D-2 DOPAMINE-RECEPTOR UP-REGULATION, TREATMENT RESPONSE, NEUROLOGICALSOFT SIGNS, AND EXTRAPYRAMIDAL SIDE-EFFECTS IN SCHIZOPHRENIA - A FOLLOW-UP-STUDY WITH I-123 IODOBENZAMIDE SINGLE-PHOTON EMISSION COMPUTED-TOMOGRAPHY IN THE DRUG-NAIVE STATE AND AFTER NEUROLEPTIC TREATMENT

Background: Animal and postmortem studies indicate that neuroleptic th erapy may induce D-2 dopamine receptor up-regulation in the basal gang lia, Methods: To address this phenomenon in a clinical study, we inves tigated the D-2 dopamine receptor binding in 15 DSM-III-R schizophreni cs in the drug-naive state and 3 days after completion of a standardiz ed neuroleptic therapy (benperidol 12-16 mg/day, for 25 days) using si ngle photon emission computed tomography (SPECT). SPECT scans were obt ained 2 hours after intravenous injection of 185 MBq I-123-iodobenzami de. For analysis, basal ganglia to frontal cortex (BG/FC) ratios were calculated and the patient sample was subgrouped into patients with a favorable versus a poor treatment response. Results: Neuroleptic treat ment led to decreased BG/FC ratios in patients with a favorable respon se, but increased ratios in the poor responders (df = 1, F = 4.1, p = .06), Changes of BG/FC ratios were significantly correlated with extra pyramidal side effects but not with neurological soft signs. Conclusio ns: Our findings suggest that neuroleptic therapy may induce D-2 dopam ine receptor up-regulation in a subgroup of patients characterized by poor treatment response and pronounced extrapyramidal side effects. (C ) 1998 Society of Biological Psychiatry.