Julian Lieb

Elevated levels of prostaglandin e2 and thromboxane B2 in depression

Plasma prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) levels were measured in 30 depressed outpatients. Plasma PGE2 was increased in all but one of these patients (p less than 0.001) and all had increased levels of TXB2 (p less than 0.001). Since monamine oxidase inhibitors inhibit brain prostaglandin synthesis, and tricyclic antidepressants may antagonize prostaglandin actions, these observations suggest new approaches to depression research.

A biochemical basis for the actions of lithium on behaviour and on immunity: Relapsing and remitting disorders of inflammation and immunity such as multiple sclerosis or recurrent herpes as manic-depression of the immune system

Abstract Lithium has actions on the immune system similar to its paradoxical effects in manic-depression in that both inhibition and stimulation of the immune system have been reported. In many disorders of immunity and inflammation there are unpredictable relapses and remissions similar to those which occur in manic/depression. We propose that in such recurrent disorders of immunity lithium may have a therapeutic role. A key aspect of this role is likely to be an effect on T suppressor lymphocytes. Lithium may prove able both to reduce excess suppressor function and to enhance the activity of defective T suppressors. There is evidence that prostaglandin (PG) E1 is a key determinant of both mood and suppressor cell activity. Excess PGE1 formation will be associated with mania when it occurs in the brain and with excess suppressor function in the immune system. Since stores of the PGE1 precursor dihomogammalinolenic acid (DGLA) are limited, excess PGE1 formation may be followed by depletion of DGLA and a fall in PGE1. Since PGE1 blocks mobilisation of arachidonic acid, a lack of PGE1 is likely to be associated with arachidonate mobilisation and an excess of 2 series PGs. This will be associated with depression in the nervous system and failure of T suppressor function with auto-immune attack in the immune system and over production of 2 series PGs. Lithium limits DGLA mobilisation and so can prevent both excess PGE1 formation and a subsequent DGLA depletion. Multiple sclerosis fits this model well since in remission T suppressor function is excessive while in relapse it is defective. Other recurrent and relapsing disorders such as rheumatoid arthritis and related conditions, familial Mediterranean fever, asthma, migraine and inflammatory disorders of the skin and the bowel may also fit the model.

Lithium and immune function

Lithium has potent antiviral and immunostimulating properties which are probably consequences of its actions on prostaglandin synthesis. Although lithium has considerable potential in the prophylaxis of some viral illnesses and other manifestations of defective immune function, it is, paradoxically, capable of activating autoimmune mechanisms in predisposed patients.

A DOUBLE‐BLIND TRIAL OF MAPROTILINE (LUDIOMIL®) AND AMITRIPTYLINE IN DEPRESSED OUTPATIENTS

The results of a double‐blind trial of a tetracyclic antidepressant, maprotiline (Ludiomil®) and a conventional tricyclic, amitriptyline (Elavil®), in 67 ambulatory depressives are reported. hamiltons Rating Scale for Depression was the main outcome criterion.

Symptom reduction in depressed outpatients treated with amitriptyline or maprotiline: Repeated measurement analysis

Abstract Preliminary open-labeled studies 1 had characterized maprotiline (Ludiomil ® ) as a tetracyclic antidepressant that enhanced both mood and drive, reduced the symptoms of agitation and retardation, and had a fast onset of action. These effects might appear in patients as an increased interest in the environment and decreased apathy during the initial weeks of treatment. To test this observation, maprotiline was compared to amitriptyline hydrochloride (Elavil ® ), a conventional tricyclic, in a 4-week double-blind clinical trial with outpatient depressives. No difference between these two compounds in timing of response, efficacy, or side effects was shown after 1 week of treatment or at the completion of the trial, 2 when utilizing a standard analysis of covariance. Using a repeated measurement analysis, we then examined the differences in rates of change between the drugs. Since the repeated measurement analysis uses the total period of observation instead of discrete points in time, it may be more sensitive to detecting those differences that were hypothesized prior to initiating the study. This paper will demonstrate the use of repeated measurement analysis to compare rates, pattern, and timing of symptom change between maprotiline and amitriptyline over the 4 weeks of treatment.

Lithium and antidepressants: inhibiting eicosanoids, stimulating immunity, and defeating microorganisms

Infection-emerging, reemerging, antibiotic-resistant, and bioengineered-increasingly threatens mankind. It is widely assumed that immunostimulating agents, were they to exist, would be ideal in battling microorganisms. Various investigators have established lithium and antidepressants as immunostimulants and antimicrobials and they have identified the mechanisms involved. Eicosanoids both depress immunity and activate microorganisms and lithium and antidepressants oppose eicosanoids. Such philosophers of science as Paul Feyerabend have argued that special interests invariably oppose revolutionary paradigms.

Brief communication treatment of delusional depression with tranylcypromine.

Patients with depressions accompanied by delusional thinking are reported to respond poorly to tricyclic antidepressants. We present four cases of delusional depression successfully treated with tranylcypromine. Three patients had previously been treated unsuccessfully with adequate trials of tricyclic antidepressants and one had been treated with a tricyclic-phenothiazine combination with a poor response. These four patients experienced a dramatic reduction in depression and delusional thinking when treated with tranylcypromine. On the basis of these cases, tranylcypromine appears to be an effective treatment for some patients with delusional depressions.

Familial Responses to Mental Illness

An understanding of the sequential pattern and the variety of reactions can enable the therapist to intervene more appropriately and efficaciously

Dual suicide in homosexuals

Although it has been reported that approximately 5 per cent of all joint suicides involve homosexuals, a detailed case study of a suicide pact involving homosexuals has not appeared in the literature. This paper attempts to fill this gap by reporting a joint suicide attempt involving two male homosexuals. One of the men involved had an extremely conflictual relationship with his mother and in the past had attempted to arrange a dual suicide with female acquaintances. Unable to find a girl who would agree to this, he turned to a fellow homosexual. The other individual accepted the proposition more out of a desire to play out homosexual and aggressive fantasies than out of any real desire to die. The episode ended when this person called for help following the joint overdose. Ernest Jones and Sadger have noted the presence of homosexual urges and the desire for eternal union with the maternal figure in cases of dual suicide. Contemporary theorists have discussed the role in homosexuality of a primary conflict involving both the desire for and the dread of union with the mother. Such dynamics are clearly demonstrated to be operative in the young man who initiated the suicide pact. The paper further discusses the role of murderous wishes and sexual fantasies as important factors in the second young mans participation in the suicide pact and calls attention to the role of aggression in homosexuality. It is conceivable that dual suicides among homosexuals may be more common than has been reported. In fact, the authors have been informed of other cases appearing in the emergency rooms of big city hospitals that have not been reported. It is hoped that this article will stimulate further investigation.

The role of prostaglandin E2 in seminal immunosuppression

Seminal plasma, which has high antigenic potential and the capacity to induce immunosuppression, has been incriminated as a possible factor in the acquired immunodeficiency syndrome (AIDS). Seminal plasma contains high concentrations of prostaglandins, which are capable of inducing immunosuppression. As prostaglandin E2 is noted for its immunosuppressive actions, we designed this study to determine whether this prostaglandin is responsible for seminal immunosuppression. Diluted and undiluted samples of semen from 5 heterosexual donors induced a significant suppression of phytohaemagglutinin-stimulated thymidine incorporation into lymphocytes. However, when the prostaglandin E2 levels of the semen samples were extrapolated to a standard prostaglandin E2 dose-response curve, the estimated values did not agree with the prostaglandin E2 levels. We conclude that prostaglandin E2 may contribute to seminal immunosuppression, but is not solely responsible for it.