RATIONALE: Current perspectives on the pathophysiology of schizophrenia direct attention to serotonergic (serotonin, 5-HT) dysregulation in the prodrome or at-risk mental state (ARMS). OBJECTIVE: To study the cerebral 5-HT(2A) receptor (5-HT(2A)R) in the ARMS with [(18)F]altanserin positron emission tomography (PET) and a bolus-infusion paradigm. MATERIALS AND METHODS: We quantified the spatial distribution of 5-HT(2A)R binding potential (BP(1)') in never-medicated subjects assigned to early (n = 6) and late (n = 8) prodromal states of schizophrenia relative to healthy controls (n = 21). Five single nucleotide polymorphisms (SNPs) in the 5-HT(2A)R-encoding gene (HTR2A; 13q14-21) were genotyped to control for a potential bias in BP(1)' due to between-group differences in genotype distributions. RESULTS: Group comparisons of partial-volume corrected PET data by statistical parametric mapping and confirmatory volume of interest analysis yielded a dissemination of BP(1)' decreases consistent with increasing levels of risk. An additional decrease in caudate BP(1)' was present in subjects who subsequently converted to first-episode psychosis (n = 5), but absent in non-converters (n = 9). Between-group differences were not confounded by a differential distribution of SNP genotypes. CONCLUSION: These results suggest a progressive reduction of cortical 5-HT(2A)R density as a surrogate biological measure of increased risk for schizophrenia, irrespective of conversion. Progressive reductions of subcortical 5-HT(2A)R density could provide an indicator of illness activity and help to predict imminent conversion to schizophrenia. Moreover, our findings substantiate the rationale for establishing a phase-specific psychopharmacological intervention in the ARMS that addresses the serotonergic component of vulnerability to schizophrenia.
RATIONALE: Current perspectives on the pathophysiology of schizophrenia direct attention to serotonergic (serotonin, 5-HT) dysregulation in the prodrome or at-risk mental state (ARMS). OBJECTIVE: To study the cerebral 5-HT(2A) receptor (5-HT(2A)R) in the ARMS with [(18)F]altanserin positron emission tomography (PET) and a bolus-infusion paradigm. MATERIALS AND METHODS: We quantified the spatial distribution of 5-HT(2A)R binding potential (BP(1)') in never-medicated subjects assigned to early (n = 6) and late (n = 8) prodromal states of schizophrenia relative to healthy controls (n = 21). Five single nucleotide polymorphisms (SNPs) in the 5-HT(2A)R-encoding gene (HTR2A; 13q14-21) were genotyped to control for a potential bias in BP(1)' due to between-group differences in genotype distributions. RESULTS: Group comparisons of partial-volume corrected PET data by statistical parametric mapping and confirmatory volume of interest analysis yielded a dissemination of BP(1)' decreases consistent with increasing levels of risk. An additional decrease in caudate BP(1)' was present in subjects who subsequently converted to first-episode psychosis (n = 5), but absent in non-converters (n = 9). Between-group differences were not confounded by a differential distribution of SNP genotypes. CONCLUSION: These results suggest a progressive reduction of cortical 5-HT(2A)R density as a surrogate biological measure of increased risk for schizophrenia, irrespective of conversion. Progressive reductions of subcortical 5-HT(2A)R density could provide an indicator of illness activity and help to predict imminent conversion to schizophrenia. Moreover, our findings substantiate the rationale for establishing a phase-specific psychopharmacological intervention in the ARMS that addresses the serotonergic component of vulnerability to schizophrenia.
Authors: R Lewis; S Kapur; C Jones; J DaSilva; G M Brown; A A Wilson; S Houle; R B Zipursky Journal: Am J Psychiatry Date: 1999-01 Impact factor: 18.112
Authors: H S Mayberg; M Liotti; S K Brannan; S McGinnis; R K Mahurin; P A Jerabek; J A Silva; J L Tekell; C C Martin; J L Lancaster; P T Fox Journal: Am J Psychiatry Date: 1999-05 Impact factor: 18.112
Authors: Tara A Niendam; Tyler A Lesh; Jong Yoon; Andrew J Westphal; Natalie Hutchison; J Daniel Ragland; Marjorie Solomon; Michael Minzenberg; Cameron S Carter Journal: Psychiatry Res Date: 2013-10-11 Impact factor: 3.222
Authors: Andreas Matusch; Carsten Saft; David Elmenhorst; Peter H Kraus; Ralf Gold; Hans-Peter Hartung; Andreas Bauer Journal: Eur J Nucl Med Mol Imaging Date: 2014-02-25 Impact factor: 9.236
Authors: Heidi W Thermenos; Richard J Juelich; Samantha R DiChiara; Raquelle I Mesholam-Gately; Kristen A Woodberry; Joanne Wojcik; Nikos Makris; Matcheri S Keshavan; Susan Whitfield-Gabrieli; Tsung-Ung W Woo; Tracey L Petryshen; Jill M Goldstein; Martha E Shenton; Robert W McCarley; Larry J Seidman Journal: Schizophr Res Date: 2016-03-07 Impact factor: 4.939
Authors: Neil M Richtand; Rebecca Ahlbrand; Paul Horn; Rabindra Tambyraja; Molly Grainger; Stefanie L Bronson; Robert K McNamara Journal: Physiol Behav Date: 2012-02-09
Authors: Wolfgang Maier; Rainald Mössner; Boris B Quednow; Michael Wagner; René Hurlemann Journal: Eur Arch Psychiatry Clin Neurosci Date: 2008-11 Impact factor: 5.270
Authors: Douglas N Greve; Claus Svarer; Patrick M Fisher; Ling Feng; Adam E Hansen; William Baare; Bruce Rosen; Bruce Fischl; Gitte M Knudsen Journal: Neuroimage Date: 2013-12-19 Impact factor: 6.556
Authors: Tiffany W Chow; David C Mamo; Hiroyuki Uchida; Ariel Graff-Guerrero; Sylvain Houle; Gwenn S Smith; Bruce G Pollock; Benoit H Mulsant Journal: BMC Med Imaging Date: 2009-07-06 Impact factor: 1.930