The active uptake of serotonin by platelets of schizophrenic patients and their families: Possibility of a genetic marker

Abstract

The active uptake of serotonin (5-HT) blood platelets of 20 schizophrenic patients and their families was studied. The uptake was studied over a wide range of 5-HT concentrations (0.1-20 microM), and Km and Vmax of the uptake process were calculated. Of 20 patients, 18 exhibited a lower rate of uptake than the family average at 5-HT concentrations lower than the Km value. At a 5-HT concentration of 0.1 microM, the average 5-HT uptake of patients was 2.15 pmol/10(8) platelets/min, while that of families was 2.99 pmol/10(8) platelets/min (33% difference). At a high 5-HT concentration, only the drug-treated patients had lower Vmax than the family average, and this might be attributed to the effect of the drugs. Km of patients and families were very similar. In eight families, one or more of the family members showed 5-HT uptake patterns very similar to that of the patient. We termed these healthy family members "schizophrenic risks". Our findings indicate the involvement of some genetic factors in this disease.

The Role of Serotonin in Schizophrenia

“…These sites appear to be specific for tricyclic antidepressants and their active metabolites (Langer et al 1981), and appear to have a functional relationship with the 5HT uptake or transport site, probably modulating inhibition of 5HT uptake (Paul et al 1980). While Rotman et al (1982 b ) reported decreased 3 H-imipramine binding and 5HT uptake in platelets of schizophrenic patients, Wood et al (1983), Gentsch et al (1985), Weizman et al (1985), Weizman et al (1987), and Kanof et al (1987) could not find any significant difference in 3 H-imipramine binding between schizophrenic and normal control subjects. Thus, it seems likely that the 3 H-imipramine binding site is intact in schizophrenia.…”

“…A number of studies conducted by Rotman's group (Modai et al 1979;Rotman et al 1979Rotman et al , 1980Rotman et al , 1982a have shown that 5HT uptake in platelets of schizophrenic patients is significantly reduced in comparison to normal controls. This finding was related High in schizophrenic patients with cortical atrophy or ventricular enlargement High in schizophrenic patients, particularly with chronic undifferentiated subtype High in schizophrenic patients, particularly correlated with auditory hallucinations High in schizophrenic patients High in schizophrenic patients, particularly correlated with cerebrospinal fluid 5hydroxyindoleacetic acid and abnormal motor behavior 62 'NS = no significant differences between groups.…”

“…A number of studies conducted by Rotman’s group (Modai et al 1979; Rotman et al 1979, 1980, 1982 a , 1982 b ) have shown that 5HT uptake in platelets of schizophrenic patients is significantly reduced in comparison to normal controls. This finding was related to a decrease in V max (Rotman et al 1979).…”

“…to a decrease in V max ). Some of the patients in these studies were receiving neuroleptic drugs, but the investigators claim to have found no effect of neuroleptics on 5HT uptake in in vitro studies of platelets of normal controls Rotman et al 1979). Decreased 5HT uptake by blood platelets of schizophrenic patients was reported by other investigators in studies of neuroleptic-treated patients (Wood et al 1983), drug-free patients (Kaplan and Mann 1982), and both drug-free and neuroleptic-treated patients (Lingjaerde 1983).…”

Factors affecting serotonin uptake into human platelets

“…Codd often interact, thus increasing the complexity of their influence. For example, intrinsic factors such as sex (Wirz-Justice and Chappuis-Arndt 1976;Guicheney and Marcel 1984) and genetic variability (Rotman et al 1982;Arora et al 1983;Codd and Walker 1987) may influence platelet 5 HT uptake differentially, depending upon their interactions with extrinsic factors such as time of day (Oxenkrug et al 1978;Humphries et al 1985; Modai et all. 1986), season (Wirz-Justice etal.…”