• The incidence of suicidal acts was studied in 68 depressed patients and related to the level of 5-hydroxyindoleacetic acid (5HIAA) in the cerebrospinal fluid. The distribution of 5-HIAA levels was bimodal. Patients in the low 5-HIAA mode (below 15 ng/ml) attempted suicide significantly more often than those in the high mode, and they used more violent means. Two of the 20 patients in the low mode, and none of the 48 patients in the high mode died from suicide.

5-HIAA in the Cerebrospinal Fluid: A Biochemical Suicide Predictor?

Normal male human subjects ingested amino acid mixtures which were tryptophan-free, balanced or contained excess tryptophan. The tryptophan-free mixture causes a marked depletion of plasma tryptophan by 5 h. At this time the subjects in the tryptophan-free group had significantly elevated scores on the depression scale of the Multiple Affect Adjective Checklist. The tryptophan-free group also performed worse than the other two groups in a proofreading task carried out while listening to a tape with themes of hopelessness and helplessness (dysphoric distractor). Cognitive theories of depression predict greater distractability of depressed individuals by dysphoric themes. Thus, both measures indicate a rapid mood lowering effect of tryptophan depletion in normal males. This effect is probably mediated by a lowering of brain 5-hydroxytryptamine. Although the mood-lowering effect was not as great as that seen in depressed patients, our results suggest that low brain 5HT might be one factor precipitating depression in some patients.

Tryptophan depletion causes a rapid lowering of mood in normal males

Prozac (fluoxetine, Lilly 110140), the first selective serotonin uptake inhibitor and an antidepressant drug: twenty years since its first publication.

Increased serotonin-2 binding sites in frontal cortex of suicide victims

Animal models of depression: an overview.

Intensification of the central serotoninergic processes as a possible determinant of the thymoleptic effect.

Involvement of brain serotonin in the stimulant action of amphetamine and of cholinolytics.

We previously described a test for screening thymoleptic drugs. This test is based on measuring sedation (loss of the righting reflex) and of twitches of the extremities in the frog. Both effects are presumably related to activation of central 5-hydroxytryptamine (5-HT) processes (Lapin, Oxenkrug & others, 1970). We now report our observations on the relation between chemical structure of tricyclic antidepressants and their activity in this test. Male frogs (Ram tempm aria) were used in our experimental procedure identical to that described earlier, except that the experiments were made in winter whilst the previous experiments were made in spring and summer. We used chlorimipramine, imipramine, amitriptyline and desipramine and nortriptyline. We measured the minimal doses that produced inhibition of the righting reflex and the appearance of twitches of the extremities 4 h after injecting reserpine. Both sedation and twitches were observed when the elevation of brain 5-HT was 3-fold or more (Oxenkrug, Osipova & Uskova, 1970). Since an increase in brain 5-HT was produced by a combination of phenelzine (25 mg/kg) with reserpine (10 mg/kg) or more so by phenelzine alone (25 mg/kg) (Oxenkrug & others, 1970), one series of our experiments was done without reserpine (Table 1).

Effect of dimethyl and monomethyl tricyclic antidepressants on central 5-hydroxytryptamine processes in the frog.

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Intensification of the central serotoninergic processes as a possible determinant of the thymoleptic effect.

Involvement of brain serotonin in the stimulant action of amphetamine and of cholinolytics.

Effect of dimethyl and monomethyl tricyclic antidepressants on central 5-hydroxytryptamine processes in the frog.