OBJECTIVE: We sought to determine whether the Val(158)Met polymorphism in the catechol-O-methyltransferase (COMT) gene influences neurodegeneration within dopamine-innervated brain regions. METHODS: A total of 252 subjects, including healthy controls and patients with Alzheimer disease, behavioral variant frontotemporal dementia, and semantic dementia, underwent COMT genotyping and structural MRI. RESULTS: Whole-brain voxel-wise regression analyses revealed that COMT Val(158)Met Val allele dosage, known to produce a dose-dependent decrease in synaptic dopamine (DA) availability, correlated with decreased gray matter in the region of the ventral tegmental area (VTA), ventromedial prefrontal cortex, bilateral dorsal midinsula, left dorsolateral prefrontal cortex, and right ventral striatum. Unexpectedly, patients carrying a Met allele showed greater VTA volumes than age-matched controls. Gray matter intensities within COMT-related brain regions correlated with cognitive and behavioral deficits. CONCLUSIONS: The results are consistent with the hypothesis that increased synaptic DA catabolism promotes neurodegeneration within DA-innervated brain regions.
OBJECTIVE: We sought to determine whether the Val(158)Met polymorphism in the catechol-O-methyltransferase (COMT) gene influences neurodegeneration within dopamine-innervated brain regions. METHODS: A total of 252 subjects, including healthy controls and patients with Alzheimer disease, behavioral variant frontotemporal dementia, and semantic dementia, underwent COMT genotyping and structural MRI. RESULTS: Whole-brain voxel-wise regression analyses revealed that COMTVal(158)MetVal allele dosage, known to produce a dose-dependent decrease in synaptic dopamine (DA) availability, correlated with decreased gray matter in the region of the ventral tegmental area (VTA), ventromedial prefrontal cortex, bilateral dorsal midinsula, left dorsolateral prefrontal cortex, and right ventral striatum. Unexpectedly, patients carrying a Met allele showed greater VTA volumes than age-matched controls. Gray matter intensities within COMT-related brain regions correlated with cognitive and behavioral deficits. CONCLUSIONS: The results are consistent with the hypothesis that increased synaptic DA catabolism promotes neurodegeneration within DA-innervated brain regions.
Authors: H J Rosen; M L Gorno-Tempini; W P Goldman; R J Perry; N Schuff; M Weiner; R Feiwell; J H Kramer; B L Miller Journal: Neurology Date: 2002-01-22 Impact factor: 9.910
Authors: D Neary; J S Snowden; L Gustafson; U Passant; D Stuss; S Black; M Freedman; A Kertesz; P H Robert; M Albert; K Boone; B L Miller; J Cummings; D F Benson Journal: Neurology Date: 1998-12 Impact factor: 9.910
Authors: Andreas Meyer-Lindenberg; Philip D Kohn; Bhaskar Kolachana; Shane Kippenhan; Aideen McInerney-Leo; Robert Nussbaum; Daniel R Weinberger; Karen Faith Berman Journal: Nat Neurosci Date: 2005-04-10 Impact factor: 24.884
Authors: Barbara Borroni; Chiara Agosti; Silvana Archetti; Chiara Costanzi; Silvia Bonomi; Diego Ghianda; Gian Luigi Lenzi; Luigi Caimi; Monica Di Luca; Alessandro Padovani Journal: Neurosci Lett Date: 2004-11-11 Impact factor: 3.046
Authors: M Matsumoto; C Shannon Weickert; M Akil; B K Lipska; T M Hyde; M M Herman; J E Kleinman; D R Weinberger Journal: Neuroscience Date: 2003 Impact factor: 3.590
Authors: Jingshan Chen; Barbara K Lipska; Nader Halim; Quang D Ma; Mitsuyuki Matsumoto; Samer Melhem; Bhaskar S Kolachana; Thomas M Hyde; Mary M Herman; Jose Apud; Michael F Egan; Joel E Kleinman; Daniel R Weinberger Journal: Am J Hum Genet Date: 2004-09-27 Impact factor: 11.025
Authors: Josh D Woolley; Baber K Khan; Alamelu Natesan; Anna Karydas; Mary Dallman; Peter Havel; Bruce L Miller; Katherine P Rankin Journal: Neurology Date: 2014-01-10 Impact factor: 9.910
Authors: Antonio Verdejo-García; Ana Beatriz Fagundo; Aida Cuenca; Joan Rodriguez; Elisabet Cuyás; Klaus Langohr; Susana de Sola Llopis; Ester Civit; Magí Farré; Jordi Peña-Casanova; Rafael de la Torre Journal: Neuropsychopharmacology Date: 2013-02-28 Impact factor: 7.853
Authors: Jennifer S Yokoyama; Luke W Bonham; Renee L Sears; Eric Klein; Anna Karydas; Joel H Kramer; Bruce L Miller; Giovanni Coppola Journal: BMC Neurol Date: 2015-03-28 Impact factor: 2.474
Authors: Laura Del Hoyo; Laura Xicota; Klaus Langohr; Gonzalo Sánchez-Benavides; Susana de Sola; Aida Cuenca-Royo; Joan Rodriguez; Jose Rodríguez-Morató; Magí Farré; Mara Dierssen; Rafael de la Torre Journal: Front Behav Neurosci Date: 2016-10-17 Impact factor: 3.558