D2 dopamine receptor up-regulation, treatment response, neurological soft signs, and extrapyramidal side effects in schizophrenia: a follow-up study with 123I-iodobenzamide single photon emission computed tomography in the drug-naive state and after neuroleptic treatment.
BACKGROUND
Animal and postmortem studies indicate that neuroleptic therapy may induce D2 dopamine receptor up-regulation in the basal ganglia.


METHODS
To address this phenomenon in a clinical study, we investigated the D2 dopamine receptor binding in 15 DSM-III-R schizophrenics in the drug-naive state and 3 days after completion of a standardized neuroleptic therapy (benperidol 12-16 mg/day, for 25 days) using single photon emission computed tomography (SPECT). SPECT scans were obtained 2 hours after intravenous injection of 185 MBq 123I-iodobenzamide. 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 treatment led to decreased BG/FC ratios in patients with a favorable response, but increased ratios in the poor responders (df = 1, F = 4.1, p = .06). Changes of BG/FC ratios were significantly correlated with extrapyramidal side effects but not with neurological soft signs.


CONCLUSIONS
Our findings suggest that neuroleptic therapy may induce D2 dopamine receptor up-regulation in a subgroup of patients characterized by poor treatment response and pronounced extrapyramidal side effects.
Schröder
J
J
Department of Psychiatry, University of Heidelberg, Germany.
Silvestri
S
S
Bubeck
B
B
Karr
M
M
Demisch
S
S
Scherrer
S
S
Geider
F J
FJ
Sauer
H
H
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001479:Basal Ganglia / Q000000981:diagnostic imaging; D001480:Basal Ganglia Diseases / Q000139:chemically induced / Q000000981:diagnostic imaging*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis* / Q000187:drug effects; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism*; D012565:Schizophrenic Psychology; D015899:Tomography, Emission-Computed, Single-Photon; D015854:Up-Regulation / Q000187:drug effects*
D014150:Antipsychotic Agents; D007457:Iodine Radioisotopes; D017448:Receptors, Dopamine D2