline in the brain, direct β-adrenergic receptor agonists have only recently been tested in the treatment of depression. Moreover, newer theories of antidepressant action suggest that a reduction in β-adrenergic receptor sensitivity is a better correlate of antidepressant treatment than noradrenaline turnover changes. Eleven depressed patients were treated with salbutamol, a β-2-adrenergic agonist, and β-2-adrenergic receptor sensitivity was evaluated before, during, and after treatment. β-Adrenergic receptor sensitivity was evaluated by measuring the plasma cyclic AMP increase after an IV dose of salbutamol. The β-adrenergic agonist exhibited antidepressant efficacy and induced subsensitivity of the β-adrenergic adenylate cyclase with a time course paralleling the antidepressant effects. The results support the concept that receptor sensitivity changes occur during antidepressant therapy.

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′‐(β,γ‐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.

Effect of imipramine treatment on the prolactin response to fenfluramine and placebo challenge in depressed patients

As an index of central serotonergic function, plasma prolactin response to fenfluramine (60 mg orally) and placebo challenge was examined in 10 depressed patients before and after treatment with imipramine 200 mg/day for 3 weeks. Although baseline prolactin levels were not altered by imipramine, the prolactin response to fenfluramine was significantly (P = 0.01) increased compared to the response in the untreated state. The response to placebo was also enhanced but this effect was of lesser magnitude and not statistically significant. These findings complement previous reports and suggest that tricyclic antidepressant treatment enhances serotonergically mediated neuroendocrine responses.

Effect of Treatment and Withdrawal from Chronic Lithium in Rats on Stimulant-Induced Responses

Chronic lithium (Li) administration to rats was found to inhibit the hyperactivity induced by 0.5 mg/kg d-amphetamine but not that induced by 1.0 mg/kg d-amphetamine. Contradictory results on the ability of Li to inhibit amphetamine-induced hyperactivity may be due to the different dosages of amphetamine employed. 2 days after withdrawal from 3 weeks of chronic Li administration, rats showed no rebound supersensitivity of the hyperactivity response to 0.5 mg/kg d-amphetamine. Surprisingly, Li-withdrawn rats showed a marked subsensitivity of the stereotypy response to apomorphine. Such subsensitivity to apomorphine in Li withdrawal may relate to recent reports of homovanillic acid increases in rat brain in Li withdrawal, and to clinical reports of Li withdrawal inducing psychosis.

Treatment of chronic schizophrenia with cyproheptadine

Dopamine receptor blockade drugs results in substantial with neuroleptic amelioration of schizophrenic delusions and hallucinations. The dopamine hypothesis, based primarily on a correlation between these antipsychotic effects of neuroleptics and their dopamine blocking propensity, has been the predominant biochemical theory of schizophrenia (Snyder 1976). However, a significant number of chronic schizophrenic patients manifest prominent negative features, such as blunted affect, psychomotor retardation, apathy, and social withdrawal, which respond poorly to neuroleptic medication (Andreasen and Olsen 1982). There is evidence linking chronic schizophrenia to abnormalities of serotonergic function (e.g., DeLisi et al. 1981), including reports of increased plasma (Garelis et al. 1975; DeLisi et al. 1981; Freedman et al. 1981) and platelet (Jackman et al. 1983) serotonin concentration and a possible relationship to cortical atrophy (DeLisi et al. 1981). Furthermore, a preliminary trial with ritanserin, an experimental serotonin @-IT,) receptor blocker,