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Studies on platelet serotonin system in hospitalized schizophrenics

Besides dopamine, being the monoamine most clearly implicated in schizophrenia, the recent introduction of antipsychotic drugs that combine antagonistic activity toward dopamine and serotonin receptors had revived interest for possible serotonergic dysfunctions in schizophrenia as well. Platelet studies in schizophrenic patients were mostly targeted to a single serotonergic measure and conclusions among different studies regarding observed alterations are not congruent. The important prerequisites for such studies are the use of standardized, well established methods and the choice of patients from clearly-defined diagnostic categories (Pletscher, 1991). After thorough methodological studies, we performed measuring of platelet variables in a large control population of healthy volunteers, in order to get acquaintance with all relevant physiological characteristics of these parameters which can influence clinical studies. Then we started with the simultaneous measurements of three platelet serotonergic parameters: platelet serotonin level (PSL), platelet serotonin uptake (PSU) and platelet monoamine oxydase activity (MAO-B) in schizophrenic patients. PSL was measured fluorimetrically, serotonin membrane transport as well as platelet MAO activity were subjected to full kinetic analysis with the calculation of kinetic constants (Km and Vmax) according to procedures reported elsewhere (v. Jernej et al., this volume). In order to obtain homogenous group of patients we used Research Diagnostic Criteria (developed by R.L. Spitzer et al., New York State Psychiatric Institute) with the application of the Schedule for Affective Disorders and Schizophrenia (SADS). Patients who were, in the course of the present illness or in the past, diagnosed as schizophrenic according to ICD IX or ICD X but do not meet RCD criteria were excluded from the study. The study included, up to this moment, 19 patients 17 of them as definite and 2 as probable. Regarding the subtyping based on the phenomenology of the present period of schizophrenic illness the group consisted of 8 paranoid, 7 schizoaffective, 2 residual, 1 disorganized and 1 undifferentiated patient. In the whole group of patients studied we have obtained following platelet measures (all values are expressed as means ± standard deviations): PSL = 713 ± 284 (N = 19) vs. controls 571 ± 128 (N = 26) expressed as ng of 5HT/10e9 platelets ; PSU (Vmax) = 112.8 ± 28.9 (N = 16) vs. controls 138 ± 19.8 (N = 26) expressed as pmol 5HT/10e8 platelets/min. ; MAO-B (Vmax) = 10.5 ± 4.9 (N = 17) v.s. controls 12.6 ± 4.8 (N = 23) expressed as nmol of product/10e8 platelets/60 min. All platelet measures in schizophrenic patients did not show statistically significant difference from the values of control subjects. Regarding MAO activity this accords with recent report of meta- analysis study where the authors concluded that in unmedicated schizophrenic patients there was no alteration in platelet MAO activity. In comparison to control group PSL and PSU in patients demonstrated wider distribution of individual values. In the case of PSU values of two patients fell under the value of 90 which is, by our experience, practically the lower border for larger normal population. Similar finding was observed in the case of PSL but in opposite direction. Namely 4 out of 19 schizophrenic patients in which measurement of PSL was performed, demonstrated values above 1000 (1006- 1192) which is rarely encountered in normal population (only 5 cases in population of 182). These results point out to higher variability (and potential disturbances) in 5HT uptake/storage processes in schizophrenic patients. However the presented results, although indicative, should be taken with caution owing to the limited number of patients studied up to this moment. References Pletscher, A. (1991) Platelets as peripheral models for neuropsychiatry: A brief review. In: G. Racagni, N. Brunello, T. Fukuda, eds. Biological psychiatry, vol 2, Excerpta Medica, Amsterdam, p. 354-356 Marcolin M.A. and Davis J.M, (1992) Platelet monoamine oxydase in schizophrenia: a meta- analysis. Schizophrenia Res. 7, 249-258.

platelet; serotonin; schizophrenia

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