Brain serotonin 5-HT(1A) receptor binding in schizophrenia measured by positron emission tomography and [11C]WAY-100635.
BACKGROUND
Results of postmortem studies show an elevation in serotonin-1A (5-hydroxytryptamine-1A [5-HT(1A)]) receptor density in the prefrontal and temporal cortices of patients with schizophrenia. This study examined 5-HT(1A) receptors in vivo in patients with schizophrenia using positron emission tomography and [carbonyl-(11)C]-N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexane carboxamide ([(11)C]WAY-100635).


METHODS
The 5-HT(1A) binding potential of 14 antipsychotic drug-naïve patients with a DSM-IV diagnosis of schizophrenia was compared with that of 14 age-matched healthy controls. Positron emission tomography data were analyzed using 9 cortical regions of interest, which were delineated on a coregistered magnetic resonance image and transferred to the positron emission tomographic image, with the cerebellum as the reference region for a simplified reference tissue model. We also performed a voxel-wise comparison using statistical parametric mapping.


RESULTS
The region of interest-based analysis revealed a significant mean +/- SD cortical 5-HT(1A) receptor binding potential increase of 7.1% +/- 6.4% in patients with schizophrenia (F = 2.975; P =.02); local differences were +20% in the left medial temporal cortex (F = 9.339;P =.005) and +13% in the right medio temporal cortex (F = 4.453; P =.045). There were no significant differences in regional tracer delivery or cerebellar [(11)C]WAY-100635 uptake. The voxel-based analysis also confirmed a group difference in the left medial temporal cortex.


CONCLUSIONS
The biological significance of elevated 5-HT(1A) receptor density in schizophrenia remains unclear. Given the location of 5-HT(1A) receptors on pyramidal cells, this elevation may reflect an abnormal glutamatergic network. Our finding needs to be viewed in light of preclinical evidence supporting a role for 5-HT(1A) receptors in mediating antipsychotic action and extrapyramidal adverse effects of drugs.
Tauscher
Johannes
J
PET Centre, Toronto, Ontario. johannes.tauscher@akh-wien.ac.at
Kapur
Shitij
S
Verhoeff
N Paul L G
NP
Hussey
Douglas F
DF
Daskalakis
Zafiris J
ZJ
Tauscher-Wisniewski
Sitra
S
Wilson
Alan A
AA
Houle
Sylvain
S
Kasper
Siegfried
S
Zipursky
Robert B
RB
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D001923:Brain Chemistry; D002531:Cerebellum / Q000737:chemistry / Q000378:metabolism; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010879:Piperazines; D017966:Pyramidal Cells / Q000737:chemistry / Q000000981:diagnostic imaging / Q000378:metabolism; D011725:Pyridines; D011985:Receptors, Serotonin / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D012559:Schizophrenia / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000378:metabolism; D012702:Serotonin Antagonists; D013702:Temporal Lobe / Q000737:chemistry / Q000378:metabolism; D014055:Tomography, Emission-Computed / Q000379:methods / Q000706:statistics & numerical data*
D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide