Background: Plasma and serum indices of monoaminergic activity reflect partly the illness of schizophrenia (e.g. HVA/deficit syndrome) and sometimes the symptoms (e.g. HVA/anhedonia). But, such studies have rarely taken both metabolites and parent amines or inter-amine activity ratios into account. We hypothesized that comparing the major symptom dimensions to measures of transmitter activity (with and without control for antipsychotic drug treatment) would show differential patterns of activity useful for the design of pharmacological treatments.

Methods: Dopamine (DA), noradrenaline (NA), serotonin (5-HT), their 3 major metabolites and prolactin were measured in the serum of 108 patients with schizophrenia and 63 matched controls: DA D2-receptor blocking-activity was estimated from a regression of butyrophenone displacement in striatum in vitro on to PET reports of drug-binding in vivo. Symptoms were factored into 4 dimensions (disorganized/thought disorder, nonparanoid/negative, ideas-of-reference and paranoid/positive symptoms).

Results: (1) Patients’ DA activity did not differ from controls: but their 5-HT and NA turnovers increased and the DA/5HT-metabolite ratio was lower. Increased DA-D2-receptor occupancy was predicted by decreased DA-metabolism and its ratio to 5-HT-metabolism. (2) Patients had higher levels of NA, DA-metabolites and DA-/5-HT-metabolite ratios on atypical vs. typical drugs. (3) Increased D2-occupancy was associated with lower DA metabolism in paranoid patients but was unrelated to relative increases of 5-HT- and NA-metabolism in nonparanoid patients. (4) Low DA-/5-HT-meta-bolite ratios, high prolactin and low DA-metabolism characterized thought-disordered patients. (5) High DA-/5-HT-metabolite ratios paralleled many ideas-of-reference. The metabolites were sensitive, respectively, to control for D2-occupancy and prolactin.

Conclusions: The role of DA in paranoid, and 5-HT in thought-disordered and ideas-of-reference dimensions point both to the mechanisms underlying the features typical of these subgroups and the type of medication appropriate.