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.
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.
Authors: Sergey Shcherbinin; Orla Doyle; Fernando O Zelaya; Sara de Simoni; Mitul A Mehta; Adam J Schwarz Journal: Psychopharmacology (Berl) Date: 2015-07-31 Impact factor: 4.530
Authors: Masakuni Horiguchi; Kayleen E Hannaway; Adesewa E Adelekun; Karu Jayathilake; Herbert Y Meltzer Journal: Neuropsychopharmacology Date: 2012-06-27 Impact factor: 7.853
Authors: W Gordon Frankle; Ilise Lombardo; Lawrence S Kegeles; Mark Slifstein; John H Martin; Yiyun Huang; Dah-Ren Hwang; Elisa Reich; Claudine Cangiano; Roberto Gil; Marc Laruelle; Anissa Abi-Dargham Journal: Psychopharmacology (Berl) Date: 2006-09-05 Impact factor: 4.530
Authors: Robert C Wolf; Michael M Plichta; Fabio Sambataro; Andreas J Fallgatter; Christian Jacob; Klaus-Peter Lesch; Martin J Herrmann; Carlos Schönfeldt-Lecuona; Bernhard J Connemann; Georg Grön; Nenad Vasic Journal: Hum Brain Mapp Date: 2009-07 Impact factor: 5.038