Relations of clinical features, subgroups and medication to serum monoamines in schizophrenia
Introduction : Plasma and serum indices of monoaminergic activity reflect partly the illness of schizophrenia (e.g. relationship of HVA levels to the deficit syndrome) and sometimes the individual symptoms (e.g. HVA levels with features of anhedonia) . But, such studies have rarely taken both the metabolites and the parent monoamines or inter - amine ratios into account. [ HVA = metabolite of dopamine (DA)] Aims : We hypothesised that a comparison of the major symptom dimensions expressed with measures of neurotransmitter activity (with and without control for the antipsychotic drug treatment) would show differential patterns of activity reflecting a) the sub-groups of schizophrenia, and would thus, b) be useful for the design of pharmacological treatments. Methods : Dopamine (DA), noradrenaline (NA), serotonin (5-HT), their three major metabolites (HVA, MHPG, 5-HIAA) and prolactin (PRL) were measured in the serum of 108 patients with schizophrenia and 63 healthy controls matched for age, gender and socio-economic factors. DA D2-receptor blocking activity was estimated from a regression of butyrophenone displacement in pig striatum in vitro on to PET reports of drug-binding in vivo. Symptoms were factor-analysed into 4 dimensions (disorganised / thought disordered, non-paranoid / negative, ideas-of-reference, and paranoid / positive dimensions) . Results : 1/ Patients' DA activity did not differ from controls': but their 5-HT activity increased, and NA activity decreased. Further the DA / 5-HT metabolite ratio (HVA/5-HIAA) was lower. Increased DA-D2 receptor occupancy was predicted by decreased DA metabolism and its ratio to 5-HT metabolism (HVA/5-HIAA). 2/ Comparing responses to atypical vs. typical neuroleptic drugs patients showed higher levels of NA, of DA metabolites and the DA/5-HT metabolite ratios (HVA/5-HIAA). 3/ In paranoid patients increased DA D2-occupancy was associated with lower DA metabolism, but this in non-paranoid patients this was unrelated to the recorded increase of D/5-HT metabolite ratio (HVA/5-HIAA) and NA metabolism (MHPG).figure 3) 4/ Low DA / 5-HT metaboite ratios (HVA / 5-HIAA), high prolactin, and low DA metabolism characterised thought-disordered patients. 5/ High DA/5-HT metabolite ratios (HVA / 5-HIAA) paralleled many ideas-of reference. The metabolic differences were sensitive to statistical control for D2-receptor occupancy and PRL levels. Conclusions : The role of DA in paranoid patients, and opposing changes (and significant role) of 5-HT in patients with thought disorder vs. ideas of reference point both to the mechanisms underlying these different symtom features typical of some sub-groups of patients with schizophrenia, and to the type of medication strategy that might be appropriate
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