Measurement of the serotonin 1A receptor availability in patients with schizophrenia during treatment with the antipsychotic medication ziprasidone.
The aim of this study was to compare 5-HT(1A) availability in vivo in individuals with schizophrenia before and during treatment with the atypical antipsychotic ziprasidone. Six individuals with schizophrenia underwent two PET scans with [(11)C]WAY 100635; the first while medication-free (baseline) and the second while taking the atypical antipsychotic ziprasidone (on-medication). Regional volumes of distribution (V(T), mL g(-1)) were derived using a two-tissue compartment kinetic model. Outcome measures included binding potential relative to the plasma (BP(P), mL g(-1)) and the binding potential relative to the nonspecific distribution volume (BP(ND), unitless). No significant differences were observed in regional BP(P) or BP(ND) with ziprasidone treatment. A significant correlation was noted between BP(P) measured in the orbitofrontal cortex during the on-medication condition and degree of improvement in negative symptoms with treatment (r = 0.96, p = 0.004). Consistent with the published literature of changes in 5-HT(1A) binding during treatment with 5-HT(1A) receptor agonists, this study did not detect a significant reduction in 5-HT(1A) binding with ziprasidone. The finding of a relationship between 5-HT(1A) binding and the degree of improvement in negative symptoms provides further support for the role of the 5-HT(1A) receptor in the pathophysiology and treatment of this symptom domain.
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, USA. franklewg@upmc.edu
W Gordon
WG
Frankle
Ilise
I
Lombardo
Lawrence S
LS
Kegeles
Mark
M
Slifstein
John H
JH
Martin
Yiyun
Y
Huang
Dah-Ren
DR
Hwang
Elisa
E
Reich
Claudine
C
Cangiano
Roberto
R
Gil
Anissa
A
Abi-Dargham
Marc
M
Laruelle
D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002250:Carbon Radioisotopes; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use*; D049268:Positron-Emission Tomography / Q000379:methods; D011569:Psychiatric Status Rating Scales; D011725:Pyridines; D011869:Radioligand Assay / Q000379:methods; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D012702:Serotonin Antagonists; D013844:Thiazoles / Q000494:pharmacology* / Q000627:therapeutic use*
D014150:Antipsychotic Agents; D002250:Carbon Radioisotopes; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D013844:Thiazoles; D044282:Receptor, Serotonin, 5-HT1A; C092292:ziprasidone; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide